Thursday, February 14, 2013

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

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






C-TYPE BSE BOVINE SPONGIFORM ENCEPHALOPATHY



C-BSE i.e. what is considered for whatever purposes, the U.K. strain of BSE, which has been linked to the nvCJD, now called vCJD in humans...tss)



C-BSE HAS BEEN DOCUMENTED IN THE USA



BSE 1st reported 1984 – 1985 ?





Ministry of Agriculture, Fisheries and Food



Central Veterinary laboratory New Haw Weybridge Surrey KT153NB

 

Telex 262318

 

Telephone By fleet (09323) 41111 Ext.
 


Director A J Stevens MA BVSc MRCVS DipBact

 

Mr J M Watkin-Jones

 

VI Centre



Winchester



YOUR reference C 1-9



Our reference VLO 12467/85/1509



Date 19 September 1985



VLO12467 A



PATHOLOGY REPORT



Gross observations: Received in formalin a well preserved bovine brain, 2 pieces of spinal cord and pieces of kidney all grossly normal.

 

Miscroscopic observations:

 

Cerebrum - mild multifocal (4 foci) non-suppurative perivascular infiltration and focal gliosis.

 

Thalamus - NVL

 

Cerebellum - NVL

 

Corpora quadrigemina - mild neuropil vacuolation



Medulla - moderate neuronal and neuropil vacuolation of the reticular formation



Spinal cord - mild neuropil vacuolation of the lumbar dorsal horns.



Kidney - chronic mild/moderate non-suppurative interstitial reaction with tubular regeneration and fibrosis.



Also a mild peracute multi focal tubular necrosis with focal hyaline droplet change.



DIAGNOSIS:



1. Moderate spongiform encephalopathy - acute.


2. Mild renal nephrosis - peracute



REMARKS:


These acute changes suggest a toxicity of some description. The non-suppurative reactions are far more chronic, mild and non-specific.



Pathologist: Carol Richardson

 

85/9.19/1.1























---------------extract 1. of the DFAL "Early days"----------------





THE EARLY DAYS



This is a Draft Factual Account of the actions of MAFF and DH in relation to events up to the decision to establish the Southwood Working Party. SCDFA refers to the Slaughter and Compensation Draft Factual Account (DFA 6), CVLDFA refers to the CVL Draft Factual Account (DFA 4) and the RFBDFA refers to the Ruminant Feed Ban Part 1 Draft Factual Account (DFA 7), all of which should be read in conjunction with this document.



1. On 22 December 1984, Mr David Bee, a veterinarian, was called to examine Cow 133, belonging to farmer Mr Peter Stent of Pitsham Farm in Sussex. She had an arched back and had lost weight. Mr Bee returned to the farm on numerous occasions to see more cattle with unusual symptoms.



2. On 11 February 1985, Cow 133 died, having developed head tremor and lack of co-ordination. By the end of April 1985, five more cows had died on the farm.



3. During Spring 1985 Mr Bee contacted Mr Watkin-Jones of the local Veterinary Investigation Centre (VIC) at Winchester, Hampshire, regarding the problems at Pitsham farm. The animals were showing aggression and were difficult to milk. Mr Bee said that they had a peculiar gait and arched backs.



4. In April 1985, veterinarian Mr Colin Whitaker was called to Plurenden Manor Farm, Kent, to examine some of Mr R Sternberg's cows showing symptoms including changes of behaviour, aggression and lack of co-ordination.



5. On 2 September 1985 a cow with these symptoms was sent from Pitsham Farm to Winchester VIC for slaughter. The VIC sent the brain and other specimens to the Central Veterinary Laboratory (CVL) at Weybridge, Surrey. This was the fourth Stent cow to be referred to the CVL, however the previous three referrals had not included brain samples.



6. The samples, received on 10 September 1985, were first examined by Ms Carol Richardson, who was the pathologist on duty. This, the subsequent examinations of these samples, and the conflict of evidence about the conclusions reached, are dealt with in the CVL DFA.



7. When Mr Watkin-Jones forwarded Mrs Richardson's report to Mr David Bee, Mr Stent's vet, he wrote:



"I enclose a histological report carried out by my colleague Carol Richardson. I have discussed her findings with her at some length and she comments that the pathological changes found would be consistent with bacterial toxin."



8 Ms Richardson did not remember having a conversation about the case with Mr Watkin-Jones.



9 Mr Bee did not accept this diagnosis. He believed there had been a fungal toxin in the cattle feed. He told the BSE Inquiry that on 4 October 1985, 'a fungal toxin called citrinin had been found in the feed. In any case, by this time, new cases had ceased to develop. I imagined that the problem had run its course'.



10 On 28 June 1986 Mr Jeffrey examined tissue sections taken from the brain of a nyala which had been kept at Marwell Zoo. This examination, and subsequent consideration of the nyala, are described in the CVL DFA.



11. Since his first callout in April 1985, Mr Whitaker had seen several more strange cases at Plurenden Manor Farm. Cattle had been exhibiting symptoms which included changes in character and in behaviour. The cattle became more nervous and aggressive. They also experienced a gradual deterioration of voluntary physical control, including lack of co-ordination and ataxia (inability to move). Mr Whitaker sought assistance from the local VIC at Wye. On referrals from Wye VIC by Mr Carl Johnson, three brain samples from the herd of Mr R. Sternberg of Plurenden Manor Farm were received at CVL (two on 27 November 1986 and one on 23 December 1986).



12. BSE was first recognised as a new disease by pathologists at the CVL in December 1986, and by 19 December 1986 CVL had identified possible repercussions for the export trade and for humans.



see much more here on this history of the first documented and or recognized BSE cases here ;



BSE DRAFT FACTUAL ACCOUNTS (they did away with that history a while back, here some parts of it...tss)













==============atypical TSE prion strains and variants==============





Atypical BSE in Cattle



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



In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.



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








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.


snip...













Thursday, August 12, 2010


Seven main threats for the future linked to prions


First threat


The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.


***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.


Second threat


snip...







Rural and Regional Affairs and Transport References Committee


The possible impacts and consequences for public health, trade and agriculture of the Government's decision to relax import restrictions on beef Final report June 2010


2.65 At its hearing on 14 May 2010, the committee heard evidence from Dr Alan Fahey who has recently submitted a thesis on the clinical neuropsychiatric, epidemiological and diagnostic features of Creutzfeldt-Jakob disease.48 Dr Fahey told the committee of his concerns regarding the lengthy incubation period for transmissible spongiform encephalopathies, the inadequacy of current tests and the limited nature of our current understanding of this group of diseases.49


2.66 Dr Fahey also told the committee that in the last two years a link has been established between forms of atypical CJD and atypical BSE. Dr Fahey said that: They now believe that those atypical BSEs overseas are in fact causing sporadic Creutzfeldt-Jakob disease. They were not sure if it was due to mad sheep disease or a different form. If you look in the textbooks it looks like this is just arising by itself. But in my research I have a summary of a document which states that there has never been any proof that sporadic Creutzfeldt-Jakob disease has arisen de novo-has arisen of itself. There is no proof of that. The recent research is that in fact it is due to atypical forms of mad cow disease which have been found across Europe, have been found in America and have been found in Asia. These atypical forms of mad cow disease typically have even longer incubation periods than the classical mad cow disease.50







Atypical BSE in Cattle


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


In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.


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







2013





Thursday, February 14, 2013


Unique Properties of the Classical Bovine Spongiform Encephalopathy Strain and Its Emergence From H-Type Bovine Spongiform Encephalopathy Substantiated by VM Transmission Studies









Saturday, January 05, 2013


Immunohistochemical Detection of Disease- Associated Prion Protein in the Peripheral Nervous System in Experimental H-Type Bovine Spongiform Encephalopathy







Atypical Bovine Spongiform Encephalopathy (BSE): transmissibility and phenotypes in humans


Classical BSE is known to cause the so-called "new variant CJD" in humans, but the transmission risk and potential features in humans of the recently discovered atypical BSE strains (L type and H-type) were unknown. Bioassays in humanized Tg mice conducted in our laboratory and others' have shown that the BSE-L strain is more virulent than the classic BSE strain (BSE-C) in Tg mice expressing human PrP-129M. We have succeeded recently to transmit BSE-H to the humanized Tg mice as well, albeit at lower efficiency. We found that BSE-H isolates from the USA, Germany, and Poland all exhibited limited transmission in the humanized Tg mice. The USA BSE-H isolate also led to two divergent phenotypes in the humanized mice, which is reminiscent of BSE-C. We have also recently demonstrtaed that a BSE isolate carrying a genetic mutation in the PrP gene is infectious, which provides the first evidence that animals can deveop a transmissible genetic prion disease.









2012





Friday, March 09, 2012


Experimental H-type and L-type bovine spongiform encephalopathy in cattle: observation of two clinical syndromes and diagnostic challenges Research article







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.









Thursday, June 23, 2011


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









P.4.23


Transmission of atypical BSE in humanized mouse models


Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1 1Case Western Reserve University, USA; 2Instituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University (Previously at USDA National Animal Disease Center), USA


Background: Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Atypical BSE cases have been discovered in three continents since 2004; they include the L-type (also named BASE), the H-type, and the first reported case of naturally occurring BSE with mutated bovine PRNP (termed BSE-M). The public health risks posed by atypical BSE were largely undefined.


Objectives: To investigate these atypical BSE types in terms of their transmissibility and phenotypes in humanized mice. Methods: Transgenic mice expressing human PrP were inoculated with several classical (C-type) and atypical (L-, H-, or Mtype) BSE isolates, and the transmission rate, incubation time, characteristics and distribution of PrPSc, symptoms, and histopathology were or will be examined and compared.


Results: Sixty percent of BASE-inoculated humanized mice became infected with minimal spongiosis and an average incubation time of 20-22 months, whereas only one of the C-type BSE-inoculated mice developed prion disease after more than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse brains was biochemically different from bovine BASE or sCJD. PrPSc was also detected in the spleen of 22% of BASE-infected humanized mice, but not in those infected with sCJD. Secondary transmission of BASE in the humanized mice led to a small reduction in incubation time.*** The atypical BSE-H strain is also transmissible with distinct phenotypes in the humanized mice, but no BSE-M transmission has been observed so far.


Discussion: Our results demonstrate that BASE is more virulent than classical BSE, has a lymphotropic phenotype, and displays a modest transmission barrier in our humanized mice. BSE-H is also transmissible in our humanized Tg mice. The possibility of more than two atypical BSE strains will be discussed.


Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.








P26 TRANSMISSION OF ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) IN HUMANIZED MOUSE MODELS


Liuting Qing1, Fusong Chen1, Michael Payne1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5*, and Qingzhong Kong1 1Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA; 2CEA, Istituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University, Diagnostic Medicine/Pathobiology Department, Manhattan, KS 66506, USA. *Previous address: USDA National Animal Disease Center, Ames, IA 50010, USA


Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Two atypical BSE strains, BSE-L (also named BASE) and BSE-H, have been discovered in three continents since 2004. The first case of naturally occurring BSE with mutated bovine PrP gene (termed BSE-M) was also found in 2006 in the USA. The transmissibility and phenotypes of these atypical BSE strains/isolates in humans were unknown. We have inoculated humanized transgenic mice with classical and atypical BSE strains (BSE-C, BSE-L, BSE-H) and the BSE-M isolate. We have found that the atypical BSE-L strain is much more virulent than the classical BSE-C.*** The atypical BSE-H strain is also transmissible in the humanized transgenic mice with distinct phenotype, but no transmission has been observed for the BSE-M isolate so far.


III International Symposium on THE NEW PRION BIOLOGY: BASIC SCIENCE, DIAGNOSIS AND THERAPY 2 - 4 APRIL 2009, VENEZIA (ITALY)







I ask Professor Kong ;


Thursday, December 04, 2008 3:37 PM Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk Assessment


''IS the h-BSE more virulent than typical BSE as well, or the same as cBSE, or less virulent than cBSE? just curious.....''


Professor Kong reply ;



.....snip



''As to the H-BSE, we do not have sufficient data to say one way or another, but we have found that H-BSE can infect humans. I hope we could publish these data once the study is complete. Thanks for your interest.''


Best regards, Qingzhong Kong, PhD Associate Professor Department of Pathology Case Western Reserve University Cleveland, OH 44106 USA



END...TSS





Thursday, December 04, 2008 2:37 PM


"we have found that H-BSE can infect humans."


personal communication with Professor Kong. ...TSS


BSE-H is also transmissible in our humanized Tg mice.


The possibility of more than two atypical BSE strains will be discussed.


Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.













Identification of a second bovine amyloidotic spongiform encephalopathy: Molecular similarities with sporadic Creutzfeldt-Jakob disease





Cristina Casalone*,†, Gianluigi Zanusso†,‡, Pierluigi Acutis*, Sergio Ferrari‡, Lorenzo Capucci§, Fabrizio Tagliavini¶, Salvatore Monaco‡,∥, and Maria Caramelli*


Author Affiliations


Edited by Stanley B. Prusiner, University of California, San Francisco, CA, and approved December 23, 2003 (received for review September 9, 2003)





Abstract





Transmissible spongiform encephalopathies (TSEs), or prion diseases, are mammalian neurodegenerative disorders characterized by a posttranslational conversion and brain accumulation of an insoluble, protease-resistant isoform (PrPSc) of the host-encoded cellular prion protein (PrPC). Human and animal TSE agents exist as different phenotypes that can be biochemically differentiated on the basis of the molecular mass of the protease-resistant PrPSc fragments and the degree of glycosylation. Epidemiological, molecular, and transmission studies strongly suggest that the single strain of agent responsible for bovine spongiform encephalopathy (BSE) has infected humans, causing variant Creutzfeldt-Jakob disease. The unprecedented biological properties of the BSE agent, which circumvents the so-called ”species barrier” between cattle and humans and adapts to different mammalian species, has raised considerable concern for human health. To date, it is unknown whether more than one strain might be responsible for cattle TSE or whether the BSE agent undergoes phenotypic variation after natural transmission. Here we provide evidence of a second cattle TSE. The disorder was pathologically characterized by the presence of PrP-immunopositive amyloid plaques, as opposed to the lack of amyloid deposition in typical BSE cases, and by a different pattern of regional distribution and topology of brain PrPSc accumulation. In addition, Western blot analysis showed a PrPSc type with predominance of the low molecular mass glycoform and a protease-resistant fragment of lower molecular mass than BSE-PrPSc. Strikingly, the molecular signature of this previously undescribed bovine PrPSc was similar to that encountered in a distinct subtype of sporadic Creutzfeldt-Jakob disease.





snip...





Phenotypic Similarities Between BASE and sCJD. The transmissibility of CJD brains was initially demonstrated in primates (27), and classification of atypical cases as CJD was based on this property (28). To date, no systematic studies of strain typing in sCJD have been provided, and classification of different subtypes is based on clinical, neuropathological, and molecular features (the polymorphic PRNP codon 129 and the PrPSc glycotype) (8, 9, 15, 19). The importance of molecular PrPSc characterization in assessing the identity of TSE strains is underscored by several studies, showing that the stability of given disease-specific PrPSc types is maintained upon experimental propagation of sCJD, familial CJD, and vCJD isolates in transgenic PrP-humanized mice (8, 29). Similarly, biochemical properties of BSE- and vCJD-associated PrPSc molecules remain stable after passage to mice expressing bovine PrP (30). Recently, however, it has been reported that PrP-humanized mice inoculated with BSE tissues may also propagate a distinctive PrPSc type, with a ”monoglycosylated-dominant” pattern and electrophoretic mobility of the unglycosylated fragment slower than that of vCJD and BSE (31). Strikingly, this PrPSc type shares its molecular properties with the a PrPSc molecule found in classical sCJD. This observation is at variance with the PrPSc type found in M/V2 sCJD cases and in cattle BASE, showing a monoglycosylated-dominant pattern but faster electrophoretic mobility of the protease-resistant fragment as compared with BSE. In addition to molecular properties of PrPSc, BASE and M/V2 sCJD share a distinctive pattern of intracerebral PrP deposition, which occurs as plaque-like and amyloid-kuru plaques. Differences were, however, observed in the regional distribution of PrPSc. While in M/V2 sCJD cases the largest amounts of PrPSc were detected in the cerebellum, brainstem, and striatum, in cattle BASE these areas were less involved and the highest levels of PrPSc were recovered from the thalamus and olfactory regions.





In conclusion, decoding the biochemical PrPSc signature of individual human and animal TSE strains may allow the identification of potential risk factors for human disorders with unknown etiology, such as sCJD. However, although BASE and sCJD share several characteristics, caution is dictated in assessing a link between conditions affecting two different mammalian species, based on convergent biochemical properties of disease-associated PrPSc types. Strains of TSE agents may be better characterized upon passage to transgenic mice. In the interim until this is accomplished, our present findings suggest a strict epidemiological surveillance of cattle TSE and sCJD based on molecular criteria.





Footnotes



∥ To whom correspondence should be addressed. E-mail: salvatore.monaco@mail.univr.it.


† C.C. and G.Z. contributed equally to this work.


This paper was submitted directly (Track II) to the PNAS office.


Abbreviations: TSE, transmissible spongiform encephalopathy, BSE, bovine spongiform encephalopathy; CJD, Creutzfeldt-Jakob disease; vCJD, variant CJD; sCJD, sporadic CJD; PrP, prion protein, PrPSc pathological PrP; BASE, bovine amyloidotic spongiform encephalopathy.


Copyright © 2004, The National Academy of Sciences









Research Article



Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate



Emmanuel E. Comoy mail,


Cristina Casalone, Nathalie Lescoutra-Etchegaray, Gianluigi Zanusso, Sophie Freire, Dominique Marcé, Frédéric Auvré, Marie-Magdeleine Ruchoux, Sergio Ferrari, Salvatore Monaco, Nicole Salès, Maria Caramelli, Philippe Leboulch, Paul Brown, Corinne I. Lasmézas, Jean-Philippe Deslys



Abstract


Background


Human variant Creutzfeldt-Jakob Disease (vCJD) results from foodborne transmission of prions from slaughtered cattle with classical Bovine Spongiform Encephalopathy (cBSE). Atypical forms of BSE, which remain mostly asymptomatic in aging cattle, were recently identified at slaughterhouses throughout Europe and North America, raising a question about human susceptibility to these new prion strains.



Methodology/Principal Findings



Brain homogenates from cattle with classical BSE and atypical (BASE) infections were inoculated intracerebrally into cynomolgus monkeys (Macacca fascicularis), a non-human primate model previously demonstrated to be susceptible to the original strain of cBSE. The resulting diseases were compared in terms of clinical signs, histology and biochemistry of the abnormal prion protein (PrPres). The single monkey infected with BASE had a shorter survival, and a different clinical evolution, histopathology, and prion protein (PrPres) pattern than was observed for either classical BSE or vCJD-inoculated animals. Also, the biochemical signature of PrPres in the BASE-inoculated animal was found to have a higher proteinase K sensitivity of the octa-repeat region. We found the same biochemical signature in three of four human patients with sporadic CJD and an MM type 2 PrP genotype who lived in the same country as the infected bovine.



Conclusion/Significance



Our results point to a possibly higher degree of pathogenicity of BASE than classical BSE in primates and also raise a question about a possible link to one uncommon subset of cases of apparently sporadic CJD. Thus, despite the waning epidemic of classical BSE, the occurrence of atypical strains should temper the urge to relax measures currently in place to protect public health from accidental contamination by BSE-contaminated products.



snip...


It is not known whether atypical strains of BSE have been circulating for years, or represent new forms of disease, and continuing research is clearly needed to answer both this and the equally important question about a possible relationship to at least certain forms of what are presently regarded as sporadic cases of human disease (sCJD) [4], [23]. Moreover, the BASE strain has been described to evolve naturally towards BSE after successive transmissions in inbred mice [6]. The stability and pathogenicity of this strain in humans remains to be determined, and it is worth recalling that the stability of the cBSE/vCJD strain, which retains its specific molecular signature in different infected hosts, is the exception rather than the rule. As has been previously observed [24]–[26], one patient (Case No. 4, cf. figure 5 sample MM2#4) exhibited both types of PrP, i.e. type 2 typical of the MM2 subtype and type 1 observed in the MM1 subtype. On the one hand, this demonstrates the interest of such a simple biochemical test to refine PrP analysis, and on the other hand it raises a question about the existence of different PrPres signatures in the same patient, i.e., different prion strains linked to multiple infections or to variants selected by the host.



In summary, we have transmitted one atypical form of BSE (BASE) to a cynomolgus macaque monkey that had a shorter incubation period than monkeys infected with classical BSE, with distinctive clinical, neuropathological, and biochemical features; and have shown that the molecular biological signature resembled that seen in a comparatively uncommon subtype of sporadic CJD. We cannot yet say whether BASE is more pathogenic for primates (including humans) than cBSE, nor can we predict whether its molecular biological features represent a clue to one cause of apparently sporadic human CJD. However, the evidence presented here and by others justifies concern about a potential human health hazard from undetected atypical forms of BSE, and despite the waning epizoonosis of classical BSE, it would be premature to abandon the precautionary measures that have been so successful in reversing the impact of cBSE. We would instead urge a gradual, staged reduction that takes into account the evolving knowledge about atypical ruminant diseases, and both a permanent ban on the use of bovine central nervous system tissue for either animal or human use, and its destruction so as to eliminate any risk of environmental contamination.



snip...


Citation: Comoy EE, Casalone C, Lescoutra-Etchegaray N, Zanusso G, Freire S, et al. (2008) Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate. PLoS ONE 3(8): e3017. doi:10.1371/journal.pone.0003017


Editor: Neil Mabbott, University of Edinburgh, United Kingdom


Received: April 24, 2008; Accepted: August 1, 2008; Published: August 20, 2008


Copyright: © 2008 Comoy 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 has been supported by the Network of Excellence NeuroPrion.


Competing interests: CEA owns a patent covering the BSE diagnostic tests commercialized by the company Bio-Rad.


* E-mail: emmanuel.comoy@cea.fr









Discussion: Our results demonstrate that BASE is more virulent than classical BSE, has a lymphotropic phenotype, and displays a modest transmission barrier in our humanized mice. BSE-H is also transmissible in our humanized Tg mice. The possibility of more than two atypical BSE strains will be discussed.




Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.











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"










Wednesday, May 19, 2010


Molecular, Biochemical and Genetic Characteristics of BSE in Canada



>>> The occurrence of atypical cases of BSE in countries such as Canada with low BSE prevalence and transmission risk argues for the occurrence of sporadic forms of BSE worldwide. <<<




RE-Molecular, Biochemical and Genetic Characteristics of BSE in Canada




Posted by flounder on 19 May 2010 at 21:21 GMT




Greetings,




>>> The occurrence of atypical cases of BSE in countries such as Canada with low BSE prevalence and transmission risk argues for the occurrence of sporadic forms of BSE worldwide. <<<





In my opinion ;




THE statement above is about as non-scientific as a statement can be. There is no proof what-so-ever that any of the atypical BSE cases or atypical scrapie cases anywhere on the globe was a spontaneous case without any route and source of the TSE agent. This is a myth. The USDA and the OIE are trying to make the atypical BSE cases and they have already made the atypical Scrapie cases a legal trading commodity, without any transmission studies first confirming that in fact these atypical TSE will not transmit via feed. I suppose it is a human transmission study in progress. IT's like what happened in England with c-BSE and the transmission to humans via nvCJD never happened to the OIE and the USDA. Canada does not have a low prevalence of BSE either, they have a high prevalence. WHO knows about North America ? it's just that the U.S.A. try's much harder at concealing cases of mad cow disease. THIS was proven with the first stumbling and staggering mad cow in Texas, that was Wisk away to be rendered without any test at all. Then, you had the second case of mad cow disease that the USDA et al was almost as successful with as the first one, but the O.I.G. stepped in and demanded testing over seas, this after many scientist around the globe spoke out. Finally, after an act of Congress, the second case of mad cow disease in Texas was confirmed. all this was done for a reason, and that reason was the OIE USDA BSE MRR policy. Again, This study reeks of TRADE policy wrangling. There is NO proof that the atypical TSE are spontaneous. please show me these transmission studies ? on the other hand, we now know that the L-type atypical BSE is much more virulent than the typical C-BSE, and we now know that the H-type atypical BSE will transmit to humans. WHY can it not be that these atypical cases are simply from feed that had different strains of TSE ? WHY is it that no one will comment on the studies that was suppose to show infectivity of tissues from atypical BSE ? WHY is it I had to file a FOIA on that issue? L-type atypical BSE (BASE) is more virulent than classical BSE, has a lymphotropic phenotype, and displays a modest transmission barrier in our humanized mice. BSE-H is also transmissible in our humanized Tg mice. SEE Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1 et al 2009 ;












Friday, March 09, 2012



Experimental H-type and L-type bovine spongiform encephalopathy in cattle: observation of two clinical syndromes and diagnostic challenges



Research article



Experimental H-type and L-type bovine spongiform encephalopathy in cattle: observation of two clinical syndromes and diagnostic challenges



Timm Konold, Gemma E Bone, Derek Clifford, Melanie J Chaplin, Saira Cawthraw, Michael J Stack and Marion M Simmons


BMC Veterinary Research 2012, 8:22 doi:10.1186/1746-6148-8-22


Published: 8 March 2012



Abstract (provisional)



Background


The majority of atypical bovine spongiform encephalopathy (BSE) cases so far identified worldwide have been detected by active surveillance. Consequently the volume and quality of material available for detailed characterisation is very limiting. Here we report on a small transmission study of both atypical forms, H- and L-type BSE, in cattle to provide tissue for test evaluation and research, and to generate clinical, molecular and pathological data in a standardised way to enable more robust comparison of the two variants with particular reference to those aspects most relevant to case ascertainment and confirmatory diagnosis within existing regulated surveillance programmes.



Results


Two groups of four cattle, intracerebrally inoculated with L-type or H-type BSE, all presented with a nervous disease form with some similarities to classical BSE, which progressed to a more dull form in one animal from each group. Difficulty rising was a consistent feature of both disease forms and not seen in two BSE-free, non-inoculated cattle that served as controls. The pathology and molecular characteristics were distinct from classical BSE, and broadly consistent with published data, but with some variation in the pathological characteristics. Both atypical BSE types were readily detectable as BSE by current confirmatory methods using the medulla brain region at the obex, but making a clear diagnostic distinction between the forms was not consistently straightforward in this brain region. Cerebellum proved a more reliable sample for discrimination when using immunohistochemistry.



Conclusions


The prominent feature of difficulty rising in atypical BSE cases may explain the detection of naturally occurring cases in emergency slaughter cattle and fallen stock. Current confirmatory diagnostic methods are effective for the detection of such atypical cases, but consistently and correctly identifying the variant forms may require modifications to the sampling regimes and methods that are currently in use.




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



One H-type BSE-inoculated steer (H3) had a ‘panic attack’ at 19 mpi: it panicked during cleaning of the pen, ran into the hay rack and the wall of the pen, slipped after circling in the pen and fell to the floor in lateral recumbency with its legs thrashing for approximately 90 seconds. It subsequently remained still in the same position for approximately 5 minutes before righting itself. The steer eventually got up 3 minutes later rising with its forelimbs first.



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



IN THE USA, that H-type BSE mad cow would have gone to the NSLP, thanks to the USDA, and your children and my children and grandchildren were exposed to the most high risk cattle i.e. dead stock downer cows, the most high risk for mad cow disease. NOW, the argument (via industry), about non-ambulatory one minute, but get up and walk the next, has been, ship those stumbling and staggering highly suspect cow the render, before the beast falls again. sometimes, they even help them up with a fork lift or stun gun. THIS is a perfect example of what I have been saying all along, cattle that fall and break a leg, are suspect mad cows, and should be treated as such. ...TSS



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




Postmortem test findings Vacuolar lesions consistent with TSE were observed throughout the neuraxis in both the Htype and L-type BSE cases. At the obex, the neuroanatomical distribution of vacuolation, and its appearance, were not distinguishable from C-type BSE (Figure 2). However, the amount of vacuolation, relative to observations in positive control animals challenged with C-type BSE by the same route (data from previous studies [9]), appeared to be increased in more rostral brain areas, noticeably the frontal cortex.


SNIP...


At the obex, the amount and distribution of immunolabelling made it difficult to see obvious differences between these cases and C-type BSE, but close examination revealed phenotypespecific features in this area too, specifically labelling in white matter tracts (Figure 4a) in the H-type BSE cases, and small aggregated forms of immunolabelling (Figure 4b) throughout the reticular formation in L-type BSE cases.




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




THUS THE OBEX ONLY DIAGNOSTIC CRITERIA BY THE USDA ET AL, when they weren’t testing perfectly healthy brains. ...TSS




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




SNIP...



PrP genotyping revealed that all cattle had six octapeptide repeats and no novel polymorphisms were detected. The only mutations detected were ‘silent’ in that they do not affect the PrP protein sequence. The lack of wild type sequences and the comparatively high number of cattle with the P113 silent mutation (found in only three of 118 Holstein-Friesians examined in the UK [35]) was unusual but may be due to the breed studied; its occurrence was higher in a study of predominantly beef breeds in the United States [36].



SNIP...



Conclusions



Cattle experimentally infected by intracerebral inoculation with L-type or H-type BSE present with two clinical phenotypes, either dull or nervous forms, which may be less clinically overt than classical BSE although difficulty in rising is consistently displayed. This may explain the detection of naturally occurring cases in apparently healthy or emergency slaughter cattle and fallen stock. Current screening and confirmatory diagnostic methods are effective for the detection of such atypical cases, but consistently and correctly identifying and discriminating the variant forms may require modifications to the sampling regimes and methods that are currently in use.













1992


IN CONFIDENCE


BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367)







2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006







IBNC BSE or IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS (IBNC)


1992


NEW BRAIN DISORDER


3. WHAT ABOUT REPORTS OF NEW FORM OF BSE ?


THE VETERINARY RECORD HAS PUBLISHED AN ARTICLE ON A NEW BRAIN DISORDER OF CATTLE DISCOVERED THROUGH OUR CONTROL MEASURES FOR BSE. ALTHOUGH IT PRESENTS SIMILAR CLINICAL SIGNS TO BSE THERE ARE MAJOR DIFFERENCES IN HISTOPATHOLOGY AND INCUBATION PERIODS BETWEEN THE TWO. MUST EMPHASISE THAT THIS IS _NOT_ BSE.


4. IS THIS NEW BRAIN DISORDER A THREAT ?


WE DO NOT EVEN KNOW WHETHER THE AGENT OF THIS DISEASE IS TRANSMISSIBLE. IN ANY CASE, CASES SO FAR IDENTIFIED HAD SHOWN SIMILAR SYMPTOMS TO THOSE OF BSE, AND THEREFORE HAVE BEEN SLAUGHTERED AND INCINERATED, SO THAT IF A TRANSMISSIBLE AGENT WERE INVOLVED IT WOULD HAVE BEEN ELIMINATED. ...








Tuesday, November 17, 2009


SEAC NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS (IBNC) FROM THE VETERINARY LABORATORIES AGENCY (VLA) SEAC 103/1








NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS


"All of the 15 cattle tested showed that the brains had abnormally accumulated PrP"


2009








''THE LINE TO TAKE'' ON IBNC $$$ 1995 $$$


1995


page 9 of 14 ;


30. The Committee noted that the results were unusual. the questioned whether there could be coincidental BSE infection or contamination with scrapie. Dr. Tyrell noted that the feeling of the committee was that this did not represent a new agent but it was important to be prepared to say something publicly about these findings. A suggested line to take was that these were scientifically unpublishable results but in line with the policy of openness they would be made publicly available and further work done to test their validity. Since the BSE precautions were applied to IBNC cases, human health was protected. Further investigations should be carried out on isolations from brains of IBNC cases with removal of the brain and subsequent handling under strict conditions to avoid the risk of any contamination.


31. Mr. Bradley informed the Committee that the CVO had informed the CMO about the IBNC results and the transmission from retina and he, like the Committee was satisfied that the controls already in place or proposed were adequate. ...


snip... see full text















Wednesday, July 28, 2010


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








IN CONFIDENCE


BSE ATYPICAL LESION DISTRIBUTION








Tuesday, November 02, 2010


IN CONFIDENCE


The information contained herein should not be disseminated further except on the basis of "NEED TO KNOW".


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










HARVARD BSE RISK ASSESSMENT AND REASSESSMENT OF SUPPRESSED HARVARD RISK ASSESSMENT THAT WAS SO FLAWED $$$












Thursday, June 23, 2011


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








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"








Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.


snip...


The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...








Thursday, June 24, 2010


Accumulation of L-type Bovine Prions in Peripheral Nerve Tissues Volume 16, Number 7–July 2010


Dispatch


The L-type BSE prion is much more virulent in primates and in humanized mice than is the classical BSE prion, which suggests the possibility of zoonotic risk associated with the L-type BSE prion. These findings emphasize the critical importance of understanding tissue distribution of L-type BSE prions in cattle because, among the current administrative measures for BSE controls, the specified risk materials removal policy plays a crucial role in consumer protection.








P.4.23


Transmission of atypical BSE in humanized mouse models


Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1 1Case Western Reserve University, USA; 2Instituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University (Previously at USDA National Animal Disease Center), USA


Background: Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Atypical BSE cases have been discovered in three continents since 2004; they include the L-type (also named BASE), the H-type, and the first reported case of naturally occurring BSE with mutated bovine PRNP (termed BSE-M). The public health risks posed by atypical BSE were largely undefined.


Objectives: To investigate these atypical BSE types in terms of their transmissibility and phenotypes in humanized mice. Methods: Transgenic mice expressing human PrP were inoculated with several classical (C-type) and atypical (L-, H-, or Mtype) BSE isolates, and the transmission rate, incubation time, characteristics and distribution of PrPSc, symptoms, and histopathology were or will be examined and compared.


Results: Sixty percent of BASE-inoculated humanized mice became infected with minimal spongiosis and an average incubation time of 20-22 months, whereas only one of the C-type BSE-inoculated mice developed prion disease after more than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse brains was biochemically different from bovine BASE or sCJD. PrPSc was also detected in the spleen of 22% of BASE-infected humanized mice, but not in those infected with sCJD. Secondary transmission of BASE in the humanized mice led to a small reduction in incubation time.*** The atypical BSE-H strain is also transmissible with distinct phenotypes in the humanized mice, but no BSE-M transmission has been observed so far.


Discussion: Our results demonstrate that BASE is more virulent than classical BSE, has a lymphotropic phenotype, and displays a modest transmission barrier in our humanized mice. BSE-H is also transmissible in our humanized Tg mice. The possibility of more than two atypical BSE strains will be discussed.


Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.







new url ;








P26 TRANSMISSION OF ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) IN HUMANIZED MOUSE MODELS



Liuting Qing1, Fusong Chen1, Michael Payne1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5*, and Qingzhong Kong1 1Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA; 2CEA, Istituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University, Diagnostic Medicine/Pathobiology Department, Manhattan, KS 66506, USA. *Previous address: USDA National Animal Disease Center, Ames, IA 50010, USA



Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Two atypical BSE strains, BSE-L (also named BASE) and BSE-H, have been discovered in three continents since 2004. The first case of naturally occurring BSE with mutated bovine PrP gene (termed BSE-M) was also found in 2006 in the USA. The transmissibility and phenotypes of these atypical BSE strains/isolates in humans were unknown. We have inoculated humanized transgenic mice with classical and atypical BSE strains (BSE-C, BSE-L, BSE-H) and the BSE-M isolate.




*** We have found that the atypical BSE-L strain is much more virulent than the classical BSE-C.




*** The atypical BSE-H strain is also transmissible in the humanized transgenic mice with distinct phenotype, but no transmission has been observed for the BSE-M isolate so far.




III International Symposium on THE NEW PRION BIOLOGY: BASIC SCIENCE, DIAGNOSIS AND THERAPY 2 - 4 APRIL 2009, VENEZIA (ITALY)








> atypical BSE strains (BSE-C, BSE-L, BSE-H) and the BSE-M isolate.




> but no transmission has been observed for the BSE-M isolate so far. ???




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




h-type atypical BSE BOVINE SPONGIFORM ENCEPHALOPATHY




DOCUMENTED IN THE USA...TSS




h-genetic atypical BSE BOVINE SPONGIFORM ENCEPHALOPATHY



DOCUMENTED IN THE USA...TSS




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...



Results and Discussion



Clinical Findings



A calf with the K211 allele was intracranially inoculated with Htype BSE from the US 2006 BSE case that also had one K211 allele. This calf demonstrated clinical signs at approximately 9.4 months (288 days) post-inoculation (PI). Initial signs were nondescript: listlessness, head down in non-physiologic position with drooping ears, and decreased feed consumption. Within a week, clinical signs had progressed to the calf separating himself from others in the pen, head pressing into the wall or gate, and intermittent reluctance to rise with a stumbling gate for a brief time after rising. The calf began to demonstrate a lip licking and accentuated chewing behavior that was not associated with feeding. The lip-licking and chewing behaviors increased in frequency and severity, and at the time of necropsy at approximately 9.8 months PI (301 days), the calf was depressed, salivating excessively, and reluctant to rise.



Progression to severe clinical signs of BSE occurred in this animal after 9.8 months, a faster onset than the 12–18 months described for other experimental cases of H-type BSE [28,29,30,31]. Previous studies describe the onset of clinical signs for BSE-H as early as 8 months PI [31], but more commonly at 12 months PI [30] or later [28] with a 2–7 month progression of disease to ataxia and inability to rise [28,30,31]. Our findings are similar to other reports in that the earliest clinical signs appear to be vague: weight loss, depression, and low head carriage. However, reports of clinical findings in BSE-H are variable: from ataxia and myoclonus that progresses to an inability to rise without nervousness or aggression [30] to a nervous disease form that is characterized by overeactivity to external stimuli, apprehension and anxiety [31]. This case of E211K BSE-H is different in that the most obvious outward clinical signs were bizarre licking and chewing behaviors not described elsewhere. While the calf affected with E211K was reluctant to rise, it was able to rise when encouraged, however, this animal was younger and smaller than cattle in other studies that had difficulty getting to their feet, which may play a role in the difference reported.



snip...



Distribution and Characterization of Lesions in BSE-H



Vacuolar lesions typical of spongiform encephalopathy were present throughout the brain of this calf. Spongiform change was most severe in the piriform cortex and hippocampus, but present at all levels of brain examined. The distribution of lesions suggests sampling at various levels of the brain, including the obex, would be fruitful for diagnosis. Vacuolation scores ranged from 1 to 3 (scale of 0 to 4), but the vast majority of regions were scored a 2 or higher, indicating definitive spongiform lesions (Fig. S1). Lesions predominantly affected gray matter with little to no involvement of white matter. Vacuoles were primarily present in the neuropil, but were also detected within the cytoplasm of neurons (Fig. 3). At all levels of the spinal cord, there were few inconclusive vacuoles present in the neuropil of the dorsal horns.



Results of microscopic examination for vacuolar change indicate that additional tools may be required to differentiate E211K BSE from classical BSE or other isolates of BSE-H that have been described in the literature [30,31]. Similar to other reports, vacuolar change was generally observed in all brain areas and moderate to severe vacuolar change was detected in cerebral cortex, cerebellum, basal ganglia, thalamus, and brainstem [30,31]. However, there were contrasts in the areas with the highest vacuolation scores. The highest levels of spongiform change were evident in piriform cortex and hippocampus in this case, whereas the highest levels were in thalamic nuclei and midbrain of other reports [30]. Profiles developed using larger numbers of animals suggest that BSE-H may be difficult to distinguish from classical BSE based on spongiform change in the obex, but may have increased numbers of vacuoles in rostral brain areas [31]. E211K BSE-H had the lowest scores in pontine and hypoglossal motor nuclei, which was similar to previous reports of BSE-H [30]. In summary, it appears that vacuolar change is variable amongst different isolates classified as BSE-H. Caution should be used when considering the lesion profile of this single animal as what role individual animal differences or the E211K polymorphism play cannot be determined without further experimentation.



Microscopic evaluation of the brain of the US 2006 H-type BSE case was limited to the obex and complicated by freeze artifact, precluding a definitive microscopic interpretation [18]. Therefore, this is the first description of the microscopic lesions in the CNS of a bovid affected with H-type BSE associated with the E211K polymorphism. No amyloid plaques were present in the tissues from the calf with E211K BSE-H, which is similar to one previous study of BSE-H [31], but contrasts with another [30].



Immunohistochemical analysis for PrPSc demonstrated widespread immunoreactivity throughout the brain, spinal cord, and retina with lesser immunoreactivity in neurohypophysis and the trigeminal ganglia (Fig. S2). Regardless of the brain region examined, PrPSc immunoreactivity was readily apparent. Immunoreactivity was most intense in the brainstem and midbrain and patterns of immunoreactivity were similar to those previously described [1,18,26,30,31]with an intraglial distribution predominating. The predominant patterns in the cortex were intraglial and stellate on a background of fine punctate and granular particulate staining that was multifocally coalescing (Fig. 4A). Perineuronal staining was also evident, but intraneuronal immunoreactivity was rare. Immunoreactivity increased in intensity from frontal cortex caudal to occipital cortex. In the white matter subjacent to the cortex, there were rare coarse particulate foci of immunoreactivity that were most often associated with glial cell margins (Fig. S3). This is in contrast to previous studies where glial staining in the white matter was a more prominent feature in BSE-H [31]. We did not see PrPSc immunoreactive plaques in the gray or white matter, but other reports indicate that this occurs as a prominent [30] or lesser [31] feature. Immunoreactivity in hippocampus, midbrain, and brainstem was markedly intense and frequently formed coalescing aggregates (Fig. 4B). While intraneuronal straining was rare in the cortex, it became the most obvious pattern in the midbrain and brainstem nuclei (Fig. 4D) with notable exception of the parasympathetic nucleus of the vagus nerve. Intraneuronal staining also was readily apparent in spinal cord (Fig. S2). Immunoreactivity was scant in the cerebellum where small, multifocal clumps of granular and particulate staining occurred in the molecular and granular layers. The cerebellar white matter was devoid of immunoreactivity except for in association with deep cerebellar nuclei (Fig. S4), which is in contrast to other studies of BSE-H where the most prominent staining of the cerebellum was in the white matter [31]. Considering the strong immunoreactivity in other regions of the brain, the scant immunoreactivity in cerebellum was surprising. This finding corroborates recent studies examining PrPSc immunoreactivity in the brainstem and cerebellum of cases of BSE-H where the cerebellum and caudal brainstem contained less PrPSc than more rostral regions of the brainstem [31,38]The immunohistochemical techniques used here failed to demonstrate PrPSc in other tissues examined. This finding is consisent with other studies of atypical BSE that suggest that no significant PrPSc depositions occur in peripheral tissues [39]. Other findings of the lesions described contrast those described for wild-type cattle with BSE-H [30] in that no PrPSc plaques were noted and that there is less immunoreactivity in the cerebellum in this case. Whether the E211K polymorphism influences lesion character or distribution when inoculated with other BSE isolates will require further study.



snip...



The disease reported here was true to the molecular characterization of the case diagnosed in 2006, which is the best approximation of H-type BSE that may occur later in life in cattle with the E211K polymorphism. Based on the case history of the original 2006 E211K BSE case and the fact that the vast majority of naturally-occurring atypical BSE cases involve older cattle (.10 yrs of age), we speculate that a pre-clinical period of at least 10 years will be required for BSE-H to naturally occur in E211K cattle without prior exposure to infectious material. While an inoculation study cannot definitely prove that the U.S. 2006 BSEH case was due to the E211K polymorphism, i.e. an inherited TSE, the results of this study do suggest that cattle with the K211 allele are predisposed to rapid onset of BSE-H when exposed.



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.



snip...



Citation: Greenlee JJ, Smith JD, West Greenlee MH, Nicholson EM (2012) Clinical and Pathologic Features of H-Type Bovine Spongiform Encephalopathy Associated with E211K Prion Protein Polymorphism. PLoS ONE 7(6): e38678. doi:10.1371/journal.pone.0038678



Editor: Corinne Ida Lasmezas, The Scripps Research Institute Scripps Florida, United States of America



Received January 6, 2012; Accepted May 11, 2012; Published June 8, 2012



This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.



Funding: This research was funded in its entirety by congressionally appropriated funds to the United States Department of Agriculture, Agriculture Research Service. The funders of the work did not influence study design, data collection and analysis, decision to publish, and preparation of the manuscript.



Competing Interests: The authors have declared that no competing interests exist. * E-mail: justin.greenlee@ars.usda.gov







see full text ;









Research Article



BSE Case Associated with Prion Protein Gene Mutation



Jürgen A. Richt mail,


S. Mark Hall



Abstract



Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy (TSE) of cattle and was first detected in 1986 in the United Kingdom. It is the most likely cause of variant Creutzfeldt-Jakob disease (CJD) in humans. The origin of BSE remains an enigma. Here we report an H-type BSE case associated with the novel mutation E211K within the prion protein gene (Prnp). Sequence analysis revealed that the animal with H-type BSE was heterozygous at Prnp nucleotides 631 through 633. An identical pathogenic mutation at the homologous codon position (E200K) in the human Prnp has been described as the most common cause of genetic CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. A recent epidemiological study revealed that the K211 allele was not detected in 6062 cattle from commercial beef processing plants and 42 cattle breeds, indicating an extremely low prevalence of the E211K variant (less than 1 in 2000) in cattle.



Author Summary



Bovine spongiform encephalopathy (BSE or Mad Cow Disease), a transmissible spongiform encephalopathy (TSE) or prion disease of cattle, was first discovered in the United Kingdom in 1986. BSE is most likely the cause of a human prion disease known as variant Creutzfeldt Jakob Disease (vCJD). In this study, we identified a novel mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United States of America. This mutation is identical to the E200K pathogenic mutation found in humans with a genetic form of CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in “the approximately 10-year-old cow” carrying the E221K mutation.



snip...



Discussion



Our results demonstrate for the first time a potential pathogenic mutation (E211K) within the Prnp gene of a bovine with an H-type BSE phenotype at a position representing the most common mutation in humans (E200K) associated with genetic TSEs [7]. This mutation was not found in the Prnp gene of other North American (1 H-type U.S.; 1 H-type and 1 L-type Canadian) and European (7 H-type and 3 L-type cases) cattle [8] and a miniature zebu (H-type) [9] with atypical BSE phenotypes. The functional significance of this finding, however, remains unknown. Importantly, the penetrance of the E200K mutation in humans is very high [7],[10]. The origin of atypical BSE cases still remains unexplained. Several hypotheses have been considered including the existence of a previously unrecognized “sporadic” form of a TSE in this species. The detection of the E211K Prnp mutation, known to be pathogenic in humans, in a 10 year old hybrid cow (Bos indicus×Bos taurus) with H-type BSE could provide additional support to the following hypotheses: (i) that U.K. BSE has been acquired from a genetic case or cases of cattle BSE, (ii) that all three etiological forms of human TSEs (sporadic, genetic and infectious) are also present in cattle, and (iii) that BSE started on the Indian subcontinent. However, more data are required to support these hypotheses. It is well known, that large amounts of mammalian protein material were imported from India to the U.K. during the relevant time period (late 1970s and early 1980s) [3]. Therefore it could be speculated that one possible route of contamination of U.K. cattle with BSE was through animal feed containing imported meat and bone meal material contaminated with a case or cases of genetic BSE.





Epidemiological investigations conducted by USDA personnel failed to reveal any evidence of a feed source contaminated with TSE material fed to this animal







snip...end





Citation: Richt JA, Hall SM (2008) BSE Case Associated with Prion Protein Gene Mutation. PLoS Pathog 4(9): e1000156. doi:10.1371/journal.ppat.1000156


Editor: David Westaway, University of Alberta, Canada


Received: June 5, 2008; Accepted: August 15, 2008; Published: September 12, 2008


This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.


Funding: This work was supported by the USDA-ARS-National Animal Disease Center (NADC) and USDA-APHIS-National Veterinary Services Laboratories (NVSL) and by the NIAID-NIH PO1 AI 77774-01 “Pathogenesis, Transmission and Detection of Zoonotic Prion Diseases”.


Competing interests: Patent pending: Dr. Jürgen A. Richt submitted a patent application entitled “Novel Polymorphism in Bovine Prion Protein Gene Sequence” (Docket Number 0078.06; Serial No. 11/787,784) on April 18, 2006.


* E-mail: jricht@vet.k-state.edu


Citation: Greenlee JJ, Smith JD, West Greenlee MH, Nicholson EM (2012) Clinical and Pathologic Features of H-Type Bovine Spongiform Encephalopathy Associated with E211K Prion Protein Polymorphism. PLoS ONE 7(6): e38678. doi:10.1371/journal.pone.0038678


Editor: Corinne Ida Lasmezas, The Scripps Research Institute Scripps Florida, United States of America


Received: January 6, 2012; Accepted: May 11, 2012; Published: June 8, 2012


This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.


Funding: This research was funded in its entirety by congressionally appropriated funds to the United States Department of Agriculture, Agriculture Research Service. The funders of the work did not influence study design, data collection and analysis, decision to publish, and preparation of the manuscript.


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


* E-mail: justin.greenlee@ars.usda.gov













I ask Professor Kong ;





Thursday, December 04, 2008 3:37 PM




Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk Assessment




''IS the h-BSE more virulent than typical BSE as well, or the same as cBSE, or less virulent than cBSE? just curious.....''





Professor Kong reply ;




.....snip





''As to the H-BSE, we do not have sufficient data to say one way or another, but we have found that H-BSE can infect humans. I hope we could publish these data once the study is complete. Thanks for your interest.''





Best regards, Qingzhong Kong, PhD Associate Professor Department of Pathology Case Western Reserve University Cleveland, OH 44106 USA





END...TSS





Thursday, December 04, 2008 2:37 PM



"we have found that H-BSE can infect humans."



personal communication with Professor Kong. ...TSS



BSE-H is also transmissible in our humanized Tg mice.



The possibility of more than two atypical BSE strains will be discussed.



Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.






















let's take a closer look at this new prionpathy or prionopathy, and then let's look at the g-h-BSEalabama mad cow.





This new prionopathy in humans? the genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_ mad cow in the world to date like this, ......wait, it get's better. this new prionpathy is killing young and old humans, with LONG DURATION from onset of symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and the plaques are very similar in some cases too, bbbut, it's not related to the g-h-BSEalabama cow, WAIT NOW, it gets even better, the new human prionpathy that they claim is a genetic TSE, has no relation to any gene mutation in that family. daaa, ya think it could be related to that mad cow with the same genetic make-up ??? there were literally tons and tons of banned mad cow protein in Alabama in commerce, and none of it transmitted to cows, and the cows to humans there from ??? r i g h t $$$




ALABAMA MAD COW g-h-BSEalabama




In this study, we identified a novel mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United States of America. This mutation is identical to the E200K pathogenic mutation found in humans with a genetic form of CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K mutation.

















her healthy calf also carried the mutation (J. A. Richt and S. M. Hall PLoS Pathog. 4, e1000156; 2008).




This raises the possibility that the disease could occasionally be genetic in origin. Indeed, the report of the UK BSE Inquiry in 2000 suggested that the UK epidemic had most likely originated from such a mutation and argued against the scrapierelated assumption. Such rare potential pathogenic PRNP mutations could occur in countries at present considered to be free of BSE, such as Australia and New Zealand. So it is important to maintain strict surveillance for BSE in cattle, with rigorous enforcement of the ruminant feed ban (many countries still feed ruminant proteins to pigs). Removal of specified risk material, such as brain and spinal cord, from cattle at slaughter prevents infected material from entering the human food chain. Routine genetic screening of cattle for PRNP mutations, which is now available, could provide additional data on the risk to the public. Because the point mutation identified in the Alabama animals is identical to that responsible for the commonest type of familial (genetic) CJD in humans, it is possible that the resulting infective prion protein might cross the bovine–human species barrier more easily. Patients with vCJD continue to be identified. The fact that this is happening less often should not lead to relaxation of the controls necessary to prevent future outbreaks.




Malcolm A. Ferguson-Smith Cambridge University Department of Veterinary Medicine, Madingley Road, Cambridge CB3 0ES, UK e-mail: maf12@cam.ac.uk Jürgen A. Richt College of Veterinary Medicine, Kansas State University, K224B Mosier Hall, Manhattan, Kansas 66506-5601, USA




NATURE|Vol 457|26 February 2009












> Epidemiological investigations conducted by USDA personnel failed to reveal any evidence of a feed source contaminated with TSE material fed to this animal









Saturday, August 14, 2010


BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY


(see mad cow feed in COMMERCE IN ALABAMA...TSS)








2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006








> Epidemiological investigations conducted by USDA personnel failed to reveal any evidence of a feed source contaminated with TSE material fed to this animal










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.









> Epidemiological investigations conducted by USDA personnel failed to reveal any evidence of a feed source contaminated with TSE material fed to this animal








what about that ALABAMA MAD COW, AND MAD COW FEED THERE FROM IN THAT STATE ???





Saturday, August 14, 2010


BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY


*** (see mad cow feed in COMMERCE IN ALABAMA...TSS)






BANNED MAD COW FEED IN COMMERCE IN ALABAMA


Date: September 6, 2006 at 7:58 am PST PRODUCT


a) EVSRC Custom dairy feed, Recall # V-130-6;


b) Performance Chick Starter, Recall # V-131-6;


c) Performance Quail Grower, Recall # V-132-6;


d) Performance Pheasant Finisher, Recall # V-133-6.


CODE None RECALLING FIRM/MANUFACTURER Donaldson & Hasenbein/dba J&R Feed Service, Inc., Cullman, AL, by telephone on June 23, 2006 and by letter dated July 19, 2006. Firm initiated recall is complete.


REASON


Dairy and poultry feeds were possibly contaminated with ruminant based protein.


VOLUME OF PRODUCT IN COMMERCE 477.72 tons


DISTRIBUTION AL


______________________________








PRODUCT Bulk custom dairy pre-mixes,


Recall # V-120-6 CODE None RECALLING FIRM/MANUFACTURER Ware Milling Inc., Houston, MS, by telephone on June 23, 2006. Firm initiated recall is complete. REASON Possible contamination of dairy animal feeds with ruminant derived meat and bone meal.


VOLUME OF PRODUCT IN COMMERCE 350 tons


DISTRIBUTION AL and MS


______________________________


PRODUCT


a) Tucker Milling, LLC Tm 32% Sinking Fish Grower, #2680-Pellet, 50 lb. bags, Recall # V-121-6;


b) Tucker Milling, LLC #31120, Game Bird Breeder Pellet, 50 lb. bags, Recall # V-122-6;


c) Tucker Milling, LLC #31232 Game Bird Grower, 50 lb. bags, Recall # V-123-6;


d) Tucker Milling, LLC 31227-Crumble, Game Bird Starter, BMD Medicated, 50 lb bags, Recall # V-124-6;


e) Tucker Milling, LLC #31120, Game Bird Breeder, 50 lb bags, Recall # V-125-6;


f) Tucker Milling, LLC #30230, 30 % Turkey Starter, 50 lb bags, Recall # V-126-6;


g) Tucker Milling, LLC #30116, TM Broiler Finisher, 50 lb bags, Recall # V-127-6


CODE All products manufactured from 02/01/2005 until 06/20/2006 RECALLING FIRM/MANUFACTURER Recalling Firm: Tucker Milling LLC, Guntersville, AL, by telephone and visit on June 20, 2006, and by letter on June 23, 2006. Manufacturer: H. J. Baker and Brothers Inc., Stamford, CT. Firm initiated recall is ongoing.


REASON Poultry and fish feeds which were possibly contaminated with ruminant based protein were not labeled as "Do not feed to ruminants".


VOLUME OF PRODUCT IN COMMERCE 7,541-50 lb bags


DISTRIBUTION AL, GA, MS, and TN


END OF ENFORCEMENT REPORT FOR AUGUST 9, 2006


###








Subject: MAD COW FEED RECALL AL AND FL VOLUME OF PRODUCT IN COMMERCE 125 TONS Products manufactured from 02/01/2005 until 06/06/2006


Date: August 6, 2006 at 6:16 pm PST PRODUCT


a) CO-OP 32% Sinking Catfish, Recall # V-100-6;


b) Performance Sheep Pell W/Decox/A/N, medicated, net wt. 50 lbs, Recall # V-101-6;


c) Pro 40% Swine Conc Meal -- 50 lb, Recall # V-102-6;


d) CO-OP 32% Sinking Catfish Food Medicated, Recall # V-103-6;


e) "Big Jim's" BBB Deer Ration, Big Buck Blend, Recall # V-104-6;


f) CO-OP 40% Hog Supplement Medicated Pelleted, Tylosin 100 grams/ton, 50 lb. bag, Recall # V-105-6;


g) Pig Starter Pell II, 18% W/MCDX Medicated 282020, Carbadox -- 0.0055%, Recall # V-106-6;


h) CO-OP STARTER-GROWER CRUMBLES, Complete Feed for Chickens from Hatch to 20 Weeks, Medicated, Bacitracin Methylene Disalicylate, 25 and 50 Lbs, Recall # V-107-6;


i) CO-OP LAYING PELLETS, Complete Feed for Laying Chickens, Recall # 108-6;


j) CO-OP LAYING CRUMBLES, Recall # V-109-6;


k) CO-OP QUAIL FLIGHT CONDITIONER MEDICATED, net wt 50 Lbs, Recall # V-110-6;


l) CO-OP QUAIL STARTER MEDICATED, Net Wt. 50 Lbs, Recall # V-111-6;


m) CO-OP QUAIL GROWER MEDICATED, 50 Lbs, Recall # V-112-6 CODE


Product manufactured from 02/01/2005 until 06/06/2006


RECALLING FIRM/MANUFACTURER Alabama Farmers Cooperative, Inc., Decatur, AL, by telephone, fax, email and visit on June 9, 2006. FDA initiated recall is complete.


REASON Animal and fish feeds which were possibly contaminated with ruminant based protein not labeled as "Do not feed to ruminants".


VOLUME OF PRODUCT IN COMMERCE 125 tons


DISTRIBUTION AL and FL


END OF ENFORCEMENT REPORT FOR AUGUST 2, 2006


###








MAD COW FEED RECALL USA EQUALS 10,878.06 TONS NATIONWIDE Sun Jul 16, 2006 09:22 71.248.128.67


RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINE -- CLASS II


______________________________


PRODUCT


a) PRO-LAK, bulk weight, Protein Concentrate for Lactating Dairy Animals, Recall # V-079-6;


b) ProAmino II, FOR PREFRESH AND LACTATING COWS, net weight 50lb (22.6 kg), Recall # V-080-6;


c) PRO-PAK, MARINE & ANIMAL PROTEIN CONCENTRATE FOR USE IN ANIMAL FEED, Recall # V-081-6;


d) Feather Meal, Recall # V-082-6 CODE


a) Bulk


b) None


c) Bulk


d) Bulk


RECALLING FIRM/MANUFACTURER H. J. Baker & Bro., Inc., Albertville, AL, by telephone on June 15, 2006 and by press release on June 16, 2006. Firm initiated recall is ongoing.


REASON


Possible contamination of animal feeds with ruminent derived meat and bone meal.


VOLUME OF PRODUCT IN COMMERCE 10,878.06 tons


DISTRIBUTION Nationwide


END OF ENFORCEMENT REPORT FOR July 12, 2006


###








Saturday, July 23, 2011


CATTLE HEADS WITH TONSILS, BEEF TONGUES, SPINAL CORD, SPECIFIED RISK MATERIALS (SRM's) AND PRIONS, AKA MAD COW DISEASE








Saturday, November 6, 2010


TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU Berne, 2010 TAFS


INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation









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





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


RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II


PRODUCT


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


CODE


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


RECALLING FIRM/MANUFACTURER


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


Firm initiated recall is ongoing.


REASON


Blood meal used to make cattle feed was recalled because it was cross- contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement. VOLUME OF PRODUCT IN COMMERCE 42,090 lbs. DISTRIBUTION WI


___________________________________


PRODUCT


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


CODE


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


RECALLING FIRM/MANUFACTURER


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


REASON


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


VOLUME OF PRODUCT IN COMMERCE


9,997,976 lbs.


DISTRIBUTION


ID and NV


END OF ENFORCEMENT REPORT FOR MARCH 21, 2007






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




IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS IBNC (just another mad cow BSE TSE prion strain)


THEY KNEW 2 DECADES AGO the damn BSE mad cow testing were not finding cases ;





NEW BRAIN DISORDER


3. WHAT ABOUT REPORTS OF NEW FORM OF BSE ?


4. IS THIS NEW BRAIN DISORDER A THREAT ?


snip...


NEW BRAIN DISORDER


3. WHAT ABOUT REPORTS OF NEW FORM OF BSE ?


THE VETERINARY RECORD HAS PUBLISHED AN ARTICLE ON A NEW BRAIN DISORDER OF CATTLE DISCOVERED THROUGH OUR CONTROL MEASURES FOR BSE. ALTHOUGH IT PRESENTS SIMILAR CLINICAL SIGNS TO BSE THERE ARE MAJOR DIFFERENCES IN THE HISTOPATHOLOGY AND INCUBATION PERIODS BETWEEN THE TWO.


MUST EMPHASIZE THAT THIS IS NOT BSE.


4. IS THIS NEW BRAIN DISORDER A THREAT ?


WE DO NOT EVEN KNOW WHETHER THE AGENT OF THIS DISEASE IS TRANSMISSIBLE. IN ANY CASE, CASES SO FAR IDENTIFIED HAD SHOWN SIMILAR SYMPTOMS TO THOSE OF BSE, AND THEREFORE HAVE BEEN SLAUGHTERED AND INCINERATED, SO THAT IF A TRANSMISSIBLE AGENT WERE INVOLVED IT WOULD HAVE BEEN ELIMINATED.









BSE-NON-CONFIRMATION OF DISEASE


3. A question posed by Mr Whaley (para 2) is that classical lesions of BSE may not occur in all cases. Supposing we had a strain variant that produced it's lesions in the cerebrum these would not be detected by our current method. I think this would be unlikely but not impossible - another reason why at least a proportion of complete brains (or blocks) should be retained during the epidemic so if the problem Mr Whaley indicates escalates, it can be investigated.


snip...


5. IF you had the information what benefit would there be ? what would you do with it ?


CONCLUSION


I do not recommend any action. The situation should be accepted. I do not think the VIS can do more at present. The situation should be kept under review particularly if there is an escalation in numbers in this category.


R BRADLEY


15 MAY 1990


90/5.15/3.2














Tuesday, November 17, 2009


SEAC NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS (IBNC) FROM THE VETERINARY LABORATORIES AGENCY (VLA) SEAC 103/1








NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS


"All of the 15 cattle tested showed that the brains had abnormally accumulated PrP"


Saturday, February 28, 2009






NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS


"All of the 15 cattle tested showed that the brains had abnormally accumulated PrP"


2009


SEAC 102/2


2009







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





PLEASE NOTE *


Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.


snip...


The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...









Saturday, December 01, 2007


Phenotypic Similarity of Transmissible Mink Encephalopathy in Cattle and L-type Bovine Spongiform Encephalopathy in a Mouse Model


Volume 13, Number 12–December 2007 Research


Phenotypic Similarity of Transmissible Mink Encephalopathy in Cattle and L-type Bovine Spongiform Encephalopathy in a Mouse Model


Thierry Baron,* Anna Bencsik,* Anne-Gaëlle Biacabe,* Eric Morignat,* andRichard A. Bessen†*Agence Française de Sécurité Sanitaire des Aliments–Lyon, Lyon, France; and†Montana State University, Bozeman, Montana, USA


Abstract


Transmissible mink encepholapathy (TME) is a foodborne transmissible spongiform encephalopathy (TSE) of ranch-raised mink; infection with a ruminant TSE has been proposed as the cause, but the precise origin of TME is unknown. To compare the phenotypes of each TSE, bovine-passaged TME isolate and 3 distinct natural bovine spongiform encephalopathy (BSE) agents (typical BSE, H-type BSE, and L-type BSE) were inoculated into an ovine transgenic mouse line (TgOvPrP4). Transgenic mice were susceptible to infection with bovine-passaged TME, typical BSE, and L-type BSE but not to H-type BSE. Based on survival periods, brain lesions profiles, disease-associated prion protein brain distribution, and biochemical properties of protease-resistant prion protein, typical BSE had a distint phenotype in ovine transgenic mice compared to L-type BSE and bovine TME.The similar phenotypic properties of L-type BSE and bovine TME in TgOvPrP4 mice suggest that L-type BSE is a much more likely candidate for the origin of TME than is typical BSE.


snip...


Conclusion


These studies provide experimental evidence that the Stetsonville TME agent is distinct from typical BSE but has phenotypic similarities to L-type BSE in TgOvPrP4 mice. Our conclusion is that L-type BSE is a more likely candidate for a bovine source of TME infection than typical BSE. In the scenario that a ruminant TSE is the source for TME infection in mink, this would be a second example of transmission of a TSE from ruminants to non-ruminants under natural conditions or farming practices in addition to transmission of typical BSE to humans, domestic cats, and exotic zoo animals(37). The potential importance of this finding is relevant to L-type BSE, which based on experimental transmission into humanized PrP transgenic mice and macaques, suggests that L-type BSE is more pathogenic for humans than typical BSE (24,38).

















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 ;



















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:










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









FSIS, USDA, REPLY TO SINGELTARY








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










2012 atypical L-type BSE BASE California reports




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








Saturday, August 4, 2012


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







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








Sunday, December 2, 2012


CANADA 19 cases of mad cow disease SCENARIO 4: ‘WE HAD OUR CHANCE AND WE BLEW IT’








Tuesday, July 14, 2009 U.S.


Emergency Bovine Spongiform Encephalopathy Response Plan Summary and BSE Red Book


Date: February 14, 2000 at 8:56 am PST


WHERE did we go wrong $$$








ALSO, SEE Scrapie Mission, Texas, did not produce _typical_ BSE... see page 17 here ;



3.57 The experiment which might have determined whether BSE and scrapie were caused by the same agent (ie, the feeding of natural scrapie to cattle) was never undertaken in the UK. It was, however, performed in the USA in 1979, when it was shown that cattle inoculated with the scrapie agent endemic in the flock of Suffolk sheep at the United States Department of Agriculture in Mission, Texas, developed a TSE quite unlike BSE.339 The findings of the initial transmission, though not of the clinical or neurohistological examination, were communicated in October 1988 to Dr Watson, Director of the CVL, following a visit by Dr Wrathall, one of the project leaders in the Pathology Department of the CVL, to the United States Department of Agriculture.340 The results were not published at this point, since the attempted transmission to mice from the experimental cow brain had been inconclusive. The results of the clinical and histological differences between scrapie-affected sheep and cattle were published in 1995. Similar studies in which cattle were inoculated intracerebrally with scrapie inocula derived from a number of scrapie-affected sheep of different breeds and from different States, were carried out at the US National Animal Disease Centre.341 The results, published in 1994, showed that this source of scrapie agent, though pathogenic for cattle,



*** did not produce the same clinical signs of brain lesions characteristic of BSE. ***



3.58 There are several possible reasons why the experiment was not performed in the UK. It had been recommended by Sir Richard Southwood (Chairman of the Working Party on Bovine Spongiform Encephalopathy) in his letter to the Permanent Secretary of MAFF, Mr (now Sir) Derek Andrews, on 21 June 1988,342 though it was not specifically recommended in the Working Party Report or indeed in the Tyrrell Committee Report (details of the Southwood Working Party and the Tyrell Committee can be found in vol. 4: The Southwood Working Party, 1988–89 and vol. 11: Scientists after Southwood respectively). The direct inoculation of scrapie into calves was given low priority, because of its high cost and because it was known that it had already taken place in the USA.343 It was also felt that the results of such an experiment would be hard to interpret. While a negative result 337 Fraser, H., Bruce, M., Chree, A., McConnell, I. and Wells, G. (1992) Transmission of Bovine Spongiform Encephalopathy and Scrapie to Mice, Journal of General Virology, 73, 1891–7; Bruce, M., Chree, A., McConnell, I., Foster, J., Pearson, G. and Fraser, H. (1994) Transmission of Bovine Spongiform Encephalopathy and Scrapie to Mice: Strain Variation and the Species Barrier, Philosophical Transactions of the Royal Society of London, Series B, Biological Sciences, 343, 405–11 338 Bruce, M., Will, R., Ironside, J., McConell, I., Drummond, D., Suttie, A., McCordie, L., Chree, A., Hope, J., Birkett, C., Cousens, S., Fraser, H. and Bostock, C. (1997) Transmissions to Mice Indicate that ‘New Variant’ CJD is Caused by the BSE Agent, Nature, 389, 498–501 339 Clark, W., Hourrigan, J. and Hadlow, W. (1995) Encephalopathy in Cattle Experimentally Infected with the Scrapie Agent, American Journal of Veterinary Research, 56, 606–12 340 YB88/10.00/1.1 341 Cutlip, R., Miller, J., Race, R., Jenny, A., Katz, J., Lehmkuhl, H., Debey, B. and Robinson, M. (1994) Intracerebral Transmission of Scrapie to Cattle, Journal of Infectious Diseases, 169, 814–20 342 YB88/6.21/1.2 343 YB88/11.17/2.4 SCIENCE 84 would be informative, a positive result would need to demonstrate that when scrapie was transmitted to cattle, the disease which developed in cattle was the same as BSE.344 Given the large number of strains of scrapie and the possibility that BSE was one of them, it would be necessary to transmit every scrapie strain to cattle separately, to test the hypothesis properly. Such an experiment would be expensive. Secondly, as measures to control the epidemic took hold, the need for the experiment from the policy viewpoint was not considered so urgent. It was felt that the results would be mainly of academic interest.345 3.59 Nevertheless, from the first demonstration of transmissibility of BSE in 1988, the possibility of differences in the transmission properties of BSE and scrapie was clear. Scrapie was transmissible to hamsters, but by 1988 attempts to transmit BSE to hamsters had failed. Subsequent findings increased that possibility.















In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells



snip...



PAGE 31


Appendix I


VISIT TO USA - DR A E WRATHALL - INFO ON BSE AND SCRAPIE


1. Dr Clark lately of the Scrapie Research Unit, Mission Texas has successfully transmitted ovine and caprine scrapie to cattle. The experimental results have not been published but there are plans to do this. This work was initiated in 1978. A summary of it is:-


Expt A 6 Her x Jer calves born in 1978 were inoculated as follows with a 2nd Suffolk scrapie passage:-


i/c 1ml i/m, 5ml; s/c 5ml; oral 30ml.


1/6 went down after 48 months with a scrapie/BSE-like disease.


Expt B 6 Her or Jer or HxJ calves were inoculated with angora Goat virus 2/6 went down similarly after 36 months.


Expt C Mice inoculated from brains of calves/cattle in expts A & B were resistant, only 1/20 going down with scrapie and this was the reason given for not publishing.


Diagnosis in A, B, C was by histopath. No reports on SAF were given.


Dr Warren Foote indicated success so far in eliminating scrapie in offspring from experimentally- (and naturally) infected sheep by ET. He had found difficulty in obtaining emhryos from naturally infected sheep (cf SPA).


3. Prof. A Robertson gave a brief account of BSE. The US approach was to



PAGE 32



accord it a very low profile indeed. Dr A Thiermann showed the picture in the "Independent" with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. BSE was not reported in USA.


4. Scrapie incidents (ie affected flocks) have shown a dramatic increase since 1978. In 1953 when the National Control Scheme was started there were 10-14 incidents, in 1978 - 1 and in 1988 so far 60.


5. Scrapie agent was reported to have been isolated from a solitary fetus.


6. A western blotting diagnostic technique (? on PrP} shows some promise.


7. Results of a questionnaire sent to 33 states on the subject of the national sheep scrapie programme survey indicated;


17/33 wished to drop it 6/33 wished to develop it 8/33 had few sheep and were neutral


Information obtained from Dr Wrathall's notes of a meeting of the U.S. Animal Health Association at Little Rock, Arkansas Nov. 1988.




please see ;




In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells








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





Thursday, March 29, 2012


atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012


NIAA Annual Conference April 11-14, 2011San Antonio, Texas







***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.







PR-26


NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS


R. Nonno1, E. Esposito1, G. Vaccari1, E. Bandino2, M. Conte1, B. Chiappini1, S. Marcon1, M. Di Bari1, S.L. Benestad3, U. Agrimi1 1 Istituto Superiore di Sanità, Department of Food Safety and Veterinary Public Health, Rome, Italy (romolo.nonno@iss.it); 2 Istituto Zooprofilattico della Sardegna, Sassari, Italy; 3 National Veterinary Institute, Department of Pathology, Oslo, Norway


Molecular variants of PrPSc are being increasingly investigated in sheep scrapie and are generally referred to as "atypical" scrapie, as opposed to "classical scrapie". Among the atypical group, Nor98 seems to be the best identified. We studied the molecular properties of Italian and Norwegian Nor98 samples by WB analysis of brain homogenates, either untreated, digested with different concentrations of proteinase K, or subjected to enzymatic deglycosylation. The identity of PrP fragments was inferred by means of antibodies spanning the full PrP sequence. We found that undigested brain homogenates contain a Nor98-specific PrP fragment migrating at 11 kDa (PrP11), truncated at both the C-terminus and the N-terminus, and not N-glycosylated. After mild PK digestion, Nor98 displayed full-length PrP (FL-PrP) and N-glycosylated C-terminal fragments (CTF), along with increased levels of PrP11. Proteinase K digestion curves (0,006-6,4 mg/ml) showed that FL-PrP and CTF are mainly digested above 0,01 mg/ml, while PrP11 is not entirely digested even at the highest concentrations, similarly to PrP27-30 associated with classical scrapie. Above 0,2 mg/ml PK, most Nor98 samples showed only PrP11 and a fragment of 17 kDa with the same properties of PrP11, that was tentatively identified as a dimer of PrP11. Detergent solubility studies showed that PrP11 is insoluble in 2% sodium laurylsorcosine and is mainly produced from detergentsoluble, full-length PrPSc. Furthermore, among Italian scrapie isolates, we found that a sample with molecular and pathological properties consistent with Nor98 showed plaque-like deposits of PrPSc in the thalamus when the brain was analysed by PrPSc immunohistochemistry. Taken together, our results show that the distinctive pathological feature of Nor98 is a PrP fragment spanning amino acids ~ 90-155. This fragment is produced by successive N-terminal and C-terminal cleavages from a full-length and largely detergent-soluble PrPSc, is produced in vivo and is extremely resistant to PK digestion.


*** Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.








A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes


Annick Le Dur*,?, Vincent Béringue*,?, Olivier Andréoletti?, Fabienne Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶, Jean-Luc Vilotte?, Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,? +Author Affiliations *Virologie Immunologie Moléculaires and ?Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France; ?Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066 Toulouse, France; §Agence Française de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon, France;


**Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway


***Edited by Stanley B. Prusiner, University of California, San Francisco, CA (received for review March 21, 2005)


Abstract


Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. *** These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.







Monday, December 1, 2008


When Atypical Scrapie cross species barriers


Authors


Andreoletti O., Herva M. H., Cassard H., Espinosa J. C., Lacroux C., Simon S., Padilla D., Benestad S. L., Lantier F., Schelcher F., Grassi J., Torres, J. M., UMR INRA ENVT 1225, Ecole Nationale Veterinaire de Toulouse.France; ICISA-INlA, Madrid, Spain; CEA, IBiTec-5, DSV, CEA/Saclay, Gif sur Yvette cedex, France; National Veterinary Institute, Postboks 750 Sentrum, 0106 Oslo, Norway, INRA IASP, Centre INRA de Tours, 3738O Nouzilly, France.


Content


Atypical scrapie is a TSE occurring in small ruminants and harbouring peculiar clinical, epidemiological and biochemical properties. Currently this form of disease is identified in a large number of countries. In this study we report the transmission of an atypical scrapie isolate through different species barriers as modeled by transgenic mice (Tg) expressing different species PRP sequence.


The donor isolate was collected in 1995 in a French commercial sheep flock. inoculation into AHQ/AHQ sheep induced a disease which had all neuro-pathological and biochemical characteristics of atypical scrapie. Transmitted into Transgenic mice expressing either ovine or PrPc, the isolate retained all the described characteristics of atypical scrapie.


Surprisingly the TSE agent characteristics were dramatically different v/hen passaged into Tg bovine mice. The recovered TSE agent had biological and biochemical characteristics similar to those of atypical BSE L in the same mouse model. Moreover, whereas no other TSE agent than BSE were shown to transmit into Tg porcine mice, atypical scrapie was able to develop into this model, albeit with low attack rate on first passage.


Furthermore, after adaptation in the porcine mouse model this prion showed similar biological and biochemical characteristics than BSE adapted to this porcine mouse model. Altogether these data indicate.


(i) the unsuspected potential abilities of atypical scrapie to cross species barriers


(ii) the possible capacity of this agent to acquire new characteristics when crossing species barrier


These findings raise some interrogation on the concept of TSE strain and on the origin of the diversity of the TSE agents and could have consequences on field TSE control measures.







Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types


Wiebke M. Wemheuer,* Sylvie L. Benestad,† Arne Wrede,* Ulf Schulze-Sturm,* Wilhelm E. Wemheuer,‡ Uwe Hahmann,* Joanna Gawinecka,§ Ekkehard Schu¨ tz,‡ Inga Zerr,§ Bertram Brenig,‡ Bjørn Bratberg,† Olivier Andre´ oletti,¶ and Walter J. Schulz-Schaeffer*


From the Prion and Dementia Research Unit,* Department of Neuropathology, and the National Transmissible Spongiform Encephalopathies Reference Center,§ Department of Neurology, University Medical Center Goettingen, Goettingen, Germany; the Department of Pathology,† National Veterinary Institute, Oslo, Norway; the Institute of Veterinary Medicine,‡ Faculty for Agricultural Sciences, University of Goettingen, Goettingen, Germany; and Animal Health,¶ Interactions Hôte Agent Pathogène, Ecole Nationale Ve´te´rinaire de Toulouse, Toulouse, France


Transmissible spongiform encephalopathies such as scrapie in sheep, Creutzfeldt-Jakob disease (CJD) in humans, and bovine sporadic encephalopathy in cattle are characterized by the accumulation of a misfolded protein: the pathological prion protein. Ever since bovine sporadic encephalopathy was discovered as the likely cause of the new variant of CJD in humans, parallels between human and animal transmissible spongiform encephalopathies must be viewed under the aspect of a disease risk for humans. In our study we have compared prion characteristics of different forms of sheep scrapie with those of different phenotypes of sporadic CJD. The disease characteristics of sporadic CJD depend considerably on the prion type 1 or 2. Our results show that there are obvious parallels between sporadic CJD type 1 and the so-called atypical/Nor98 scrapie. These parelleles apply to the deposition form of pathological prion protein in the brain, detected by the paraffin-embedded- tissue blot and the prion aggregate stability with regard to denaturation by the chaotropic salt guanidine hydrochloride. The same applies to sporadic CJD type 2 and classical scrapie. The observed parallels between types of sporadic CJD and types of sheep scrapie demonstrate that distinct groups of prion disease exist in different species. This should be taken into consideration when discussing interspecies transmission. (Am J Pathol 2009, 175:2566–2573; DOI: 10.2353/ajpath.2009.090623)


snip...


Discussion


In humans, different prion types are linked with clinically and neuropathologically distinct prion diseases.8 The present work emphasizes that the differences in deposition characteristics and stability with regard to denaturation between atypical/Nor98 and classical scrapie also account for different prion types. Moreover, the two scrapie types that have been characterized show a number of striking similarities with human PrPSc types in sporadic CJD. Hence, we propose that the existence of different PrPSc types might be a common denominator of prion diseases in humans and animals. Since these two prion types show an across-the-species comparability with similar biochemical and pathological


characteristics, it is most likely that they exist due to a different conformational pattern of the disease-related prion protein.


snip...


Conclusion


As the prion protein is a highly conserved protein in terms of evolution, parallels between characteristics of prion types in TSEs of different species are of interest. In the present study, we report previously unknown similarities between sheep scrapie forms and human sporadic CJD types. We propose that the observed similarities between sheep scrapie and sporadic CJD in humans justify new interspecies groups of prion diseases in which prion types, not prion strains, are the major determinant for prion disease forms. While epidemiology implies that classical scrapie is not related to human TSEs,47 the atypical/Nor98 scrapie risk for human transmission has not yet been elucidated. Currently there is no compelling evidence that sCJD has a different origin than sporadic genesis. However, the finding of prion types with an across-the-species comparability might provide further understanding of the pathogenesis in prion diseases. Prion Types Encode Interspecies TSEs 2571 AJP December 2009, Vol. 175, No. 6









CHRONIC WASTING DISEASE CWD


P35


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


Chad Johnson1, Judd Aiken2,3,4 and Debbie McKenzie4,5 1 Department of Comparative Biosciences, University of Wisconsin, Madison WI, USA 53706 2 Department of Agriculture, Food and Nutritional Sciences, 3 Alberta Veterinary Research Institute, 4.Center for Prions and Protein Folding Diseases, 5 Department of Biological Sciences, University of Alberta, Edmonton AB, Canada T6G 2P5


The identification and characterization of prion strains is increasingly important for the diagnosis and biological definition of these infectious pathogens. Although well-established in scrapie and, more recently, in BSE, comparatively little is known about the possibility of prion strains in chronic wasting disease (CWD), a disease affecting free ranging and captive cervids, primarily in North America. We have identified prion protein variants in the white-tailed deer population and demonstrated that Prnp genotype affects the susceptibility/disease progression of white-tailed deer to CWD agent. The existence of cervid prion protein variants raises the likelihood of distinct CWD strains. Small rodent models are a useful means of identifying prion strains. We intracerebrally inoculated hamsters with brain homogenates and phosphotungstate concentrated preparations from CWD positive hunter-harvested (Wisconsin CWD endemic area) and experimentally infected deer of known Prnp genotypes. These transmission studies resulted in clinical presentation in primary passage of concentrated CWD prions. Subclinical infection was established with the other primary passages based on the detection of PrPCWD in the brains of hamsters and the successful disease transmission upon second passage. Second and third passage data, when compared to transmission studies using different CWD inocula (Raymond et al., 2007) indicate that the CWD agent present in the Wisconsin white-tailed deer population is different than the strain(s) present in elk, mule-deer and white-tailed deer from the western United States endemic region.







PPo2-7:


Biochemical and Biophysical Characterization of Different CWD Isolates


Martin L. Daus and Michael Beekes Robert Koch Institute; Berlin, Germany


Key words: CWD, strains, FT-IR, AFM


Chronic wasting disease (CWD) is one of three naturally occurring forms of prion disease. The other two are Creutzfeldt-Jakob disease in humans and scrapie in sheep. CWD is contagious and affects captive as well as free ranging cervids. As long as there is no definite answer of whether CWD can breach the species barrier to humans precautionary measures especially for the protection of consumers need to be considered. In principle, different strains of CWD may be associated with different risks of transmission to humans. Sophisticated strain differentiation as accomplished for other prion diseases has not yet been established for CWD. However, several different findings indicate that there exists more than one strain of CWD agent in cervids. We have analysed a set of CWD isolates from white-tailed deer and could detect at least two biochemically different forms of disease-associated prion protein PrPTSE. Limited proteolysis with different concentrations of proteinase K and/or after exposure of PrPTSE to different pH-values or concentrations of Guanidinium hydrochloride resulted in distinct isolate-specific digestion patterns. Our CWD isolates were also examined in protein misfolding cyclic amplification studies. This showed different conversion activities for those isolates that had displayed significantly different sensitivities to limited proteolysis by PK in the biochemical experiments described above. We further applied Fourier transform infrared spectroscopy in combination with atomic force microscopy. This confirmed structural differences in the PrPTSE of at least two disinct CWD isolates. The data presented here substantiate and expand previous reports on the existence of different CWD strains.





PPo2-22:


CWD Strain Emergence in Orally Inoculated White-tailed Deer (Odocoileus virginianus) with Different PRNP Genotypes


Camilo Duque-Velasquez,1 Chad Johnson,2 Allen Herbst,1 Judd Aiken1 and Debbie McKenzie1 1Centre for Prions and Protein Folding Diseases; University of Alberta; Edmonton, Alberta Canada; 2Department of Soil Science; University of Wisconsin; Madison, Wisconsin USA


Key words: CWD, strains, emergence


Chronic wasting disease (CWD) is a prion disease affecting captive and free-ranging cervids in North America. We have previously demonstrated that specific Prnp polymorphisms are linked to susceptibility/resistance to CWD infection in free-ranging white-tailed deer populations. The “wild-type” alleles (with glutamine at aa 95 and a Glycine at aa 96) were over-represented in the infected deer while the polymorphisms at aa 95 (Q95H) and 96 (G96S) were under-represented in the CWD-positive animals. Experimental oral infection of white-tailed deer with known Prnp genotypes (with inocula from CWD-positive wt/wt deer) confirmed this link between Prnp primary sequence and incubation period. All orally infected animals became clinically positive for CWD. The wt/wt had the shortest incubation period (693 dpi) and the Q95H/G96S the longest (1596 dpi). Brain homogenates prepared from clinically affected deer of each genotype were treated with proteinase K and resolved by western blot; differences in the glycosylation pattern and PK resistance were observed and are suggestive of different PrPSc isoforms. Subsequent experiments regarding biochemical properties like detergent solubility, structural stability, host range and the stability of these characteristics upon serial passages will allow us to further define potential CWD strain emergence in white-tailed deer.


Wednesday, September 08, 2010


CWD PRION CONGRESS SEPTEMBER 8-11 2010







Chronic Wasting Disease CWD cervids interspecies transmission


Wednesday, January 5, 2011


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


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


+ Author Affiliations


1Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, California 94143 2Department of Neurology, University of California, San Francisco, San Francisco, California 94143 Correspondence: stanley@ind.ucsf.edu


SNIP...


Greetings,


I believe the statement and quote below is incorrect ;


"CWD has been transmitted to cattle after intracerebral inoculation, although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This finding raised concerns that CWD prions might be transmitted to cattle grazing in contaminated pastures."


Please see ;


Within 26 months post inoculation, 12 inoculated animals had lost weight, revealed abnormal clinical signs, and were euthanatized. Laboratory tests revealed the presence of a unique pattern of the disease agent in tissues of these animals. These findings demonstrate that when CWD is directly inoculated into the brain of cattle, 86% of inoculated cattle develop clinical signs of the disease.






"although the infection rate was low (4 of 13 animals [Hamir et al. 2001])."


shouldn't this be corrected, 86% is NOT a low rate. ...


kindest regards,


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





MARCH 1, 2011


UPDATED CORRESPONDENCE FROM AUTHORS OF THIS STUDY I.E. COLBY, PRUSINER ET AL, ABOUT MY CONCERNS OF THE DISCREPANCY BETWEEN THEIR FIGURES AND MY FIGURES OF THE STUDIES ON CWD TRANSMISSION TO CATTLE ;


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


From: David Colby


To: flounder9@verizon.net


Cc: stanley@XXXXXXXX


Sent: Tuesday, March 01, 2011 8:25 AM


Subject: Re: FW: re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 + Author Affiliations


Dear Terry Singeltary,


Thank you for your correspondence regarding the review article Stanley Prusiner and I recently wrote for Cold Spring Harbor Perspectives. Dr. Prusiner asked that I reply to your message due to his busy schedule. We agree that the transmission of CWD prions to beef livestock would be a troubling development and assessing that risk is important. In our article, we cite a peer-reviewed publication reporting confirmed cases of laboratory transmission based on stringent criteria. The less stringent criteria for transmission described in the abstract you refer to lead to the discrepancy between your numbers and ours and thus the interpretation of the transmission rate. We stand by our assessment of the literature--namely that the transmission rate of CWD to bovines appears relatively low, but we recognize that even a low transmission rate could have important implications for public health and we thank you for bringing attention to this matter.


Warm Regards, David Colby


--


David Colby, PhDAssistant ProfessorDepartment of Chemical EngineeringUniversity of Delaware




====================END...TSS==============




SNIP...SEE FULL TEXT ;













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





Monday, January 14, 2013


Gambetti et al USA Prion Unit change another highly suspect USA mad cow victim to another fake name i.e. sporadic FFI at age 16 CJD Foundation goes along with this BSe







Monday, December 31, 2012


Creutzfeldt Jakob Disease and Human TSE Prion Disease in Washington State, 2006–2011-2012







Tuesday, December 25, 2012


CREUTZFELDT JAKOB TSE PRION DISEASE HUMANS END OF YEAR REVIEW DECEMBER 25, 2012







Friday, November 23, 2012


sporadic Creutzfeldt-Jakob Disease update As at 5th November 2012 UK, USA, AND CANADA







Tuesday, August 03, 2010


Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein







Monday, August 9, 2010


Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein or just more PRIONBALONEY ?


snip...see full text ;








O.K. let's compare some recent cases of this prionpathy in other countries besides Gambetti's first 10 recently, that he claims is a spontaneous event, from a genetic disorder, that is not genetic, but sporadic, that is related to no animal TSE in North America, or the world. ...























Sunday, August 09, 2009


CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009







Tuesday, August 18, 2009


BSE-The Untold Story - joe gibbs and singeltary 1999 - 2009







Needless conflict



Journal name: Nature Volume: 485, Pages: 279–280 Date published: (17 May 2012) DOI: doi:10.1038/485279b Published online 16 May 2012









Creutzfeldt-Jakob Disease Surveillance in Texas








Sunday, July 11, 2010


CJD or prion disease 2 CASES McLennan County Texas population 230,213 both cases in their 40s











see the continuing rise of sporadic CJD in Texas here ;











Saturday, March 5, 2011


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







Sunday, August 21, 2011


The British disease, or a disease gone global, The TSE Prion Disease


(see video here)







U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ?


(see video at bottom)







Sunday, September 6, 2009


MAD COW USA 1997


(SEE SECRET VIDEO)







Thursday, August 4, 2011


Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011







Friday, November 23, 2012


sporadic Creutzfeldt-Jakob Disease update As at 5th November 2012 UK, USA, AND CANADA







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.


snip...











Thursday, August 12, 2010


Seven main threats for the future linked to prions


First threat


The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.


***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.


Second threat


snip...









IT is of my opinion, that the OIE and the USDA et al, are the soul reason, and responsible parties, for Transmissible Spongiform Encephalopathy TSE prion diseases, including typical and atypical BSE, typical and atypical Scrapie, and all strains of CWD, and human TSE there from, spreading around the globe.


I have lost all confidence of this organization as a regulatory authority on animal disease, and consider it nothing more than a National Trading Brokerage for all strains of animal TSE, just to satisfy there commodity. AS i said before, OIE should hang up there jock strap now, since it appears they will buckle every time a country makes some political hay about trade protocol, commodities and futures. IF they are not going to be science based, they should do everyone a favor and dissolve there organization.


JUST because of low documented human body count with nvCJD and the long incubation periods, the lack of sound science being replaced by political and corporate science in relations with the fact that science has now linked some sporadic CJD with atypical BSE and atypical scrapie, and the very real threat of CWD being zoonosis, I believed the O.I.E. has failed terribly and again, I call for this organization to be dissolved. ...







Tuesday, July 17, 2012


O.I.E. BSE, CWD, SCRAPIE, TSE PRION DISEASE Final Report of the 80th General Session, 20 - 25 May 2012








Saturday, October 6, 2012


TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES 2011 Annual Report







re-Human Prion Diseases in the United States Posted by flounder on 01 Jan 2010 at 18:11 GMT



I kindly disagree with your synopsis for the following reasons ;









Tuesday, November 08, 2011


Can Mortality Data Provide Reliable Indicators for Creutzfeldt-Jakob Disease Surveillance? A Study in France from 2000 to 2008 Vol. 37, No. 3-4, 2011 Original Paper


Conclusions:These findings raise doubt about the possibility of a reliable CJD surveillance only based on mortality data.








Views & Reviews


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


Ermias D. Belay, MD, Ryan A. Maddox, MPH, Pierluigi Gambetti, MD and Lawrence B. Schonberger, MD


+ Author Affiliations


From the Division of Viral and Rickettsial Diseases (Drs. Belay and Schonberger and R.A. Maddox), National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA; and National Prion Disease Pathology Surveillance Center (Dr. Gambetti), Division of Neuropathology, Institute of Pathology, Case Western Reserve University, Cleveland, OH.


Address correspondence and reprint requests to Dr. Ermias D. Belay, 1600 Clifton Road, Mailstop A-39, Atlanta, GA 30333.









26 March 2003


Terry S. Singeltary, retired (medically) CJD WATCH


I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?









Diagnosis and Reporting of Creutzfeldt-Jakob Disease Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA


Diagnosis and Reporting of Creutzfeldt-Jakob Disease


To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.


Terry S. Singeltary, Sr Bacliff, Tex


1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323. FREE FULL TEXT









2 January 2000


British Medical Journal


U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well









15 November 1999


British Medical Journal


vCJD in the USA * BSE in U.S.









Saturday, January 2, 2010


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








14th ICID International Scientific Exchange Brochure -


Final Abstract Number: ISE.114


Session: International Scientific Exchange


Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America update October 2009


T. Singeltary


Bacliff, TX, USA


Background:


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


Methods:


12 years independent research of available data


Results:


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


Conclusion:


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








re-Human Prion Diseases in the United States Posted by flounder on 01 Jan 2010 at 18:11 GMT


I kindly disagree with your synopsis for the following reasons ;








Wednesday, May 16, 2012


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


Proposal ID: 29403








Monday, August 20, 2012


CASE REPORTS CREUTZFELDT-JAKOB DISEASE: AN UNDER-RECOGNIZED CAUSE OF DEMENTIA








Friday, October 05, 2012


Differential Diagnosis of Jakob-Creutzfeldt Disease








see the Duke, Pa, Yale, and Mexican study here, showing the misdiagnosis of CJD TSE prion disease as Alzheimers ;








Monday, July 23, 2012


The National Prion Disease Pathology Surveillance Center July 2012








layperson




Terry S. Singeltary Sr.





mom dod 12/14/97 hvCJD confirmed...

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