Sunday, June 9, 2013

TSEAC March 14, 2013: Transmissible Spongiform Encephalopathies Advisory Committee Meeting Webcast

March 14, 2013: Transmissible Spongiform Encephalopathies Advisory Committee Meeting Webcast




Webcast


























































































































Volume 19, Number 7—July 2013




Dispatch


Asynchronous Onset of Clinical Disease in BSE-Infected Macaques


Judith Montag1, Walter Schulz-Schaeffer, Annette Schrod, Gerhard Hunsmann, and Dirk Motzkus Author affiliations: German Primate Center, Göttingen, Germany (J. Montag, A. Schrod, G. Hunsmann, D. Motzkus); University of Göttingen, Göttingen (W. Schulz-Schaeffer)


Abstract


To estimate the effect of the variability of prion disease onset on primary bovine spongiform encephalopathy transmission to humans, we studied 6 cynomolgus macaques. The preclinical incubation period was significantly prolonged in 2 animals, implying that onset of variant Creutzfeldt-Jacob disease in humans could be more diverse than previously expected.


Prion diseases, such as bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep, and Creutzfeldt-Jakob disease (CJD) in humans, are fatal, transmissible, neurodegenerative disorders associated with the aggregation of an infectivity-associated isoform (PrPSc) of the cellular prion protein (PrP) (1). Seventeen years ago, it became apparent that the BSE-infectious agent had entered the food chain and was identified as the causative agent for a new variant CJD (vCJD) (2). Since then, several risk assessment studies have investigated the number of expected vCJD cases in human populations (reviewed in [3]). Although thousands to millions of consumers of beef products were estimated to be affected, thus far only a few more than 200 vCJD cases have been observed worldwide.


This discrepancy was assumed to be attributable to the so-called species barrier, defined as the hindrance of an infectious agent to change its natural host. Upon crossing the species barrier, prion diseases often show a low attack rate in conjunction with a high variability in the preclinical incubation time. Thus, the consumption of BSE-contaminated products may have led either to a restricted infection or to a prolonged asymptomatic phase in some exposed persons. Therefore, concerns have been raised that asymptomatic carriers of vCJD might exist, posing a risk for unintentional human-to-human transmission.


First indications that transmission of BSE to primates may lead to variances in the preclinical incubation times were obtained by inoculating cynomolgus macaques with cattle-derived BSE material (4–6), even though in those studies not more than 3 animals were used. We have now used a group of 6 macaques that were infected with BSE at a comparable age and kept under identical and controlled experimental conditions.


The Study Six captive-bred female cynomolgus macaques (Macaca fascicularis, purchased from the Centre de Recherche en Primatologie, Mauritius) were inoculated intracerebrally with 1 dose of 50 mg brain homogenate (10% wt/vol) derived from 11 BSE-infected cattle. Animal experimentation was performed in accordance with section 8 of the German Animal Protection Law in compliance with Directive 86/609/EEC. Macaques were housed in a social group, and behavioral changes were assessed on a daily basis by experienced animal care takers.


After inoculation, all 6 macaques remained healthy and asymptomatic for >30 months (Table). At 931 days postinfection, 1 animal showed indications of slight coordination disorders. Within a few days, afferent ataxia developed, and when the animal was separated from the others animals, she apparently became tame. After 2 weeks, the animal showed severe dysmetria of the extremities without obvious myoclonia. Dementia was apparent but could not be diagnosed by objective measures. For ethical reasons, the animal was euthanized 17 days after disease onset. Within the next 14 weeks, 3 more animals became symptomatic. After appearance of neurologic symptoms (ataxia, tremors), the affected animals were occasionally separated from the group when symptoms became more severe or attacks from asymptomatic animals occurred. The disease course in these animals was comparable to that of the first animal, but the progression was slower (91–103 days).


Figure 1


Figure 1. . Survival of intracerebrally BSE-infected cynomolgus macaques. Six age- and sex-matched cynomolgus macaques were inoculated intracerebrally with 50 mg brain homogenate (10% in sucrose) derived from 11 BSE-infected cattle. Macaques were...


Two of the 6 animals remained asymptomatic for ≈1 additional year. Although daily monitoring was facilitated by the fact that only 2 macaques remained and that the caretakers were more experienced to recognize minor changes in behavior, symptoms were first detected 1,340 and 1,398 days postinfection, respectively. Clinical signs were similar to those observed in the previous 4 animals. The symptomatic periods before euthanasia for these macaques lasted 103 and 143 days, respectively (Table). Direct comparison revealed that the difference between the short (931–1,025 days) and the long (1,340–1,398 days) preclinical incubation time was statistically significant (Figure 1, log-rank [Mantel-Cox] test, p<0 .05="" div="">

Test results of brain samples from all animals were positive for macaque-adapted BSE by Western blot analysis. In brief, brain tissue from each animal was homogenized and subjected to proteinase K (PK) treatment for 1 h at 37°C. Samples were separated on acrylamide gels and transferred to nitrocellulose membranes. Macaque-adapted BSE (PrPSc) was detected by using the monoclonal anti-PrP antibody 11C6. PK-resistant PrP was detected in all 6 macaques, confirming that BSE was transmitted to the animals.


Figure 2


Figure 2. . PrPSc profile of macaque-adapted BSE in comparison to human CJD. Brain homogenates from human sCJD type 1, sCJD type 2, vCJD, and BSE-infected macaques were subjected to PK treatment, separated...


The individual glycopattern and band migration of macaque-adapted PrPSc was compared with human sporadic CJD (sCJD) type 1, sCJD type 2, and vCJD. PK-resistant PrP from BSE-infected macaques co-migrated with type 2 sCJD and was clearly distinguishable from type 1 sCJD (Figure 2). The glycosylation pattern of macaque-adapted BSE was comparable with vCJD (6,7), which is characterized by an overrepresentation of diglycosylated PrPSc (8,9). Using 11C6 antibody (10), we detected a slightly decreased signal of the diglycosylated PrPSc isoform for sCJD, vCJD, and macaque-adapted BSE. We assume that this effect is related to a reduced affinity of the diglycosylated isoform to 11C6 that otherwise shows high sensitivity to macaque-adapted PrPSc. Nevertheless, direct comparison showed a higher amount of the diglysosylated PrPSc isoform in vCJD and macaque-adapted BSE than sCJD, which was also shown with a different monoclonal antibody, 3F4. This finding confirms that BSE transmission to macaques is comparable with, and can be used as a model for, human vCJD infection.


Conclusions


Several susceptibility studies using nonhuman primates as a model for human prion diseases hint to heterogeneity of the preclinical incubation period upon crossing the species barrier (5,11,12). However, because of the low number of no more than 3 animals, this variability was not always evident (4). Therefore, there was an urgent need to determine whether the transmission of BSE to humans is likely to lead to a similar diversity.


Our study using 6 cynomolgus macaques shows that the transmission of BSE to primates led to a significantly prolonged asymptomatic phase in 2 animals. Disease onset is influenced by several factors (13). Our study design enabled us to exclude that the route of transmission influenced the disease progression because the infectious agent was injected into the same brain region of each animal. Also, a limited infectious dose cannot be responsible, as shown by the attack rate of 100%. In addition, endogenous factors, such as age, the MM genotype at codon 129 (Table), and housing conditions, were comparable for all macaques.


Thus, we conclude that the variable asymptomatic phase is most likely influenced by the infectious agent (14) or the genomic diversity of the macaques (13). The animals in our study were not inbred. Therefore, differences in the genomic background may have influenced the time of disease onset. In contrast, the PrPSc migration patterns of the animals give no indications for different types or strains that evolved from the mixed BSE inoculum. However, further studies will have to verify this.


Nevertheless, during the BSE epidemics, the human population with its natural genomic diversity was also exposed to a nonhomogenous prion source. Therefore, our study closely mimics the human situation. Our results imply that a prolonged asymptomatic phase can be expected for vCJD. In light of the transmissibility of vCJD through blood transfusions (15), our findings emphasize the need for continued attention to the risks of secondary human-to-human transmission.


Dr Montag is a microbiologist at the Department of Molecular and Cell Physiology at the Hannover Medical School. Her primary research interests are the molecular mechanisms of disease pathology, including prion disorders and inherited cardiac diseases.


Acknowledgments We thank J.P. Deslys for providing vCJD material.


This study was supported by European Union grant QLK1-CT-2002-01096 and BMH4-CT-98-6029.


References




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Monday, October 10, 2011


EFSA Journal 2011 The European Response to BSE: A Success Story


snip...


EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.




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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


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Tuesday, March 05, 2013


A closer look at prion strains Characterization and important implications Prion


7:2, 99–108; March/April 2013; © 2013 Landes Bioscience








Friday, April 19, 2013


APHIS 2013 Stakeholder Meeting (March 2013) BSE TSE PRION








Monday, May 6, 2013


Warning of mad cow disease threat to blood transfusions








Sunday, May 19, 2013


CJD BLOOD SCREENING, DONORS, AND SILENT CARRIERS House of Commons Written Answers 16 May 2013








Tuesday, May 21, 2013


CJD, TSE, PRION, BLOOD Abstracts of the 23rd Regional Congress of the International Society of Blood Transfusion, Amsterdam, The Netherlands, June 2-5, 2013








Tuesday, March 5, 2013


Use of Materials Derived From Cattle in Human Food and Cosmetics; Reopening of the Comment Period FDA-2004-N-0188-0051 (TSS SUBMISSION)


FDA believes current regulation protects the public from BSE but reopens comment period due to new studies









FC5.1.1


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


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


Background: Rodent and sheep models of Transmissible Spongiform Encephalopathy (TSE) have documented blood infectivity in both the pre-clinical and clinical phases of disease. Results in a (presumably more appropriate) non-human primate model have not been reported.


Objective: To determine if blood components (red cells, white cells, platelets, and plasma) from various forms of human TSE are infectious.


Methods: Blood components were inoculated intra-cerebrally (0.1 ml) and intravenously (0.5 ml) into squirrel monkeys from 2 patients with sporadic Creutzfeldt- Jakob disease (sCJD) and 3 patients with variant Creutzfeldt-Jakob disease (vCJD). Additional monkeys were inoculated with buffy coat or plasma samples from chimpanzees infected with either sCJD or Gerstmann-Sträussler-Scheinker disease (GSS). Animals were monitored for a period of 5 years, and all dying or sacrificed animals had post-mortem neuropathological examinations and Western blots to determine the presence or absence of the misfolded prion protein (PrPTSE).


Results: No transmissions occurred in any of the animals inoculated with blood components from patients with sporadic or variant CJD. All donor chimpanzees (sCJD and GSS) became symptomatic within 6 weeks of their pre-clinical phase plasmapheresis, several months earlier than the expected onset of illness. One monkey inoculated with purified leukocytes from a pre-clinical GSS chimpanzee developed disease after 36 months.


Conclusion: No infectivity was found in small volumes of blood components from 4 patients with sporadic CJD and 3 patients with variant CJD. ***However, a single transmission from a chimpanzee-passaged strain of GSS shows that infectivity may be present in leukocytes, and the shock of general anaesthesia and plasmspheresis appears to have triggered the onset of illness in pre-clinical donor chimpanzees.






Saturday, September 5, 2009


TSEAC MEETING FEBRUARY 12, 2004 THE BAXTER STUDY GSS


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Saturday, September 5, 2009


TSEAC MEETING FEBRUARY 12, 2004 THE BAXTER STUDY GSS


snip...see full text ;


Monday, May 6, 2013


Warning of mad cow disease threat to blood transfusions









Tuesday, April 30, 2013


Mad cow infected blood 'to kill 1,000’








Sunday, February 10, 2013


Creutzfeldt-Jakob disease (CJD) biannual update (February 2013) Infection report/CJD







Tuesday, May 28, 2013


Late-in-life surgery associated with Creutzfeldt-Jakob disease: a methodological outline for evidence-based guidance








Thursday, June 6, 2013


BSE TSE PRION USDA FDA MAD COW FEED COMPLIANCE REPORT and NAI, OAI, and VAI ratings as at June 5, 2013








Thursday, February 14, 2013


The Many Faces of Mad Cow Disease Bovine Spongiform Encephalopathy BSE and TSE prion disease








Saturday, December 15, 2012


Bovine spongiform encephalopathy: the effect of oral exposure dose on attack rate and incubation period in cattle -- an update 5 December 2012









Thursday, May 30, 2013


World Organization for Animal Health (OIE) has upgraded the United States' risk classification for mad cow disease to "negligible" from "controlled", and risk further exposing the globe to the TSE prion mad cow type disease


U.S. gets top mad-cow rating from international group and risk further exposing the globe to the TSE prion mad cow type disease










Friday, December 14, 2012


Susceptibility Chronic Wasting Disease (CWD) in wild cervids to Humans 2005 - December 14, 2012








Sunday, June 2, 2013


Characterisation of an Unusual TSE in a Goat by Transmission in Knock-in Transgenic Mice








Monday, June 3, 2013


Unsuccessful oral transmission of scrapie from British sheep to cattle


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I have often pondered if the whole damn mad cow follies started over here in the USA, and somehow, the USA shipped it over to the UK ?


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but I still am not so sure that the mad cow follies did not start long ago right here in the USA i.e. Richard Marsh and deadstock downer cattle to those mink, and then the USA shipped it to hell and back. just pondering out loud here. ...tss






The exact same recipe for B.S.E. existed in the U.S. for years




and years. In reading over the Qualitative Analysis of BSE




Risk Factors-1, this is a 25 page report by the




USDA:APHIS:VS. It could have been done in one page. The




first page, fourth paragraph says it all;




"Similarities exist in the two countries usage of continuous




rendering technology and the lack of usage of solvents,




however, large differences still remain with other risk factors




which greatly reduce the potential risk at the national level."




Then, the next 24 pages tries to down-play the high risks of




B.S.E. in the U.S., with nothing more than the cattle to sheep




ratio count, and the geographical locations of herds and flocks.




That's all the evidence they can come up with, in the next 24




pages.






Something else I find odd, page 16;






"In the United Kingdom there is much concern for a specific




continuous rendering technology which uses lower




temperatures and accounts for 25 percent of total output. This




technology was _originally_ designed and imported from the




United States. However, the specific application in the




production process is _believed_ to be different in the two




countries."






A few more factors to consider, page 15;






"Figure 26 compares animal protein production for the two




countries. The calculations are based on slaughter numbers,




fallen stock estimates, and product yield coefficients. This




approach is used due to variation of up to 80 percent from




different reported sources. At 3.6 million tons, the United




States produces 8 times more animal rendered product than




the United Kingdom."






"The risk of introducing the BSE agent through sheep meat and




bone meal is more acute in both relative and absolute terms in




the United Kingdom (Figures 27 and 28). Note that sheep




meat and bone meal accounts for 14 percent, or 61 thousand




tons, in the United Kingdom versus 0.6 percent or 22 thousand




tons in the United States. For sheep greater than 1 year, this is




less than one-tenth of one percent of the United States supply."




"The potential risk of amplification of the BSE agent through




cattle meat and bone meal is much greater in the United States




where it accounts for 59 percent of total product or almost 5




times more than the total amount of rendered product in the




United Kingdom."






Considering, it would only take _one_ scrapie infected sheep




to contaminate the feed. Considering Scrapie has run rampant




in the U.S. for years, as of Aug. 1999, 950 scrapie infected




flocks. Also, Considering only one quarter spoonful of scrapie




infected material is lethal to a cow. Considering all this, the




sheep to cow ration is meaningless. As I said, it's 24 pages of




B.S.e.




To be continued...




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




_____________________________________________________________________











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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"




Emmanuel Comoy,1,† Valérie Durand,1 Evelyne Correia,1 Sophie Freire,1 Jürgen Richt,2 Justin Greenlee,3 Juan-Maria Torres,4 Paul Brown,1 Bob Hills5 and Jean-Philippe Deslys1




1Atomic Energy Commission; Fontenay-aux-Roses, France; 2Kansas State University; Manhattan, KS USA; 3USDA; Ames, IA USA; 4INIA; Madrid, Spain; 5Health Canada; Ottawa, ON Canada†Presenting author; Email: emmanuel.comoy@cea.fr




The epidemiology of Transmissible mink encephalopathy (TME) indicates an alimentary origin. Several inter-species transmission experiments have not succeeded in establishing with certainty any natural reservoir of this prion strain, although both ovine and bovine sources have been suspected. Cattle exposed to TME develop a spongiform encephalopathy that is distinct from classical Bovine Spongiform Encephalopathy (c-BSE).




Inoculation of c-BSE to cynomolgus macaque provided early evidence of a possible risk to humans, and remains an important model to define the risk of both primary (oral transmission from cattle to primate) and secondary (intravenous intra-species transmission) exposures. We have also evaluated the transmissibility of other cattle prion strains to macaques, including L- and H- atypical forms of BSE, namely BSE-L and BSE-H, and cattle-adapted TME.




BSE-L induced a neurological disease distinct from c-BSE. Peripheral exposures demonstrate the transmissibility of BSE-L by oral, intravenous, and intra-cerebral routes, with incubation periods similar to c-BSE. Cattle-adapted TME also induced a rapid disease in cynomolgus macaque. The clinical features, lesion profile, and biochemical signature of the induced disease was similar to the features observed in animals exposed to BSE-L, suggesting a link between the two prion strains. Secondary transmissions to a common host (transgenic mouse overexpressing bovine PrP) of cattle-TME and BSE-L before or after passage in primates induced diseases with similar incubation periods: like the c-BSE strain, these cattle strains maintained their distinctive features regardless of the donor species and passages.




If the link between TME and BSE-L is confirmed, our results would suggest that BSE-L in North America may have existed for decades, and highlight a possible preferential transmission of animal prion strains to primates after passage in cattle.






=====================end...tss====================




link url not available, please see PRION 2011 ;




















ALSO, SEE Scrapie Mission, Texas, did not produce _typical_ BSE...






see page 17 here ;




snip...see full text ;




Monday, June 3, 2013


Unsuccessful oral transmission of scrapie from British sheep to cattle








*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies.








*** The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.






VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE ...price of prion poker goes up again $


OR-10: Variably protease-sensitive prionopathy is transmissible in bank voles


Romolo Nonno,1 Michele Di Bari,1 Laura Pirisinu,1 Claudia D’Agostino,1 Stefano Marcon,1 Geraldina Riccardi,1 Gabriele Vaccari,1 Piero Parchi,2 Wenquan Zou,3 Pierluigi Gambetti,3 Umberto Agrimi1 1Istituto Superiore di Sanità; Rome, Italy; 2Dipartimento di Scienze Neurologiche, Università di Bologna; Bologna, Italy; 3Case Western Reserve University; Cleveland, OH USA


Background. Variably protease-sensitive prionopathy (VPSPr) is a recently described “sporadic”neurodegenerative disease involving prion protein aggregation, which has clinical similarities with non-Alzheimer dementias, such as fronto-temporal dementia. Currently, 30 cases of VPSPr have been reported in Europe and USA, of which 19 cases were homozygous for valine at codon 129 of the prion protein (VV), 8 were MV and 3 were MM. A distinctive feature of VPSPr is the electrophoretic pattern of PrPSc after digestion with proteinase K (PK). After PK-treatment, PrP from VPSPr forms a ladder-like electrophoretic pattern similar to that described in GSS cases. The clinical and pathological features of VPSPr raised the question of the correct classification of VPSPr among prion diseases or other forms of neurodegenerative disorders. Here we report preliminary data on the transmissibility and pathological features of VPSPr cases in bank voles.


Materials and Methods. Seven VPSPr cases were inoculated in two genetic lines of bank voles, carrying either methionine or isoleucine at codon 109 of the prion protein (named BvM109 and BvI109, respectively). Among the VPSPr cases selected, 2 were VV at PrP codon 129, 3 were MV and 2 were MM. Clinical diagnosis in voles was confirmed by brain pathological assessment and western blot for PK-resistant PrPSc (PrPres) with mAbs SAF32, SAF84, 12B2 and 9A2.


Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission in BvM109. Overall, 3 voles were positive with survival time between 290 and 588 d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form of the typical PrP27–30, which was indistinguishable to that previously observed in BvM109 inoculated with sCJDMM1 cases.


In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission until now. Overall, 5 voles were positive with survival time between 281 and 596 d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like PrPSc electrophoretic pattern, characterized by low molecular weight PrPres. These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus and the N-terminus. Second passages are in progress from these first successful transmissions.


Conclusions. Preliminary results from transmission studies in bank voles strongly support the notion that VPSPr is a transmissible prion disease. Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of voles, with sCJD-like features in BvM109 and GSS-like properties in BvI109.


The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.









Wednesday, March 28, 2012


VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE, price of prion poker goes up again $






Volume 33, Issue 3, Article first published online: 20 JAN 2013


Special Lecture


Human prion diseases: Molecular, cellular and population biology


Mark W. Head


National CJD Research & Surveillance Unit, Centre for Clinical Brain Sciences, School of Clinical Sciences,


The University of Edinburgh, Edinburgh, UK


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Potential future zoonoses


Scrapie is endemic in many countries around the world, yet there is no evidence to suggest that it is pathogenic for humans. The intense investigations of ruminant TSEs that followed the BSE epidemic have resulted in the identification of several distinct animal prion diseases, atypical or Nor98 scrapie in sheep and H-type and L-type BSE in cattle.32 Moreover, BSE is experimentally transmissible to sheep and there are concerns that if BSE were to have infected the national flock in the UK its presence might be masked by endemic scrapie, but it might retain its pathogenicity for humans.33,34 Another concern, particularly for the North American countries, is the spread of chronic wasting disease in farmed and free-ranging deer and elk.35 There is no known epidemiological link between any of these animal prion diseases and human disease, but there are active efforts to try to quantify strain-related species barriers between the diseases known to be a risk (BSE/ vCJD), those thought not to represent a risk (scrapie) and those for which data is lacking (atypical scrapie, H- and L-type BSE and BSE in sheep).36 In assessing whether or not human prion diseases might have an animal origin, it is important to have a proper understanding of the clinicopathological heterogeneity of the sporadic human prion diseases, because it is against this backdrop that any new acquired forms of the disease will be seen and from which it will need to be distinguished.


Sporadic CJD and variably protease-sensitive prionopathy


Sporadic CJD is the most commonly occurring human prion disease; it occurs world-wide and it has long been known to be clinically and pathologically heterogeneous. The molecular basis for this heterogeneity is currently thought to reside in a combination of the PRNP codon 129 polymorphic status of the patient (MM, MV, or VV) and the type (type 1 or type 2) of the protease-resistant component of PrPSc determined by protease K digestion and Western blotting (termed PrPres).37,38 The original sCJD sub-classification system of Parchi et al. that recognized six sCJD subtypes (MM1/MV1, MM2c, MM2t, MV2,VV2 and VV1) has had to be modified to accommodate the growing number of cases recognized to contain both type 1 and type 2 PrPres in different or sometimes the same regions of the brain.39,40 Moreover, intensive surveillance and investigation of forms of human prion disease that lack PRNP mutation and known risk factors has identified another sporadic human prion disease, termed protease-sensitive prionopathy (VPSPr).41While intensively investigated, the etiology and diversity of the sporadic human prion diseases remain poorly understood.


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There is also a potentially important practical corollary to the idea of prion-like spread, which may affect future stem cell therapies for neurodegenerative diseases. Presumably therapeutic stem cell-derived neurons would be equally susceptible to “infection” (with misfolded protein aggregates) as the patient’s own cells, unless steps were taken to prevent this,55 the most obvious of which would be to prevent expression of the gene product that can be converted to a pathological prion-like isoform.The suggestion that a prion-like mechanism of spread of molecular pathology underlies diseases as diverse as Alzheimer’s disease and Parkinson’s disease has led some researchers to explore whether the molecular pathology of these diseases is transmissible in an experimental setting56–58 and to suggest that perhaps some cases of these more common neurodegenerative illnesses might, like CJD, be acquired.58,59


snip...


MOLECULAR BASIS OF HUMAN PRION DISEASES Molecular strain typing Molecular strain typing in the form of classifying the mobility and glycoform ratio of protease-resistant prion protein byWestern blotting is a remarkably useful adjunct to neuropathological assessment during the post-mortem diagnosis of human prion diseases (Fig. 1). The glycoform ratio difference between vCJD and all forms of sCJD is a remarkably robust phenomenon, although the mechanism underlying it remains obscure. All cases of vCJD examined show type 2B PrPres, irrespective of brain region assayed and the PrPres type is also found in lymphoreticular tissues, albeit with presumably tissue-specific minor modification of mobility and an accentuation of the glycoform ratio. Similarly sCJD cases are characterized by a narrow range of glycoform ratios, distinct from vCJD, and the presence of either type 1 or type 2 PrPres (type 1A and type 2A).The PrPres types found in the brain in iCJD and kuru resemble those found in sCJD (type 1A and type 2A), from which they were presumably derived. Individual cases of gCJD, GSS and FFI usually have type 1 or type 2 PrPres, but with a glycoform ratio in which the non-glycosylated component is under-represented (which we have termed A/B). However, this is not always true and a broad spectrum of glycoform ratios can be found in genetic prion diseases. Moreover, some cases of GSS are characterized by an approximately 8 kDa (N- and C-terminally truncated) PrPres fragment, and some cases of FFI have little detectable PrPres at all. Despite the diagnostic utility, a simple one-to-one correspondence between PrPres type and disease phenotype (and by implication to agent strain) seems unlikely in principle and is complicated by the facts. First, the choice of analyzing only that fraction of PrPSc which survives a particular concentration of protease may seem arbitrary. Second, the interpretation of a molecular population variable, such as glycosylation site occupancy, as conforming to two or three discrete types, could be seen as simplistic. Lastly, protease digestion may be considered to be a somewhat blunt instrument to distinguish secondary and higherorder conformational differences in PrPSc. Even when genotype (mutations and polymorphisms) is taken into account, three major types (1, 2, 8 kDa) and three wild-type genotypes (MM,MV and VV) provide insufficient molecular variation to account for all the phenotypic variations observed. For example, two forms of sCJD share methione homozygosity and type 2A PrPres but one form closely resembles FFI (without the causative mutation) and the other is CJD-like.8 Two more substantial problems, which may point toward a more subtle and perhaps informative approach to PrPSc analysis, are discussed below. The co-occurrence of PrPres types 1 and 2 Once controversial, the idea that PrPSc in individual cases might be composed of mixtures (or different types co-occurring) is now well recognized and accepted.40,70 There are probably two phenomena at play here. One is the finding of different predominant types in individual samples from different parts of the brain or more rarely approximately equal amounts of type 1A and type 2A in the same sCJD brain samples.The other is the observation made using antibodies that specifically recognize type 1 or type 2 PrPres, that a minority type always accompanies a majority type in sCJD and vCJD, albeit at sub-detectable levels when conventional antibodies are used.71–75 The former issue is more tractable and a consensus is beginning to emerge that when multiple brain sampling and sensitive co-detection is performed on cohorts of sCJD cases, a plateau is reached at between 30–40% of cases showing co-occurrence. Our own data examining four regions (temporal cortex, parietal cortex, occipital cortex and thalamus) instead of frontal cortex only, shows a rise in detected co-occurrence from 3% to 24% of cases.76 Interestingly, only very rarely did this re-analysis involve a change in the predominant type found in the brain overall. Parchi et al. have offered a revised version of their 1999 sporadic CJD classification system that adds mixed type to the original “pure” types and have shown that the most common of these 12 sCJD subtypes can be recognized on histological grounds, without reference to biochemical analysis.39,40,77 It will be interesting to see in the fullness of time whether this additional complexity reflects a more refined series of discrete clinicopathological phenotypes or whether it is indicative of a spectrum of phenotypes depending on the spacio-temporal accumulation of PrPSc types set against the patient genotype.78


Variably protease-sensitive prionopathy The phenotypic complexity of the sporadic forms of human prion disease has increased with the report of a new sporadic human prion disease, termed variably proteasesensitive prionopathy (VPSPr) that is distinct from previously recognized sub-types of sCJD.41,79 There are no mutations in the open reading frame of PRNP. The patients have no known risk factors for the disease, but the disease is most common in theVV genotype, as opposed to sCJD, which is most common in the MM genotype. The neuropathology involves medium-sized vacuolation and characteristic microplaques. Durations of illness can be very long and this coupled with symptoms that do not conform well to CJD have prompted speculation that the condition may be under-ascertained. The most interesting aspect of the disease from a biochemical perspective is that although PrPSc is abundantly present in the brain, PrPres is difficult to detect because of its sensitivity to proteolysis and because what remains after proteinase K (PK) digestion is both C- and N-terminally cleaved by PK digestion and seen as a faint 8 kDa band on Western blots (Fig. 2). The degree of protease resistance is reported to reflect the codon 129 genotype, withVV being least resistant andMM being most resistant, despite having the same 8 kDa PrPres fragment predominating.79We have identified two cases of VPSPr prospectively in the UK80,81 and recently completed a retrospective review for such cases confirming many of the original observations by Gambetti and colleagues.41,79 Our work has shown that some areas of the VPSPr brain contain PrPres similar in appearance to that found in sCJD and conversely that some cases of sCJD have a very minor PrPres band similar to the 8 kDa PrPres band that typifies VPSPr.82


snip...


The biochemical basis of the strain phenomenon The results of transmission of individual samples from single examples of the six different Parchi et al.39 sCJD subtypes (MM1/MV1, VV1, MM2c, MV2, VV2) into humanized transgenic mice suggest the existence of four distinct sCJD agents, termed M1, M2, V1 and V2, and a fifth strain corresponding to MM2t or sporadic fatal insomnia.99,100 Interestingly, when we performed formally analogous experiments in the cell-free PMCA reaction, similar results were obtained: The PrPres type of the seed was conserved in the PMCA product and the efficiency of conversion appeared to be determined by compatibility at codon 129 of PRNP.101 The behavior of the seeds from heterozygous patients were particularly interesting, in that MV1 sCJD seeds selectively amplified in MM substrate producing type 1 PrPres and MV2 sCJD seeds selectively amplified in VV substrate producing type 2 PrPres (Fig. 6). These results reinforce the association between methionine at codon 129 and the production of type 1 PrPres and valine at codon 129 and the production of type 2 PrPres.


EMERGING RISKS Zoonotic disease BSE is the only animal prion strain with demonstrated pathogenicity for humans.While it is tempting to suggest that scrapie might represent the animal reservoir that results in some cases of sCJD, there is no epidemiological evidence to support this hypothesis. The pathogenicity of new or newly described animal prion diseases for humans is unclear and this is particularly true for H- and L-type BSE, atypical scrapie and for chronic wasting disease (CWD), all of which are probably consumed. Human susceptibility has been modeled by attempted transmission to (humanized) transgenic mice with sometimes conflicting results, depending on the transgenic model used and depending upon whether central or peripheral tissues are examined.102–106 We have attempted to establish whether PMCA can model the molecular component of these hypothetical cross-species transmission events.107 The existing data correspond well with the established facts. First, PrPSc in vCJD brain samples amplifies most efficiently in humanized mouse MM substrate, less efficiently in MV substrate and not at all in VV. Cattle BSE PrPres is less efficient than vCJD, but shows the same substrate genotypic preference. Sheep scrapie fails to amplify detectably in any of the three substrates; however, sheep BSE PrPres does amplify, again with a codon 129 preference for methionine (Fig. 7). We are currently extending this approach to encompass atypical scrapie, H- and L-type BSE and CWD using human rather than humanized PMCA substrates.


Secondary infection


In the same way that animal reservoirs cannot be completely excluded as causes of individual sCJD cases, neither can other environmental sources, such as medical procedures. The known routes of iatrogenic CJD acquisition are historically growth hormone therapy, dura mater grafting, corneal grafting and certain highly specialized neurosurgical procedures. The secondary transmission of vCJD by blood transfusion and experimental evidence showing the efficiency of the transfusion of viable blood cells between scrapie and BSE-infected and naive sheep have prompted a reappraisal of transfusion-transmitted CJD, including consideration being given to the possibility of prion blood testing or filtration.25,26,108,109


Blood transfusion is the original and most extensively used cellular therapy, but we may be on the threshold of a new era of cellular therapies based on embryonic stem cell and induced pluripotent stem cell technologies. Although the potential for stem cell therapy-mediated prion transmission might be judged remote, this was also considered to be the case for transfusion transmission of CJD before 2004.


snip...




SUMMARY AND PERSPECTIVE


While the prospect of a major epidemic of vCJD in the UK and elsewhere seems to be receding, there remain a series of uncertainties surrounding the eventual numbers of individuals that will suffer from this devastating condition.The issues include the effects of genotype on susceptibility and the possible existence of substantial numbers of asymptomatic infected individuals that may pose risks of onward transmission. sCJD remains the most frequently occurring human prion disease and arguably the least well understood. Other idiopathic forms of human prion disease (such as VPSPr), characterized by protease-sensitive forms of the prion protein, also exist and their true prevalence may be hard to ascertain. The possible risks from newly described animal prion diseases and from emerging cellular therapies are currently poorly quantified. On a more theoretic level the prion hypothesis has provided a unifying conceptual framework for TSE research and provided a paradigm to interrogate the similarities and differences between the diverse neurodegenerative conditions involving prion-like mechanisms of molecular pathology.










Sunday, March 31, 2013


Creutzfeldt Jakob Disease CJD worlds youngest documented victim, 11 years old, shall we pray








Tuesday, June 26, 2012


Creutzfeldt Jakob Disease Human TSE report update North America, Canada, Mexico, and USDA PRION UNIT as of May 18, 2012


type determination pending Creutzfeldt Jakob Disease (tdpCJD), is on the rise in Canada and the USA








Monday, July 23, 2012


The National Prion Disease Pathology Surveillance Center July 2012








2011 Monday, September 26, 2011


L-BSE BASE prion and atypical sporadic CJD









Wednesday, June 29, 2011


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









Wednesday, June 29, 2011 TSEAC JUNE 2, 1999 Welcome to the FDA traveling road show 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









Wednesday, March 2, 2011


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


October 28, 2010


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









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 ???









October 29, 2010


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








Monday, October 18, 2010


TSEAC Transmissible Spongiform Encephalopathies Advisory Committee Draft Agenda and Meeting Materials,


Posted: 10/18/2010


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










Tuesday, September 14, 2010


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








Saturday, September 5, 2009



TSEAC MEETING FEBRUARY 12, 2004 THE BAXTER STUDY GSS









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 ;








snip...see full text ;



Sunday, May 10, 2009



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



TO : william.freas@fda.hhs.gov







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:




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:













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...










Wednesday, October 17, 2007 TSEAC MEETINGS ----- Original Message -----


From: Terry S. Singeltary Sr.


To: FREAS@CBER.FDA.GOV


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


Sent: Wednesday, November 29, 2006 1:24 PM


Subject: TSE advisory committee for the meeting December 15, 2006 [TSSSUBMISSION]November 29, 2006


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


a kind and warm Holiday Greetings to you all.i kindly wish to submit the following to the TSE advisory committee for the meeting December 15, 2006, about the assessment for potential exposure to vCJD in human plasma-derivedantihemophilic factor (FVIII) productsmanufactured from U.S. plasma donors and related communication material ;




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






however, i seem to disagree. from my primitive ciphering, i see it another way. this is a huge catastrophic risk. 3 in 160 is 1.9%. so call that 2% which is 1 in 50 or twenty per thousand or 20,000 per million. also, wha tabout the mixed genotypes/mixed susceptibility?


what about the silent carriers that donated tainted blood?


what about the sporadic CJDs of UNKNOWN strain or phenotype?


this risk assessment is just more BSe to me. just another in a long line of industry fed crap. i pray that my assessment is the one that is wrong. but it is THEY who roll the dice with your life. it is THEY who refuse to regulate an industry that has run amok. just from are call aspect of potentially tainted blood, and these are just recent recalls ;


PRODUCT


Source Plasma, Recall # B-0054-7CODEUnits: 03MMNC5465, 03MMNC6361, 03MMNC6801, 03MMNC7510, 03MMNC7891,03MMNC8252, 03MMNC8801, 03MMNC9144, 03MMND1122, 03MMND1478, 03MMND1969,03MMND2350, 03MMND2825, 03MMND3211, 03MMND3708, 03MMND4072, 03MMND4588,03MMND4831, 03MMND5320, 03MMND5719, 03MMND6268, 03MMND6683, 03MMND7228,03MMND7656, 03MMND8211, 03MMND8652, 03MMND9195, 03MMND9618, 03MMNE0628,03MMNE0884, 03MMNE1597, 03MMNE1979, 03MMNE2644, 03MMNE3064, 03MMNE3707,03MMNE4122, 03MMNE4750, 03MMNE5080, 03MMNE5876, 03MMNE6218, 03MMNE7189,03MMNE7587, 03MMNE8027, 03MMNE8645, 03MMNE9029, 03MMNE9641, 03MMNE9979,03MMNF0491, 03MMNF0685, 03MMNF0937, 03MMNF1260, 04MMNA0351, 04MMNA0707,04MMNA1241, 04MMNA1650, 04MMNA2291, 04MMNA2646, 04MMNA3340, 04MMNA3719,04MMNA4312, 04MMNA4683, 04MMNA5298, 04MMNA5750, 04MMNA6407, 04MMNA6816,04MMNA7482, 04MMNA7915, 04MMNA8632, 04MMNA9076, 04MMNA9723, 04MMNB0063,04MMNB0696, 04MMNB1100, 04MMNB1845, 04MMNB2285, 04MMNB3035, 04MMNB3485,04MMNB4213, 04MMNB4672, 04MMNB5841, 04MMNB6652, 04MMNB7162, 04MMNB7930,04MMNB8453, 04MMNB9239, 04MMNB9747, 04MMNC0456, 04MMNC0931, 04MMNC1578


RECALLING FIRM/MANUFACTURER


BioLife Plasma Services, L.P., Mankato, MN, by facsimile on June 4, 2004.


Firm initiated recall is complete.


REASON


Blood products, collected from a donor who was at increased risk for new variant Creutzfeldt-Jakob Disease (nvCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


89 units


DISTRIBUTION


CA and Austria


END OF ENFORCEMENT REPORT FOR October 25, 2006


###






USA FDA MAD COW BLOOD HUMANS RECALL (these are dime a dozen)RECALLS AND FIELD CORRECTIONS: BIOLOGICS -- CLASS II


______________________________




PRODUCTSource Plasma, Recall # B-1708-6CODEUnits: MI180733, MI180927, MI181625, MI181780, MI182337, MI182519, MI183140,MI183311, MI183955, MI185006, MI185278, MI185822, MI186081, MI186855,MI187183, MI187903, MI188273, MI188695, MI189257, MI189553, MI190136,MI190473, MI191073, MI191395, MI191972, MI192303, MI193473, MI194343,04MINA0377, 04MINA0801, 05MINA7147, 05MINA7451, 05MINA8094, 05MINA8504,05MINA9548, 05MINA9883, 05MINB0489, 05MINB0875, 05MINB1469, 05MINB1874,05MINB3116, 05MINB7192, 05MINB7529, 05MINB8246, 05MINB8612, 05MINB9236,05MINB9366, 05MINB9475, 05MINB9641, 05MINC0031, 05MINC0237, 05MINC0336,05MINC0894, 05MINC0964, 05MINC1138, 05MINC1619, 05MINC1750, 05MINC1907,05MINC1977, 05MINC2375, 05MINC2774, 05MINC3113, 05MINC3484, 05MINC4277,05MINC4623, 05MINC5623, 05MINC5914, 05MINC7545, 05MINC7870, 05MINC8355,05MINC8689, 05MINC9437, 05MINC9775, 05MIND0067, 05MIND0393, 05MIND0892,05MIND0951, 05MIND1836, 05MIND2183 and 05MIND2962


RECALLING FIRM/MANUFACTURER


BioLife Plasma Services L.P., Muncie, IN, by facsimile on November 22, 2005.


Firm initiated recall is complete.


REASON


Blood products, collected from unsuitable donors based on risk factors for Creutzfeldt-Jakob Disease (CJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


80 units


DISTRIBUTION CA, NC, and MD


______________________________


PRODUCT


a) Red Blood Cells, Leukocytes Reduced, Recall # B-1714-6;b) Fresh Frozen Plasma, Recall # B-1715-6;c) Platelets, Recall # B-1716-6CODEa),


b), and c) Unit: 2443732RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by letters dated November 11, 2003 and December 18, 2003. Firm initiated recall is complete.


REASON


Blood products, collected from a donor who was at increased risk for new variant Creutzfeldt-Jakob Disease (nvCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


3 units


DISTRIBUTION


TX and WI




END OF ENFORCEMENT REPORT FOR SEPTEMBER 13, 2006


###






PRODUCT


Fresh Frozen Plasma, Recall # B-1751-6


CODE


Unit: 4936623


RECALLING FIRM/MANUFACTURER


Gulf Coast Regional Blood Center, Houston, TX, by facsimile dated September 16, 2005.


Firm initiated recall is complete.


REASON


Blood product, which was collected from an unsuitable donor based on risk factors for variant Creutzfeldt-Jakob Disease (vCJD), was distributed.


VOLUME OF PRODUCT IN COMMERCE


1 unit


DISTRIBUTION


TX


END OF ENFORCEMENT REPORT FOR SEPTEMBER 6, 2006


###






Mon Aug 7, 2006 10:2471.248.132.189


PRODUCT


a) Red Blood Cells, Recall # B-1587-6;b) Cryoprecipitated AHF, Recall # B-1588-6;c) Recovered Plasma, Recal # B-1589-6


CODE


a), b) and c)




Unit: 2016719




RECALLING FIRM/MANUFACTURER




Walter Shepeard Community Blood Center, Inc., Augusta, GA, by facsimile on March 13, 2003.


Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


3 units


DISTRIBUTION


GA and Germany


______________________________


PRODUCT


a) Red Blood Cells Leukocytes Reduced, Recall # B-1590-6;b) Fresh Frozen Plasma, Recall # B-1591-6


CODE


a) and b)


Unit: 2443595


RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on June30, 2004.


Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


2 units


DISTRIBUTION


TX


______________________________


PRODUCT


a) Red Blood Cells Leukocytes Reduced, Recall # B-1592-6;b) Fresh Frozen Plasma, Recall # B-1593-6


CODEa) and b)


Unit: 2545596


RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on December 14, 2004 and January 3, 2005.


Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


2 units


DISTRIBUTION


TX


______________________________






PRODUCT


a) Red Blood Cells Leukocytes Reduced, Recall # B-1550-6;b) Fresh Frozen Plasma, Recall # B-1551-6


CODEa) and b)


Unit 2395371


RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by fax on August 20,2003.


Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


2 units


DISTRIBUTION


TX


______________________________


PRODUCT


a) Red Blood Cells Leukocytes Reduced, Recall # B-1552-6;b) Platelets, Recall # B-1553-6;c) Fresh Frozen Plasma, Recall # B-1554-6


CODE


a), b) and c)


Unit 2438702


RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by fax on May 29,2003.


Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increasedrisk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


3 units


DISTRIBUTION


TX


______________________________


PRODUCT


a) Red Blood Cells Leukocytes Reduced, Recall # B-1555-6;b) Fresh Frozen Plasma, Recall # B-1556-6


CODEa) and b)


Unit 2454970


RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by fax on July 23 and December 11. 2003.


Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


2 units


DISTRIBUTION


TX


______________________________


PRODUCT


a) Red Blood Cells, Recall # B-1494-6b) Cryoprecipitated AHF, Recall # B-1495-6


CODEa) and b)


Unit 5013100


RECALLING FIRM/MANUFACTURER


Walter L. Shepeard Community Blood Center, Inc., Augusta, GA, by fax on May17, 2005. Firm initiated recall is complete.REASONBlood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


2 units


DISTRIBUTION


GA


______________________________


PRODUCT


Source Plasma, Recall # B-1450-6


CODE


Unit numbers ST0824313 and ST0824764


RECALLING FIRM/MANUFACTURER


Stillwater Plasma Center LLC, Stillwater, OK, by fax on November 21, 2003.


Firm initiated recall is complete.REASON


Blood products, which were collected from a donor whose suitability pertaining to risk factors for Creutzfeldt-Jakob Disease (vCJD) was not adequately determined, were distributed.


VOLUME OF PRODUCT IN COMMERCE


2 units


DISTRIBUTION


UK


______________________________




PRODUCT


Plasma Frozen, Recall # B-1422-6;Recovered Plasma, Recall # B-1423-6


CODE


a) Unit 03E42218;


b) Unit 03E38153


RECALLING FIRM/MANUFACTURER


American Red Cross Blood Services, Atlanta, GA, by telephone, e-mail orletter on February 20 or 21, 2004. Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


2 units


DISTRIBUTION


GA and Switzerland


______________________________


PRODUCT


a) Red Blood Cells Leukocytes Reduced, Recall # B-1374-6;


b) Recovered Plasma, Recall # B-1375-6CODEa) and b) unit 2453906


RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by fax on October 31 and November 5, 2003. Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


2 units


DISTRIBUTION


TX and Austria


______________________________


PRODUCT


Source Plasma.


Recall # B-1295-6


CODE


Units: NG0046551, NG0045950


RECALLING FIRM/MANUFACTURERD


CI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax onDecember 20, 2002, Firm initiated recall is complete.


REASON


Blood products, collected from a donor who did not answer the questions on the new variant Creutzfeldt-Jacob disease (nvCJD) questionnaire appropriately, were distributed.


VOLUME OF PRODUCT IN COMMERCE


2 units


DISTRIBUTION


KY


______________________________


PRODUCT


Source Plasma. Recall # B-1296-6


CODE


Unit: NG 0044520RECALLING FIRM/MANUFACTURERDCI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax onDecember 12, 2002. Firm initiated recall is complete.


REASON


Blood product, collected from a donor who did not answer the questions on the new variant Creutzfeldt-Jacob disease (nvCJD) questionnaire, was distributed.


VOLUME OF PRODUCT IN COMMERCE


1 unit


DISTRIBUTION


KY


______________________________


PRODUCT


Source Plasma. Recall # B-1297-6


CODE


Units: NG0042874, NG0043139, NG0043312, NG0043618, NG0043797, NG0044020,NG0044209, NG0044507, NG0044718, NG0044977, NG0045161, NG0045412, NG0045555RECALLING FIRM/MANUFACTURERDCI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax onDecember 20, 2002. Firm initiated recall is complete.


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


13 units


DISTRIBUTION


KY


______________________________


PRODUCT


Source Plasma, Recall # B-1298-6


CODE


Units: NG 0046823, NG 0046671, NG 0045205, NG 0044635, NG 0043095, NG0042525, NG 0042341RECALLING FIRM/MANUFACTURERDCI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax onDecember 20, 2002. Firm initiated recall is complete.


REASON


Blood products, collected from a donor who answered questions on the variant Creutzfeldt-Jacob disease (vCJD) questionnaire inappropriately, were distributed.


VOLUME OF PRODUCT IN COMMERCE


7 units


DISTRIBUTION


KY


______________________________


PRODUCT


Recovered Plasma, Recall # B-1299-6CODEUnit: 4357117


RECALLING FIRM/MANUFACTURER


Department of the Navy, Naval Medical Center, San Diego, CA, by fax and letter on September 25, 2003. Firm initiated recall is complete.


REASON


Blood product, collected from a donor considered to be at risk of exposure to Creutzfeldt-Jacob Disease (CJD), was distributed.


VOLUME OF PRODUCT IN COMMERCE


1 unit


DISTRIBUTION


Germany


END OF ENFORCEMENT REPORT FOR July 12, 2006


###






CJD WATCH MESSAGE BOARD


TSS


FDA mad cow nvCJD 'only' blood recalls 1ST WEEK JULY Fri Jul 7, 2006 09:3770.110.83.160


FDA mad cow nvCJD 'only' blood recalls 1ST WEEK JULY


PRODUCT


a) Red Blood Cells Leukocytes Reduced, Recall # B-1379-6;


b) Platelets, Recall # B-1380-6;


c) Fresh Frozen Plasma, Recall # 1381-6;


d) Recovered Plasma, Recall # B-1382-6


CODE


a) Unit numbers: 2343106, 2377779, and 2403533;


b) and c) Unit numbers: 2377779;


d) Unit numbers: 2343106 and 2403533




RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on June12, 2003. Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


7 units


DISTRIBUTIONTX and Austria


______________________________


PRODUCT


a) Red Blood Cells Leukocytes Reduced, Recall # B-1467-6;


b) Recovered Plasma, Recall # B-1468-6


CODE


a) and b)


Unit numbers: 2329380


RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on May 8,2003. Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


2 units


DISTRIBUTIONTX and Switzerland


______________________________


PRODUCT


a) Red Blood Cells Leukocytes Reduced, Recall # B-1479-6;


b) Cryoprecipitated AHF, Recall # B-1480-6;


c) Recovered Plasma, Recall # B-1481-6


CODE


a), b), and c)


Unit numbers: 2383280


RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on July23 and 29, 2004. Firm initiated recall is complete.


REASONBlood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


3 units


DISTRIBUTION


TX and Switzerland


______________________________


PRODUCT


a) Red Blood Cells Leukocytes Reduced, Recall # B-1482-6;


b) Fresh Frozen Plasma, Recall # B-1483-6


CODE


a) and b)


Unit number: 2501452


RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by facsimile onOctober 5, 2004. Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


2 units


DISTRIBUTION


TX and NY


______________________________


PRODUCT


a) Red Blood Cells Leukocytes Reduced, Recall # B-1484-6;


b) Plasma Cryoprecipitated Reduced, Recall # B-1485-6;


c) Recovered Plasma, Recall # B-1486-6


CODE


a) and c)


Unit number: 2554077;


b) Unit number: 2415708


RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on August13, 2004. Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


3 units


DISTRIBUTION


TX and Austria


_____________________________________


END OF ENFORCEMENT REPORT FOR July 5, 2006


###






Greetings again Dr. Freas et al at FDA,



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






snip...see full text ;




Wednesday, October 17, 2007 TSEAC MEETINGS ----- Original Message -----


From: Terry S. Singeltary Sr.


To: FREAS@CBER.FDA.GOV


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


Sent: Wednesday, November 29, 2006 1:24 PM


Subject: TSE advisory committee for the meeting December 15, 2006 [TSSSUBMISSION]November 29, 2006


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


a kind and warm Holiday Greetings to you all.i kindly wish to submit the following to the TSE advisory committee for the meeting December 15, 2006, about the assessment for potential exposure to vCJD in human plasma-derivedantihemophilic factor (FVIII) productsmanufactured from U.S. plasma donors and related communication material ;




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






however, i seem to disagree. from my primitive ciphering, i see it another way. this is a huge catastrophic risk. 3 in 160 is 1.9%. so call that 2% which is 1 in 50 or twenty per thousand or 20,000 per million. also, wha tabout the mixed genotypes/mixed susceptibility?


what about the silent carriers that donated tainted blood?


what about the sporadic CJDs of UNKNOWN strain or phenotype?


this risk assessment is just more BSe to me. just another in a long line of industry fed crap. i pray that my assessment is the one that is wrong. but it is THEY who roll the dice with your life. it is THEY who refuse to regulate an industry that has run amok. just from are call aspect of potentially tainted blood, and these are just recent recalls ;


PRODUCT


Source Plasma, Recall # B-0054-7CODEUnits: 03MMNC5465, 03MMNC6361, 03MMNC6801, 03MMNC7510, 03MMNC7891,03MMNC8252, 03MMNC8801, 03MMNC9144, 03MMND1122, 03MMND1478, 03MMND1969,03MMND2350, 03MMND2825, 03MMND3211, 03MMND3708, 03MMND4072, 03MMND4588,03MMND4831, 03MMND5320, 03MMND5719, 03MMND6268, 03MMND6683, 03MMND7228,03MMND7656, 03MMND8211, 03MMND8652, 03MMND9195, 03MMND9618, 03MMNE0628,03MMNE0884, 03MMNE1597, 03MMNE1979, 03MMNE2644, 03MMNE3064, 03MMNE3707,03MMNE4122, 03MMNE4750, 03MMNE5080, 03MMNE5876, 03MMNE6218, 03MMNE7189,03MMNE7587, 03MMNE8027, 03MMNE8645, 03MMNE9029, 03MMNE9641, 03MMNE9979,03MMNF0491, 03MMNF0685, 03MMNF0937, 03MMNF1260, 04MMNA0351, 04MMNA0707,04MMNA1241, 04MMNA1650, 04MMNA2291, 04MMNA2646, 04MMNA3340, 04MMNA3719,04MMNA4312, 04MMNA4683, 04MMNA5298, 04MMNA5750, 04MMNA6407, 04MMNA6816,04MMNA7482, 04MMNA7915, 04MMNA8632, 04MMNA9076, 04MMNA9723, 04MMNB0063,04MMNB0696, 04MMNB1100, 04MMNB1845, 04MMNB2285, 04MMNB3035, 04MMNB3485,04MMNB4213, 04MMNB4672, 04MMNB5841, 04MMNB6652, 04MMNB7162, 04MMNB7930,04MMNB8453, 04MMNB9239, 04MMNB9747, 04MMNC0456, 04MMNC0931, 04MMNC1578


RECALLING FIRM/MANUFACTURER


BioLife Plasma Services, L.P., Mankato, MN, by facsimile on June 4, 2004.


Firm initiated recall is complete.


REASON


Blood products, collected from a donor who was at increased risk for new variant Creutzfeldt-Jakob Disease (nvCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


89 units


DISTRIBUTION


CA and Austria


END OF ENFORCEMENT REPORT FOR October 25, 2006


###






USA FDA MAD COW BLOOD HUMANS RECALL (these are dime a dozen)RECALLS AND FIELD CORRECTIONS: BIOLOGICS -- CLASS II


______________________________




PRODUCTSource Plasma, Recall # B-1708-6CODEUnits: MI180733, MI180927, MI181625, MI181780, MI182337, MI182519, MI183140,MI183311, MI183955, MI185006, MI185278, MI185822, MI186081, MI186855,MI187183, MI187903, MI188273, MI188695, MI189257, MI189553, MI190136,MI190473, MI191073, MI191395, MI191972, MI192303, MI193473, MI194343,04MINA0377, 04MINA0801, 05MINA7147, 05MINA7451, 05MINA8094, 05MINA8504,05MINA9548, 05MINA9883, 05MINB0489, 05MINB0875, 05MINB1469, 05MINB1874,05MINB3116, 05MINB7192, 05MINB7529, 05MINB8246, 05MINB8612, 05MINB9236,05MINB9366, 05MINB9475, 05MINB9641, 05MINC0031, 05MINC0237, 05MINC0336,05MINC0894, 05MINC0964, 05MINC1138, 05MINC1619, 05MINC1750, 05MINC1907,05MINC1977, 05MINC2375, 05MINC2774, 05MINC3113, 05MINC3484, 05MINC4277,05MINC4623, 05MINC5623, 05MINC5914, 05MINC7545, 05MINC7870, 05MINC8355,05MINC8689, 05MINC9437, 05MINC9775, 05MIND0067, 05MIND0393, 05MIND0892,05MIND0951, 05MIND1836, 05MIND2183 and 05MIND2962


RECALLING FIRM/MANUFACTURER


BioLife Plasma Services L.P., Muncie, IN, by facsimile on November 22, 2005.


Firm initiated recall is complete.


REASON


Blood products, collected from unsuitable donors based on risk factors for Creutzfeldt-Jakob Disease (CJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


80 units


DISTRIBUTION CA, NC, and MD


______________________________


PRODUCT


a) Red Blood Cells, Leukocytes Reduced, Recall # B-1714-6;b) Fresh Frozen Plasma, Recall # B-1715-6;c) Platelets, Recall # B-1716-6CODEa),


b), and c) Unit: 2443732RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by letters dated November 11, 2003 and December 18, 2003. Firm initiated recall is complete.


REASON


Blood products, collected from a donor who was at increased risk for new variant Creutzfeldt-Jakob Disease (nvCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


3 units


DISTRIBUTION


TX and WI




END OF ENFORCEMENT REPORT FOR SEPTEMBER 13, 2006


###






PRODUCT


Fresh Frozen Plasma, Recall # B-1751-6


CODE


Unit: 4936623


RECALLING FIRM/MANUFACTURER


Gulf Coast Regional Blood Center, Houston, TX, by facsimile dated September 16, 2005.


Firm initiated recall is complete.


REASON


Blood product, which was collected from an unsuitable donor based on risk factors for variant Creutzfeldt-Jakob Disease (vCJD), was distributed.


VOLUME OF PRODUCT IN COMMERCE


1 unit


DISTRIBUTION


TX


END OF ENFORCEMENT REPORT FOR SEPTEMBER 6, 2006


###






Mon Aug 7, 2006 10:2471.248.132.189


PRODUCT


a) Red Blood Cells, Recall # B-1587-6;b) Cryoprecipitated AHF, Recall # B-1588-6;c) Recovered Plasma, Recal # B-1589-6


CODE


a), b) and c)




Unit: 2016719




RECALLING FIRM/MANUFACTURER




Walter Shepeard Community Blood Center, Inc., Augusta, GA, by facsimile on March 13, 2003.


Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


3 units


DISTRIBUTION


GA and Germany


______________________________


PRODUCT


a) Red Blood Cells Leukocytes Reduced, Recall # B-1590-6;b) Fresh Frozen Plasma, Recall # B-1591-6


CODE


a) and b)


Unit: 2443595


RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on June30, 2004.


Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


2 units


DISTRIBUTION


TX


______________________________


PRODUCT


a) Red Blood Cells Leukocytes Reduced, Recall # B-1592-6;b) Fresh Frozen Plasma, Recall # B-1593-6


CODEa) and b)


Unit: 2545596


RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on December 14, 2004 and January 3, 2005.


Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


2 units


DISTRIBUTION


TX


______________________________






PRODUCT


a) Red Blood Cells Leukocytes Reduced, Recall # B-1550-6;b) Fresh Frozen Plasma, Recall # B-1551-6


CODEa) and b)


Unit 2395371


RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by fax on August 20,2003.


Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


2 units


DISTRIBUTION


TX


______________________________


PRODUCT


a) Red Blood Cells Leukocytes Reduced, Recall # B-1552-6;b) Platelets, Recall # B-1553-6;c) Fresh Frozen Plasma, Recall # B-1554-6


CODE


a), b) and c)


Unit 2438702


RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by fax on May 29,2003.


Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increasedrisk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


3 units


DISTRIBUTION


TX


______________________________


PRODUCT


a) Red Blood Cells Leukocytes Reduced, Recall # B-1555-6;b) Fresh Frozen Plasma, Recall # B-1556-6


CODEa) and b)


Unit 2454970


RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by fax on July 23 and December 11. 2003.


Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


2 units


DISTRIBUTION


TX


______________________________


PRODUCT


a) Red Blood Cells, Recall # B-1494-6b) Cryoprecipitated AHF, Recall # B-1495-6


CODEa) and b)


Unit 5013100


RECALLING FIRM/MANUFACTURER


Walter L. Shepeard Community Blood Center, Inc., Augusta, GA, by fax on May17, 2005. Firm initiated recall is complete.REASONBlood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


2 units


DISTRIBUTION


GA


______________________________


PRODUCT


Source Plasma, Recall # B-1450-6


CODE


Unit numbers ST0824313 and ST0824764


RECALLING FIRM/MANUFACTURER


Stillwater Plasma Center LLC, Stillwater, OK, by fax on November 21, 2003.


Firm initiated recall is complete.REASON


Blood products, which were collected from a donor whose suitability pertaining to risk factors for Creutzfeldt-Jakob Disease (vCJD) was not adequately determined, were distributed.


VOLUME OF PRODUCT IN COMMERCE


2 units


DISTRIBUTION


UK


______________________________




PRODUCT


Plasma Frozen, Recall # B-1422-6;Recovered Plasma, Recall # B-1423-6


CODE


a) Unit 03E42218;


b) Unit 03E38153


RECALLING FIRM/MANUFACTURER


American Red Cross Blood Services, Atlanta, GA, by telephone, e-mail orletter on February 20 or 21, 2004. Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


2 units


DISTRIBUTION


GA and Switzerland


______________________________


PRODUCT


a) Red Blood Cells Leukocytes Reduced, Recall # B-1374-6;


b) Recovered Plasma, Recall # B-1375-6CODEa) and b) unit 2453906


RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by fax on October 31 and November 5, 2003. Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


2 units


DISTRIBUTION


TX and Austria


______________________________


PRODUCT


Source Plasma.


Recall # B-1295-6


CODE


Units: NG0046551, NG0045950


RECALLING FIRM/MANUFACTURERD


CI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax onDecember 20, 2002, Firm initiated recall is complete.


REASON


Blood products, collected from a donor who did not answer the questions on the new variant Creutzfeldt-Jacob disease (nvCJD) questionnaire appropriately, were distributed.


VOLUME OF PRODUCT IN COMMERCE


2 units


DISTRIBUTION


KY


______________________________


PRODUCT


Source Plasma. Recall # B-1296-6


CODE


Unit: NG 0044520RECALLING FIRM/MANUFACTURERDCI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax onDecember 12, 2002. Firm initiated recall is complete.


REASON


Blood product, collected from a donor who did not answer the questions on the new variant Creutzfeldt-Jacob disease (nvCJD) questionnaire, was distributed.


VOLUME OF PRODUCT IN COMMERCE


1 unit


DISTRIBUTION


KY


______________________________


PRODUCT


Source Plasma. Recall # B-1297-6


CODE


Units: NG0042874, NG0043139, NG0043312, NG0043618, NG0043797, NG0044020,NG0044209, NG0044507, NG0044718, NG0044977, NG0045161, NG0045412, NG0045555RECALLING FIRM/MANUFACTURERDCI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax onDecember 20, 2002. Firm initiated recall is complete.


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


13 units


DISTRIBUTION


KY


______________________________


PRODUCT


Source Plasma, Recall # B-1298-6


CODE


Units: NG 0046823, NG 0046671, NG 0045205, NG 0044635, NG 0043095, NG0042525, NG 0042341RECALLING FIRM/MANUFACTURERDCI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax onDecember 20, 2002. Firm initiated recall is complete.


REASON


Blood products, collected from a donor who answered questions on the variant Creutzfeldt-Jacob disease (vCJD) questionnaire inappropriately, were distributed.


VOLUME OF PRODUCT IN COMMERCE


7 units


DISTRIBUTION


KY


______________________________


PRODUCT


Recovered Plasma, Recall # B-1299-6CODEUnit: 4357117


RECALLING FIRM/MANUFACTURER


Department of the Navy, Naval Medical Center, San Diego, CA, by fax and letter on September 25, 2003. Firm initiated recall is complete.


REASON


Blood product, collected from a donor considered to be at risk of exposure to Creutzfeldt-Jacob Disease (CJD), was distributed.


VOLUME OF PRODUCT IN COMMERCE


1 unit


DISTRIBUTION


Germany


END OF ENFORCEMENT REPORT FOR July 12, 2006


###






CJD WATCH MESSAGE BOARD


TSS


FDA mad cow nvCJD 'only' blood recalls 1ST WEEK JULY Fri Jul 7, 2006 09:3770.110.83.160


FDA mad cow nvCJD 'only' blood recalls 1ST WEEK JULY


PRODUCT


a) Red Blood Cells Leukocytes Reduced, Recall # B-1379-6;


b) Platelets, Recall # B-1380-6;


c) Fresh Frozen Plasma, Recall # 1381-6;


d) Recovered Plasma, Recall # B-1382-6


CODE


a) Unit numbers: 2343106, 2377779, and 2403533;


b) and c) Unit numbers: 2377779;


d) Unit numbers: 2343106 and 2403533




RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on June12, 2003. Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


7 units


DISTRIBUTIONTX and Austria


______________________________


PRODUCT


a) Red Blood Cells Leukocytes Reduced, Recall # B-1467-6;


b) Recovered Plasma, Recall # B-1468-6


CODE


a) and b)


Unit numbers: 2329380


RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on May 8,2003. Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


2 units


DISTRIBUTIONTX and Switzerland


______________________________


PRODUCT


a) Red Blood Cells Leukocytes Reduced, Recall # B-1479-6;


b) Cryoprecipitated AHF, Recall # B-1480-6;


c) Recovered Plasma, Recall # B-1481-6


CODE


a), b), and c)


Unit numbers: 2383280


RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on July23 and 29, 2004. Firm initiated recall is complete.


REASONBlood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


3 units


DISTRIBUTION


TX and Switzerland


______________________________


PRODUCT


a) Red Blood Cells Leukocytes Reduced, Recall # B-1482-6;


b) Fresh Frozen Plasma, Recall # B-1483-6


CODE


a) and b)


Unit number: 2501452


RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by facsimile onOctober 5, 2004. Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


2 units


DISTRIBUTION


TX and NY


______________________________


PRODUCT


a) Red Blood Cells Leukocytes Reduced, Recall # B-1484-6;


b) Plasma Cryoprecipitated Reduced, Recall # B-1485-6;


c) Recovered Plasma, Recall # B-1486-6


CODE


a) and c)


Unit number: 2554077;


b) Unit number: 2415708


RECALLING FIRM/MANUFACTURER


South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on August13, 2004. Firm initiated recall is complete.


REASON


Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.


VOLUME OF PRODUCT IN COMMERCE


3 units


DISTRIBUTION


TX and Austria


_____________________________________


END OF ENFORCEMENT REPORT FOR July 5, 2006


###






Greetings again Dr. Freas et al at FDA,


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













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 ...









Tuesday, February 8, 2011


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








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











Wednesday, May 16, 2012


Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?


Proposal ID: 29403









Saturday, May 25, 2013


Brain homogenates from human tauopathies induce tau inclusions in mouse brain

 







Tuesday, May 21, 2013


IS ALZHEIMER’S DISEASE A PRION DISEASE? the possible secondary transmission by blood transfusion are posed









Tuesday, May 7, 2013


Proteinopathies, a core concept for understanding and ultimately treating degenerative disorders?










Monday, September 26, 2011


Variably Protease-Sensitive Prionopathy, Prionpathy, Prionopathy, FFI, GSS, gCJD, hvCJD, sCJD, TSE, PRION, update 2011










Friday, September 3, 2010


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

 
 








Tuesday, June 4, 2013


INTERPRETING RESULTS OF FSIS VERIFICATION SAMPLING OF DOMESTIC BEEF PRODUCT DERIVED FROM ADVANCED MEAT RECOVERY SYSTEMS (AMR01/FAMR01) FSIS Notice 38-12
















 
 


 
 
 



 
 











 












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