Monday, March 19, 2012

Infectivity in Skeletal Muscle of Cattle with Atypical Bovine Spongiform Encephalopathy

PLoS One. 2012; 7(2): e31449.

Published online 2012 February 21. doi: 10.1371/journal.pone.0031449

PMCID: PMC3283643

Copyright Suardi 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.


Infectivity in Skeletal Muscle of Cattle with Atypical Bovine Spongiform Encephalopathy


Silvia Suardi,#1 Chiara Vimercati,#1 Cristina Casalone,#2 Daniela Gelmetti,3 Cristiano Corona,2 Barbara Iulini,2 Maria Mazza,2 Guerino Lombardi,3 Fabio Moda,1 Margherita Ruggerone,1 Ilaria Campagnani,1 Elena Piccoli,1 Marcella Catania,1 Martin H. Groschup,4 Anne Balkema-Buschmann,4 Maria Caramelli,2 Salvatore Monaco,5 Gianluigi Zanusso,5 and Fabrizio Tagliavini1*

1Instituto Di Ricoveroe Cura a Carattere Scientifico (IRCCS), Foundation “Carlo Besta” Neurological Institute, Milano, Italy

2Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, Torino, Italy

3Istituto Zooprofilattico Sperimentale della Lombardia ed Emilia Romagna, Brescia, Italy

4Friedrich-Loeffler-Institut, Greifswald, Insel Riems, Germany

5Policlinico G.B. Rossi, University of Verona, Verona, Italy

Jason Bartz, Editor

Creighton University, United States of America

#Contributed equally.

* E-mail: ftagliavini@istituto-besta.it

Conceived and designed the experiments: SS CV C. Casalone DG C. Corona GL SM M. Caramelli GZ FT. Performed the experiments: SS CV DG C. Corona BI MM FM MR IC EP M. Catania. Analyzed the data: SS CV C. Casalone DG C. Corona GL SM MHG AB M. Caramelli GZ FT. Contributed reagents/materials/analysis tools: SS CV C. Casalone DG C. Corona GL SM MHG AB M. Caramelli GZ FT. Wrote the paper: SS CV C. Casalone DG C. Corona GL SM MHG AB M.Caramelli GZ FT.

Received December 13, 2011; Accepted January 8, 2012.



Abstract


The amyloidotic form of bovine spongiform encephalopathy (BSE) termed BASE is caused by a prion strain whose biological properties differ from those of typical BSE, resulting in a clinically and pathologically distinct phenotype. Whether peripheral tissues of BASE-affected cattle contain infectivity is unknown. This is a critical issue since the BASE prion is readily transmissible to a variety of hosts including primates, suggesting that humans may be susceptible. We carried out bioassays in transgenic mice overexpressing bovine PrP (Tgbov XV) and found infectivity in a variety of skeletal muscles from cattle with natural and experimental BASE. Noteworthy, all BASE muscles used for inoculation transmitted disease, although the attack rate differed between experimental and natural cases (~70% versus ~10%, respectively). This difference was likely related to different prion titers, possibly due to different stages of disease in the two conditions, i.e. terminal stage in experimental BASE and pre-symptomatic stage in natural BASE. The neuropathological phenotype and PrPres type were consistent in all affected mice and matched those of Tgbov XV mice infected with brain homogenate from natural BASE. The immunohistochemical analysis of skeletal muscles from cattle with natural and experimental BASE showed the presence of abnormal prion protein deposits within muscle fibers. Conversely, Tgbov XV mice challenged with lymphoid tissue and kidney from natural and experimental BASE did not develop disease. The novel information on the neuromuscular tropism of the BASE strain, efficiently overcoming species barriers, underlines the relevance of maintaining an active surveillance.


snip...


Introduction


In 2004 an atypical form of bovine spongiform encephalopathy (BSE) termed BASE or BSE-L was identified in Italy through active surveillance [1] and subsequently recognized in different European countries, North America, Canada and Japan [1]–[6]. BASE affects relatively old cattle (all cases were older than 9 years) and differs from BSE with regard to the neuropathological phenotype, the biochemical profile of the disease-associated prion protein (PrPSc) and the biological properties of the agent strain [1], [3], [7]. The neuropathological hallmark of BASE is the presence of PrP amyloid plaques and the preferential involvement of olfactory areas, hippocampus and thalamus with a relatively low involvement of the brainstem, as opposed to classical BSE. The molecular signature of BASE is a PrPSc type distinguished by a protease-resistant core (PrPres) of lower molecular mass than BSE-PrPSc, with predominance of the monoglycosylated protein band by western immunoblot.


Intra-species transmission revealed that the clinical picture of BASE differs substantially from that of BSE, being characterized by mental dullness and amyotrophy rather than hyper-reactivity and aggressiveness [8], [9]. As a consequence, the recognition of BASE in vivo can be difficult and may represent a major challenge for passive surveillance. Transmission studies to transgenic mice overexpressing bovine PrP (Tgbov mice) showed that the BASE strain is more aggressive than the BSE strain [10]. Furthermore, Tg mice overexpressing human PrP as well as non-human primates are more susceptible to infection with BASE than with BSE [11]–[14]. Overall these data raise concern about the potential risk of transmission of BASE to humans and it is urgent to determine the presence and distribution of infectivity in peripheral tissues of BASE-affected cattle. To investigate this issue, we inoculated Tgbov mice with different peripheral tissues from experimentally and naturally BASE-affected cattle and found that various skeletal muscles contained infectivity and PrP-immunoreactive deposits within individual fibers.


snip...


Discussion


This is the first report on the occurrence and distribution of infectivity in peripheral tissues of BASE-affected cattle. We found that different skeletal muscles (i.e., M. longissimus dorsi, M. intercostalis and M. gluteus) from experimental and natural BASE carried infectivity, whereas spleen, cervical lymph node and kidney did not, as highly susceptible Tgbov XV mice did not develop disease up to 850 days after challenge. Noteworthy, all BASE muscles used for inoculation transmitted disease, although the attack rate differed between experimental and natural cases. This difference is likely related to different prion titers in the two conditions, possibly due to different stages of disease. In fact, the experimentally infected cattle was sacrificed at the terminal stage when clinical signs were severe [8], while the cattle with natural BASE was identified through active surveillance at a pre-symptomatic stage.


Infectivity in skeletal muscles has been detected in various natural and experimental prion diseases, including sheep affected by classical and Nor/98 atypical scrapie [17], deer with chronic wasting disease [18] and rodent models of scrapie [19]. A large pathogenesis study on BSE-infected cattle in the UK failed to detect infectivity in muscle tissue at any time during the course of the disease by inoculation of inbred mice [20]. However, in a subsequent study with Tgbov XV mice, M. semitendinosus from a field case of clinically symptomatic BSE transmitted disease to one out of ten inoculated rodents. This low amount of infectivity was tentatively related to the terminal nerve fibres [21].


A major clinical feature of cattle experimentally infected with BASE is amyotrophy, as a result of motor neuron disease [8]. Although we were unable to detect PrPSc in the peripheral nerves of infected cattle and follow the kinetics of PrP spreading through the neural pathway, a study of intra-species transmission of a Japanese case of BASE showed that PrPres was first detectable by immunoblot in the nerve roots and subsequently in the peripheral nerves [22]. PrPres deposition in skeletal muscles has been found in a variety of prion diseases, including experimental scrapie in hamsters [23], natural scrapie in sheep [24], and mouse and primate models of BSE and CJD [25]–[27]. These reports agree that PrPres in muscle tissue is associated with terminal nerve endings.


In our study, immunohistochemistry showed the presence of amorphous or granular, small PrP deposits in different skeletal muscles from both experimental and natural BASE-affected cattle. PrP aggregates were found in isolated muscle fibers with a scattered distribution which was at variance with the topology of PrPres reported in the previous studies [23], [24], [26], [27]. Noteworthy, identical results were obtained using two different fixatives and immunostaining protocols. Since PrPC is expressed in bovine muscles and skeletal muscles are intrinsically capable of propagating prions [19], [28], we argue that PrPSc deposition in BASE muscles might be the result of a primary PrP replication through a neural-independent pathway. This possibility has been previously considered in a patient affected by sporadic CJD and inclusion body myositis where PrPC to PrPSc conversion occurred in skeletal muscle [29].


The limited number and irregular distribution of PrP positive fibers within a muscle sample accounts for the absence of a detectable PrPres signal on Western blot. The inhomogeneous distribution of PrPres and infectivity among different muscles of the same animal and within the same muscle has been previously observed in mice and in primates infected with different prion strains. These findings have been tentatively related to biochemical differences in skeletal muscles of different body regions and/or number of nerve endings [19], [25], [26].


In the present study, Tgbov XV mice challenged with BASE muscles reproduced the monoglycosylated-dominant PrPres type of BASE as well as a histopathological lesion profile and pattern of PrPres deposition that matched those observed in mice challenged with BASE brain. These findings indicate that, in Tgbov XV mice, muscle and brain tissues maintain the same biological properties of the BASE strain.


Although serial transmission studies in Tgbov XV mice showed that the BASE prion is capable to replicate in the spleen converting, in part, into a BSE-like strain (personal observation), we did not detect infectivity in lymph node and spleen from cattle with experimental and natural BASE. This observation opposes the possibility that the BASE agent might re-circulate, potentially as BSE-like strain, in different hosts. Kidney is an edible organ and infectivity found in urine is kidney-associated [30]. Lack of transmission from kidney of natural and experimental BASE is an important issue, since infectivity in kidney has been demonstrated by bioassay in human prion diseases [31], and PrPSc has been observed in kidney of scrapie infected sheep and CWD affected deer [32]–[34].


The present data offer novel information on the tropism of the BASE agent and highlight relevant public health issues. While the transmission barrier for classical BSE is high in most species, BASE prions are readily transmissible to a variety of mammals including non-human primates [11]–[13], [35]. Accordingly, the possibility of spreading of BASE prions through skeletal muscle to other species should be taken into account and evaluated in risk analysis studies.


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3283643/?tool=pubmed





Saturday, June 25, 2011

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

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

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





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

snip...

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


http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf





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...


http://www.efsa.europa.eu/en/efsajournal/pub/e991.htm?emt=1




http://www.efsa.europa.eu/en/efsajournal/doc/e991.pdf




see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;


http://transmissiblespongiformencephalopathy.blogspot.com/2011/10/efsa-journal-2011-european-response-to.html






Thursday, August 12, 2010

Seven main threats for the future linked to prions

First threat

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

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

Second threat

snip...


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






Rural and Regional Affairs and Transport References Committee

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

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

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


http://www.aph.gov.au/senate/committee/rrat_ctte/mad_cows/report/report.pdf






Atypical BSE in Cattle

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

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

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


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






When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

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


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






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.


http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf




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

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

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

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


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






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.


http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf




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






Tuesday, July 14, 2009 U.S.

Emergency Bovine Spongiform Encephalopathy Response Plan Summary and BSE Red Book

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

WHERE did we go wrong $$$

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






LET'S take a closer look at this new prionpathy or prionopathy, and then let's look at the g-h-BSEalabama mad cow. This new prionopathy in humans? the genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_ mad cow in the world to date like this, ......wait, it get's better. this new prionpathy is killing young and old humans, with LONG DURATION from onset of symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and the plaques are very similar in some cases too, bbbut, it's not related to the g-h-BSEalabama cow, WAIT NOW, it gets even better, the new human prionpathy that they claim is a genetic TSE, has no relation to any gene mutation in that family. daaa, ya think it could be related to that mad cow with the same genetic make-up ??? there were literally tons and tons of banned mad cow protein in Alabama in commerce, and none of it transmitted to cows, and the cows to humans there from ??? r i g h t $$$ ALABAMA MAD COW g-h-BSEalabama In this study, we identified a novel mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United States of America. This mutation is identical to the E200K pathogenic mutation found in humans with a genetic form of CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K mutation.


http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000156




http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.ppat.1000156&representation=PDF




Saturday, August 14, 2010

BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY (see mad cow feed in COMMERCE IN ALABAMA...TSS)

http://prionpathy.blogspot.com/2010/08/bse-case-associated-with-prion-protein.html





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 J├╝rgen A. Richt College of Veterinary Medicine, Kansas State University, K224B Mosier Hall, Manhattan, Kansas 66506-5601, USA NATURE|Vol 457|26 February 2009


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






SEE FULL TEXT OF ALL THIS HERE ;

2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006

http://bse-atypical.blogspot.com/2006/08/bse-atypical-texas-and-alabama-update.html





Friday, December 23, 2011

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

Volume 18, Number 1—January 2012 Dispatch

http://transmissiblespongiformencephalopathy.blogspot.com/2011/12/oral-transmission-of-l-type-bovine.html





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.

http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf





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


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

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

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

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

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

http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf






Saturday, July 23, 2011

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

http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/cattle-heads-with-tonsils-beef-tongues.html




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

http://madcowfeed.blogspot.com/2010/11/tafs1-position-paper-on-position-paper.html





Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject PRO/AH/EDR>

Prion disease update 2010 (11) PRION DISEASE UPDATE 2010 (11)

http://www.promedmail.org/direct.php?id=20101206.4364





Sunday, February 5, 2012

February 2012 Update on Feed Enforcement Activities to Limit the Spread of BSE

http://transmissiblespongiformencephalopathy.blogspot.com/2012/02/february-2012-update-on-feed.html



Wednesday, March 7, 2012

Case-control study of cases of bovine spongiform encephalopathy born after July 31, 1996 (BARB cases) in Great Britain Veterinary Record doi:10.1136/vr.100097

http://madcowfeed.blogspot.com/2012/03/case-control-study-of-cases-of-bovine.html



Wednesday, March 7, 2012

The epidemiology of bovine spongiform encephalopathy in the Republic of Ireland before and after the reinforced feed ban

http://madcowfeed.blogspot.com/2012/03/epidemiology-of-bovine-spongiform.html





Thursday, February 23, 2012

EIGHT FORMER SECRETARIES OF AGRICULTURE SPEAKING AT USDA'S 2012 AGRICULTURE OUTLOOK FORUM INDUCTED INTO USA MAD COW HALL OF SHAME

http://madcowusda.blogspot.com/2012/02/eight-former-secretaries-of-agriculture.html





Tuesday, February 14, 2012

White House budget proposes cuts to ag programs including TSE PRION disease aka mad cow type disease

http://transmissiblespongiformencephalopathy.blogspot.com/2012/02/white-house-budget-proposes-cuts-to-ag.html





Thursday, February 16, 2012

Bovine Spongiform Encephalopathy BSE

31 USA SENATORS ASK PRESIDENT OBAMA TO HELP SPREAD MAD COW DISEASE 2012

http://transmissiblespongiformencephalopathy.blogspot.com/2012/02/bovine-spongiform-encephalopathy-bse-31.html





> > > Ackerman says downed cattle are 50 times more likely to have mad cow disease (also known as Bovine Spongiform Encephalopathy, or BSE) than ambulatory cattle that are suspected of having BSE. Of the 20 confirmed cases of mad cow disease in North America since 1993, at least 16 have involved downer cattle, he said. < < <

don’t forget the children...

PLEASE be aware, for 4 years, the USDA fed our children all across the Nation (including TEXAS) dead stock downer cows, the most high risk cattle for BSE aka mad cow disease and other dangerous pathogens.

who will watch our children for CJD for the next 5+ decades ???

WAS your child exposed to mad cow disease via the NSLP ???

SCHOOL LUNCH PROGRAM FROM DOWNER CATTLE UPDATE

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



http://downercattle.blogspot.com/


DID YOUR CHILD CONSUME SOME OF THESE DEAD STOCK DOWNER COWS, THE MOST HIGH RISK FOR MAD COW DISEASE ???

you can check and see here ;



http://www.fns.usda.gov/fns/safety/pdf/Hallmark-Westland_byState.pdf





Wednesday, March 14, 2012


PINK SLIME, MRM’s, BSE AKA MAD COW DISEASE, AND THE USDA NSLP



http://madcowusda.blogspot.com/2012/03/pink-slime-mrms-bse-aka-mad-cow-disease.html





Saturday, March 5, 2011

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

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



Sunday, February 12, 2012

National Prion Disease Pathology Surveillance Center Cases Examined1 (August 19, 2011) including Texas

http://transmissiblespongiformencephalopathy.blogspot.com/2012/02/national-prion-disease-pathology.html





Thursday, March 01, 2012

Variant Creutzfeldt-Jakob disease Fact sheet N°180 Revised February 2012 W.H.O.

http://vcjd.blogspot.com/2012/03/variant-creutzfeldt-jakob-disease-fact.html





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

http://bse-atypical.blogspot.com/2012/03/experimental-h-type-and-l-type-bovine.html





Friday, December 23, 2011



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



Volume 18, Number 1—January 2012 Dispatch



http://transmissiblespongiformencephalopathy.blogspot.com/2011/12/oral-transmission-of-l-type-bovine.html







Thursday, March 15, 2012


Another cow enters food supply without being tested for BSE aka mad cow disease UK 15 March 2012



http://transmissiblespongiformencephalopathy.blogspot.com/2012/03/another-cow-enters-food-supply-without.html




Sunday, March 11, 2012


APHIS Proposes New Bovine Spongiform Encephalopathy Import Regulations in Line with International Animal Health Standards Proposal Aims to Ensure Health of the U.S. Beef Herd, Assist in Negotiations


while at the same time, reducing safety for humans via BSE aka mad cow type disease in North America and abroad via the OIE USDA trading of all strains of TSE prion disease via the BSE MRR policy $$$


http://transmissiblespongiformencephalopathy.blogspot.com/2012/03/aphis-proposes-new-bovine-spongiform.html






THANKS TO THE USDA AND THE OIE ET AL, they expose you and your children to mad cow type disease, because they refuse to go by their own science. see their junk science and policy there from ;



Research Project: STUDY OF ATYPICAL BSE Location: Virus and Prion Research Unit

Project Number: 3625-32000-086-05 Project Type: Specific Cooperative Agreement

Start Date: Sep 15, 2004 End Date: Sep 14, 2009

Objective: The objective of this cooperative research project with Dr. Maria Caramelli from the Italian BSE Reference Laboratory in Turin, Italy, is to conduct comparative studies with the U.S. bovine spongiform encephalopathy (BSE) isolate and the atypical BSE isolates identified in Italy. The studies will cover the following areas: 1. Evaluation of present diagnostics tools used in the U.S. for the detection of atypical BSE cases. 2. Molecular comparison of the U.S. BSE isolate and other typical BSE isolates with atypical BSE cases. 3. Studies on transmissibility and tissue distribution of atypical BSE isolates in cattle and other species.

Approach: This project will be done as a Specific Cooperative Agreement with the Italian BSE Reference Laboratory, Istituto Zooprofilattico Sperimentale del Piemonte, in Turin, Italy. It is essential for the U.S. BSE surveillance program to analyze the effectiveness of the U.S diagnostic tools for detection of atypical cases of BSE. Molecular comparisons of the U.S. BSE isolate with atypical BSE isolates will provide further characterization of the U.S. BSE isolate. Transmission studies are already underway using brain homogenates from atypical BSE cases into mice, cattle and sheep. It will be critical to see whether the atypical BSE isolates behave similarly to typical BSE isolates in terms of transmissibility and disease pathogenesis. If transmission occurs, tissue distribution comparisons will be made between cattle infected with the atypical BSE isolate and the U.S. BSE isolate. Differences in tissue distribution could require new regulations regarding specific risk material (SRM) removal.



http://www.ars.usda.gov/research/projects/projects.htm?accn_no=408490






3.Progress Report This report documents research conducted under a Specific Cooperative Agreement between ARS and the IST ZOOPROFIL SPERIMENT PIEMONTE. Additional details for the research can be found in the report for the parent project 3625-32000-086-00D, TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

The aim of the cooperative research project was to: 1. Evaluate present diagnostic tools used in the U.S. for the detection of atypical bovine spongiform encephalopathy (BSE) cases. 2. Perform molecular comparison of the U.S. BSE isolate and other typical BSE isolates with atypical BSE cases. 3. Support studies on transmissibility and tissue distribution of atypical BSE isolates in cattle and other species. To complete objectives 1 and 2 (i.e., to compare Italian and U.S. BSE confirmatory protocols for detection of classical (C-) and atypical (H- and L-type) BSE cases), samples of Italian C-BSE and Italian L-type BSE (BASE), both frozen and formalin fixed, were sent to USDA laboratories in Ames, Iowa, to undergo Western blot (WB) and immunohistochemistry (IHC) comparison studies for PrPSc detection according to U.S. and Italian methods. A Western blot expert from the cooperating Italian lab assisted ARS scientists in performing the protocols from each laboratory in parallel. A comparative IHC study between U.S. and Italian BSE confirmatory protocols was also performed when the collaborator sent a scientist to Ames to assist in performing the Italian IHC protocol on BSE samples chosen for the study. Results obtained showed the Italian and U.S. IHC procedures were alike in PrPSc detection regarding its tissue distribution, deposition pattern and intensity of staining on all the C-, L- and H-type BSE cases considered. In addition, the U.S. protocol evidenced the characteristic presence of plaques in the frontal cortex of the Italian BASE case similar to the Italian protocol. Data from studies on objectives 1 & 2 has been presented at several international meetings in 2008 and 2009, and has been finalized into manuscript form for publication in a peer-reviewed journal (Journal of Veterinary Diagnostic Investigation). In support of objective 3, the cooperators completed and published their transmissibility and tissue distribution work on BASE cases in a peer-reviewed journal in 2008 (PLoS Pathogens Volume 4, page e1000075). They reported that in all experimentally infected atypical BSE animals, no PrPSc was detected in peripheral tissues either by standard Western blot analysis or following phosphotungstic acid precipitation. Peripheral issues examined included cervical and mesenteric lymph nodes, spleen, thymus, liver, lung, peripheral nerves, and forelimb and hind limb muscles. These findings support the conclusion there is no scientific evidence to expand the list of tissues included in the Specified Risk Material ban based on atypical BSE research data, thus confirming other studies indicating the pathogenesis of BSE in cattle is fundamentally different from that in sheep and mice, due to an exclusive intraneuronal spread of infectivity from the gut to the central nervous system. Methods used for monitoring included email, site visits, and periodic written reports.



http://www.ars.usda.gov/research/projects/projects.htm?ACCN_NO=408490&showpars=true&fy=2010







THE USDA AND THE OIE are industry friendly groups, tied to the hips for one reason, TRADE $$$


THERE is nothing science based about policy making for the TSE prion disease with neither one of these two groups i.e. OIE and the USDA.


IN MY OPINION, both organizations should be shut down for good, with an International Tribunal for their gross negligence with the TSE prion disease, thus, exposing humans and animals around the globe.


HOW many more will die ?


Neither the OIE or the USDA care about a slow incubating disease (as long as 50 years in some cases), that is 100% fatal, due to the fact that since the long incubation period, there is no way to trace back source.


I assure you, both the OIE and the USDA plan to keep it that way. ...





DEEP THROAT TO TSS 2000-2001 (take these old snips of emails with how ever many grains of salt you wish. ...tss)


The most frightening thing I have read all day is the report of Gambetti's finding of a new strain of sporadic cjd in young people...Dear God, what in the name of all that is holy is that!!! If the US has different strains of scrapie.....why????than the UK...then would the same mechanisms that make different strains of scrapie here make different strains of BSE...if the patterns are different in sheep and mice for scrapie.....could not the BSE be different in the cattle, in the mink, in the humans.......I really think the slides or tissues and everything from these young people with the new strain of sporadic cjd should be put up to be analyzed by many, many experts in cjd........bse.....scrapie Scrape the damn slide and put it into mice.....wait.....chop up the mouse brain and and spinal cord........put into some more mice.....dammit amplify the thing and start the damned research.....This is NOT rocket science...we need to use what we know and get off our butts and move....the whining about how long everything takes.....well it takes a whole lot longer if you whine for a year and then start the research!!! Not sure where I read this but it was a recent press release or something like that: I thought I would fall out of my chair when I read about how there was no worry about infectivity from a histopath slide or tissues because they are preserved in formic acid, or formalin or formaldehyde.....for God's sake........ Ask any pathologist in the UK what the brain tissues in the formalin looks like after a year.......it is a big fat sponge...the agent continues to eat the brain ......you can't make slides anymore because the agent has never stopped........and the old slides that are stained with Hemolysin and Eosin......they get holier and holier and degenerate and continue...what you looked at 6 months ago is not there........Gambetti better be photographing every damned thing he is looking at.....


Okay, you need to know. You don't need to pass it on as nothing will come of it and there is not a damned thing anyone can do about it. Don't even hint at it as it will be denied and laughed at.......... USDA is gonna do as little as possible until there is actually a human case in the USA of the nvcjd........if you want to move this thing along and shake the earth....then we gotta get the victims families to make sure whoever is doing the autopsy is credible, trustworthy, and a saint with the courage of Joan of Arc........I am not kidding!!!! so, unless we get a human death from EXACTLY the same form with EXACTLY the same histopath lesions as seen in the UK nvcjd........forget any action........it is ALL gonna be sporadic!!!


And, if there is a case.......there is gonna be every effort to link it to international travel, international food, etc. etc. etc. etc. etc. They will go so far as to find out if a sex partner had ever traveled to the UK/europe, etc. etc. .... It is gonna be a long, lonely, dangerous twisted journey to the truth. They have all the cards, all the money, and are willing to threaten and carry out those threats....and this may be their biggest downfall...

Thanks as always for your help. (Recently had a very startling revelation from a rather senior person in government here..........knocked me out of my chair........you must keep pushing. If I was a power person....I would be demanding that there be a least a million bovine tested as soon as possible and agressively seeking this disease. The big players are coming out of the woodwork as there is money to be made!!! In short: "FIRE AT WILL"!!! for the very dumb....who's "will"! "Will be the burden to bare if there is any coverup!"


again it was said years ago and it should be taken seriously....BSE will NEVER be found in the US! As for the BSE conference call...I think you did a great service to freedom of information and making some people feign integrity...I find it scary to see that most of the "experts" are employed by the federal government or are supported on the "teat" of federal funds. A scary picture! I hope there is a confidential panel organized by the new government to really investigate this thing.


You need to watch your back........but keep picking at them.......like a buzzard to the bone...you just may get to the truth!!! (You probably have more support than you know. Too many people are afraid to show you or let anyone else know. I have heard a few things myself... you ask the questions that everyone else is too afraid to ask.)


END...TSS





IN CONFIDENCE

Perceptions of unconventional slow virus in the USA

GAH WELLS

Report of a visit to the U.S.A. April-May 1989


3. Prof. A Robertson gave a brief account of BSE. The US approach was to 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 fantical incident to be avoided in the USA AT ALL COSTS.


http://web.archive.org/web/20060307063531/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf





and they meant it !



TSS

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