Sunday, August 26, 2012

Susceptibility of young sheep to oral infection with bovine spongiform encephalopathy decreases significantly after weaning

Susceptibility of young sheep to oral infection with bovine spongiform encephalopathy decreases significantly after weaning.



Nora Hunter1,#, Fiona Houston2, James Foster1, Wilfred Goldmann1, Dawn Drummond1, David Parnham1, Iain Kennedy1, Andrew Green1, Paula Stewart1 and Angela Chong1


+ Author Affiliations


1Neurobiology Division, The Roslin Institute and R(D)SVS, University of Edinburgh, Roslin, Midlothian, United Kingdom 2School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom


ABSTRACT


Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy (TSE or prion disease) which is readily transmissible to sheep by experimental infection and animals of ARQ/ARQ PRNP genotype (at codons 136, 154 and 171) have the shortest incubation period. Because it is possible that sheep in the UK could have been infected with BSE via feeding of contaminated meat and bone meal supplements at the same time as cattle, there is considerable interest in the responses of sheep to BSE inoculation. Epidemiological evidence suggests that very young individuals are more susceptible to TSE infection however this has never been properly tested in sheep. In the present study, low doses of BSE were fed to lambs of a range of ages (∼24 hours, 2-3 weeks, 3 months, 6 months) and adult sheep. The incidence of clinical BSE disease was high when unweaned lambs (∼24 hours and 2-3 weeks) were inoculated but older weaned animals were much less susceptible. Incubation period was also found to be influenced by genotype at codon 141 of the PRNP gene as LF heterozygotes had a longer mean incubation period than either homozygote. The results suggest that UK sheep would have been at high risk of BSE infection only if contaminated supplementary foodstuffs had inadvertently been ingested by neonatal animals.


FOOTNOTES


↵#corresponding author email: nora.hunter@roslin.ed.ac.uk Copyright © 2012, American Society for Microbiology. All Rights Reserved.






>>> The results suggest that UK sheep would have been at high risk of BSE infection only if contaminated supplementary foodstuffs had inadvertently been ingested by neonatal animals.





THE RISK OF TRANSMISSION OF BSE TO SHEEP VIA FEED


snip...









Wednesday, February 16, 2011


IN CONFIDENCE


SCRAPIE TRANSMISSION TO CHIMPANZEES


IN CONFIDENCE








Sunday, April 18, 2010



SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010








Monday, April 25, 2011



Experimental Oral Transmission of Atypical Scrapie to Sheep



Volume 17, Number 5-May 2011








1: J Infect Dis 1980 Aug;142(2):205-8



Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.



Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.



Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.



snip...



The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.



PMID: 6997404








12/10/76



AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE



Office Note CHAIRMAN: PROFESSOR PETER WILDY



snip...



A The Present Position with respect to Scrapie A] The Problem Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries. The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep. It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible. Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates.



One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias" Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.



snip...



76/10.12/4.6








Nature. 1972 Mar 10;236(5341):73-4.



Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).



Gibbs CJ Jr, Gajdusek DC. Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0



Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)



C. J. GIBBS jun. & D. C. GAJDUSEK National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland



SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).









Sunday, March 28, 2010



Nor-98 atypical Scrapie, atypical BSE, spontaneous TSE, trade policy, sound science ?








Monday, November 30, 2009



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








I strenuously urge the USDA and the OIE et al to revoke the exemption of the legal global trading of atypical Nor-98 scrapie TSE. ...TSS





Friday, February 11, 2011



Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues








Sheep and Goat BSE Propagate More Efficiently than Cattle BSE in Human PrP Transgenic Mice



Danielle Padilla1., Vincent Be´ringue2., Juan Carlos Espinosa1, Olivier Andreoletti3, Emilie Jaumain2, Fabienne Reine2, Laetitia Herzog2, Alfonso Gutierrez-Adan4, Belen Pintado4, Hubert Laude2, Juan Maria Torres1*



1 Centro de Investigacio´n en Sanidad Animal (CISA-INIA), Madrid, Spain, 2 INRA, UR892, Virologie Immunologie Mole´culaires, Jouy-en-Josas, France, 3UMR INRA-ENVT 1225, Interactions HoĖ† te Agent Pathoge`ne, Ecole Nationale Ve´te´ rinaire de Toulouse, Toulouse, France, 4 Departamento de Reproduccio´n Animal-INIA, Madrid, Spain



Abstract



A new variant of Creutzfeldt Jacob Disease (vCJD) was identified in humans and linked to the consumption of Bovine Spongiform Encephalopathy (BSE)-infected meat products. Recycling of ruminant tissue in meat and bone meal (MBM) has been proposed as origin of the BSE epidemic. During this epidemic, sheep and goats have been exposed to BSEcontaminated MBM. It is well known that sheep can be experimentally infected with BSE and two field BSE-like cases have been reported in goats. In this work we evaluated the human susceptibility to small ruminants-passaged BSE prions by inoculating two different transgenic mouse lines expressing the methionine (Met) allele of human PrP at codon 129 (tg650 and tg340) with several sheep and goat BSE isolates and compared their transmission characteristics with those of cattle BSE. While the molecular and neuropathological transmission features were undistinguishable and similar to those obtained after transmission of vCJD in both transgenic mouse lines, sheep and goat BSE isolates showed higher transmission efficiency on serial passaging compared to cattle BSE. We found that this higher transmission efficiency was strongly influenced by the ovine PrP sequence, rather than by other host species-specific factors. Although extrapolation of results from prion transmission studies by using transgenic mice has to be done very carefully, especially when human susceptibility to prions is analyzed, our results clearly indicate that Met129 homozygous individuals might be susceptible to a sheep or goat BSE agent at a higher degree than to cattle BSE, and that these agents might transmit with molecular and neuropathological properties indistinguishable from those of vCJD. Our results suggest that the possibility of a small ruminant BSE prion as vCJD causal agent could not be ruled out, and that the risk for humans of a potential goat and/or sheep BSE agent should not be underestimated.



Citation: Padilla D, Be´ringue V, Espinosa JC, Andreoletti O, Jaumain E, et al. (2011) Sheep and Goat BSE Propagate More Efficiently than Cattle BSE in Human PrP Transgenic Mice. PLoS Pathog 7(3): e1001319. doi:10.1371/journal.ppat.1001319


Editor: Umberto Agrimi, Istituto Superiore di Sanita` , Italy


Received August 24, 2010; Accepted February 15, 2011; Published March 17, 2011


Copyright: 2011 Padilla et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Funding: This work was supported by grants from European Union (CT-2001-01309, CT2004-023183 and CT2005-036353), Spanish Ministerio de Ciencia e Inovacion (RTA2006-00091) and from UK Food Standards Agency (M03043). D.P. was supported by a fellowship from the Alban Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.


Competing Interests: The authors have declared that no competing interests exist.


* E-mail: jmtorres@inia.es


. These authors contributed equally to this work.




snip...




Whatever the mechanism, the notion that a passage through an intermediate species can profoundly alter prion virulence for the human species has important public-health issues, regarding emerging and/or expanding TSEs, like atypical scrapie or CWD.





Although extrapolation of results from prion transmission studies by using transgenic mice has to be done very carefully, especially when human susceptibility to prions is analyzed, our results clearly indicate that Met129 homozygous individuals might be susceptible to a sheep or goat BSE agent at a higher degree than to cattle BSE, and that these agents might transmit with molecular and neuropathological properties indistinguishable from those of vCJD. Although no vCJD cases have been described in Val129 homozygous individuals so far it is relevant to analyze if similar results will be observed in this genotype. This issue is currently being addressed in transmission experiments using transgenic mice expressing Val129 human PrP.





Taken all together, our results suggest that the possibility of a small ruminant BSE prion as vCJD causal agent could not be ruled out, which has important implications on public and animal health policies. On one hand, although the exact magnitude and characteristic of the vCJD epidemic is still unclear, its link with cattle BSE is supported by strong epidemiological ground and several experimental data. On the other hand, the molecular typing performed in our studies, indicates that the biochemical characteristics of the PrPres detected in brains of our sheep and goat BSE-inoculated mice seem to be indistinguishable from that observed in vCJD. Considering the similarity in clinical manifestation of BSE- and scrapie-affected sheep [48], a masker effect of scrapie over BSE, as well as a potential adaptation of the BSE agent through subsequent passages, could not be ruled out. As BSE infected sheep PrPSc have been detected in many peripheral organs, small ruminant-passaged BSE prions might be a more widespread source of BSE infectivity compared to cattle [19], [49], [50]. This fact is even more worrying since our transmission studies suggest that apparently Met129 human PrP favours a BSE agent with ovine rather than a bovine sequence. Finally, it is evident that, although few natural cases have been described and so far we cannot draw any definitive conclusion about the origin of vCJD, we can not underestimate the risk of a potential goat and/or sheep BSE agent.















J Virol. 2011 February; 85(3): 1174–1181. Published online 2010 November 17. doi: 10.1128/JVI.01578-10 PMCID: PMC3020518




Increased Susceptibility of Human-PrP Transgenic Mice to Bovine Spongiform Encephalopathy Infection following Passage in Sheep †




Chris Plinston,1 Patricia Hart,1 Angela Chong,1 Nora Hunter,1 James Foster,1 Pedro Piccardo,1,2 Jean C. Manson,1 and Rona M. Barron1,* Neuropathogenesis Division, The Roslin Institute, and R(D)SVS, University of Edinburgh, Roslin, Midlothian, United Kingdom,1 Laboratory of Bacterial and TSE Agents, Food and Drug Administration, Rockville, Maryland2 *Corresponding author. Mailing address: Neuropathogenesis Division, The Roslin Institute and R(D)SVS, University of Edinburgh, Roslin, Midlothian EH25 9PS, United Kingdom. Phone: 0131 527 4200. Fax: 0131 440 0434. E-mail: rona.barron@roslin.ed.ac.uk




Author information ► Article notes ► Copyright and License information ►




Received July 28, 2010; Accepted November 9, 2010. Copyright © 2011, American Society for Microbiology This article has been cited by other articles in PMC.






Abstract


The risk of the transmission of ruminant transmissible spongiform encephalopathy (TSE) to humans was thought to be low due to the lack of association between sheep scrapie and the incidence of human TSE. However, a single TSE agent strain has been shown to cause both bovine spongiform encephalopathy (BSE) and human vCJD, indicating that some ruminant TSEs are transmissible to humans. While the transmission of cattle BSE to humans in transgenic mouse models has been inefficient, indicating the presence of a significant transmission barrier between cattle and humans, BSE has been transmitted to a number of other species. Here, we aimed to further investigate the human transmission barrier following the passage of BSE in a sheep. Following inoculation with cattle BSE, gene-targeted transgenic mice expressing human PrP showed no clinical or pathological signs of TSE disease. However, following inoculation with an isolate of BSE that had been passaged through a sheep, TSE-associated vacuolation and proteinase K-resistant PrP deposition were observed in mice homozygous for the codon 129-methionine PRNP gene. This observation may be due to higher titers of the BSE agent in sheep or an increased susceptibility of humans to BSE prions following passage through a sheep. However, these data confirm that, contrary to previous predictions, it is possible that a sheep prion is transmissible to humans and that BSE from other species is a public health risk.




snip...




Although sheep can be experimentally infected with BSE by oral, intravenous, or intracerebral exposure (18), no cases of sheep BSE have been reported in the field. The possible increased risk of disease transmission identified in these studies thus is not of major concern to the public at present. Natural BSE infection has, however, been identified in goats (14, 25), indicating that small ruminants have been exposed to sources of contamination. We cannot rule out the possibility that sheep have been infected with BSE during the height of the BSE epidemic, as these animals undoubtedly were exposed to similar feed sources (although with different levels of exposure compared to those of cattle). Such infection may have been limited and/or localized and resolved very quickly. BSE in small ruminants may, however, represent an increased risk to humans due to the wider distribution of BSE infectivity identified in peripheral sheep tissues (2, 17, 19, 29) compared to that of BSE in cattle, mainly which is restricted to the CNS (10). While TSEs remain in the environment and continue to infect animals (even at low prevalence), there remains the potential for cross-species transmission and the emergence of TSE isolates with altered strain properties or host ranges. Our data therefore emphasize the need for continued surveillance to identify, monitor, and characterize any new emerging TSE agents that are identified in ruminants and the assessment of the potential risks posed to other species.












*** CONFIDENTIAL ***



DRAFT



SHEEP AND BSE



A. The experimental transmission of BSE to sheep.



http://web.archive.org/web/20060517080024/http://www.bseinquiry.gov.uk/files/sc/seac33/tab02.pdf



http://web.archive.org/web/20060517075652/http://www.bseinquiry.gov.uk/files/sc/seac33/tab03.pdf






The only circumstance in which infection with the natural isolate produces an higher incidence of disease compared to BSE, is in intracerebrally (and possibly orally) challenged ''positive'' line sheep. Notwithstanding the possibility of indigenous natural scrapie in some of these sheep, there are still sufficient numbers of transmission cases with PrP genotypes which preclude the natural disease developing i.e. those typed as VA136/RR154/QR171.


As an extension to this study, it has been possible to recover BSE by passage in mice from brain and spleen taken from ''negative'' line sheep infected with BSAE by ic and oral challenge (Foster and others 1996). The close similarity of incubation periods and pathology from the passage of these tissues in mice to those seen in direct BSE transmission studies from cattle to mice suggests that passaging BSE in sheep does not alter its bilogical properties (Bruce and others 1994). IN FACT, because it has been possible to isolate BSE infectivity from ovine spleens, when this proved impossible from the spleens of naturally infected BSE cows (Fraser and Foster 1993), experimentally-induced BSE in sheep appears to behave more like the natural disease of scrapie.Whether this putative similarity to natural scrapie extends to the possibility of maternal transmission of experimentally-induced BSE in sheep, has till to be elucidated...







http://web.archive.org/web/20060517075749/http://www.bseinquiry.gov.uk/files/mb/m09/tab01.pdf











TSS

Detection of PrPSc in peripheral tissues of clinically affected cattle after oral challenge with BSE

Detection of PrPSc in peripheral tissues of clinically affected cattle after oral challenge with BSE




Martin Franz1, Martin Eiden1, Anne Balkema-Buschmann1, Justin Greenlee2, Hermann M Schaetzl3, Christine Fast1, Juergen Richt4, Jan-Peter Hildebrandt5 and Martin Groschup1,6


+ Author Affiliations


1 Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany; 2 National Animal Disease Center, ARS-USDA, Ames, IA, USA; 3 Depts of Veterinary Sciences and Molecular Biology, University of Wyoming, Laramie, WY, USA; 4 Kansas State University, College of Veterinary Medicine, Manhattan, KS, USA; 5 University Greifswald, Germany


↵6 E-mail: martin.groschup@fli.bund.de


Received 6 June 2012. Accepted 20 August 2012.



Abstract



Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative prion disease that mainly affects cattle. Transmission of BSE to humans caused a variant form of Creutzfeldt-Jakob disease (vCJD). Following infection the protease-resistant, disease-associated isoform of prion protein (PrPSc) accumulates in the central nervous system and in other tissues. Many countries have defined bovine tissues that may contain prions as specified risk materials (SRMs), which must not enter the human or animal food chains and therefore must be discarded. Ultrasensitive techniques such as the protein misfolding cyclic amplification (PMCA) have been developed to detect PrPSc when present in miniscule amounts that are not readily detected by other diagnostic methods such as immunohistochemistry or western blot. This study was conducted to determine when and where PrPSc can be found by PMCA in cattle orally challenged with BSE. A total of 48 different tissue samples from 4 orally BSE-infected cattle at clinical stages of disease were examined using a standardized PMCA protocol. The protocol used brain homogenate from bovine PrP transgenic mice (Tgbov XV) as substrate and three consecutive rounds of PMCA. Using this protocol PrPSc was found in brain, spinal cord, nerve ganglia, optic nerve, and Peyer’s patches. We could confirm the presence of PrPSc in adrenal gland as well as in mesenteric lymph node – a finding, which was recently reported by another group. Interestingly, additional positive results were obtained for the first time in oesophagus, abomasum, rumen, and rectum of clinically affected cattle.








Wednesday, May 2, 2012


ARS FLIP FLOPS ON SRM REMOVAL FOR ATYPICAL L-TYPE BASE BSE RISK HUMAN AND ANIMAL HEALTH






Wednesday, July 28, 2010


re-Freedom of Information Act Project Number 3625-32000-086-05, Study of Atypical BSE UPDATE July 28, 2010


Sent: Wednesday, July 28, 2010 11:42 AM


Subject: re-Freedom of Information Act Project Number 3625-32000-086-05, Study of Atypical BSE UPDATE


Greetings again Ms Williams et al at FOIA USDA,


Thank You again for your kind reply on this important information. However, I am concerned that you may not be aware of new transmission studies. You (USDA et al) state Ma'am ;



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


The SCA with Italy was mainly to confirm our respective country’s diagnostic tests would detect the various atypical BSE cases as seen in each country), in the meantime, the Italians have published their transmissibility and pathogenesis work on their BASE cases in the following article:


Lombardi G, Casalone C, A DA, Gelmetti D, Torcoli G, Barbieri I, Corona C, Fasoli E, Farinazzo A, Fiorini M, Gelati M, Iulini B, Tagliavini F, Ferrari S, Caramelli M, Monaco S, Capucci L, Zanusso G (2008) Intraspecies transmission of BASE induces clinical dullness and amyotrophic changes. PLoS Pathog 4:e1000075


The above mentioned paper concludes, “In all experimentally infected animals, no PrP**TSE was detected in peripheral tissues, including cervical and mesenteric lymph nodes, spleen, thymus, liver, lung, peripheral nerves and forelimb and limb muscles, either by standard Western blot analysis or following phosphotungstic acid precipitation.“


It is not necessary to change SRM removal due to any different tissue infectivity distribution between classical BSE and atypical BSE. At this time, there is no scientific evidence to suggest a need for expanding the list of tissues included in the Specified Risk Material (SRM) ban as a result of published studies on atypical BSE.


snip...


Moreover, in the paper by Buschmann A, Groschup MH (2005,) Highly bovine spongiform encephalopathy-sensitive transgenic mice confirm the essential restriction of infectivity to the nervous system in clinically diseased cattle. J Infect Dis 192:934-942; the authors, when speaking about the classical BSE food-borne epidemic in Europe, concluded their “results provide further indication that the pathogenesis of BSE in cattle is fundamentally different from that in sheep and mice, due to an exclusive intraneuronal spread of infectivity from the gut to the central nervous system.”


end...



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



Again, in my opinion, the USDA is cherry picking the science they want to use, and in doing so, I believe they are putting human lives at risk.


I disagree for the following reasons. New studies indeed show that ;



July 10, 2010


see full text ;



Wednesday, July 28, 2010


re-Freedom of Information Act Project Number 3625-32000-086-05, Study of Atypical BSE UPDATE July 28, 2010








USDA TRIPLE BSE MAD COW FIREWALL, SRM, FEED, AND SURVEILLANCE


2012


***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...







MAD COW USDA ATYPICAL L-TYPE BASE BSE, the rest of the story...


***Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate Model






***Infectivity in skeletal muscle of BASE-infected cattle






***feedstuffs- It also suggests a similar cause or source for atypical BSE in these countries.






***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans.







The present study demonstrated successful intraspecies transmission of H-type BSE to cattle and the distribution and immunolabeling patterns of PrPSc in the brain of the H-type BSE-challenged cattle. TSE agent virulence can be minimally defined by oral transmission of different TSE agents (C-type, L-type, and H-type BSE agents) [59]. Oral transmission studies with H-type BSEinfected cattle have been initiated and are underway to provide information regarding the extent of similarity in the immunohistochemical and molecular features before and after transmission.


In addition, the present data will support risk assessments in some peripheral tissues derived from cattle affected with H-type BSE.








Friday, May 11, 2012


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



***support risk assessments in some peripheral tissues derived from cattle affected with H-type BSE










Thursday, June 21, 2012


Clinical and Pathologic Features of H-Type Bovine Spongiform Encephalopathy Associated with E211K Prion Protein Polymorphism


Justin J. Greenlee1*, Jodi D. Smith1, M. Heather West Greenlee2, Eric M. Nicholson1


1 National Animal Disease Center, United States Department of Agriculture, Agricultural Research Service, Ames, Iowa, United States of America, 2 Iowa State University, Ames, Iowa, United States of America


Abstract


The majority of bovine spongiform encephalopathy (BSE) cases have been ascribed to the classical form of the disease. Htype and L-type BSE cases have atypical molecular profiles compared to classical BSE and are thought to arise spontaneously. However, one case of H-type BSE was associated with a heritable E211K mutation in the prion protein gene. The purpose of this study was to describe transmission of this unique isolate of H-type BSE when inoculated into a calf of the same genotype by the intracranial route. Electroretinograms were used to demonstrate preclinical deficits in retinal function, and optical coherence tomography was used to demonstrate an antemortem decrease in retinal thickness. The calf rapidly progressed to clinical disease (9.4 months) and was necropsied. Widespread distribution of abnormal prion protein was demonstrated within neural tissues by western blot and immunohistochemistry. While this isolate is categorized as BSE-H due to a higher molecular mass of the unglycosylated PrPSc isoform, a strong labeling of all 3 PrPSc bands with monoclonal antibodies 6H4 and P4, and a second unglycosylated band at approximately 14 kDa when developed with antibodies that bind in the C-terminal region, it is unique from other described cases of BSE-H because of an additional band 23 kDa demonstrated on western blots of the cerebellum. This work demonstrates that this isolate is transmissible, has a BSE-H phenotype when transmitted to cattle with the K211 polymorphism, and has molecular features that distinguish it from other cases of BSE-H described in the literature.


snip...


Most significantly it must be determined if the molecular phenotype of this cattle TSE remains stable when transmitted to cattle without the E211K polymorphism as several other isolates of atypical BSE have been shown to adopt a molecular profile consistent with classical BSE after passage in transgenic mice expressing bovine PrPC [40] or multiple passages in wild type mice [23]. Results of ongoing studies, namely passage of the E211K Htype isolate into wild-type cattle, will lend further insight into what role, if any, genetic and sporadic forms of BSE may have played in the origins of classical BSE. Atypical cases presumably of spontaneous or, in the case of E211K BSE-H, genetic origins highlight that it may not be possible to eradicate BSE entirely and that it would be hazardous to remove disease control measures such as prohibiting the feeding of meat and bone meal to ruminants.







Saturday, May 26, 2012


Are USDA assurances on mad cow case 'gross oversimplification'?


SNIP...


What irks many scientists is the USDA’s April 25 statement that the rare disease is “not generally associated with an animal consuming infected feed.”


The USDA’s conclusion is a “gross oversimplification,” said Dr. Paul Brown, one of the world’s experts on this type of disease who retired recently from the National Institutes of Health. "(The agency) has no foundation on which to base that statement.”


“We can’t say it’s not feed related,” agreed Dr. Linda Detwiler, an official with the USDA during the Clinton Administration now at Mississippi State.


In the May 1 email to me, USDA’s Cole backed off a bit. “No one knows the origins of atypical cases of BSE,” she said


The argument about feed is critical because if feed is the cause, not a spontaneous mutation, the California cow could be part of a larger outbreak.


SNIP...






October 2009 O.11.3 Infectivity in skeletal muscle of BASE-infected cattle


Silvia Suardi1, Chiara Vimercati1, Fabio Moda1, Ruggerone Margherita1, Ilaria Campagnani1, Guerino Lombardi2, Daniela Gelmetti2, Martin H. Groschup3, Anne Buschmann3, Cristina Casalone4, Maria Caramelli4, Salvatore Monaco5, Gianluigi Zanusso5, Fabrizio Tagliavini1 1Carlo Besta" Neurological Institute,Italy; 2IZS Brescia, Italy; 33FLI Insel Riems, D, Germany; 4CEA-IZS Torino, Italy; 5University of Verona, Italy


Background: BASE is an atypical form of bovine spongiform encephalopathy caused by a prion strain distinct from that of BSE. Upon experimental transmission to cattle, BASE induces a previously unrecognized disease phenotype marked by mental dullness and progressive atrophy of hind limb musculature. Whether affected muscles contain infectivity is unknown. This is a critical issue since the BASE strain is readily transmissible to a variety of hosts including primates, suggesting that humans may be susceptible.


Objectives: To investigate the distribution of infectivity in peripheral tissues of cattle experimentally infected with BASE. Methods: Groups of Tg mice expressing bovine PrP (Tgbov XV, n= 7-15/group) were inoculated both i.c. and i.p. with 10% homogenates of a variety of tissues including brain, spleen, cervical lymph node, kidney and skeletal muscle (m. longissimus dorsi) from cattle intracerebrally infected with BASE. No PrPres was detectable in the peripheral tissues used for inoculation either by immunohistochemistry or Western blot.


Results: Mice inoculated with BASE-brain homogenates showed clinical signs of disease with incubation and survival times of 175±15 and 207±12 days. Five out of seven mice challenged with skeletal muscle developed a similar neurological disorder, with incubation and survival times of 380±11 and 410±12 days. At present (700 days after inoculation) mice challenged with the other peripheral tissues are still healthy. The neuropathological phenotype and PrPres type of the affected mice inoculated either with brain or muscle were indistinguishable and matched those of Tgbov XV mice infected with natural BASE.


Discussion: Our data indicate that the skeletal muscle of cattle experimentally infected with BASE contains significant amount of infectivity, at variance with BSE-affected cattle, raising the issue of intraspecies transmission and the potential risk for humans. Experiments are in progress to assess the presence of infectivity in skeletal muscles of natural BASE.






Friday, December 05, 2008


Detection of Prion Infectivity in Fat Tissues of Scrapie-Infected Mice


Brent Race1#, Kimberly Meade-White1#, Michael B. A. Oldstone2, Richard Race1, Bruce Chesebro1*






Prion Infectivity in Fat of Deer with Chronic Wasting Disease▿


Brent Race#, Kimberly Meade-White#, Richard Race and Bruce Chesebro*






P.9.21


Molecular characterization of BSE in Canada


Jianmin Yang1, Sandor Dudas2, Catherine Graham2, Markus Czub3, Tim McAllister1, Stefanie Czub1 1Agriculture and Agri-Food Canada Research Centre, Canada; 2National and OIE BSE Reference Laboratory, Canada; 3University of Calgary, Canada


Background: Three BSE types (classical and two atypical) have been identified on the basis of molecular characteristics of the misfolded protein associated with the disease. To date, each of these three types have been detected in Canadian cattle.


Objectives: This study was conducted to further characterize the 16 Canadian BSE cases based on the biochemical properties of there associated PrPres. Methods: Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases was determined using modified Western blot analysis.


Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and changes in glycosylation similar to other atypical BSE cases. PK digestion under mild and stringent conditions revealed a reduced protease resistance of the atypical cases compared to the C-type cases. N terminal- specific antibodies bound to PrPres from H type but not from C or L type. The C-terminal-specific antibodies resulted in a shift in the glycoform profile and detected a fourth band in the Canadian H-type BSE.


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.






Monday, July 9, 2012


Spread of Classic BSE Prions from the Gut via the Peripheral Nervous System to the Brain


Study Finds "Mad Cow Disease" in Cattle Can Spread Widely in Autonomic Nervous System before Detectable in the Central Nervous System






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:






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






Owens, Julie


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


Sent: Monday, July 24, 2006 1:09 PM


To: FSIS RegulationsComments


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



Page 1 of 98 8/3/2006



Greetings FSIS,




I would kindly like to comment on the following ;



snip...




HOWEVER, JAPAN has already shown infectivity in tissues other than CNS in there atypical TSE in cattle, so why should we wait, and expose many to this agent needlessly, since the last two mad cows in the USA were also atypical TSE ?


PrPSc distribution of a natural case of bovine spongiform encephalopathy


Yoshifumi Iwamaru, Yuka Okubo, Tamako Ikeda, Hiroko Hayashi, Mori- kazu Imamura, Takashi Yokoyama and Morikazu Shinagawa Priori Disease Research Center, National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba 305-0856 Japan gan@affrc.go.jp


Abstract


Bovine spongiform encephalopathy (BSE) is a disease of cattle that causes progressive neurodegeneration of the central nervous system. Infectivity of BSE agent is accompanied with an abnormal isoform of prion protein (PrPSc).


The specified risk materials (SRM) are tissues potentially carrying BSE infectivity. The following tissues are designated as SRM in Japan: the skull including the brain and eyes but excluding the glossa and the masse- ter muscle, the vertebral column excluding the vertebrae of the tail, spinal cord, distal illeum. For a risk management step, the use of SRM in both animal feed or human food has been prohibited. However, detailed PrPSc distribution remains obscure in BSE cattle and it has caused controversies about definitions of SRM. Therefore we have examined PrPSc distribution in a BSE cattle by Western blotting to reassess definitions of SRM.


The 11th BSE case in Japan was detected in fallen stock surveillance. The carcass was stocked in the refrigerator. For the detection of PrPSc, 200 mg of tissue samples were homogenized. Following collagenase treatment, samples were digested with proteinase K. After digestion, PrPSc was precipitated by sodium phosphotungstate (PTA). The pellets were subjected to Western blotting using the standard procedure. Anti-prion protein monoclonal antibody (mAb) T2 conjugated horseradish peroxidase was used for the detection of PrPSc.


PrPSc was detected in brain, spinal cord, dorsal root ganglia, trigeminal ganglia, sublingual ganglion, retina. In addition, PrPSc was also detected in the peripheral nerves (sciatic nerve, tibial nerve, vagus nerve).





Our results suggest that the currently accepted definitions of SRM in BSE cattle may need to be reexamined.





T. Kitamoto (Ed.)PRIONSFood and Drug Safety




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





ALSO from the International Symposium of Prion Diseases held in Sendai, October 31, to November 2, 2004; Bovine spongiform encephalopathy (BSE) in Japan


snip...


"Furthermore, current studies into transmission of cases of BSE that are atypical or that develop in young cattle are expected to amplify the BSE prion"


NO. Date conf. Farm Birth place and Date Age at diagnosis


1. 8. 2003.10.6. Fukushima Tochigi 2001.10.13. 23


2. 9. 2003.11.4. Hiroshima Hyogo 2002.1.13. 21


Test results


# 8b, 9c cows Elisa Positive, WB Positive, IHC negative, histopathology negative


b = atypical BSE case


c = case of BSE in a young animal


b,c, No PrPSc on IHC, and no spongiform change on histology


International Symposium of Prion Diseases held in Sendai, October 31, to November 2, 2004.


Page 6 of 98


8/3/2006


Tetsuyuki Kitamoto Professor and Chairman Department of Prion Research Tohoku University School of Medicine 2-1 SeiryoAoba-ku, Sendai 980-8575, JAPAN TEL +81-22-717-8147 FAX +81-22-717-8148 e-mail; kitamoto@mail.tains.tohoku.ac.jp Symposium Secretariat Kyomi Sasaki TEL +81-22-717-8233 FAX +81-22-717-7656 e-mail: kvomi-sasaki@mail.tains.tohoku.ac.ip




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













Sunday, February 14, 2010


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











Friday, February 11, 2011


Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues








Monday, January 2, 2012


EFSA Minutes of the 6th Meeting of the EFSA Scientific Network on BSE-TSE Brussels, 29-30 November 2011








UPDATE CALIFORNIA JULY 2012 ATYPICAL L-TYPE BASE BSE MAD COW


Saturday, May 26, 2012


Are USDA assurances on mad cow case 'gross oversimplification'?


SNIP...


What irks many scientists is the USDA’s April 25 statement that the rare disease is “not generally associated with an animal consuming infected feed.”


The USDA’s conclusion is a “gross oversimplification,” said Dr. Paul Brown, one of the world’s experts on this type of disease who retired recently from the National Institutes of Health. "(The agency) has no foundation on which to base that statement.”


“We can’t say it’s not feed related,” agreed Dr. Linda Detwiler, an official with the USDA during the Clinton Administration now at Mississippi State.


In the May 1 email to me, USDA’s Cole backed off a bit. “No one knows the origins of atypical cases of BSE,” she said


The argument about feed is critical because if feed is the cause, not a spontaneous mutation, the California cow could be part of a larger outbreak.


SNIP...






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



Saturday, August 4, 2012


*** Final Feed Investigation Summary - California BSE Case - July 2012






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




SUMMARY REPORT CALIFORNIA BOVINE SPONGIFORM ENCEPHALOPATHY CASE INVESTIGATION JULY 2012


Summary Report BSE 2012


Executive Summary






Saturday, August 4, 2012


Update from APHIS Regarding Release of the Final Report on the BSE Epidemiological Investigation






in the url that follows, I have posted


SRM breaches first, as late as 2011.


then


MAD COW FEED BAN BREACHES AND TONNAGES OF MAD COW FEED IN COMMERCE up until 2007, when they ceased posting them.


then,


MAD COW SURVEILLANCE BREACHES.




Friday, May 18, 2012


Update from APHIS Regarding a Detection of Bovine Spongiform Encephalopathy (BSE) in the United States Friday May 18, 2012






October 2009 O.11.3



Infectivity in skeletal muscle of BASE-infected cattle




Silvia Suardi1, Chiara Vimercati1, Fabio Moda1, Ruggerone Margherita1, Ilaria Campagnani1, Guerino Lombardi2, Daniela Gelmetti2, Martin H. Groschup3, Anne Buschmann3, Cristina Casalone4, Maria Caramelli4, Salvatore Monaco5, Gianluigi Zanusso5, Fabrizio Tagliavini1 1Carlo Besta" Neurological Institute,Italy; 2IZS Brescia, Italy; 33FLI Insel Riems, D, Germany; 4CEA-IZS Torino, Italy; 5University of Verona, Italy


Background: BASE is an atypical form of bovine spongiform encephalopathy caused by a prion strain distinct from that of BSE. Upon experimental transmission to cattle, BASE induces a previously unrecognized disease phenotype marked by mental dullness and progressive atrophy of hind limb musculature. Whether affected muscles contain infectivity is unknown. This is a critical issue since the BASE strain is readily transmissible to a variety of hosts including primates, suggesting that humans may be susceptible.


Objectives: To investigate the distribution of infectivity in peripheral tissues of cattle experimentally infected with BASE. Methods: Groups of Tg mice expressing bovine PrP (Tgbov XV, n= 7-15/group) were inoculated both i.c. and i.p. with 10% homogenates of a variety of tissues including brain, spleen, cervical lymph node, kidney and skeletal muscle (m. longissimus dorsi) from cattle intracerebrally infected with BASE. No PrPres was detectable in the peripheral tissues used for inoculation either by immunohistochemistry or Western blot.


Results: Mice inoculated with BASE-brain homogenates showed clinical signs of disease with incubation and survival times of 175±15 and 207±12 days. Five out of seven mice challenged with skeletal muscle developed a similar neurological disorder, with incubation and survival times of 380±11 and 410±12 days. At present (700 days after inoculation) mice challenged with the other peripheral tissues are still healthy. The neuropathological phenotype and PrPres type of the affected mice inoculated either with brain or muscle were indistinguishable and matched those of Tgbov XV mice infected with natural BASE.


Discussion: Our data indicate that the skeletal muscle of cattle experimentally infected with BASE contains significant amount of infectivity, at variance with BSE-affected cattle, raising the issue of intraspecies transmission and the potential risk for humans. Experiments are in progress to assess the presence of infectivity in skeletal muscles of natural BASE.










Sunday, November 13, 2011


California BSE mad cow beef recall, QFC, CJD, and dead stock downer livestock








Wednesday, August 22, 2012


USDA, McDonald's suspend slaughterhouse buys from Central Valley Meat Co. over deadstock downer cows








Wednesday, August 01, 2012


Behavioural and Psychiatric Features of the Human Prion Diseases: Experience in 368 Prospectively Studied Patients








Monday, August 06, 2012


Atypical neuropathological sCJD-MM phenotype with abundant white matter Kuru-type plaques sparing the cerebellar cortex








Monday, July 23, 2012


The National Prion Disease Pathology Surveillance Center July 2012









layperson



Terry S. Singeltary SR. P.O. Box 42 Bacliff, Texas USA 77518 flounder9@verizon.net

Friday, August 24, 2012

Iatrogenic prion diseases in humans: an update

Iatrogenic prion diseases in humans: an update


Gorka Barrenetxea Affiliations Tel.: +34 4396062; fax: +34 4395424. Quiron Bilbao, Assisted Reproduction Center, Universidad del PaĆ­s Vasco/Euskal Herriko Unibertsitatea, Ribera Botica Vieja 23, 48014 Bilbao, Spain


Received 8 January 2012; received in revised form 2 July 2012; accepted 8 August 2012. published online 24 August 2012. Uncorrected Proof




Abstract


Although Creutzfeldt–Jakob disease (CJD) was first identified in 1920, prevention of transmission raised particular concern all over the world when a new variant of the disease was first described in 1996. There is good evidence of iatrogenic transmission of this new variant among human beings through blood, blood components, tissues and growth hormone. Furthermore, four cases of iatrogenic transmission of CJD through fertility treatment with human pituitary-derived gonadotrophins have been reported.


It is important to distinguish the categories of infectivity and categories of risk, which require consideration not only of the level of infectivity of a given tissue or fluid, but also the amount of tissue/fluid to which a person is exposed, the duration of exposure and the route by which infection is transmitted.


The potential presence and infectivity of prion proteins in human urinary gonadotrophin preparations is a matter of debate. Differences in the sensitivity of bioassay methods are of paramount importance when considering the infectivity of a tissue. Some new methods might detect small amounts of agent in some tissues currently thought to be free of infectivity.


No cases of human prion disease due to the use of urinary gonadotrophins have been recognized to date. However, the detection of prions in the urine of experimental animals and in some urine-based preparations, and the young age of fertility drug recipients, require the application of the precautionary principle to urinary preparations.


Keywords: Prion diseases, Urine-derived gonadotrophins, Transmissible spongiform encephalopathy, Iatrogenic Creutzfeldt–Jakob disease, Prionuria, Tissue infectivity











Friday, March 25, 2011


Detection of Prion Protein in Urine-Derived Injectable Fertility Products by a Targeted Proteomic Approach


http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/detection-of-prion-protein-in-urine.html




Friday, August 10, 2012


Incidents of Potential iatrogenic Creutzfeldt-Jakob disease (CJD) biannual update (July 2012)






North America has NO surveillance system for iatrogenic CJD. a few mishaps of late ;



Tuesday, July 31, 2012


11 patients may have been exposed to fatal disease Creutzfeldt-Jakob Disease CJD Greenville Memorial Hospital






Thursday, August 02, 2012


CJD case in Saint John prompts letter to patients Canada CJD case in Saint John prompts letter to patients







Friday, June 29, 2012


Highly Efficient Prion Transmission by Blood Transfusion







Sunday, June 3, 2012


A new neurological disease in primates inoculated with prion-infected blood or blood components









Thursday, August 16, 2012


Blood products, collected from a donor who was at risk for variant Creutzfeldt-Jakob disease ( vCJD) USA JUNE, JULY, AUGUST 2012








Wednesday, May 16, 2012


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


Proposal ID: 29403







Monday, August 13, 2012


Summary results of the second national survey of abnormal prion prevalence in archived appendix specimens August 2012







RedCross Request Jerome H. Holland Laboratory is collecting small volumes of blood from patients afflicted with various forms of transmissible spongiform encephalopathies (TSE)/prion diseases and their blood-related family members 2012


UPDATED INFORMATION AUGUST 2012


REDCROSS REQUEST


The American National Red Cross (Red Cross) Jerome H. Holland Laboratory for Biomedical Research in Rockville, Maryland is collecting small volumes of blood from patients afflicted with various forms of transmissible spongiform encephalopathies (TSE)/prion diseases and their blood-related family members. The purpose of the research is to build a blood sample repository for studies on ways to detect the presence of prion protein or other markers of the disease in human blood.


Recent epidemiological evidence indicates that blood of patients with variant form of Creutzfeldt-Jakob disease (vCJD), that is prevalent in the United Kingdom, is infectious.


The questions about the possibility that blood from patients with the sporadic and familial forms of TSE might also be infectious is still not resolved even though 10 years of searching has not revealed any examples of blood-related transmission from patients with these non-variant forms of disease.


The development of a blood test to identify affected people in the pre-clinical stage of disease could eliminate the uncertainty about TSE-related blood safety. Some tests have been successful for testing animals infected with TSEs, but in order to know if any test will be reliable in humans, we need to test human blood.


CJD patients and their families are the only source of blood specimens that can answer this question, and we therefore ask you to support our effort.


If you or an affected relative is interested in participating, please contact the name listed below. No more than 50 ml of blood should be collected at a location convenient to you through your own arrangements with your physician and the blood sample should be sent to the Holland Laboratory at no cost to you. The samples will be processed and stored, frozen indefinitely, at the Holland Laboratory in Rockville, Maryland. The Red Cross will provide access to only designated research staff at the Red Cross or other research groups that have provided convincing evidence for a test to detect TSE in animals.


Participating individuals will NOT be notified about test results because the tests that will be performed on blood are experimental and their significance is not known and will remain uncertain for some years to come. The CJD foundation will be notified of any publications coming from our research.


Contact information:


Dr. Larisa Cervenakova; Phone: 301-738-0765; e-mail: cervenakl@usa.redcross.org




Dr. Larisa Cervenakova


Senior Scientist, Biomedical Services


American Red Cross


15601 Crabbs Branch Way


Rockville, MD 20855


(240) 314-3536 (p)


(240) 888-3615 (c)


(301) 610-4120 (f)


larisa.cervenakova@redcross.org


Coordinator for the CJD Lookback Study. The study is ongoing and we are looking for blood donors who subsequently develop CJD.


Below is my contact information, please feel free to pass on my information to those family members who want to participate in the Lookback Study.


Kerri Dorsey, MPH


Project Manager 1


American Red Cross


Holland Laboratory


Transmissible Disease Department


15601 Crabbs Branch Way


Rockville, MD 20855


Ph: 240-314-3523


Fax: 301-610-4121


END...TSS




CJD LOOKBACK STUDY

















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...














Saturday, May 26, 2012


Are USDA assurances on mad cow case 'gross oversimplification'?


SNIP...


What irks many scientists is the USDA’s April 25 statement that the rare disease is “not generally associated with an animal consuming infected feed.”


The USDA’s conclusion is a “gross oversimplification,” said Dr. Paul Brown, one of the world’s experts on this type of disease who retired recently from the National Institutes of Health. "(The agency) has no foundation on which to base that statement.”


“We can’t say it’s not feed related,” agreed Dr. Linda Detwiler, an official with the USDA during the Clinton Administration now at Mississippi State.


In the May 1 email to me, USDA’s Cole backed off a bit. “No one knows the origins of atypical cases of BSE,” she said


The argument about feed is critical because if feed is the cause, not a spontaneous mutation, the California cow could be part of a larger outbreak.


SNIP...








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


Saturday, August 4, 2012


Final Feed Investigation Summary - California BSE Case - July 2012





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




SUMMARY REPORT CALIFORNIA BOVINE SPONGIFORM ENCEPHALOPATHY CASE INVESTIGATION JULY 2012




Summary Report BSE 2012


Executive Summary






Saturday, August 4, 2012


Update from APHIS Regarding Release of the Final Report on the BSE Epidemiological Investigation






in the url that follows, I have posted




SRM breaches first, as late as 2011.


then


MAD COW FEED BAN BREACHES AND TONNAGES OF MAD COW FEED IN COMMERCE up until 2007, when they ceased posting them.


then,


MAD COW SURVEILLANCE BREACHES.



Friday, May 18, 2012


Update from APHIS Regarding a Detection of Bovine Spongiform Encephalopathy (BSE) in the United States Friday May 18, 2012






Monday, August 6, 2012


TAFS BSE in USA August 6, 2012


BSE in USA

































Monday, July 23, 2012



The National Prion Disease Pathology Surveillance Center July 2012










TSS

Saturday, August 4, 2012

Update from APHIS Regarding Release of the Final Report on the BSE Epidemiological Investigation

Contact: Lyndsay Cole (970) 494-7410


Update from APHIS Regarding Release of the Final Report on the BSE Epidemiological Investigation


Today, USDA is releasing its final report on the epidemiological investigation of a dairy cow from California that tested positive for bovine spongiform encephalopathy (BSE) in April 2012. This epidemiological report is the result of months of close coordination with the U.S. Food and Drug Administration (FDA), the California Department of Food and Agriculture (CDFA), local officials, and the associated dairy and rendering facility.


In accordance with World Organization for Animal Health guidance, USDA conducted a thorough epidemiological investigation following the BSE detection. This included on-the-ground investigations and records review from the rendering facility, the index farm, and associated premises, as well as traceback for progeny and birth cohorts of the index cow. The results of this thorough investigation confirmed that at no time was the U.S. food supply or human health at risk, and that the United States’ longstanding system of interlocking safeguards against BSE continues to be effective.


This case was found in an animal that was sampled for the disease at a rendering facility in central California. This animal was never presented for slaughter for human consumption, so at no time presented a risk to the food supply, or to human health in the United States.


The index animal was a 10 year 7 month-old Holstein cow from a central California dairy. The animal was humanely euthanized after it developed lameness and became recumbent, and was sampled by a renderer contracted to collect samples as part of USDA’s ongoing BSE surveillance. Results from immunohistochemistry and Western blot tests at USDA’s National Veterinary Services Laboratories (NVSL) confirmed the animal positive for atypical BSE. Samples were also sent to the World Organization for Animal Health (OIE) reference laboratories in Canada and England. The laboratories confirmed that the index cow was positive for atypical (L-type) BSE.


As a result of on-the-ground investigation and records review, USDA and CDFA identified only one live offspring of the cow, which was humanely euthanized and found to be negative for BSE. No birth cohorts of the index animal were found alive.


The carcass of the index animal (along with approximately 90 other carcasses being held at the renderer’s transfer station), were disposed of in a landfill in accordance with all Federal, State and local regulations. The carcass of the index animal did not enter the human or animal food chain.


In conjunction with USDA’s investigation, FDA and CDFA conducted an extensive feed investigation. Twelve feed suppliers were identified to the index premises; one of which was no longer in business. The remaining 11 were found to be in compliance with FDA and CDFA regulations and requirements. FDA has released a full report on the feed investigation. It is available at www.fda.gov.


The United States has a longstanding system of three interlocking safeguards against BSE that protects human and animal health, the most important of which is the removal of specified risk materials – or the parts of an animal that would contain the BSE agent should an animal have the disease – from all animals presented for slaughter in the United States. The second safeguard is a strong feed ban that protects cattle from the disease. The third safeguard—which led to this detection— is our ongoing BSE surveillance program that allows USDA to detect the disease if it exists at very low levels in the U.S. cattle population and provides assurances to consumers and our international trading partners that the interlocking system of safeguards in place to prevent BSE are working.


View Final Report







#


Note to Reporters: USDA news releases, program announcements and media advisories are available on the Internet and through Really Simple Syndication (RSS) feeds.


USDA is an equal opportunity provider and employer. To file a complaint of discrimination, write: USDA, Office of the Assistant Secretary for Civil Rights, Office of Adjudication, 1400 Independence Ave., SW, Washington, DC 20250-9410 or call (866) 632-9992 (Toll-free Customer Service), (800) 877-8339 (Local or Federal relay), (866) 377-8642 (Relay voice users).








SUMMARY REPORT CALIFORNIA BOVINE SPONGIFORM ENCEPHALOPATHY CASE INVESTIGATION JULY 2012



Summary Report BSE 2012



Executive Summary







Saturday, August 4, 2012



Final Feed Investigation Summary - California BSE Case - July 2012







TSS