Saturday, January 20, 2024

Ten years of BSE surveillance in Italy: Neuropathological findings in clinically suspected cases

Please Note, this post is an old post that I had in a draft that I never posted. So I reposted today for archive…Terry

doi:10.1016/j.rvsc.2011.10.008 | How to Cite or Link Using DOI

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Ten years of BSE surveillance in Italy: Neuropathological findings in clinically suspected cases

B. Iulinia, C. Maurellaa, M.D. Pintorea, E. Vallino Costassaa, D. Corbellinia, C. Porcarioa, A. Pautassoa, C. Salatab, D. Gelmettic, T. Avanzatoa, G. Palùb, A. D’Angelod, M. Caramellia, C. Casalonea, ,

Purchase

aReference Center for Transmissible Spongiform Encephalopathy (CEA), Istituto Zooprofilattico Sperimentale of Piemonte, Liguria and Valle D’Aosta, Italy

bDepartment of Histology, Microbiology and Medical Biotechnologies, University of Padova, Italy

cIstituto Zooprofilattico Sperimentale of Lombardia and Emilia Romagna, Italy

dDepartment of Animal Pathology, University of Turin, Italy

Received 20 June 2011; Accepted 16 October 2011. Available online 13 November 2011.

Abstract

Between 2001 and 2010, 244 clinically suspected cases of bovine spongiform encephalopathy (BSE) were reported in Italy. This report summarizes the neuropathological findings in cattle displaying clinical signs consistent with a diagnosis of BSE. All animal specimens were submitted for confirmatory testing; samples testing negative underwent neuropathological examination to establish the differential diagnosis. Immunohistochemistry for scrapie prion protein (PrPSc) at the level of frontal cortex was carried out to exclude atypical BSE.

Neuropathological changes were detected in 34.9% of cases; no histological lesions were found in 52.3% of subjects; 12.8% of samples were found unsuitable for analysis. BSE was detected in one case, but no cases of atypical BSE were observed.

This study identified the diseases most commonly encountered in the differential diagnosis of BSE; furthermore, it demonstrated that the surveillance system is necessary for monitoring neuropathological disease in cattle and for the detection of BSE cases.

Keywords: Bovine; Brain; BSE; Neuropathology; Immunohistochemistry; Surveillance


"BSE was detected in one case, but no cases of atypical BSE were observed."

i don't understand this statement ???

atypical BSE has been detected and confirmed in Italy.

please see ;

We recently reported two Italian atypical cases with a PrPTSE type identical to BSE-L, pathologically characterized by PrP amyloid plaques and known as bovine amyloidotic spongiform encephalopathy (BASE).


The L-type has been found in cattle in Italy (10), Japan (11), Germany (12) and Belgium (13). So far, the H-type has been described in cattle from France (14), Germany (12) and the United States (15). The U.S. cases were animals born and raised in the U.S. (Texas, Alabama).


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

*Centro di Referenza Nazionale per le Encefalopatie Animali, Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, Via Bologna, 148, 10195 Turin, Italy; ‡Department of Neurological and Visual Science, Section of Clinical Neurology, Policlinico G.B. Rossi, Piazzale L.A. Scuro, 10, 37134 Verona, Italy; §Istituto Zooprofilattico Sperimentale della Lombardia ed Emilia Romagna, Via Bianchi, 9, 25124 Brescia, Italy; and ¶Istituto Nazionale Neurologico ”Carlo Besta,” Via Celoria 11, 20133 Milan, Italy

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

Next Section 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.

The transmissible spongiform encephalopathies (TSEs), or prion diseases (1), encompass a group of progressive neurodegenerative disorders, including Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep, and bovine spongiform encephalopathy (BSE) (1-4). These disorders are characterized by brain deposition of an insoluble, protease-resistant isoform of the host-encoded cellular prion protein (PrPC), named PrPSc (1, 4, 5) In different TSE phenotypes, PrPSc exhibits disease-specific properties, including distinctive cleavage sites after proteolytic treatment, ratio of glycoforms, and deposition patterns, all features useful in providing a means of strain identification (6-10).

Although not contagious, TSEs are potentially infective, and in humans may present as sporadic, inherited, and acquired diseases. Human-to-human transmission of TSE is well documented and has occurred either through oral or mucocutaneous route of infection, as in kuru (11), or after medical and surgical procedures, as in iatrogenic CJD (12). Recently, animal-to-human transmission has also occurred. Epidemiological (13), experimental transmission (14), and biochemical PrPSc typing (8) have provided strong evidence that the single prion strain responsible for BSE has infected humans, causing variant CJD (vCJD), in addition to several animal species. In BSE and BSE-related disorders, including vCJD, the molecular typing of disease-associated PrPSc shows identical PrP fragment sizes and predominance of the high molecular mass glycoform both in natural hosts and in experimentally inoculated animals. To date, at variance with CJD in humans and scrapie in sheep, only a single strain and a single PrPSc type have been detected in BSE.

The spreading of the BSE agent across mammalian species barriers has aroused considerable concern for the following reasons: (i) the possible existence of new or previously unrecognized cattle TSE strains, potentially pathogenic for humans; and (ii) the occurrence of phenotypic variation of the BSE strain, with propagation of a new agent encoding distinctive molecular and biological properties.

In Italy, an active surveillance system on BSE in cattle was started in January 2001, and by August 2003 a total of 103 BSE cases had been diagnosed of 1,638,275 statutory tested brainstem samples. Confirmatory positive results have been obtained in all cases by immunohistochemical and Western immunoblot demonstration of disease-specific protease-resistant PrPSc.

To assess molecular and neuropathological characteristics in Italian BSE cases, we have over the last few months collected whole brains of eight Italian cattle that were PrPSc-positive in Western immunoblots. In two cattle, older than other affected bovines, the PrPSc glycotype was clearly different from the BSE-associated PrPSc molecule, and widespread PrP-amyloid plaques were seen in supratentorial brain regions. Unlike typical BSE, the brainstem was less involved and no PrP deposition was detected in the dorsal nucleus of the vagus nerve. Given the biochemical and pathological similarities with sporadic CJD (sCJD) cases linked to type-2 PrPSc (9) and methionine/valine (M/V) polymorphism at codon 129 in the prion protein gene (PRNP), these findings have prompted ongoing strain typing in inbred mice. Although the present findings dictate caution, here we show that a PrPSc type associated with sCJD and the previously undescribed bovine PrPSc show convergent molecular signatures.

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.


Sunday, May 01, 2011

STUDY OF ATYPICAL BSE 2010 Annual Report May 2011


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...


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

IN CONFIDENCE

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


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.


Monday, May 23, 2011

Atypical Prion Diseases in Humans and Animals 2011

Top Curr Chem (2011)

DOI: 10.1007/128_2011_161

# Springer-Verlag Berlin Heidelberg 2011

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

Abstract

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

M.A. Tranulis (*)

Norwegian School of Veterinary Science, Oslo, Norway

e-mail: :Michael.Tranulis@nvh.no

S.L. Benestad

Norwegian Veterinary Institute, Oslo, Norway

T. Baron

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

H. Kretzschmar

Ludwig-Maximilians University of Munich, Munich, Germany

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


snip...SEE MORE HERE ;


Sunday, June 07, 2009

L-TYPE-BSE, H-TYPE-BSE, C-TYPE-BSE, IBNC-TYPE-BSE, TME, CWD, SCRAPIE, CJD, NORTH AMERICA


Sunday, May 10, 2009

Identification and characterization of bovine spongiform encephalopathy cases diagnosed and NOT diagnosed in the United States


Sunday, December 28, 2008

MAD COW DISEASE USA DECEMBER 28, 2008 an 8 year review of a failed and flawed policy


Wednesday, August 20, 2008

Bovine Spongiform Encephalopathy Mad Cow Disease typical and atypical strains, was there a cover-up ?


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


Wednesday, July 28, 2010

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


Sunday, September 6, 2009

MAD COW USA 1997 (SEE SECRET VIDEO)


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.


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

This is an interesting editorial about the Mad Cow Disease debacle, and it's ramifications that will continue to play out for decades to come ;

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...



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 ;


Wednesday, August 20, 2008

Bovine Spongiform Encephalopathy Mad Cow Disease typical and atypical strains, was there a cover-up ?

SNIP...

IN CONFIDENCE

This is a highly competitive field and it really will be a pity if we allow many of the key findings to be published by overseas groups while we are unable to pursue our research findings because of this disagreement, which I hope we can make every effort to solve.

http://www.bseinquiry.gov.uk/files/yb/1992/10/26002001.pdf

SEE ;


COLLINGE THREATENS TO GO TO MEDIA

http://www.bseinquiry.gov.uk/files/yb/1992/12/16005001.pdf

SEE ;


2. The discovery might indicate the existence of a different strain of BSE from that present in the general epidemic or an unusual response by an individual host.

3. If further atypical lesion distribution cases are revealed in this herd then implications of misdiagnosis of 'negative' cases in other herds may not be insignificant.

snip...

This minute is re-issued with a wider distribution. The information contained herein should NOT be disseminated further except on the basis of ''NEED TO KNOW''.

R Bradley

http://www.bseinquiry.gov.uk/files/yb/1993/02/17001001.pdf

SEE ;


IN CONFIDENCE

BSE ATYPICAL LESION DISTRIBUTION

http://www.bseinquiry.gov.uk/files/yb/1993/03/14001001.pdf

SEE ;


1983

BSE CONSULTANT

APPROVAL OF MATERIAL FOR PUBLICATIONS

All material for publication including written works to be published in scientific journals, books, proceedings of scientific meetings, abstracts of verbally delivered papers and the like should be scrutinized for risk to the Ministry before dispatch to the publishers.............

full text;

http://www.bseinquiry.gov.uk/files/yb/1983/10/12001001.pdf

SEE ;


- 10 -

19. On 18th February, 1987 (YB87/2.18/1.1) I reported to Dr Watson and Dr Shreeve on a further case which we had received from Truro VIC. The brain had shown neuronal vacuolation and in brain extracts there were fibrils that were similar in size and appearance to SAFs from sheep with scrapie. The Virology Department was studying the brain further and considering a transmission study. A few weeks before this, I had discussed the possibility of a transmission study with Michael Dawson, a research officer in the Virology Department and an expert in viral diseases in sheep, and we were considering carefully the safety aspects. In my note I raised the question of whether we should disclose the information we had more widely to the VIS because this may assist in getting any other cases referred to CVL but there was the difficulty that we knew very little about the disorder and would be unable to deal with queries that might be raised.

20. On 23rd February, 1987 (YB87/2.23/1.1) I sent Mr Wells a note asking him to prepare a statement for publication in Vision, the in-house newsheet prepared by the VIS for the SVS, setting out details of what we had discovered. On 24th February, 1987 (YB87/2.25/2.1) Gerald Wells indicated in a note to me that he had discussed the proposed article with Mr Dawson and they both believed that it could be damaging to publish anything at that stage. They believed cases would be referred to CVL in any event because they were unusual and they did not feel "Vision" was an appropriate publication because its confidentiality was questionable and might lead to referrals to veterinary schools rather than CVL. Gerald Wells was also concerned about the resources available in his section to deal with referred cases. I replied (YB87/2.25/2.1) indicating a draft statement was needed by the Director before a decision on publication could be made. Gerald Wells prepared a draft statement (YB87/3.2/2.1) and sent it to me on 2nd March, 1987. In his cover note (YB87/3.2/1.1) he commented that he believed the distribution of any statement about the new disease outside of CVL to be premature because there was so little information available about the new disease. I passed on a copy of Gerald Wells' note to Dr Watson (YB87/3.2/3.1). I discussed the matter of publication with Dr Watson. No decision had been taken to publish any material at that stage and I sent a note to Gerald Wells letting him know the position and confirming that his views and those of Michael Dawson would be taken into account when a decision was taken.

- 11 -

21. In March, 1987 serious consideration was given to possible transmission (e.g. to hamsters) and other experiments (other than the collection of epidemiological data by the VIS and clinicopathology which had been in progress since the first cases were recognised in November, 1986).

22. On 23rd April, 1987 I sent a report (YB87/4.23/1.1) to Dr Watson and Dr Shreeve informing them that nine control brains were being examined for SAFs and a cow which appeared to be affected with BSE had been purchased for observation. The cow had come from the farm where the original cases had developed and had arrived at CVL on 22nd April, 1987.

23. On 15th May, 1987 Dr Watson informed me that the proposed "Vision" draft would be circulated to VICs in England and Wales if it was approved by management. On 22nd May, 1987 I was copied in on a note (YB87/5.22/2.1) from B.M Williams, (who I believe was Head of the VIS at this time but retired shortly after this), to Dr Watson. This confirmed that the draft prepared for publication in Vision was approved but that the final paragraph should be amended to make it clear that knowledge of the new disease should not be communicated to other research institutes or university departments. At a meeting with Dr Watson on 2nd June, 1987 he informed me that no communication should be made with NPU until after the meeting with the CVO on 5th June, 1987 (see my note of 3rd June, 1987 – YB87/6.3/1.1). We needed much more data and information to answer inevitable queries. ...

http://www.bseinquiry.gov.uk/files/ws/s071.pdf

SEE ;


http://www.publications.parliament.uk/pa/cm199900/cmselect/cmsctech/465/465m48.htm

*This case study accompanies the IRGC report “Risk Governance Deficits: An analysis and illustration of the most common deficits in risk governance”.

The Bovine Spongiform Encephalopathy (BSE) Epidemic in the United Kingdom

By Belinda Cleeland1

SNIP...

A6 Misrepresenting information about risk

From the very beginning of the BSE outbreak, not only was knowledge misrepresented by the British government, but in some cases it was even withheld. For example, after the initial diagnosis of BSE by the SVS in late 1986, there was an embargo placed on the sharing, or making public, of any BSE-related information that ran until mid-1987. Also, up until at least 1990, outside scientists that requested access to BSE data to conduct further studies were denied, despite the fact the improved scientific understanding of the disease had the greatest potential to minimise the impact of the epidemic. Even government scientists within the CVL have acknowledged that there was a culture of suppressing information, to the point that studies revealing damaging evidence (e.g. that there was a causal link between BSE and the new encephalopathy found in cats) were denied publication permission [Ashraf, 2000].

The withholding of such information allowed the government to publicly assert that BSE was just like another version of scrapie – not transmissible to humans – and that there was “clear scientific evidence that British beef is perfectly safe” [UK House of Commons, 1990].2 This was certainly a misrepresentation of the knowledge held at the time, and one that was only possible due to the suppression of some scientific findings and recommendations. Of course, the main reason for this misrepresentation of knowledge was the protection of agricultural and industrial interests – the specific stakeholder favoured in this case was the British beef industry, which stood to lose billions of pounds if a large number of its animals had to be slaughtered, if export bans were put in place, or if costly regulations were implemented.

To protect the interests of the beef industry, the government would assert on many occasions that British beef was safe to eat and that regulatory controls already implemented would prevent any 2 This comment was made by the Agriculture Minister to the House of Commons.

contaminated material from entering the food chain. This was also a misrepresentation of knowledge, as the government was fully aware that their measures were not designed to eliminate exposure, but only to diminish the risk [van Zwanenberg & Millstone, 2002:161].

What’s more, many uncertainties relating to the transmissibility of the disease were either down-played or ignored, resulting in an overstatement of certainty that British beef was completely safe to eat and that BSE was not transmissible to humans. The way uncertainty was dealt with in this case was the result of a number of factors, including the desire to protect specific stakeholder interests.

One crucial factor was the underlying element of risk political culture in the UK that linked the identity of the actor to the consistency of his policy positions. This led to consistency of position being prioritised over accuracy [Dressel, 2000], and resulted in the government insisting on the absence of risk to the population, maintaining this public position despite mounting evidence to the contrary. Although aware of them, policy-makers chose not to overtly acknowledge the levels of uncertainty and the complexity of the risks involved with BSE and its spread because the ramifications of these were too great for the interests they were trying to safeguard.

B1 Responding to early warnings

The incorporation of rendered meat and bone meal into animal feed creates a number of risks related to the transmission, recycling and amplification of pathogens. Such risks were recognised well before the emergence of BSE. In the US in the mid-1970s, concerns that scrapie may be linked to CJD (although there is no evidence that scrapie is transmissible to humans) led to some regulations being placed on the incorporation of sheep or goat carcasses into human and animal foods [van Zwanenberg & Millstone, 2002:158]. In the UK, too, the Royal Commission on Environmental Pollution recommended in 1979 that minimum processing standards be implemented by the rendering industries in order to minimise the potential for disease spread [RCEP, 1979]. The incoming Thatcher government withdrew these proposed regulations, preferring to let industry decide for itself what standards to use. In retrospect, the failure to act at this point to mitigate the general risk of disease transmission may have had a crucial impact on the later outbreak of BSE, given that the disease “probably originated from a novel source in the early 1970s” [BSE Inquiry, 2000b].

Early warnings that BSE might be transmissible to humans were, in fact, observed by scientists and government officials throughout the period from 1986 (the time of first diagnosis in cattle) to 1995 (when vCJD was first observed in humans). Such observations are noted in, for example, the minutes of a meeting of the National Institute for Biological Standards and Control in May 1988, where the probability of transmission of BSE to humans is assessed as more than remote. The diagnosis in 1990 of a domestic cat with a previously unknown spongiform encephalopathy resembling BSE indicated that the disease could infect a wider range of hosts. Responses to such early warnings of potential dangers to human health were either too weak or came too late. This may have been partly a result of an ‘unwillingness to know’ due to the economic harm this knowledge would cause the UK beef industry (related to deficit A6); and partly due to institutional capacities and procedures (related to deficits B5, 9 and 10).


Tuesday, July 28, 2009

MAD COW COVER-UP USA MASKED AS SPORADIC CJD


SEE THE VIDEO NOW AT THE BOTTOM OF THE BLOG BELOW ;


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 $$$


MY GOD, HOW MANY CASES GOT INTO THE FOOD CHAIN ??? IATROGENIC THERE FROM ??? ATYPICAL BSE MORE VIRULENT, HOW MANY MORE WILL DIE NEEDLESSLY IN THE YEARS AND DECADES TO COME. ...TSS

Wednesday, January 4, 2012

A Bovine Prion Acquires an Epidemic Bovine Spongiform Encephalopathy Strain-Like Phenotype on Interspecies Transmission


Monday, January 2, 2012 

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


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... 


2011 

Monday, September 26, 2011


Harvard Risk Assessment of Bovine Spongiform Encephalopathy Update, October 31, 2005 

INTRODUCTION 

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

http://www.fsis.usda.gov/Science/Risk_Assessments/index.asp. 

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

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

Saturday, June 19, 2010 U.S. 

DENIED UPGRADED BSE STATUS FROM OIE 


Friday, August 20, 2010 

USDA: Animal Disease Traceability August 2010 


Friday, November 18, 2011 

country-of-origin labeling law (COOL) violates U.S. obligations under WTO rules WT/DS384/R WT/DS386/R 



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 RFEPLY TO TSS ;

L-BSE BASE prion and atypical sporadic CJD

Thursday, August 4, 2011

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


2011 Monday, September 26, 2011

L-BSE BASE prion and atypical sporadic CJD 



tss



posted by Terry S. Singeltary Sr. at 12:36 PM 0 Comments

Thursday, January 11, 2024

China, Ireland, Mad Cow, atypical BSE TSE Prion, you can expect every two, three, four years we’ll have a sporadic case like this?

China, Ireland, Mad Cow, atypical BSE TSE Prion, you can expect every two, three, four years we’ll have a sporadic case like this? 


Beef: Bord Bia ‘wouldn’t envisage’ long-term lock out from China

Charles O Charles O'Donnell January 10, 2024 5:30 pm Beef: Bord Bia ‘wouldn’t envisage’ long-term lock out from China L-R: Minister Charlie McConalogue and Bord Bia CEO Jim O'Toole. Source: Fennell Photography

The CEO of Bord Bia has said that the food board “wouldn’t envisage” a repeat of the last time Ireland lost access to the Chinese market for beef, when exports were stopped for almost three years.

In November, beef exports to China from Ireland were suspended after the discovery of an atypical case of bovine spongiform encephalopathy (BSE) in a 10-year-old cow.

Atypical BSE is a rare spontaneous event that may occur in any bovine population. It is not related to feed contamination.

Notwithstanding that, beef exports to China were stopped as a result, and Minister for Agriculture, Food and the Marine Charlie McConalogue has repeatedly said that his department is working on regaining access.

The suspension of exports sparked fears that exporters would see a repeat of the period from May 2020 to January 2023, when Irish beef was locked out of China due, again, to the discovery of a case of atypical BSE, on that occasion in a 14-year-old cow.

However, Bord Bia CEO Jim O’Toole has said that there are indications that market access to China can be regained sooner than the 33 months it took the last time this happened.

Speaking to Agriland at the launch of the Bord Bia Exports Performance and Prospects Report 2023/24 today (Wednesday, January 10), O’Toole said: “What I understand is that all the indications we can get from this process are positive.

“Obviously it is within the gift of the Chinese government, but there is, my sense is, some optimism that it will be resolved early.

“How many days, weeks, or months is ‘early’ is probably hard to say, we just don’t know that. But I suppose we wouldn’t envisage the length of time it tool to resolve previously repeating itself,” O’Toole added.

Minister McConalogue, who also attended the launch of the report today, stressed the importance of a quick resolution to getting the most out of the Chinese beef market in the long term.

He said: “For the long-term health of building an export beef sector to China, it’s important that it be a short [time].

“It was a sporadic case [of BSE]. These do happen and will happen into the future in every country but we have very thorough systems here to make sure we catch them and that they’re identified.”

“You can expect every two, three, four years we’ll have a sporadic case like this, and therefore a situation where it led to long disruption in the market would mean that the long term success of the market would be very much affected,” the minister added.

Minister McConalogue said that his department is continuing to engage with the Chinese authorities on the matter.

“We have been through this process before once, since we got access to China originally. That was a long process, but that process involved going through the same process that’s there now, providing the epidemiological reports, going through those steps, and getting to the stage where [the Chinese authorities] are absolutely reassured of the systems in place,” he said.

“I’m hopeful, and we have been hopeful from the outset, that given that we’ve been through the process before, that we could repeat it in a much more concise manner,” the minister added.



***> China, Ireland, Mad Cow BSE TSE Prion, you can expect every two, three, four years we’ll have a sporadic case like this? 

Research Project: Elucidating the Pathobiology and Transmission of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research

Title: Cattle with the EK211 PRNP polymorphism are susceptible to the H-type bovine spongiform encephalopathy agent from either E211K or wild type donors after oronasal inoculation

Author item Greenlee, Justin item Cassmann, Eric item MOORE, SARA JO - Oak Ridge Institute For Science And Education (ORISE) item WEST GREENLEE, HEATHER - Iowa State University

Submitted to: Meeting Abstract Publication Type: Abstract Only Publication Acceptance Date: 6/24/2022 Publication Date: 9/16/2022 Citation: Greenlee, J.J., Cassmann, E.D., Moore, S., West Greenlee, H.M. 2022. Cattle with the EK211 PRNP polymorphism are susceptible to the H-type bovine spongiform encephalopathy agent from either E211K or wild type donors after oronasal inoculation. Prion 2022 Conference abstracts: pushing the boundaries. 16(1):150. https://doi.org/10.1080/19336896.2022.2091286. DOI: https://doi.org/10.1080/19336896.2022.2091286 Interpretive Summary:

Technical Abstract: In 2006, a case of H-type bovine spongiform encephalopathy (H-BSE) was reported in a cow with a previously unreported prion protein polymorphism (E211K). The E211K polymorphism is heritable and homologous to the E200K mutation in humans that is the most frequent PRNP mutation associated with familial Creutzfeldt-Jakob disease. Although the prevalence of the E211K polymorphism is low, cattle carrying the K211 allele develop H-type BSE with a rapid onset after experimental inoculation by the intracranial route. The purpose of this study was to investigate whether the agents of H-type BSE or H-type BSE associated with the E211K polymorphism transmit to wild type cattle or cattle with the K211 allele after oronasal exposure. Wild type (EE211) or heterozygous (EK211) cattle were oronasally inoculated with the H-BSE agent from either the US 2004 case (wild type donor; n=3) or from the US 2006 case with the E211K polymorphism (n=4). Cattle were observed daily throughout the course of the experiment for the development of clinical signs. When signs were noted, animals were euthanized and necropsied. Cattle were confirmed positive for abnormal BSE prions by enzyme immunoassay (EIA; Idexx HerdChek BSE Ag Test), anti-PrP immunohistochemistry (IHC) on brainstem, and microscopic examination for vacuolation. Three-out-of-four (75%) calves with the EK211 genotype developed clinical signs of H-BSE including inattentiveness, loss of body condition, weakness, ataxia, and muscle fasciculations and were euthanized. Two of the positive EK211 steers received H-BSE US 2004 inoculum (Incubation Period (IP): 59.3 and 72.3 months) while the other positive steer received the E211K H-BSE inoculum (IP: 49.7 months). EIA confirmed that abundant misfolded protein (O.D. 2.57-4.0) in the brainstem, and IHC demonstrated PrPSc throughout the brain. All cattle in the EE211 recipient group remain asymptomatic for the duration of the experiment (approximately 7 years post-inoculation). This study demonstrates that the H-type BSE agent is transmissible by the oronasal route. Cattle with the EK211 genotype are oronasally susceptible to small doses of the H-BSE agent from either EK211 or EE211 (wild type) donors. Wild-type EE211 cattle remained asymptomatic for the duration of the experiment with this small dose (0.1g) of inoculum. These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains.


Highlights

This study demonstrates that the H-type BSE agent is transmissible by the oronasal route. 

Cattle with the EK211 genotype are oronasally susceptible to small doses of the H-BSE agent from either EK211 or EE211 (wild type) donors. 

Wild-type EE211 cattle remained asymptomatic for the duration of the experiment with this small dose (0.1g) of inoculum. 

These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains.


Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies

Location: Virus and Prion Research

Title: The agent of transmissible mink encephalopathy passaged in sheep is similar to BSE-L

Author CASSMANN, E - Oak Ridge Institute For Science And Education (ORISE) Greenlee, Justin BALKEMA-BUSCHMANN, A - Friedrich-Loeffler-institut GROSCHUP, M - Friedrich-Loeffler-institut MOORE, S - Oak Ridge Institute For Science And Education (ORISE) Kokemuller, Robyn Submitted to: Meeting Abstract Publication Type: Abstract Only Publication Acceptance Date: 3/29/2019 Publication Date: 5/18/2019 Citation: Cassmann, E.D., Greenlee, J.J., Balkema-Buschmann, A., Groschup, M.H., Moore, S.J., Kokemuller, R. 2019. The agent of transmissible mink encephalopathy passaged in sheep is similar to BSE-L. Prion. 13. Article 49.

https://doi.org/10.1080/19336896.2019.1615197.


Interpretive Summary: Technical Abstract: Transmissible mink encephalopathy (TME) is a fatal neurologic prion disease of farmed mink. Epidemiologic and experimental evidence following a Wisconsin outbreak in 1985 has linked TME to low-type bovine spongiform encephalopathy (BSE-L). Evidence suggests that farmed mink were likely exposed to BSE-L infected downer cattle that were fed to the mink. The interspecies transmission of TME to cattle has been documented. Recently, we demonstrated the susceptibility of sheep to cattle passaged TME by intracranial inoculation.

The aim of the present study was to compare ovine passaged cattle TME to other prion diseases of food-producing animals. Using a transgenic mouse model, we characterized the disease phenotype of sheep TME to BSE-C and BSE-L. Separate inoculants of sheep passaged TME were derived from animals with the VRQ/VRQ (VV136) and ARQ/VRQ (AV136) prion protein genotype. Transgenic bovinized mice (TgBovXV) were intracranially inoculated with 20 µl of 1% w/v brain homogenate. The disease phenotypes were characterized by comparing the attack rates, incubation periods, and vacuolation profiles in TgBovXV mice.

The attack rate for BSE-C (13/13), BSE-L (18/18), and TMEVV (21/21) was 100%; whereas, the TMEAV group (15/19) had an incomplete attack rate. The average incubation periods were 299, 280, 310, and 535 days, respectively. The vacuolation profiles of BSE-L and TMEVV were most similar with mild differences observed in the thalamus and medulla. Vacuolation profiles from the BSE-C and TMEAV experimental groups were different than TMEVV and BSE-L. Overall the phenotype of disease in TME inoculated transgenic mice was dependent on the sheep donor genotype (VV vs AV). The results of the present study indicate that TME isolated from VRQ/VRQ sheep is similar to BSE-L by incubation period, attack rate, and vacuolation profile.

Our findings are in agreement with previous research that found similarities between BSE-L and TME. In this study, the similarities between TME and BSE-L are maintained after multiple interspecies passages.


update


Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies

Location: Virus and Prion Research

2021 Annual Report

snip...

4. Passing Transmissible Mink Encephalopathy (TME) prions from cattle to sheep changed the ability of the prions to infect mice. Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal brain diseases that affect livestock species. Prion diseases have been shown to jump species as exhibited when classical bovine spongiform encephalopathy (BSE) infected cattle products were consumed by humans resulting in variant Creutzfeldt-Jakob disease. Another example of cross-species transmission results in a disease of farmed mink known as transmissible mink encephalopathy (TME), the origins of which were not previously understood; however, one possible source is L- BSE from cattle. The present study was designed to determine the effect of cross-species transmission of TSEs in livestock on the ability to infect mice expressing the cattle prion protein. We found that passing cattle adapted TME (TME that was previously passaged in cattle) to sheep changed the ability of the prions to infect bovinized mice in a laboratory inoculation. These results were compared to atypical BSE (L-BSE type) and Classical BSE in bovinized mice. Depending on the genotype of sheep used, the disease in mice appeared similar by histologic and western blot analysis to either L-BSE or C-BSE. These results indicate a shift in the disease presentation based on transmission through sheep with different genotypes. This information gives insight into origins and development of new prion strains. Because disease in one of the groups of mice resembled the L-BSE phenotype, it supports the hypothesis that TME can originate from feeding mink protein from cattle afflicted with L-BSE.


Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle 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...




NOW, back to those mad mink i.e. TME. let me throw a curve ball here ;

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,* and Richard A. Bessen† Emerging Infectious

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, Htype 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 profi les, 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. Transmissible mink encephalopathy (TME) is a rare prion disease in ranch-raised mink (Mustela vison) in North America and Europe (1–4). Six outbreaks have been reported from 1947 through 1985 in North America, and several have been linked to contaminated commercial feed (1). Although contamination of feed with scrapie-infected sheep parts has been proposed as the cause of TME, the origin of the disease remains elusive. The idea that scrapie in sheep may be a source of TME infection is supported by fi ndings that scrapie-infected mink have a similar distribution of vacuolar pathologic features in the brain and the same clinical signs as mink with natural and experimental TME (5). However, mink are not susceptible to scrapie infection following oral exposure for up to 4 years postinoculation, which suggests that either the scrapie agent may not be the source of natural TME infection or that only specifi c strains of the scrapie agent are able to induce TME (6,7). Epidemiologic investigations in the Stetsonville, Wisconsin, outbreak of TME in 1985 suggested a possible cattle origin, since mink were primarily fed downer or dead dairy cattle but not sheep products (8). Experimental transmission of Stetsonville TME into cattle resulted in transmissible spongiform encephalopathy (TSE) disease with an incubation period of 18.5 months. Back passage of bovine TME into mink resulted in incubation periods of 4 and 7 months after oral or intracerebral inoculation, respectively, which was similar to that found following inoculation of Stetsonville TME into mink by these same routes (8). These findings indicated that cattle are susceptible to TME, and that bovine-passaged TME did not result in a reduced pathogenicity for mink. These studies raised the question as to whether an unknown TSE in cattle was the source of TME infection in the Stetsonville outbreak. Several additional TME outbreaks in the United States have been associated with mink diet that contained downer or dead cattle (9). ...

snip...full text ;



What about that TME TSE Prion surveillance and testing program, I’m still waiting?

WEDNESDAY, JANUARY 12, 2022

Bovine Spongiform Encephalopathy BSE TSE Prion Origin USA, what if?


THURSDAY, FEBRUARY 03, 2022

Transmissible Mink Encephalopathy TME, Atypical L-Type BSE PrP, and typical C-Type BSE, which came first, the cart or the horse?


Bovine Spongiform Encephalopathy BSE TSE Prion Origin USA?


USA 50 State Emergency BSE Conference Call 2001


FRIDAY, DECEMBER 22, 2023

The Mad Cow That Stole Christmas, 20 Years Later


2023-2023 TSE PRION UPDATE

PLEASE NOTE, USDA ET AL ONLY TESTING <25k CATTLE FOR MAD COW DISEASE, woefully inadequate, yet USDA just documented a case Atypical L-Type BSE, the most virulent strain to date...

Monday, May 22, 2023 

***> BSE TSE Prion MAD COW TESTING IN THE USA COMPARED TO OTHER COUNTRIES? 


Wednesday, May 24, 2023 

***> WAHIS, WOAH, OIE, United States of America Bovine spongiform encephalopathy Immediate notification




SATURDAY, MAY 20, 2023 

***> Tennessee State Veterinarian Alerts Cattle Owners to Disease Detection Mad Cow atypical L-Type BSE



MAY 19, 2023


2 weeks before the announcement of this recent mad cow case in the USA, i submitted this to the APHIS et al;

***> APPRX. 2 weeks before the recent mad cow case was confirmed in the USA, in Tennessee, atypical L-Type BSE, I submitted this to the APHIS et al;

Document APHIS-2023-0027-0001 BSE Singeltary Comment Submission May 2, 2023

''said 'burden' cost, will be a heavy burden to bear, if we fail with Bovine Spongiform Encephalopathy BSE TSE Prion disease, that is why this information collection is so critical''...



WEDNESDAY, NOVEMBER 08, 2023 

Ireland Atypical BSE confirmed November 3 2023 


TUESDAY, NOVEMBER 14, 2023 

Ireland Atypical BSE case, 3 progeny of case cow to be culled 


SUNDAY, JULY 16, 2023 

Switzerland Atypical BSE detected in a cow in the canton of St. Gallen 


WAHIS, WOAH, OIE, REPORT Switzerland Bovine Spongiform Encephalopathy Atypical L-Type

Switzerland Bovine Spongiform Encephalopathy Atypical L-Type

Switzerland - Bovine spongiform encephalopathy - Immediate notification



Monday, March 20, 2023 

WAHIS, WOAH, OIE, REPORT United Kingdom Bovine Spongiform Encephalopathy Atypical H-Type 





BRAZIL BSE START DATE 2023/01/18

BRAZIL BSE CONFIRMATION DATE 2023/02/22

BRAZIL BSE END DATE 2023/03/03



SPAIN BSE START DATE 2023/01/21

SPAIN BSE CONFIRMATION DATE 2023/02/03

SPAIN BSE END DATE 2023/02/06



NETHERLANDS BSE START DATE 2023/02/01

NETHERLANDS BSE CONFIRMATION DATE 2023/02/01

NETHERLANDS BSE END DATE 2023/03/13



PLEASE NOTE, USDA ET AL ONLY TESTING <25k CATTLE FOR MAD COW DISEASE, woefully inadequate, yet USDA just documented a case Atypical L-Type BSE, the most virulent strain to date...

Monday, May 22, 2023 

***> BSE TSE Prion MAD COW TESTING IN THE USA COMPARED TO OTHER COUNTRIES? 


THURSDAY, NOVEMBER 9, 2023 

EFSA Annual Report of the Scientific Network on BSE-TSE 2023


Annual Report of the Scientific Network on BSE-TSE 2023

European Food Safety Authority (EFSA

APPROVED: 25 October 2023


FRIDAY, JANUARY 20, 2023 

***> EPIDEMIOLOGY OF SCRAPIE IN THE UNITED STATES 


FRIDAY, NOVEMBER 25, 2022 

***> USA National Scrapie Eradication Program (NSEP) 2021 to 2003 A Year by Year Review


WEDNESDAY, FEBRUARY 03, 2021 

***> Scrapie TSE Prion United States of America a Review February 2021 Singeltary et al


Chronic Wasting Disease Carcass Disposal Dumpster Management and Biosecurity

BACKGROUND INFORMATION:

State and tribal wildlife agencies may identify collection points (dumpsters) within an identified chronic wasting disease (CWD) management zone for the disposal of hunter-harvested cervid carcasses to remove potentially infected carcasses off the landscape for disposal by an approved method (Gillin & Mawdsley, 2018, chap.14). However, depending on their placement and maintenance these dumpsters could potentially increase the risk of CWD transmission.

In several different states, photographic evidence has shown dumpsters in state identified CWD management zones overflowing with deer carcasses and limbs scattered on the land nearby. This could provide an opportunity for scavengers to potentially move infected carcass material to non-infected zones or increase contamination of the ground material around the dumpster’s location.

Federal guidance does not explicitly address uniform standards for collection locations for carcasses of free-ranging cervids; however, the United States Department of Agriculture, Animal and Plant Health Inspection Service, Veterinary Services Program Standards on CWD outlines procedures for carcass disposal, equipment sanitation, and decontamination of premises for captive cervid facilities.

RESOLUTION:

The United States Animal Health Association urges the Association of Fish and Wildlife Agencies (AFWA), Wildlife Health Committee to further refine the AFWA Technical Report on Best Management Practices for Prevention, Surveillance, and Management of Chronic Wasting Disease; Chapter 14, Carcass Disposal to address the placement and management of chronic wasting disease carcass disposal dumpsters or other carcass collection containers.

Reference:

1. Gillin, Colin M., and Mawdsley, Jonathan R. (eds.). 2018. AFWA Technical Report on Best Management Practices for Surveillance, Management and Control of Chronic Wasting Disease. Association of Fish and Wildlife Agencies, Washington, D. C. 111 pp. 


2023 UPDATED SCIENCE ON TSE PRION TO DATE

Transmission of the chronic wasting disease agent from elk to cattle after oronasal exposure

Justin Greenlee, Jifeng Bian, Zoe Lambert, Alexis Frese, and Eric Cassmann Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA 

Aims: The purpose of this study was to determine the susceptibility of cattle to chronic wasting disease agent from elk. 

Materials and Methods: Initial studies were conducted in bovinized mice using inoculum derived from elk with various genotypes at codon 132 (MM, LM, LL). Based upon attack rates, inoculum (10% w/v brain homogenate) from an LM132 elk was selected for transmission studies in cattle. At approximately 2 weeks of age, one wild type steer (EE211) and one steer with the E211K polymorphism (EK211) were fed 1 mL of brain homogenate in a quart of milk replacer while another 1 mL was instilled intranasally. The cattle were examined daily for clinical signs for the duration of the experiment. One steer is still under observation at 71 months post-inoculation (mpi). 

Results: Inoculum derived from MM132 elk resulted in similar attack rates and incubation periods in mice expressing wild type or K211 bovine PRNP, 35% at 531 days post inoculation (dpi) and 27% at 448 dpi, respectively. Inoculum from LM132 elk had a slightly higher attack rates in mice: 45% (693 dpi) in wild type cattle PRNP and 33% (468) in K211 mice. Inoculum from LL132 elk resulted in the highest attack rate in wild type bovinized mice (53% at 625 dpi), but no K211 mice were affected at >700 days. At approximately 70 mpi, the EK211 genotype steer developed clinical signs suggestive of prion disease, depression, low head carriage, hypersalivation, and ataxia, and was necropsied. Enzyme immunoassay (IDEXX) was positive in brainstem (OD=4.00, but non-detect in retropharyngeal lymph nodes and palatine tonsil. Immunoreactivity was largely limited to the brainstem, midbrain, and cervical spinal cord with a pattern that was primarily glia-associated. 

Conclusions: Cattle with the E211K polymorphism are susceptible to the CWD agent after oronasal exposure of 0.2 g of infectious material. 

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

"Cattle with the E211K polymorphism are susceptible to the CWD agent after oronasal exposure of 0.2 g of infectious material."

=====end

Strain characterization of chronic wasting disease in bovine-PrP transgenic mice 

Nuria Jerez-Garrido1, Sara Canoyra1, Natalia Fernández-Borges1, Alba Marín Moreno1, Sylvie L. Benestad2, Olivier Andreoletti3, Gordon Mitchell4, Aru Balachandran4, Juan María Torres1 and Juan Carlos Espinosa1. 1 Centro de Investigación en Sanidad Animal, CISA-INIA-CSIC, Madrid, Spain. 2 Norwegian Veterinary Institute, Ås, Norway. 3 UMR Institut National de la Recherche Agronomique (INRA)/École Nationale Vétérinaire de Toulouse (ENVT), Interactions Hôtes Agents Pathogènes, Toulouse, France. 4 Canadian Food Inspection Agency, Ottawa, Canada. 

Aims: Chronic wasting disease (CWD) is an infectious prion disease that affects cervids. Various CWD prion strains have been identified in different cervid species from North America and Europe. The properties of the infectious prion strains are influenced by amino acid changes and polymorphisms in the PrP sequences of different cervid species. This study, aimed to assess the ability of a panel of CWD prion isolates from diverse cervid species from North America and Europe to infect bovine species, as well as to investigate the properties of the prion strains following the adaptation to the bovine-PrP context. 

Materials and Methods: BoPrP-Tg110 mice overexpressing the bovine-PrP sequence were inoculated by intracranial route with a panel of CWD prion isolates from both North America (two white-tailed deer and two elk) and Europe (one reindeer, one moose and one red deer). 

Results: Our results show distinct behaviours in the transmission of the CWD isolates to the BoPrP-Tg110 mouse model. Some of these isolates did not transmit even after the second passage. Those able to transmit displayed differences in terms of attack rate, survival times, biochemical properties of brain PrPres, and histopathology. 

Conclusions: Altogether, these results exhibit the diversity of CWD strains present in the panel of CWD isolates and the ability of at least some CWD isolates to infect bovine species. Cattle being one of the most important farming species, this ability represents a potential threat to both animal and human health, and consequently deserves further study. 

Funded by: MCIN/AEI /10.13039/501100011033 and by European Union NextGeneration EU/PRTR 

Grant number: PCI2020-120680-2 ICRAD

"Altogether, these results exhibit the diversity of CWD strains present in the panel of CWD isolates and the ability of at least some CWD isolates to infect bovine species. Cattle being one of the most important farming species, this ability represents a potential threat to both animal and human health, and consequently deserves further study."

=====end


Detection of classical BSE prions in asymptomatic cows after inoculation with atypical/Nor98 scrapie

Marina Betancor1, Belén Marín1, Alicia Otero1#, Carlos Hedman1, Antonio Romero2, Tomás Barrio3, Eloisa Sevilla1, Jean Yves Douet3, Alvina Huor3, Juan José Badiola1, Olivier Andréoletti3, Rosa Bolea1.

1Centro de Encefalopatías y Enfermedades Transmisibles Emergentes, Facultad de Veterinaria, Universidad de Zaragoza, Instituto Agroalimentario de Aragón - IA2, 50013, Zaragoza, Spain. 2 Servicio de Cirugía y Medicina Equina, Hospital Veterinario, Universidad de Zaragoza, 50013, Zaragoza, Spain 3 UMR École Nationale Vétérinaire de Toulouse (ENVT) - Institut National pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) - 1225 Interactions Hôtes Agents Pathogènes (IHAP), 31300 Toulouse, France.

Aims: The emergence of bovine spongiform encephalopathy (BSE) prions from atypical scrapie has been recently proved in rodent and swine models. This study aimed to assess whether the inoculation of atypical scrapie could induce BSE-like disease in cattle.

Materials and Methods: Four calves were intracerebrally challenged with atypical scrapie. Animals were euthanized without clinical signs of prion disease between 7.2 and 11.3 years post-inoculation and tested for the accumulation of prions by conventional techniques and protein misfolding cyclic amplification (PMCA).

Results: None of the bovines showed signs compatible with prion disease. In addition, all tested negative for PrPSc accumulation by immunohistochemistry and western blotting. However, an emergence of BSE-like prions was detected during in vitro propagation of brain samples from the inoculated animals.

Conclusions: These findings suggest that atypical scrapie may represent a potential source of BSE infection in cattle.

Funded by: This work was supported financially by the following Spanish and European Interreg grants: Ministerio de Ciencia, Innovación y Universidades (Spanish Government), cofunded by Agencia Estatal de Investigación and the European Union and POCTEFA, which was 65% co-financed by the European Regional Development Fund (ERDF) through the Interreg V-A Spain-France-Andorra program (POCTEFA 2014– 2020).

Grant number: n° PID2021-125398OB-I00, EFA148/16 REDPRION

Acknowledgement: The authors would like to thank Sandra Felices and Daniel Romanos for their excellent technical assistance. Authors would also like to acknowledge the use of Servicio General de Apoyo a la Investigación-SAI, Universidad de Zaragoza

=====

Evolution of Nor98/ Atypical scrapie by iterative propagation in a homologous ovine PrPC context

Sara Canoyra1, Alba Marín-Moreno1, Juan Carlos Espinosa1, Natalia Fernández-Borges1, Nuria Jerez-Garrido1, Sylvie L. Benestad2, Enric Vidal3, Leonor Orge4, Olivier Andreoletti5 and Juan María Torres1.

1Centro de Investigación en Sanidad Animal, CISA-INIA-CSIC, Madrid, Spain. 2Norwegian Veterinary Institute, Ås, Norway. 3Centre de Recerca en Sanitat Animal, Universitat Autònoma de Barcelona (UAB)–Institut de Recerca i Tecnologia Agroalimentàries, Barcelona, Spain. 4Laboratory of Pathology, National Institute for Agrarian and Veterinary Research, Oeiras, Portugal 5UMR Institut National de la Recherche Agronomique (INRA)/École Nationale Vétérinaire de Toulouse (ENVT), Interactions Hôtes Agents Pathogènes, Toulouse, France

Aims: Nor98/ Atypical scrapie (AS) is a prion disease that causes sporadic casesin sheep and goats. Previous studies have shown that the transmission of AS to otherspecies led to the emergence of new prion strains. In the bovine and porcine PrP, there has been reported the emergence of classical BSE prions (Huor et al., 2019, Espinosa et al., 2009, Marin et. al., 2021) and in the bank vole M109I-PrP context, a classical scrapie-like prion strain emerges(Pirisinu et al., 2022). In this study, we analysed the possible evolution of the AS prion within the same specie by modelling the transmission in a homologous ovine PrP context.

Materials and Methods: A panel of AS isolates with different genotypes and geographical origins both from sheep and goats were inoculated in the wild-type transgenic mice model (ARQ-PrP, Aguilar-Calvo et al., 2014).

Results: The isolates infect the ovine ARQ-PrP mice with homogeneous survival time and a complete attack rate. For several AS isolatesthe transmission led to the emergence of 19kDa (with BSE-like characteristics), 21kDa or atypical prions and mixtures of these agents.

Conclusions:

Iterative subpassages of AS isolates into transgenic mice carrying ovine PrP showed an emergence of classical prions during in vivo propagation. This could be caused by the coexistence of strains in the isolate or the evolution of the AS through propagation in the ovine PrP.

These results allow us to hypothesize whether atypical prions might be the origin of prion diversity, where atypical prions tend to acquire classical forms. These results are relevant to control the exposure of farmed animals and humans to AS.

Funded by: MCIN/AEI/ 10.13039/501100011033 Grant number: PID2019-105837RB-I00


Monday, November 13, 2023

Food and Drug Administration's BSE Feed Regulation (21 CFR 589.2000) Singeltary Another Request for Update 2023


FRIDAY, JULY 07, 2023

***> TME, 589.2000 (21 C.F.R. 589.2000), atypical L-BSE, who’s testing MINK for TSE?


Research Project: Elucidating the Pathobiology and Transmission of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research

Title: Disease phenotype of classical sheep scrapie is changed upon experimental passage through white-tailed deer

Author item Kokemuller, Robyn item MOORE, S.JO - Oak Ridge Institute For Science And Education (ORISE) item Bian, Jifeng item WEST GREENLEE, HEATHER - Iowa State University item Greenlee, Justin

Submitted to: PLoS Pathogens Publication Type: Peer Reviewed Journal Publication Acceptance Date: 11/9/2023 Publication Date: 12/4/2023 Citation: Kokemuller, R., Moore, S., Bian, J., West Greenlee, H.M., Greenlee, J.J. 2023. Disease phenotype of classical sheep scrapie is changed upon experimental passage through white-tailed deer. PLoS Pathogens. https://doi.org/10.1371/journal.ppat.1011815. DOI: https://doi.org/10.1371/journal.ppat.1011815 Interpretive Summary: Transmissible spongiform encephalopathies (TSEs) are a group of fatal diseases caused by the accumulation of misfolded prion protein in the brain. Ruminant species such as sheep, deer, and elk can get prion diseases. In sheep the disease is called scrapie. In deer and elk, the disease is called chronic wasting disease (CWD). The source of CWD is unknown, but one possibility is that scrapie jumped from sheep to deer. When we experimentally exposed white-tailed deer to the sheep scrapie agent, all deer developed scrapie. The purpose of the current experiment was to determine if sheep can get scrapie derived from white-tailed deer. Some sheep developed scrapie after oronasal exposure to the scrapie agent from white-tailed deer. Passage through white-tailed deer results in a scrapie isolate with different strain properties than the original inoculum. The detection of new strain properties was an unexpected result that will be the subject of further studies. These results indicate that sheep could be susceptible to the scrapie agent after passage through deer if exposed to the agent in natural or agricultural settings, which could be a confounding factor to the scrapie eradication program. National and state regulatory and wildlife officials should consider this information when developing plans to reduce or eliminate TSEs.

Technical Abstract: Transmissible spongiform encephalopathy (TSE) agents have strain variations that influence disease phenotype and may affect the potential for interspecies transmission. Since deer and sheep may use the same grazing land, it is important to understand the potential transmission of TSEs between these species. The US scrapie isolate (No.13-7) had a 100% attack rate in white-tailed deer after oronasal challenge. The purpose of this study was to determine if sheep are susceptible to oronasal challenge with the scrapie agent from white-tailed deer. Suffolk lambs of various prion protein genotypes were challenged by the oronasal route with a 10% brain homogenate from scrapie-affected white-tailed deer. Sheep were euthanized and necropsied upon development of clinical signs or at the end of the experiment (72 months post-inoculation). Tissues were tested for PrPSc by enzyme immunoassay, western blot, and immunohistochemistry. The first sheep (2/2) to develop clinical signs at approximately 29 months post-inoculation (MPI) had the VRQ/VRQ genotype. One of the two sheep with the ARQ/ARQ genotype also developed clinical signs at 48 MPI. This is in contrast to the original No.13-7 inoculum that has a faster incubation period in sheep with the ARQ/ARQ genotype compared to sheep of the VRQ/VRQ genotype. The shorter incubation period in VRQ/VRQ sheep than ARQ/ARQ sheep after passage through deer indicates a phenotype change. This is important because scrapie infected deer could transmit disease to sheep resulting in new scrapie strain properties. This work raises the concern that scrapie infected deer could serve as a confounding factor to scrapie eradication programs as the scrapie agent from deer is transmissible to sheep by the oronasal route.


Research Project: Elucidating the Pathobiology and Transmission of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research

Title: The chronic wasting disease agent from white-tailed deer is highly infectious to humanized mice after passage through raccoons

Author item Cassmann, Eric item QI, XU - Case Western Reserve University (CWRU) item KONG, QINGZHONG - Case Western Reserve University (CWRU) item Greenlee, Justin

Submitted to: Meeting Abstract Publication Type: Abstract Only Publication Acceptance Date: 3/15/2023 Publication Date: 5/30/2023 Citation: Cassmann, E.D., Qi, X., Kong, Q., Greenlee, J.J. 2023. The chronic wasting disease agent from white-tailed deer is highly infectious to humanized mice after passage through raccoons (abstract). Meeting Abstract. 4th International Chronic Wasting Disease Symposium, May 30-June 3, 2023, Denver, Colorado. Interpretive Summary:

Technical Abstract: The aim of this study was to evaluate the zoonotic potential of the raccoon passaged chronic wasting disease (CWD) agent in humanized transgenic mice in comparison with the North American CWD agent from the original white-tailed deer (WTD) host. Pooled brain (GG96) from CWD positive deer was used to intracranially inoculate two WTD and one raccoon. Brain homogenates (10% w/v) from the raccoon and the WTD were used to intracranially inoculate transgenic mice (Tg40h) expressing the methionine 109 human prion protein. Brains and spleens were collected from mice at experimental endpoints of clinical disease or approximately 700 days post-inoculation. Tissues were divided and homogenized or fixed in 10% buffered neutral formalin. Immunohistochemistry, enzyme immunoassay, and western blot were used to detect misfolded prion protein (PrPSc) in tissue. Tg40h mice inoculated with the raccoon passaged CWD agent from WTD exhibited a 100% (12/12) attack rate with an average incubation period of 605 days. PrPSc was detected in brain tissue by enzyme immunoassay with an average optical density of 3.6/4.0 for positive brains. PrPSc also was detected in brain tissue by western blot and immunohistochemistry. No PrPSc was detected in the spleens of mice inoculated with the raccoon passaged CWD agent. Humanized mice inoculated with the CWD agent from WTD did not have detectable PrPSc using conventional immunoassay techniques. These results demonstrated that the host range of the CWD agent from WTD was expanded in our experimental model after one passage through raccoons.


2023

OIE Conclusions on transmissibility of atypical BSE among cattle

Given that cattle have been successfully infected by the oral route, at least for L-BSE, it is reasonable to conclude that atypical BSE is potentially capable of being recycled in a cattle population if cattle are exposed to contaminated feed. In addition, based on reports of atypical BSE from several countries that have not had C-BSE, it appears likely that atypical BSE would arise as a spontaneous disease in any country, albeit at a very low incidence in old cattle. In the presence of livestock industry practices that would allow it to be recycled in the cattle feed chain, it is likely that some level of exposure and transmission may occur. As a result, since atypical BSE can be reasonably considered to pose a potential background level of risk for any country with cattle, the recycling of both classical and atypical strains in the cattle and broader ruminant populations should be avoided.


Annex 7 (contd) AHG on BSE risk assessment and surveillance/March 2019

34 Scientific Commission/September 2019

3. Atypical BSE

The Group discussed and endorsed with minor revisions an overview of relevant literature on the risk of atypical BSE being recycled in a cattle population and its zoonotic potential that had been prepared ahead of the meeting by one expert from the Group. This overview is provided as Appendix IV and its main conclusions are outlined below. With regard to the risk of recycling of atypical BSE, recently published research confirmed that the L-type BSE prion (a type of atypical BSE prion) may be orally transmitted to calves1 . In light of this evidence, and the likelihood that atypical BSE could arise as a spontaneous disease in any country, albeit at a very low incidence, the Group was of the opinion that it would be reasonable to conclude that atypical BSE is potentially capable of being recycled in a cattle population if cattle were to be exposed to contaminated feed. Therefore, the recycling of atypical strains in cattle and broader ruminant populations should be avoided.

4. Definitions of meat-and-bone meal (MBM) and greaves


Title: Transmission of atypical BSE: a possible origin of Classical BSE in cattle

Authors: Sandor Dudas1, Samuel James Sharpe1, Kristina Santiago-Mateo1, Stefanie Czub1, Waqas Tahir1,2, *

Affiliation: 1National and WOAH reference Laboratory for Bovine Spongiform Encephalopathy, Canadian Food inspection Agency, Lethbridge Laboratory, Lethbridge, Canada. 2Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, Canada.

*Corresponding and Presenting Author: waqas.tahir@inspection.gc.ca

Background: Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative disease of cattle and is categorized into classical and atypical forms. Classical BSE (CBSE) is linked to the consumption of BSE contaminated feed whereas atypical BSE is considered to be spontaneous in origin. The potential for oral transmission of atypical BSE is yet to be clearly defined.

Aims: To assess the oral transmissibility of atypical BSE (H and L type) in cattle. Should transmission be successful, determine the biochemical characteristics and distribution of PrPSc in the challenge cattle.

Material and Methods: For oral transmission, calves were fed with 100 g of either H (n=3) or L BSE (n=3) positive brain material. Two years post challenge, 1 calf from each of the H and L BSE challenge groups exhibited behavioural signs and were euthanized. Various brain regions of both animals were tested by traditional and novel prion detection methods with inconclusive results. To detect infectivity, brain homogenates from these oral challenge animals (P1) were injected intra-cranially (IC) into steer calves. Upon clinical signs of BSE, 3/4 of IC challenged steer calves were euthanized and tested for PrPSc with ELISA, immunohistochemistry and immunoblot.

Results: After 6 years of incubation, 3/4 animals (2/2 steers IC challenged with brain from P1 L-BSE oral challenge and 1/2 steer IC challenged with brain from P1 H-BSE oral challenge) developed clinical disease. Analysis of these animals revealed high levels of PrPSc in their brains, having biochemical properties similar to that of PrPSc in C-BSE.

Conclusion: These results demonstrate the oral transmission potential of atypical BSE in cattle. Surprisingly, regardless of which atypical type of BSE was used for P1 oral challenge, PrPSc in the P2 animals acquired biochemical characteristics similar to that of PrPSc in C-BSE, suggesting atypical BSE as a possible origin of C-BSE in UK.

Presentation Type: Oral Presentation

Funded by: CFIA, Health Canada, Alberta Livestock and Meat Agency, Alberta Prion Research Institute

Grant Number: ALMA/APRI: 201400006, HC 414250


Molecular phenotype shift after passage of low-type bovine spongiform encephalopathy (L-BSE). 

Zoe J. Lambert, M. Heather West Greenlee, Jifeng Bian, Justin J. Greenlee Ames, USA 

Aims: The purpose of this study is to compare the molecular phenotypes of L-BSE in wild type cattle and cattle with the E211K polymorphism to samples of other cattle TSEs, such as classical BSE (C-BSE), hightype BSE (H-BSE), and transmissible mink encephalopathy (TME). 

Materials and Methods: Two wild type cattle (EE211 PRNP) and one steer with the E211K polymorphism (EK211) were intracranially inoculated with 1 mL of brain homogenate that originated from a 2005 French L-BSE case. Multiple assays were used to compare and differentiate tissues, including enzyme immunoassay, western blot (Sha31, 12B2, SAF84), stability (Sha31), and immunohistochemistry (F99/97). 

Results: Approximately 16.6 months post-inoculation, Steer 6 (EK211 L-BSE) developed neurologic signs, including agitation, difficulty eating accompanied by weight loss, head tremor, ataxia, and fasciculations in the forelimbs, and was necropsied. Enzyme immunoassays demonstrated misfolded prion protein in the brainstem (4.0 O.D) but not in peripheral tissues, such as the retropharyngeal lymph node and palatine tonsil. When compared by western blot, the molecular phenotype of the brainstem of Steer 6 (EK211 L-BSE) is higher than that of wildtype cattle inoculated with L-BSE, requiring careful differentiation from C-BSE. Ongoing mouse studies in bovinized mice (K211 and TgBov) will provide data to compare to all other BSE strains available, including L-BSE, C-BSE, H-BSE, E211K H-BSE, and TME. 

Conclusions: Further study of L-BSE in EK211 cattle with a higher molecular phenotype in the brainstem may give more insight into the origin of C-BSE. 

Funded by: This research was funded in its entirety by congressionally appropriated funds to the United States Department of Agriculture, Agricultural Research Service. The funders of the work did not influence study design, data collection and analysis, decision to publish, or preparation of the manuscript. This research was supported in part by an appointment to the Agricultural Research Service (ARS) Research Participation Program administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy (DOE) and the U.S. Department of Agriculture (USDA). ORISE is managed by ORAU under DOE contract number DE-SC0014664. All opinions expressed in this paper are the author’s and do not necessarily reflect the policies and views of USDA, ARS, DOE, or ORAU/ORISE. 

Grant number: DOE contract number DE-SC0014664 Acknowledgements: NA Theme: Animal prion diseases

=====end


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


Consumption of L-BSE–contaminated feed may pose a risk for oral transmission of the disease agent to cattle.


Thus, it is imperative to maintain measures that prevent the entry of tissues from cattle possibly infected with the agent of L-BSE into the food chain.


Atypical L-type bovine spongiform encephalopathy (L-BSE) transmission to cynomolgus macaques, a non-human primate

Fumiko Ono 1, Naomi Tase, Asuka Kurosawa, Akio Hiyaoka, Atsushi Ohyama, Yukio Tezuka, Naomi Wada, Yuko Sato, Minoru Tobiume, Ken'ichi Hagiwara, Yoshio Yamakawa, Keiji Terao, Tetsutaro Sata

Affiliations expand

PMID: 21266763

Abstract

A low molecular weight type of atypical bovine spongiform encephalopathy (L-BSE) was transmitted to two cynomolgus macaques by intracerebral inoculation of a brain homogenate of cattle with atypical BSE detected in Japan. They developed neurological signs and symptoms at 19 or 20 months post-inoculation and were euthanized 6 months after the onset of total paralysis. Both the incubation period and duration of the disease were shorter than those for experimental transmission of classical BSE (C-BSE) into macaques. Although the clinical manifestations, such as tremor, myoclonic jerking, and paralysis, were similar to those induced upon C-BSE transmission, no premonitory symptoms, such as hyperekplexia and depression, were evident. Most of the abnormal prion protein (PrP(Sc)) was confined to the tissues of the central nervous system, as determined by immunohistochemistry and Western blotting. The PrP(Sc) glycoform that accumulated in the monkey brain showed a similar profile to that of L-BSE and consistent with that in the cattle brain used as the inoculant. PrP(Sc) staining in the cerebral cortex showed a diffuse synaptic pattern by immunohistochemistry, whereas it accumulated as fine and coarse granules and/or small plaques in the cerebellar cortex and brain stem. Severe spongiosis spread widely in the cerebral cortex, whereas florid plaques, a hallmark of variant Creutzfeldt-Jakob disease in humans, were observed in macaques inoculated with C-BSE but not in those inoculated with L-BSE.


see full text;


''H-TYPE BSE AGENT IS TRANSMISSIBLE BY THE ORONASAL ROUTE''

This study demonstrates that the H-type BSE agent is transmissible by the oronasal route. These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains.


2023 PRION CONFERENCE

Comparing the Distribution of Ovine Classical Scrapie and Sporadic Creutzfeldt-Jakob Disease in Italy: Spatial and Temporal Associations (2002-2014) 

Aim: This study aims to investigate potential spatial and temporal associations between Creutzfeldt-Jakob disease (CJD) in humans (2010-2014) and ovine classical scrapie (CS) (2002- 2006) in Italy, serving as a proxy for exposure. 

Results: The analysis of data at the district level revealed no significant association. However, when considering aggregated regional data, all four models consistently indicated a statistically significant positive association, suggesting a higher incidence of the disease in humans as the regional incidence of sheep scrapie increased. 

Conclusions: While the results are intriguing, it is important to acknowledge the inherent limitations of ecological studies. Nevertheless, these findings provide valuable evidence to formulate a hypothesis regarding the zoonotic potential of classical scrapie. Further investigations are necessary, employing specific designs such as analytical epidemiology studies, to test this hypothesis effectively. 


Experimental transmission of the chronic wasting disease agent to swine after oral or intracranial inoculation

Running Title: The chronic wasting disease agent transmits to swine

S. Jo Moore1,2 , M. Heather West Greenlee3 , Naveen Kondru3 , Sireesha Manne3 , Jodi D. Smith1,# , Robert A. Kunkle1 , Anumantha Kanthasamy3 , Justin J. Greenlee1*

Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, Iowa, United States of America

Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee, United States of America

Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa, United States of America

Current Address: Department of Veterinary Pathology, Iowa State University College of Veterinary Medicine, Ames, Iowa, United States of America * Corresponding author Email: justin.greenlee@ars.usda.gov

JVI Accepted Manuscript Posted Online 12 July 2017 J. Virol. doi:10.1128/JVI.00926-17

This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

 on July 27, 2017 by guest http://jvi.asm.org/ Downloaded from

Abstract

Chronic wasting disease (CWD) is a naturally occurring, fatal neurodegenerative disease of cervids. The potential for swine to serve as a host for the agent of chronic wasting disease is unknown. The purpose of this study was to investigate the susceptibility of swine to the CWD agent following experimental oral or intracranial inoculation . Crossbred piglets were assigned to one of three groups: intracranially inoculated (n=20), orally inoculated (n=19), or non -inoculated (n=9). At approximately the age at which commercial pigs reach market weight, half of the pigs in each group were culled (‘market weight’ groups). The remaining pigs (‘aged’ groups) were allowed to incubate for up to 73 months post inoculation (MPI ). Tissues collected at necropsy were examined for disease -associated prion protein (PrPSc) by western blotting (WB), antigen -capture immunoassay (EIA), immunohistochemistry (IHC) and in vitro real -time quaking induced conversion (RT -QuIC). Brain samples from selected pigs were also bioassayed in mice expressing porcine prion protein. Four intracranially inoculated aged pigs and one orally inoculated aged pig were positive by EIA, IHC and/or WB. Using RT -QuIC, PrPSc was detected in lymphoid and/or brain tissue from one or more pigs in each inoculated group. Bioassay was positive in 4 out of 5 pigs assayed.

This study demonstrates that pigs can support low-level amplification of CWD prions, although the species barrier to CWD infection is relatively high. However, detection of infectivity in orally inoculated pigs using mouse bioassay raises the possibility that naturally exposed pigs could act as a reservoir of CWD infectivity.

Discussion

snip...

In the case of feral pigs, exposure to the agent of CWD through scavenging of CWD-affected cervid carcasses or through consumption of prion contaminated plants or soil could allow feral pigs to serve as reservoirs of CWD infectivity. The range and numbers of feral pigs is predicted to continue to increase due to the ability of pigs to adapt to many climates, reproduce year-round, and survive on a varied diet (55 ). The range of CWD-affected cervids also continues to spread, increasing the likelihood of overlap of ranges of feral pigs and CWD -affected environments.

We demonstrate here that PrPSc accumulates in lymphoid tissues from pigs inoculated intracranially or orally with the CWD agent, and can be detected as early as 6 months after inoculation. Clinical disease suggestive of prion disease developed only in a single pig after a long (64 months) incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. However, the low amounts of PrPSc detected in the study pigs combined with the low attack rates in Tg002 mice suggest that there is a relatively strong species barrier to CWD prions in pigs.


cwd scrapie pigs oral routes 

***> However, at 51 months of incubation or greater, 5 animals were positive by one or more diagnostic methods. Furthermore, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study) suggesting that swine are potential hosts for the agent of scrapie. <*** 

>*** Although the current U.S. feed ban is based on keeping tissues from TSE infected cattle from contaminating animal feed, swine rations in the U.S. could contain animal derived components including materials from scrapie infected sheep and goats. These results indicating the susceptibility of pigs to sheep scrapie, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health. <*** 

***> Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 month group was positive by EIA. PrPSc was detected by QuIC in at least one of the lymphoid tissues examined in 5/6 pigs in the intracranial <6 months group, 6/7 intracranial >6 months group, 5/6 pigs in the oral <6 months group, and 4/6 oral >6 months group. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%). 

***> Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains. 




Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.


CONFIDENTIAL

EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY

LINE TO TAKE

3. If questions on pharmaceuticals are raised at the Press conference, the suggested line to take is as follows:- 

 "There are no medicinal products licensed for use on the market which make use of UK-derived porcine tissues with which any hypothetical “high risk" ‘might be associated. The results of the recent experimental work at the CSM will be carefully examined by the CSM‘s Working Group on spongiform encephalopathy at its next meeting.

DO Hagger RM 1533 MT Ext 3201


While this clearly is a cause for concern we should not jump to the conclusion that this means that pigs will necessarily be infected by bone and meat meal fed by the oral route as is the case with cattle. ...


we cannot rule out the possibility that unrecognised subclinical spongiform encephalopathy could be present in British pigs though there is no evidence for this: only with parenteral/implantable pharmaceuticals/devices is the theoretical risk to humans of sufficient concern to consider any action.


May I, at the outset, reiterate that we should avoid dissemination of papers relating to this experimental finding to prevent premature release of the information. ...


3. It is particularly important that this information is not passed outside the Department, until Ministers have decided how they wish it to be handled. ...


But it would be easier for us if pharmaceuticals/devices are not directly mentioned at all. ...


Our records show that while some use is made of porcine materials in medicinal products, the only products which would appear to be in a hypothetically ''higher risk'' area are the adrenocorticotrophic hormone for which the source material comes from outside the United Kingdom, namely America China Sweden France and Germany. The products are manufactured by Ferring and Armour. A further product, ''Zenoderm Corium implant'' manufactured by Ethicon, makes use of porcine skin - which is not considered to be a ''high risk'' tissue, but one of its uses is described in the data sheet as ''in dural replacement''. This product is sourced from the United Kingdom.....


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

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

From: "Terry S. Singeltary Sr."

Reply-To: Bovine Spongiform Encephalopathy

To: BSE-L@uni-karlsruhe.de 


Transmission of Idiopathic human prion disease CJD MM1 to small ruminant mouse models (Tg338 and Tg501). 

Results: No evidence of transmission was found on a first passage in Tg338 nor Tg501ovinized mice, but on second passage, 4/10 Tg338 mice succumbed to CJDMM1 (40% attack rate after 645 dpi) and 1/12 Tg501 mice (519dpi, 10 still alive). The remaining 2nd passages are still ongoing. Conclusions: In this poster, the neuropathological features of the resulting strain are discussed. 


Transmission of scrapie prions to primate after an extended silent incubation period

*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.

*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.

*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.


***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.

***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.

***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.


***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***

Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.



O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations 

*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period, 

***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014), 

***is the third potentially zoonotic PD (with BSE and L-type BSE), 

***thus questioning the origin of human sporadic cases. 

============== 

PRION 2015 CONFERENCE


PRION 2016 TOKYO

Saturday, April 23, 2016

SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 1933-690X 

WS-01: Prion diseases in animals and zoonotic potential

Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. 

These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions. 


Tuesday, December 16, 2014 

Evidence for zoonotic potential of ovine scrapie prions 

Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier Andréoletti1, Affiliations Contributions Corresponding author Journal name: Nature Communications 

Volume: 5, Article number: 5821 DOI: doi:10.1038/ncomms6821 Received 07 August 2014 Accepted 10 November 2014 Published 16 December 2014 

Abstract 

Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie prions remains unknown. Mice genetically engineered to overexpress the human​prion protein (tgHu) have emerged as highly relevant models for gauging the capacity of prions to transmit to humans. These models can propagate human prions without any apparent transmission barrier and have been used used to confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie prions transmit to several tgHu mice models with an efficiency comparable to that of cattle BSE. 

***The serial transmission of different scrapie isolates in these mice led to the propagation of prions that are phenotypically identical to those causing sporadic CJD (sCJD) in humans. 

***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions. 

Subject terms: Biological sciences• Medical research At a glance


why do we not want to do TSE transmission studies on chimpanzees $ 5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis. 

snip... R. BRADLEY 


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

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

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

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

snip... 

The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease. PMID: 6997404


Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias" Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously. snip... 76/10.12/4.6 


 Nature. 1972 Mar 10;236(5341):73-4. 

Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis) 

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

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis) 

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

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





spontaneous/sporadic CJD in 85%+ of all human TSE, or spontaneous BSE in cattle, is a pipe dream, dreamed up by USDA/OIE et al, that has never been proven. let me repeat, NEVER BEEN PROVEN FOR ALL HUMAN OR ANIMAL TSE I.E. ATYPICAL BSE OR SPORADIC CJD! please see;

***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***

Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.






Detection of chronic wasting disease prions in processed meats

Rebeca Benavente1 , Francisca Bravo1,2, J. Hunter Reed3 , Mitch Lockwood3 , Glenn Telling4 , Rodrigo Morales1,2 1 Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA; 2 Universidad Bernardo O’Higgins. Santiago, Chile; 3 Texas Parks and Wildlife Department, Texas, USA. 4 Prion Research Center, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA 

Aims: identify the presence of CWD prions in processed meats derived from elk. 

Materials and Methods: In this study, we analyzed different processed meats derived from a CWD-positive (pre-clinical) free-ranging elk. Products tested included filets, sausages, boneless steaks, burgers, seasoned chili meats, and spiced meats. The presence of CWD-prions in these samples were assessed by PMCA using deer and elk substrates. The same analyses were performed in grilled and boiled meats to evaluate the resistance of the infectious agent to these procedures. 

Results: Our results show positive prion detection in all the samples analyzed using deer and elk substrates. Surprisingly, cooked meats displayed increased seeding activities. This data suggests that CWD-prions are available to people even after meats are processed and cooked. 

Conclusions: These results suggest CWD prions are accessible to humans through meats, even after processing and cooking. Considering the fact that these samples were collected from already processed specimens, the availability of CWD prions to humans is probably underestimated. 

Funded by: NIH and USDA 

Grant number: 1R01AI132695 and APP-20115 to RM 

Acknowledgement: We would like to thank TPWD personnel for providing us with valuable samples

"Our results show positive prion detection in all the samples analyzed using deer and elk substrates. Surprisingly, cooked meats displayed increased seeding activities."

end... 

Fortuitous generation of a zoonotic cervid prion strain 

Manuel Camacho, Xu Qi, Liuting Qing, Sydney Smith, Jieji Hu, Wanyun Tao, Ignazio Cali, Qingzhong Kong. Department of Pathology, Case Western Reserve University, Cleveland, USA 

Aims: Whether CWD prions can infect humans remains unclear despite the very substantial scale and long history of human exposure of CWD in many states or provinces of USA and Canada. Multiple in vitro conversion experiments and in vivo animal studies indicate that the CWD-to-human transmission barrier is not unbreakable. A major long-term public health concern on CWD zoonosis is the emergence of highly zoonotic CWD strains. We aim to address the question of whether highly zoonotic CWD strains are possible. 

Materials and Methods: We inoculated several sCJD brain samples into cervidized transgenic mice (Tg12), which were intended as negative controls for bioassays of brain tissues from sCJD cases who had potentially been exposed to CWD. Some of the Tg12 mice became infected and their brain tissues were further examined by Western blot as well as serial passages in humanized or cervidized mice. 

Results: Passage of sCJDMM1 in transgenic mice expressing elk PrP (Tg12) resulted in a “cervidized” CJD strain that we termed CJDElkPrP. We observed 100% transmission of the original CJDElkPrP in transgenic mice expressing human PrP. We passaged CJDElkPrP two more times in the Tg12 mice. We found that such second and third passage CJDElkPrP prions retained 100% transmission rate in the humanized mice, despite that the natural elk CWD isolates and CJDElkPrP share the same elk PrP sequence. In contrast, we and others found zero or poor transmission of natural elk CWD isolates in humanized mice. 

Conclusions: Our data indicate that highly zoonotic cervid prion strains are not only possible but also can retain zoonotic potential after serial passages in cervids, suggesting a very significant and serious long-term risk of CWD zoonosis given that the broad and continuing spread of CWD prions will provide fertile grounds for the emergence of zoonotic CWD strains over time. 

Funded by: NIH Grant number: R01NS052319, R01NS088604, R01NS109532 

Acknowledgement: We want to thank the National Prion Disease Pathology Surveillance Center and Drs. Allen Jenny and Katherine O'Rourke for providing the sCJD samples and the CWD samples used in this study, respectively

"Our data indicate that highly zoonotic cervid prion strains are not only possible but also can retain zoonotic potential after serial passages in cervids, suggesting a very significant and serious long-term risk of CWD zoonosis given that the broad and continuing spread of CWD prions will provide fertile grounds for the emergence of zoonotic CWD strains over time."


A probable diagnostic marker for CWD infection in humans 

Xu Qi, Liuting Qing, Manuel Camacho, Ignazio Cali, Qingzhong Kong. Department of Pathology, Case Western Reserve University, Cleveland, USA 

Aims: Multiple in vitro CWD-seeded human PrP conversion experiments and some animal model studies indicate that the species barrier for CWD to human transmission can be overcome, but whether CWD prion can infect humans in real life remains controversial. The very limited understanding on the likely features of CWD infection in humans and the lack of a reliable diagnostic marker for identification of acquired human CWD cases contribute to this uncertainty. We aim to stablish such a reliable diagnostic marker for CWD infections in humans should they occur. 

Materials and Methods: A couple of PrPSc-positive spleens were identified from humanized transgenic mice inoculated with either CWD or sCJDMM1. Prions in these spleens were compared by bioassays in cervidized or humanized transgenic mice. A couple of PrPSc-positive spleens from UK sCJDMM1 patients were also examined similarly as controls with no exposure to CWD. 

Results: We have detected two prion-positive spleens in humanized transgenic mice inoculated with some CWD isolates. Such experimentally generated splenic “humanized” CWD prions (termed eHuCWDsp) appear indistinguishable from prions in the brain of sCJDMM1 patients on Western blot. We compared eHuCWDsp with prions in the spleen from humanized mice infected with sCJDMM1 (termed sCJDMM1sp) by bioassays in cervidized or humanized transgenic mice. Significantly, we found that eHuCWDsp can efficiently infect not only the humanized mice but also cervidized transgenic mice, and cervidized mice infected by eHuCWDsp produced PrPSc and brain pathology that are practically identical to those of CWD-infected cervidized mice. In contrast, sCJDMM1sp, similar to prions from sCJDMM1 patient brains, is poorly transmissible in the cervidized mice. 

Conclusions: Our data demonstrate that high transmissibility with CWD features of splenic prions in cervidized transgenic mice is unique to acquired human CWD prions, and it may serve as a reliable marker to identify the first acquired human CWD cases. 

Funded by: NIH Grant number: R01NS052319, R01NS088604, R01NS109532 

Acknowledgement: We want to thank the National Prion Disease Pathology Surveillance Center and Drs. Allen Jenny and Katherine O'Rourke for providing the sCJD samples and the CWD samples used in this study, respectively.

=====end 
The detection and decontamination of chronic wasting disease prions during venison processing 

Marissa S. Milstein1,2, Marc D. Schwabenlander1,2, Sarah C. Gresch1,2, Manci Li1,2, Stuart Lichtenberg1,2, Rachel Shoemaker1,2, Gage R. Rowden1,2, Jason C. Bartz2,3 , Tiffany M. Wolf2,4, Peter A. Larsen1,2 Presenting author: Tiffany M. Wolf 1 Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA 2 Minnesota Center for Prion Research and Outreach, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA 3 Department of Medical Microbiology and Immunology, School of Medicine, Creighton University, Omaha, Nebraska, USA 4 Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, USA 

Aims: There is a growing concern that chronic wasting disease (CWD) prions in venison pose a risk to human health. CWD prions accumulate in infected deer tissues that commonly enter the human food chain through meat processing and consumption. The United States (US) Food and Drug Administration and US Department of Agriculture now formally consider CWD-positive venison unfit for human and animal consumption. Yet, the degree to which prion contamination occurs during routine venison processing is unknown. Here, we use environmental surface swab methods to: a) experimentally test meat processing equipment (i.e., stainless steel knives and polyethylene cutting boards) before and after processing CWD-positive venison and b) test the efficacy of five different disinfectant types (i.e., Dawn dish soap, Virkon-S, Briotech, 10% bleach, and 40% bleach) to determine prion decontamination efficacy. 

Materials and Methods: We used a real-time quaking-induced conversion (RT-QuIC) assay to determine CWD infection status of venison and to detect CWD prions in the swabs. We collected three swabs per surface and ran eight technical replicates on RT-QuIC. 

Results: CWD prions were detected on all cutting boards (n= 3; replicates= 8/8, 8/8, 8/8 and knives (n= 3; replicates= 8/8, 8/8, 8/8) used in processing CWD-positive venison, but not on those used for CWD-negative venison. After processing CWD-positive venison, allowing the surfaces to dry, and washing the cutting board with Dawn dish soap, we detected CWD prions on the cutting board surface (n= 3; replicates= 8/8, 8/8, 8/8) but not on the knife (n= 3, replicates = 0/8, 0/8, 0/8). Similar patterns were observed with Briotech (cutting board: n= 3; replicates= 7/8, 1/8, 0/8; knife: n= 3; replicates = 0/8, 0/8, 0/8). We did not detect CWD prions on the knives or cutting boards after disinfecting with Virkon-S, 10% bleach, and 40% bleach. 

Conclusions: These preliminary results suggest that Dawn dish soap and Briotech do not reliably decontaminate CWD prions from these surfaces. Our data suggest that Virkon-S and various bleach concentrations are more effective in reducing prion contamination of meat processing surfaces; however, surface type may also influence the ability of prions to adsorb to surfaces, preventing complete decontamination. Our results will directly inform best practices to prevent the introduction of CWD prions into the human food chain during venison processing. 

Acknowledgement: Funding was provided by the Minnesota Environment and Natural Resources Trust Fund as recommended by the Legislative-Citizen Commission on Minnesota Resources (LCCMR), the Rapid Agriculture Response Fund (#95385/RR257), and the Michigan Department of Natural Resources. 

Theme: Animal prion diseases

=====end
Prion 2023 Detection of CWD prions in plants collected from white-tailed deer farms 

Francisca Bravo Risi1,3, Paulina Soto1,3, Yumeng Huang1 , Tracy A. Nichols4 & Rodrigo Morales1,2* Affiliations: 1 Department of Neurology, The University of Texas Health Science Center at Houston, 6431 Fannin St.,Houston, TX 77030, USA. 2 Centro Integrativo de Biologia y Quimica Aplicada (CIBQA), Universidad Bernardo O’Higgins, Santiago, Chile. 3 Universidad Bernardo O’Higgins, Doctorado en Ciencias con Mención en Materiales Funcionales, General Gana 1702, Santiago, Chile. 4 Veterinary Services Cervid Health Program, United States Department of Agriculture, Animal and Plant Health Inspection Service, Fort Collins, Colorado, 
USA 

Chronic wasting disease (CWD) affects both farmed and free-ranging cervids. Transmission of CWD is thought to occur by direct animal-to-animal contact and by exposure to contaminated environmental fomites. CWD-prion seeding activity has been detected in natural and experimentally-contaminated environmental samples including mineral licks, water sources, dust, manmade surfaces, soils, and plants. Importantly, prion infectivity in some of these samples has been proven. However, whether CWD exposed plants carry prion levels relevant to sustain infectivity has not been tested. 

The aim of this study is to explore if plants collected in a CWD contaminated facility are able to spread prion. 

Materials and Methods: In this study, we optimized the detection of CWD-prions in plants using the protein misfolding cyclic amplification (PMCA). We compared NaPTA pretreatment and direct spiking of the sample into the PMCA reactions. After achieving technical optimizations, we screened multiple plant specimens collected from white-tailed deer breeding facilities displaying variable CWD prevalence. Plants from a site displaying the highest CWD prevalence were tested for infectivity in meadow voles, a co-existing animal species that feed from grass plants. 

Results: Our results demonstrated that CWD-prion detection in plants was optimal when samples were pre-treated with a NaPTA-based protocol. Our screening results showed positive PMCA activity for specimens collected from the farm with the highest CWD prevalence. Although meadow voles were highly susceptible to CWD-prions by intra-cranial administration, consumption of contaminated grass did not induce prion infection in these rodents. 

Conclusions: Pre-PMCA treatment with NaPTA increase the detection of CWD-prionsin vitro in plant specimens. Although the detection of CWD in naturally contaminated vegetation was possible, the amount of prion was apparently low. This was demonstrated by the lack of transmission to meadow voles exposed to these plants. These findings further contribute to understand how CWD prions interact with multiple environmental elements. 

Funded by: NIH and USDA Grant number: 1R01AI132695 and AP20VSSPRS00C143

=====end

PRION 2023 CONTINUED;  


Unforeseen decrease of full-length prion protein in macaques exposed to prion contaminated blood products 

Emmanuel COMOY, Nina JAFFRE, Jérôme DELMOTTE, Jacqueline MIKOL, and Jean Philippe DESLYS Commissariat à l’Energie Atomique, DRF/IBFJ/SEPIA, 18 Route du Panorama, 92265 Fontenay-aux-Roses, France.

Aims: The presence of prion infectivity in blood from patients affected by variant of Creutzfeldt-Jakob disease (v-CJD) questions the risk of its inter-human transmission through transfusion. We have previously described that several cynomolgus macaques experimentally exposed to prion-contaminated blood products developed c-BSE/v-CJD; however, after an exposure to low infectious doses, the vast majority of them developed an unexpected, fatal disease phenotype focused on spinal cord involvement which does not fulfill the classical diagnostic criteria of v-CJD, notably concerning the pathognomonic accumulation of abnormal prion protein. Here we aim to investigate the etiology and physiopathology of this original myelopathy.

Materials and Methods: CNS (brain and spinal cord) samples from myelopathic macaques were tested with different biochemical approaches in comparison to samples derived from either healthy animals or their counterparts exposed to different strains of prion diseases.

Results: Current conventional techniques failed to detect any accumulation of abnormal prion protein (PrPv-CJD) in the CNS of these myelopathic animals. Conversely, in their spinal cord we observed an alteration of their physiological cellular PrP pattern: PrP was not detectable under its full-length classical expression but mainly under its physiological terminal-truncated C1 fragment.

Conclusions: We here confirm the prion origin of this original syndrome, with a very specific biochemical signature linked to changes in PrP at the level of spinal cord lesions: contrary to what is classically described in prion diseases, host PrP is here altered in a form that is abnormally sensitive to degradation by cellular catabolism. This could provide the first experimental evidence of a link between loss of function of the cellular prion protein and the onset of disease. These observations open up new horizons in the field of prion diseases, which has hitherto been limited to pathologies associated with abnormal changes in cellular PrP towards highly structured conformations, with the possibility of unsuspected prion mechanisms/origins in certain neurodegenerative disorders.

Funded by: Financial support for the study was provided by the French National Research Agency (ANR).

Grant number: ANR-10-BLAN-133001 and BIOTECS2010-BloodSecur

Acknowledgement: We specially thank N. Lescoutra, A. Culeux, V. Durand, E. Correia, C. Durand and S. Jacquin for precious technical assistance


Transmission of prion infectivity from CWD-infected macaque tissues to rodent models demonstrates the zoonotic potential of chronic wasting disease

Samia Hannaoui1,2, Ginny Cheng1,2, Wiebke Wemheuer3, Walter Schulz-Schaeffer3, Sabine Gilch1,2, Hermann Schatzl1,2 1University of Calgary, Calgary, Canada. 2Calgary Prion Research Unit, Calgary, Canada. 3Institute of Neuropathology, Medical Faculty, Saarland University, Homburg/Saar, Germany

***> Further passage to cervidized mice revealed transmission with a 100% attack rate.

***> Our findings demonstrate that macaques, considered the best model for the zoonotic potential of prions, were infected upon CWD challenge, including the oral one.

****> The disease manifested as atypical in macaques and initial transgenic mouse transmissions, but with infectivity present at all times, as unveiled in the bank vole model with an unusual tissue tropism.

***> Epidemiologic surveillance of prion disease among cervid hunters and people likely to have consumed venison contaminated with chronic wasting disease

=====


Transmission of Cervid Prions to Humanized Mice Demonstrates the Zoonotic Potential of CWD 

Samia Hannaouia, Irina Zemlyankinaa, Sheng Chun Changa, Maria Immaculata Arifina, Vincent Béringueb, Debbie McKenziec, Hermann M. Schatzla, and Sabine Gilcha 

 Results: Here, we provide the strongest evidence supporting the zoonotic potential of CWD prions, and their possible phenotype in humans. Inoculation of mice expressing human PrPCwith deer CWD isolates (strains Wisc-1 and 116AG) resulted in atypical clinical manifestations in > 75% of the mice, with myoclonus as leading clinical sign. Most of tg650brain homogenates were positive for seeding activity in RT-QuIC. Clinical disease and presentation was transmissible to tg650 mice and bank voles. Intriguingly, protease-resistant PrP in the brain of tg650 mice resembled that found in a familial human prion disease and was transmissible upon passage. Abnormal PrP aggregates upon infection with Wisc-1 were detectable in thalamus, hypothalamus, and midbrain/pons regions. 

 Unprecedented in human prion disease, feces of CWD-inoculated tg650 mice harbored prion seeding activity and infectious prions, as shown by inoculation of bank voles and tg650 with fecal homogenates. 

 Conclusions: This is the first evidence that CWD can infect humans and cause disease with a distinctive clinical presentation, signature, and tropism, which might be transmissible between humans while current diagnostic assays might fail to detect it. These findings have major implications for public health and CWD-management.


The finding that infectious PrPSc was shed in fecal material of CWD-infected humanized mice and induced clinical disease, different tropism, and typical three banding pattern-PrPres in bank voles that is transmissible upon second passage is highly concerning for public health. The fact that this biochemical signature in bank voles resembles that of the Wisc-1 original deer isolate and is different from that of bvWisc-1, in the migration profile and the glyco-form-ratio, is valid evidence that these results are not a product of contamination in our study. If CWD in humans is found to be contagious and transmissible among humans, as it is in cervids [57], the spread of the disease within humans might become endemic.

Transmission of cervid prions to humanized mice demonstrates the zoonotic potential of CWD

Acta Neuropathol 144, 767–784 (2022). https://doi.org/10.1007/s00401-022-02482-9

Published

22 August 2022


Transmission of cervid prions to humanized mice demonstrates the zoonotic potential of CWD

Samia Hannaoui1 · Irina Zemlyankina1 · Sheng Chun Chang1 · Maria Immaculata Arifn1 · Vincent Béringue2 · Debbie McKenzie3 · Hermann M. Schatzl1 · Sabine Gilch1

Accepted: 7 August 2022

HIGHLIGHTS OF THIS STUDY

Our results suggest that CWD might infect humans, although the transmission barrier is likely higher compared to zoonotic transmission of cattle prions. Notably, our data suggest a different clinical presentation, prion signature, and tissue tropism, which causes challenges for detection by current diagnostic assays. Furthermore, the presence of infectious prions in feces is concerning because if this occurs in humans, it is a source for human-to-human transmission. These findings have strong implications for public health and CWD management.

Our results are the first evidence of a zoonotic risk of CWD when using one of the most common CWD strains, Wisc-1/CWD1 for infection. We demonstrated in a human transgenic mouse model that the species barrier for transmission of CWD to humans is not absolute.

Our findings strongly suggest that CWD should be regarded as an actual public health risk. Here, we use humanized mice to show that CWD prions can cross the species barrier to humans, and remarkably, infectious prions can be excreted in feces.

suggesting a potential for human-to-human transmission and a real iatrogenic risk that might be unrecognizable.

If CWD in humans is found to be contagious and transmissible among humans, as it is in cervids [57], the spread of the disease within humans might become endemic.

Supplementary Information The online version contains supplementary material available at 


snip...see full text;



Detection of chronic wasting disease prions in processed meats

Rebeca Benavente1 , Francisca Bravo1,2, J. Hunter Reed3 , Mitch Lockwood3 , Glenn Telling4 , Rodrigo Morales1,2 1 Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA; 2 Universidad Bernardo O’Higgins. Santiago, Chile; 3 Texas Parks and Wildlife Department, Texas, USA. 4 Prion Research Center, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA 

Aims: identify the presence of CWD prions in processed meats derived from elk. 

Materials and Methods: In this study, we analyzed different processed meats derived from a CWD-positive (pre-clinical) free-ranging elk. Products tested included filets, sausages, boneless steaks, burgers, seasoned chili meats, and spiced meats. The presence of CWD-prions in these samples were assessed by PMCA using deer and elk substrates. The same analyses were performed in grilled and boiled meats to evaluate the resistance of the infectious agent to these procedures. 

Results: Our results show positive prion detection in all the samples analyzed using deer and elk substrates. Surprisingly, cooked meats displayed increased seeding activities. This data suggests that CWD-prions are available to people even after meats are processed and cooked. 

Conclusions: These results suggest CWD prions are accessible to humans through meats, even after processing and cooking. Considering the fact that these samples were collected from already processed specimens, the availability of CWD prions to humans is probably underestimated. 

Funded by: NIH and USDA 

Grant number: 1R01AI132695 and APP-20115 to RM 

Acknowledgement: We would like to thank TPWD personnel for providing us with valuable samples

"Our results show positive prion detection in all the samples analyzed using deer and elk substrates. Surprisingly, cooked meats displayed increased seeding activities."

end... 

PRION 2023 CONTINUED; 


''Currently, there is scientific evidence to suggest that CWD has zoonotic potential; however, no confirmed cases of CWD have been found in humans.''

PART 2. TPWD CHAPTER 65. DIVISION 1. CWD

31 TAC §§65.82, 65.85, 65.88

The Texas Parks and Wildlife Commission in a duly noticed meeting on May 25, 2023 adopted amendments to 31 TAC §§65.82, 65.85, and §65.88, concerning Disease Detection and Response, without changes to the proposed text as published in the April 21, 2023, issue of the Texas Register (48 TexReg 2048). The rules will not be republished.

Currently, there is scientific evidence to suggest that CWD has zoonotic potential; however, no confirmed cases of CWD have been found in humans.


17 DETECTION OF CHRONIC WASTING DISEASE PRIONS IN PROCESSED MEATS.

Rebeca Benavente1, Francisca Bravo1,2, Paulina Soto1,2, J. Hunter Reed3, Mitch Lockwood3, Rodrigo Morales1,2

1Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, USA. 2Universidad Bernardo O’Higgins, Santiago, Chile. 3Texas Parks and Wildlife, Austin, USA

Abstract

The zoonotic potential of chronic wasting disease (CWD) remains unknown. Currently, there are no known natural cases of CWD transmission to humans but increasing evidence suggests that the host range of CWD is not confined only to cervid species. Alarmingly, recent experimental evidence suggests that certain CWD isolates can induce disease in non-human primates. While the CDC strongly recommends determining CWD status in animals prior to consumption, this practice is voluntary. Consequently, it is plausible that a proportion of the cervid meat entering the human food chain may be contaminated with CWD. Of additional concern is that traditional diagnostic techniques used to detect CWD have relatively low sensitivity and are only approved for use in tissues other than those typically ingested by humans. In this study, we analyzed different processed meats derived from a pre-clinical, CWD-positive free-ranging elk. Products tested included filets, sausages, boneless steaks, burgers, ham steaks, seasoned chili meats, and spiced meats. CWD-prion presence in these products were assessed by PMCA using deer and elk substrates. Our results show positive prion detection in all products. To confirm the resilience of CWD-prions to traditional cooking methods, we grilled and boiled the meat products and evaluated them for any remnant PMCA seeding activity. Results confirmed the presence of CWD-prions in these meat products suggesting that infectious particles may still be available to people even after cooking. 

Our results strongly suggest ongoing human exposure to CWD-prions and raise significant concerns of zoonotic transmission through ingestion of CWD contaminated meat products.

***> Products tested included filets, sausages, boneless steaks, burgers, ham steaks, seasoned chili meats, and spiced meats.

***> CWD-prion presence in these products were assessed by PMCA using deer and elk substrates.

***> Our results show positive prion detection in all products.

***> Results confirmed the presence of CWD-prions in these meat products suggesting that infectious particles may still be available to people even after cooking.

***> Our results strongly suggest ongoing human exposure to CWD-prions and raise significant concerns of zoonotic transmission through ingestion of CWD contaminated meat products.

=====

9 Carrot plants as potential vectors for CWD transmission.

Paulina Soto1,2, Francisca Bravo-Risi1,2, Claudio Soto1, Rodrigo Morales1,2

1Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, USA. 2Universidad Bernardo O’Higgins, Santiago, Chile

***> We show that edible plant components can absorb prions from CWD-contaminated soils and transport them to their aerial parts.

***> Our results indicate that edible plants could participate as vectors of CWD transmission.

=====

Transmission of prion infectivity from CWD-infected macaque tissues to rodent models demonstrates the zoonotic potential of chronic wasting disease.

Samia Hannaoui1,2, Ginny Cheng1,2, Wiebke Wemheuer3, Walter Schulz-Schaeffer3, Sabine Gilch1,2, Hermann Schatzl1,2 1University of Calgary, Calgary, Canada. 2Calgary Prion Research Unit, Calgary, Canada. 3Institute of Neuropathology, Medical Faculty, Saarland University, Homburg/Saar, Germany

***> Further passage to cervidized mice revealed transmission with a 100% attack rate.

***> Our findings demonstrate that macaques, considered the best model for the zoonotic potential of prions, were infected upon CWD challenge, including the oral one.

****> The disease manifested as atypical in macaques and initial transgenic mouse transmissions, but with infectivity present at all times, as unveiled in the bank vole model with an unusual tissue tropism.

***> Epidemiologic surveillance of prion disease among cervid hunters and people likely to have consumed venison contaminated with chronic wasting disease

=====


FRIDAY, JANUARY 05, 2024 

Texas CWD Cases Mount, 624 documented cases statewide, with 181 cases reported in 2023 alone


spontaneous TSE Prion in any species documented?

not a documented species to date, has had a naturally occurring spontaneous TSE Prion disease been documented. 

***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***


It is interesting to consider the potential virulence in common domestic species in which spontaneous prion diseases have never been reported. 


However, the crucial prediction that a disease-associated PrP mutation can, in fact, spontaneously generate infectivity has never been experimentally demonstrated.


NOW, considering all the factors, IF there was ever a documented case of atypical TSE Prion in any species, especially cattle, cervid, sheep, and so on, that would be the industries worst nightmare i.e. BSE feed ban, surveillance, regulations, and SRM removals etc., would have to therefore be indefinite. 


all iatrogenic cjd is, is sporadic cjd, before the iatrogenic event is discovered, traced back, proven, documented, put into the academic domain, and then finally the public domain, this very seldom happens, thus problem solved, it's all sporadic cjd, PLUS, SPORADIC CJD HAS NOW BEEN LINKED TO ATYPICAL AND TYPICAL BSE, SCRAPIE, AND NOW CWD. ...terry

NOW, again, think cwd, zoonosis to humans as some strain of sporadic cjd exposure, or what about hunters field dressing their deer, cervid, knives, utensils, cutting boards, etc.,  iatrogenic spread, what if?

An investigation has been opened into the death of a scientist who was studying a transmissible and deadly disease CJD in Spain DEGENERATIVE DISEASES

An investigation has been opened into the death of a scientist who was studying a transmissible and deadly disease in Spain 

Three institutions are trying to ascertain the origin of the infectious Creutzfeldt-Jakob disease samples discovered in the biochemist’s laboratory. The 45-year-old investigator died in 2022

The University of Barcelona’s School of Medicine, in L’Hospitalet de Llobregat, where laboratory 4141 is located.

MASSILIANO MINOCRI

Manuel Ansede

MANUEL ANSEDE

Madrid - OCT 19, 2023 - 16:15 EDT

A prestigious Spanish researcher of Creutzfeldt-Jakob disease died last year after experiencing symptoms consistent with this deadly ailment, as EL PAÍS has learned from multiple sources at the three institutions involved. Three months ago, the University of Barcelona opened an internal investigation to ascertain the origin of thousands of unauthorized samples, some of them infectious, discovered in a freezer in its laboratory 4141, where the deceased biochemist worked. He was a member of the Bellvitge Biomedical Research Institute (IDIBELL) and the CIBER public consortium. These two institutions have joined the internal investigation, after noting concern among colleagues at the facility, who did not know the level of risk to which they were exposed without their knowledge. This neurodegenerative disease incubates silently for years, but when symptoms appear — rapid dementia and muscle stiffness — it is fatal. Life expectancy after diagnosis is barely six months. Its best-known animal equivalent is mad cow disease.

The biochemist joined the 4141 lab at the University of Barcelona in January 2018 as a principal investigator with a group of his own; his wife joined shortly after. Together, they identified characteristic substances in human cerebrospinal fluid, useful for the diagnosis of rapid dementia. In November 2020, the now deceased scientist began to feel unwell and asked to leave. After his colleagues found out that his symptoms were consistent with Creutzfeldt-Jakob disease, he demanded absolute privacy and decided to hide his diagnosis, according to the sources consulted for this article. He died at the age of 45.

On December 18, 2020, the head of the 4141 laboratory, Isidre Ferrer, a professor of Pathology at the University of Barcelona and a member of IDIBELL, informed the directors of both institutions that suspicious samples of cerebrospinal fluid from people with Creutzfeldt-Jakob disease and other neurodegenerative types of dementia had been discovered by chance in a freezer at 80 degrees below zero, according to internal documentation to which EL PAÍS had access. The thousands of unauthorized samples from patients and animals were in a drawer reserved for the sick researcher’s group and lacked records indicating their presence. The University of Barcelona then ordered the immediate closure and decontamination of laboratory 4141, located in the School of Medicine at L’Hospitalet de Llobregat.

Doctor Gabriel Capellá, the director of IDIBELL, explains that they have identified “a maximum of eight people” who worked in the laboratory at that time, in addition to the deceased scientist and Isidre Ferrer. Some of these coworkers have required months of psychological care. The university’s safety office and IDIBELL’s prevention service determined that there was “an unacceptable risk,” although Capellá emphasizes that “there is no record of any occupational accident” in which a researcher could have been infected with contaminated material. Creutzfeldt-Jakob disease and other human transmissible spongiform encephalopathies are caused by abnormal proteins called prions, which accumulate in the brain and cause a microscopic sponge-like appearance. There are only one or two cases per million inhabitants, the vast majority of which are of unknown cause, but cases of the disease have also been reported after contact with surgical instruments contaminated by these prions.

The three institutions involved took more than two years to send the suspect samples for analysis to a specialized center, the CIC bioGUNE, in Derio, Spain. A spokeswoman for the University of Barcelona says that they sent them in December 2022 and the three organizations received the results in March 2023. Four months later, in July, the legal departments at the three institutions finally informed the 4141 laboratory workers that the Creutzfeldt-Jakob disease samples were potentially infectious, as feared. “You can debate whether we have been quick [in our response] or not, but we have been transparent. We are [part of] three institutions that had to agree, and we have acted as guarantors,” says Capellá. A similar situation also occurred in France; following the death of a researcher from Creutzfeldt-Jakob in 2019 and the discovery of another suspected case, all public laboratories investigating prion diseases decided to temporarily close in July 2021 to review their protocols.

Laboratory 4141 was not equipped to handle high biohazard samples. It did not even have a biosafety hood. At the end of 2018, the CIBER public consortium signed an agreement so that the group could work with these dangerous samples at the high-security laboratory of the Animal Health Research Center (CReSA) in Bellaterra, Spain, near Barcelona. According to the sources we consulted, there was no reason to have the contaminated material in laboratory 4141, beyond saving time during experiments, since the CReSA bunker is 30 kilometers (about 19 miles) away and required waiting one’s turn to use. Isidre Ferrer, the head of the facility at the time, who has since retired, prefers not to comment on the case until the internal investigation is completed, but he emphasizes that he was unaware of the existence of these dangerous samples.

The IDIBELL director recalls that the deceased scientist was “a promising and brilliant researcher.” From 2013 to 2017, he worked at the University Medical Center of Göttingen (Germany) under neurologist Inga Zerr, a leading international expert in Creutzfeldt-Jakob disease. Physician Margarita Blázquez, who manages the CIBER public consortium, notes that the disease’s incubation period can last several years, so, if the deceased researcher really had it, he also could have become infected with it in Germany or at another of his previous laboratories. This newspaper has tried to contact the scientist’s widow via email but has not received a response. She asked to be discharged shortly after her husband did. The three institutions are now investigating whether the couple handled the dangerous samples without authorization in lab 4141. A third person affiliated with CIBER, a member of the now-deceased biochemist’s research group, worked with potentially infectious Creutzfeldt-Jakob samples without being informed that they were infectious.

The security office of the University of Barcelona believes that the samples would only have been a problem in the case of accidental inoculation or ingestion while handling them. But internal documents confirm the alarm the situation has caused on campus. “The laboratory technicians and investigators express their enormous concern about the fact that, so far, it has not been possible to determine the origin of the doctor’s illness. They are left to worry about whether they may suffer the same fate in a few years’ time as a result of uncontrolled contamination that may have been created in the laboratory,” according to the minutes of a December 22, 2020, meeting between workers and Carles Solsona, the director of the Department of Pathology at the University of Barcelona. “This fear causes them to suffer a state of permanent anguish, causing insomnia and irritability.”

The IDIBELL director sent a message to the center’s entire staff on the 11th, five days after EL PAÍS informed him that it was investigating the case. Gabriel Capellá then told his workers of “a very serious incident that became known on campus for the first time at the end of 2020.″ With “deep dismay,” Capellá announced the researcher’s death “due to a possible prion condition,” with “a possible iatrogenic [a disease acquired by contact with contaminated materials during a medical procedure].” The director also reported finding “potentially dangerous samples” in a freezer. “Our priority is to ensure that this situation is handled rigorously and transparently to limit the damage to the reputation of our institutions,” he said.

Do you have more information about this case or other similar ones? You can write to us at mansede@elpais.es.

Sign up for our weekly newsletter to get more English-language news coverage from EL PAÍS USA Edition


Friendly fire, pass it forward, they call it iatrogenic cjd, or what i call 'tse prion poker', are you all in $$$

all iatrogenic cjd is, is sporadic cjd, before the iatrogenic event is discovered, traced back, proven, documented, put into the academic domain, and then finally the public domain, this very seldom happens, thus problem solved, it's all sporadic cjd...

Direct neural transmission of vCJD/BSE in macaque after finger incision CORRESPONDENCE

Direct neural transmission of vCJD/BSE in macaque after finger incision

Jacqueline Mikol1 · Jérôme Delmotte1 · Dolorès Jouy1 · Elodie Vaysset1 · Charmaine Bastian1 · Jean‑Philippe Deslys1 ·

Emmanuel Comoy1 Received: 10 July 2020 / Revised: 8 September 2020 / Accepted: 25 September 2020 / Published online: 6 October 2020 © The Author(s) 2020

Non-human primates appeared as the closest model to study human iatrogenic prion diseases [14]: we report here the consequences of variant Creutzfeldt–Jakob disease/bovine spongiform encephalopathy (vCJD/BSE) inoculation in a cynomolgus macaque finger, with the demonstration of an original mode of propagation and the practical risk for professional exposure.

The distal right middle finger handpad of a 4-year-old macaque was incised on both lateral sides to induce local inflammation, and then injected with the equivalent of 10 mg of a BSE, orally challenged macaque brain [18]. After an 18 months period of finger clumsiness, the clinical disease (behaviour abnormalities, fear, hyperesthesia, gait disturbances, shaking) began 7.5 years after inoculation and euthanasia took place 2 months later for welfare reasons. Motor conduction velocity of the right median nerve was reduced to one-third of the left counterpart and sensory potential was not detected.

Histological and biochemical studies were performed as previously described. All the elements of the triad were present [7–9]: spongiform change was moderate in neocortex, striatum, brain stem, mild in spinal cord but severe in thalamus and cerebellum; neuronal loss was globally moderate, but severe in cerebellum and sacral spinal cord (vacuolated neurons); gliosis was severe in thalamus, cerebellum and brain stem and moderate elsewhere (Supplementary Fig. 1). ELISA and western blot (WB) showed the expected accumulation of PrPres with BSE glycophoretic pattern at all levels of brain and spinal cord (Supplementary Fig. 2).

In the brain, PrPd deposits were laminar into the cortical deep layers, massive into thalamus, basal ganglia, cerebellum, and brain stem. In spinal cord, PrPd was symmetrically distributed, intense in the Substantia gelatinosa and nucleus dorsal of Clarke while decreased at sacral level. Deposits were diverse into the whole CNS: synaptic, perineuronal, reticular aggregates, mini-plaques, plaques, and incomplete florid plaques. The retinal plexiform layers were labelled (Supplementary Fig. 1i). There were no amyloid or tau deposits.

Unusual PrPd deposits were observed along dendrites, short and long axons, neuritic threads tracing fne networks of straight lines or like strings of pearls (Supplementary Fig. 3). They were present into deep neocortex, basal ganglia, and motoneurons. Such long processes are not frequent but have been reported in human [13] and experimental studies [10, 22]. PrPd deposits were also noted as very mild into striato-pallidal projections, both limbs of internal capsule and fornix (Supplementary Fig. 3). The presence of PrPd in white matter has been reported (Supplementary text 4).

Peripherally, the expected PrPd was undetectable in lymphoid organs, including spleen, through biochemical or immunohistochemical analyses, while prion replication was detected in the peripheral nervous system (PNS): PrPd staining was visualized in many dorsal root ganglia (DRG) but only in nerves innervating the forelimb site of injection (median and ulnar nerves). At the cellular level, PrPd was limited to ganglia and satellite cells in DRG and Schwann cells (Scs) all along nerves whereas axons were never labelled (Fig. 1). Previously, using postmortem immunohistochemical studies (listed in Supplementary text 5), PrPd has been shown in peripheral nervous system in all forms of human neuropathies, albeit more frequently in vCJD, mostly in posterior root nerve fbres at adaxonal location and/or in ganglion and satellite cells. The restricted amount of PrPd was repeatedly underlined but, recently, prion RTQuiC was positive in all nerves examined [2]. PrPd has also been described, frst in scrapie [17] then in BSE, as limited “adaxonal deposits” or/and Sc deposits, with or without DRG cell involvement (review in [4] and Supplementary text 6). Previous studies of the mode of propagation of PrPd have reported variable observations and analyses depending on strains, host species and genotype (Supplementary text 6); the authors discussed the role of the sensory route of trafficking of prions, the modifications of axonal transport, the centrifugal versus centripetal spread of PrPd .

After peripheral infection, accumulation of infectious agent is reputed to occur in lymphoid tissues before direct neuroinvasion [18, 19], even with very little apparent peripheral lymphoreticular deposition [6, 20]. Here, there is no apparent replication/amplification of vCJD/BSE agent in the lymphoid tissues of the exposed macaque. In this model, the neural contamination occurred directly in the highly innervated finger while neuroinvasion appears to occur in Scs along the median nerve to the DRG, with the appearance of the classical labelling of ganglion cells which indicates the onset of the first level of neuronal infection. This model provides direct evidence of the hypothesis of a sequential infection of Scs from the periphery to the CNS, followed by a secondary diffusion into the spinal cord, as already considered by our group [15] and others [1, 3, 11, 12, 21]. It is to note that studies based on intra-sciatic nerve injections in hamsters [16] and transgenic mice [12] had established a rate of transport of infectivity of, respectively, 0.5–2 mm and 0.7 mm per day. This key role of Scs could explain both the low speed of propagation and the discrepancy between the paucity of PrPd into the distal part of the sensory nerves followed by the positivity of DRG, satellite cells and proximal roots.

In conclusion, we have observed that the exposure of a primate to vCJD/BSE through a distal finger lesion induces, after more than 7.5 years of silent incubation, a massive deposit of PrPd , strictly restricted to the nervous system and the eye.

Our data suggest a new type of pure unique peripheral nervous contamination in which the Scs would have a major role in the mode of centripetal progression of PrPd in the peripheral nervous system. Moreover, considering the fact that, recently, “a variant CJD diagnosed 7.5 years after occupational exposure” (cryomicrotomy) in a technician was observed [5], this experimental case report supports the risk linked to professional exposure and reinforces the necessity of adequate measures of prevention. 


Second death in France in a laboratory working on prions

Creutzfeldt-Jakob disease has killed a person who handled this infectious agent at Inrae in Toulouse. After a first death in 2019, a moratorium on work on this pathogen has been extended.

By Hervé Morin

Creutzfeldt-Jakob disease killed a few days ago a retired research technician from the National Research Institute for Agriculture, Food and the Environment (Inrae), who had worked in Toulouse in contact of biological tissue infected with prions. This death sows consternation and concern in the scientific community working with these infectious agents. It follows the death, on June 17, 2019, of Emilie Jaumain, a 33-year-old laboratory technician, suffering from the same incurable neurodegenerative disease. The young woman is said to have contracted it in 2010, cutting herself while handling fragments of the brains of mice infected with prions, in another unit of INRAE, in Jouy-en-Josas.

Computer representation of part of a prion protein on a light micrograph of pyramidal nerve cells (neurons, in black) in the cerebellum of the brain. ALFRED PASIEKA / SCIENCE PHOTO LIBRARY

Regarding the retiree from Toulouse, it will be necessary to determine whether she was the victim of a genetic or sporadic form of Creutzfeldt-Jakob disease, if the disease may have been caused by the ingestion of meat contaminated by the agent of encephalopathy. bovine spongiform (BSE, also called mad cow disease) or, as in the case of Emilie Jaumain, if accidental occupational exposure can be claimed. Prion diseases are caused by proteins taking an aberrant conformation, which gives them the property of replicating to form aggregates that are deleterious for neurons. There are around 150 cases per year in France, resulting in fatal degeneration of the central nervous system.


Temporary suspension of work on prions in French public research laboratories

PRESS RELEASE - The general directorates of ANSES, CEA, CNRS, INRAE ​​and Inserm, have decided jointly and in agreement with the Ministry of Higher Education, Research and Innovation to suspend as a precaution all their research and experimentation work relating to prion diseases, for a period of three months.

This precautionary measure is motivated by the knowledge of a possible new case of a person suffering from Creutzfeldt-Jakob disease and who worked in a laboratory for research on prions.

Posted on July 27, 2021

The suspension period put in place as of this day will make it possible to study the possibility of a link between the observed case and the person's former professional activity and to adapt, if necessary, the preventive measures in force in the research laboratories. 

The person with Creutzfeldt-Jakob disease (CJD)1, whose form is not yet known, is a retired INRAE ​​agent. This could be the second case of infectious CJD affecting a scientist who worked on prions, after that of an assistant engineer who died of the disease in 2019, and who was injured in 2010 during of an experiment.

Following this death, a general inspection mission was launched in July 2019 by the ministries of research and agriculture with French laboratories handling prions. Submitted in October 2020, the report concluded on the regulatory compliance of the laboratories visited as well as the presence of a risk control culture within the research teams.

Research around prion proteins, with high public health issues, allows major advances in the understanding of the functioning of these infectious pathogens, and contributes to results that are transferable to other related degenerative diseases such as Alzheimer's and Alzheimer's diseases. Parkinson's.

At the level of each establishment, regular and transparent information will be provided to all the working communities concerned by this measure.

1 The disease Creutzfeldt-Jakob disease (CJD) is one of prion diseases - still called encephalopathies subacute spongiform transmitted(TSE) - of diseases rare, characterized by a degeneration rapid and fatal the system nervous central. They are caused by the accumulation in the brain of a normally expressed protein but poorly conformed - the prion protein - which leads to the formation of deleterious aggregates for neurons. For now , no treatment will allow to change the course of these diseases. It can be of origin sporadic , form the most frequent , original genetic or finally to form infectious following a contamination. 



France issues moratorium on prion research after fatal brain disease strikes two lab workers

By Barbara CasassusJul. 28, 2021 , 4:35 AM

PARIS—Five public research institutions in France have imposed a 3-month moratorium on the study of prions—a class of misfolding, infectious proteins that cause fatal brain diseases—after a retired lab worker who handled prions in the past was diagnosed with Creutzfeldt-Jakob disease (CJD), the most common prion disease in humans. An investigation is underway to find out whether the patient, who worked at a lab run by the National Research Institute for Agriculture, Food and Environment (INRAE), contracted the disease on the job.

If so, it would be the second such case in France in the past few years. In June 2019, an INRAE lab worker named Émilie Jaumain died at age 33, 10 years after pricking her thumb during an experiment with prion-infected mice. Her family is now suing INRAE for manslaughter and endangering life; her illness had already led to tightened safety measures at French prion labs.

The aim of the moratorium, which affects nine labs, is to “study the possibility of a link with the [new patient’s] former professional activity and if necessary to adapt the preventative measures in force in research laboratories,” according to a joint press release issued by the five institutions yesterday.

“This is the right way to go in the circumstances,” says Ronald Melki, a structural biologist at a prion lab jointly operated by the French national research agency CNRS and the French Alternative Energies and Atomic Energy Commission (CEA). “It is always wise to ask questions about the whole working process when something goes wrong.” "The occurrence of these harsh diseases in two of our scientific colleagues clearly affects the whole prion community, which is a small 'familial' community of less than 1000 people worldwide," Emmanuel Comoy, deputy director of CEA's Unit of Prion Disorders and Related Infectious Agents, writes in an email to Science. Although prion research already has strict safety protocols, "it necessarily reinforces the awareness of the risk linked to these infectious agents," he says.

In Jaumain’s case, there is little doubt she was infected on the job, according to a paper published in The New England Journal of Medicine (NEJM) in 2020. She had variant CJD (vCJD), a form typically caused by eating beef contaminated with bovine spongiform encephalopathy (BSE), or mad cow disease. But Europe’s BSE outbreak ended after 2000 and vCJD virtually disappeared; the chance that someone of Jaumain’s age in France would contract food-borne vCJD is “negligible or non-existent,” according to the paper.

A scientist with inside knowledge says the new patient, a woman who worked at INRAE’s Host-Pathogen Interactions and Immunity group in Toulouse, is still alive. French authorities were apparently alerted to her diagnosis late last week. The press release suggests it’s not yet clear whether the new case is vCJD or “classic” CJD, which is not known to be caused by prions from animals. Classic CJD strikes an estimated one person per million. Some 80% of cases are sporadic, meaning they have no known cause, but others are genetic or contracted from infected human tissues during transplantations. The two types of CJD can only be distinguished through a postmortem examination of brain tissue.

Lab infections are known to occur with many pathogens, but exposure to CJD-causing prions is unusually risky because there are no vaccines or treatments and the condition is universally fatal. And whereas most infections reveal themselves within days or weeks, CJD’s average incubation period is about 10 years.

For Jaumain, who worked at INRAE’s Molecular Virology and Immunology Unit in Jouy-en-Josas, outside Paris, that long period of uncertainty began on 31 May 2010, when she stabbed her left thumb with a curved forceps while cleaning a cryostat—a machine that can cut tissues at very low temperatures—that she used to slice brain sections from transgenic mice infected with a sheep-adapted form of BSE. She pierced two layers of latex gloves and drew blood. “Émilie started worrying about the accident as soon as it had happened, and mentioned it to every doctor she saw,” says her widower, Armel Houel.

In November 2017, Jaumain developed a burning pain in her right shoulder and neck that worsened and spread to the right half of her body over the following 6 months, according to the NEJM paper. In January 2019, she became depressed and anxious, suffering memory impairment and hallucinations. “It was a descent into hell,” Houel says. She was diagnosed with “probable vCJD” in mid-March of that year and died 3 months later. A postmortem confirmed the diagnosis.

“The occurrence of these harsh diseases in two of our scientific colleagues clearly affects the whole prion community.” Emmanuel Comoy, French Alternative Energies and Atomic Energy Commission

INRAE only recently admitted the likely link between Jaumain’s illness and the accident. “We recognize, without ambiguity, the hypothesis of a correlation between Emilie Jaumain-Houel’s accident … and her infection with vCJD,” INRAE chair and CEO Philippe Mauguin wrote in a 24 June letter to an association created by friends and colleagues to publicize Jaumain’s case and lobby for improvements in lab safety. (Science has obtained a copy of the letter, which has not been made public.)

Jaumain’s family has filed both criminal charges and an administrative suit against INRAE, alleging a range of problems at Jaumain’s lab. She had not been trained in handling dangerous prions or responding to accidents and did not wear both metal mesh and surgical gloves, as she was supposed to, says Julien Bensimhon, the family’s lawyer. The thumb should have been soaked in a bleach solution immediately, which did not happen, Bensimhon adds.

Independent reports by a company specializing in occupational safety and by government inspectors have found no safety violations at the lab; one of them said there was a “strong culture” of risk management. (Bensimhon calls the reports “biased.”)

The government inspectors’ report concluded that Jaumain’s accident was not unique, however. There had been at least 17 accidents among the 100 or so scientists and technicians in France working with prions in the previous decade, five of whom stabbed or cut themselves with contaminated syringes or blades. Another technician at the same lab had a fingerprick accident with prions in 2005, but has not developed vCJD symptoms so far, Bensimhon says. “It is shocking that no precautionary measures were taken then to ensure such an accident never happened again,” he says.

In Italy, too, the last person to die of vCJD, in 2016, was a lab worker with exposure to prion-infected brain tissue, according to last year’s NEJM paper, although an investigation did not find evidence of a lab accident. That patient and the lab they worked at have not been identified.

After Jaumain’s diagnosis, “We contacted all the research prion labs in France to suggest they check their safety procedures and remind staff about the importance of respecting them,” says Stéphane Haïk, a neuroscientist at the Paris Brain Institute at Pitié-Salpêtrière Hospital who helped diagnose Jaumain and is the corresponding author on the paper. Many labs tightened procedures, according to the government inspectors' report, for instance by introducing plastic scissors and scalpels, which are disposable and less sharp, and bite and cut-resistant gloves. A team of experts from the five research agencies is due to submit proposals for a guide to good practice in prion research to the French government at the end of this year.

The scientific community has long recognized that handling prions is dangerous and an occupational risk for neuropathologists, says neuropathologist Adriano Aguzzi of the University of Zurich. Aguzzi declined to comment on the French CJD cases, but told Science his lab never handles human or bovine prions for research purposes, only for diagnostics. “We conduct research only on mouse-adapted sheep prions, which have never been shown to be infectious to humans,” Aguzzi says. In a 2011 paper, his team reported that prions can spread through aerosols, at least in mice, which “may warrant re-thinking on prion biosafety guidelines in research and diagnostic laboratories,” they wrote. Aguzzi says he was “totally shocked” by the finding and introduced safety measures to prevent aerosol spread at his own lab, but the paper drew little attention elsewhere.

The moratorium will "obviously" cause delays in research, but given the very long incubation periods in prion diseases, the impact of a 3-month hiatus will be limited, Comoy says. His research team at CEA also works on other neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, and will shift some of its efforts to those.

Although Jaumain’s diagnosis upset many in the field, it hasn't led to an exodus among researchers in France, Haïk says: “I know of only one person who resigned because they were so worried.”

With reporting by Martin Enserink.

Posted in: EuropeHealthScientific Community

doi:10.1126/science.abl6587


Variant Creutzfeldt–Jakob Disease Diagnosed 7.5 Years after Occupational Exposure

Variant Creutzfeldt–Jakob disease was identified in a technician who had cut her thumb while handling brain sections of mice infected with adapted BSE 7.5 years earlier. The long incubation period was similar to that of the transfusion-transmitted form of the disease.

Variant Creutzfeldt–Jakob Disease Diagnosed 7.5 Years after Occupational Exposure

TO THE EDITOR:

We report a case of variant Creutzfeldt–Jakob disease (CJD) that was plausibly related to accidental occupational exposure in a technician who had handled murine samples contaminated with the agent that causes bovine spongiform encephalopathy (BSE) 7.5 years earlier.

In May 2010, when the patient was 24 years of age, she worked in a prion research laboratory, where she handled frozen sections of brain of transgenic mice that overexpressed the human prion protein with methionine at codon 129. The mice had been infected with a sheep-adapted form of BSE. During this process, she stabbed her thumb through a double pair of latex gloves with the sharp ends of a curved forceps used to handle the samples. Bleeding was noted at the puncture site.

In November 2017, she began having burning pain in the right shoulder and neck. The pain worsened and spread to the right half of her body during the following 6 months. In November 2018, an examination of a sample of cerebrospinal fluid (CSF) obtained from the patient was normal. Magnetic resonance imaging (MRI) of the brain showed a slight increase in the fluid-attenuated inversion recovery (FLAIR) signal in the caudates and thalami (Fig. S1A and S1B in the Supplementary Appendix, available with the full text of this letter at NEJM.org). In January 2019, she became depressed and anxious and had memory impairment and visual hallucinations. There was hypertonia on the right side of her body. At that time, an analysis of CSF for 14-3-3 protein was negative. In March 2019, MRI showed an increased FLAIR signal in pulvinar and dorsomedial nuclei of thalami (Fig. S1C through S1E).

Figure 1.

Detection of Abnormal Prion Protein in Biologic Fluid Samples and Postmortem Findings.

The patient was found to be homozygous for methionine at codon 129 of the prion protein gene without mutation. An analysis of a sample of CSF on real-time quaking-induced conversion analysis was negative for a diagnosis of sporadic CJD. However, an analysis of plasma and CSF by means of protein misfolding cyclic amplification was positive for the diagnosis of variant CJD (Figure 1A and 1B). The patient died 19 months after the onset of symptoms. Neuropathological examination confirmed the diagnosis of variant CJD (Figure 1C and 1D). Western blot analysis showed the presence of type 2B protease-resistant prion protein in all sampled brain areas. The clinical characteristics of the patient and the postmortem neuropathological features were similar to those observed in 27 patients with variant CJD who had previously been reported in France.1 (Additional details are provided in the Supplementary Appendix.)

There are two potential explanations for this patient’s condition. Oral transmission from contaminated cattle products cannot be ruled out because the patient was born at the beginning of the French BSE outbreak in cattle. However, the last two patients who had confirmed variant CJD with methionine homozygosity at codon 129 in France and the United Kingdom died in 2014 and 2013, respectively, which makes oral transmission unlikely. In France, the risk of variant CJD in 2019 was negligible or nonexistent in the post-1969 birth cohort.2

Percutaneous exposure to prion-contaminated material is plausible in this patient, since the prion strain that she had handled was consistent with the development of variant CJD.3 The 7.5-year delay between the laboratory accident and her clinical symptoms is congruent with the incubation period in the transfusion-transmitted form of the disease. The ability of this strain to propagate through the peripheral route has been documented, and experimental studies with scrapie strains have shown that scarification and subcutaneous inoculation are effective routes.4,5 The last known Italian patient with variant CJD, who died in 2016, had had occupational contact with BSE-infected brain tissues, although subsequent investigation did not disclose a laboratory accident (Pocchiari M, Italian Registry of CJD: personal communication). Thus, the last two cases of variant CJD outside the United Kingdom have been associated with potential occupational exposure. Such cases highlight the need for improvements in the prevention of transmission of variant CJD and other prions that can affect humans in the laboratory and neurosurgery settings, as outlined in the Supplementary Appendix.

Jean-Philippe Brandel, M.D. Assistance Publique–Hôpitaux de Paris, Paris, France

M. Bustuchina Vlaicu, M.D. Groupe Hospitalier Nord-Essonne, Orsay, France

Audrey Culeux, B.Sc. INSERM Unité 1127, Paris, France

Maxime Belondrade, M.Sc. Daisy Bougard, Ph.D. Etablissement Français du Sang, Montpellier, France

Katarina Grznarova, Ph.D. Angeline Denouel, M.Sc. INSERM Unité 1127, Paris, France

Isabelle Plu, M.D. Elodie Bouaziz-Amar, Pharm.D., Ph.D. Danielle Seilhean, M.D., Ph.D. Assistance Publique–Hôpitaux de Paris, Paris, France

Michèle Levasseur, M.D. Groupe Hospitalier Nord-Essonne, Orsay, France

Stéphane Haïk, M.D., Ph.D. INSERM Unité 1127, Paris, France stephane.haik@upmc.fr

Supported by a grant (ANR-10-IAIHU-06) from Programme d’Investissements d’Avenir and Santé Publique France.

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

5 References

July 2, 2020

N Engl J Med 2020; 383:83-85

DOI: 10.1056/NEJMc2000687

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Friday, October 20, 2023

An investigation has been opened into the death of a scientist who was studying a transmissible and deadly disease CJD in Spain


February 14, 2001

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

Terry S. Singeltary, Sr

Author Affiliations

JAMA. 2001;285(6):733-734. doi:10-1001/pubs.JAMA-ISSN-0098-7484-285-6-jlt0214 

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.


PLEASE NOTE, CJD IS NOW 1 IN 5,000 GLOBALLY, COLLINGE ET AL 2023!

Professor John Collinge on tackling prion diseases, sCJD accounts for around 1 in 5000 deaths worldwide

MONDAY, SEPTEMBER 11, 2023 

Professor John Collinge on tackling prion diseases “The best-known human prion disease is sporadic Creutzfeldt-Jakob disease (sCJD), a rapidly progressive dementia which accounts for around 1 in 5000 deaths worldwide.” There is accumulating evidence also for iatrogenic AD. Understanding prion biology, and in particular how propagation of prions leads to neurodegeneration, is therefore of central research importance in medicine.



MONDAY, DECEMBER 18, 2023

Change in Epidemiology of Creutzfeldt-Jakob Disease in the US, 2007-2020


TUESDAY, DECEMBER 12, 2023 

CREUTZFELDT JAKOB DISEASE TSE PRION DISEASE UPDATE USA DECEMBER 2023 


GOOD LUCK!

wasted days and wasted nights...FREDDY FENDER

Terry S. Singeltary Sr. flounder9@verizon.net

posted by Terry S. Singeltary Sr. at 2:54 PM 0 Comments