Research Editorial
Do we need to explain the occurrence of atypical scrapie?
Giuseppe Ru, DVM, PhD, MSE, Head of BEAR Author affiliations http://dx.doi.org/10.1136/vr.j1893
Statistics from Altmetric.com No Altmetric data available for this article. WHY do diseases occur? A recent paper by Tomasetti and colleagues (2017) tries to provide new evidence in support of their hypothesis that most cancers may be accounted for by mutations due to unpredictable, random mistakes made during normal DNA replication in the division of normal stem cells (somatic mutations) (Tomasetti and Vogelstein 2015). They suggest that other mutations that arise due to environmental or heredity factors may only play a minor role. The debate on this issue is still open while the media translated the hypothesis into the concept of ‘bad luck’.
As highlighted in a Centers for Disease Control and Prevention (CDC) reference manual, ‘epidemiologists assume that illness does not occur randomly in a population, but happens only when the right accumulation of risk factors or determinants exists in an individual’ (CDC 2011). The same assumption should also hold when applied to transmissible spongiform encephalopathies (TSEs), whose origin and causes are not obvious. That is the case for sporadic Creutzfeldt Jakob disease (CJD) in humans or for livestock TSEs other than classical bovine spongiform encephalopathy (BSE) or scrapie. Let's take a step back.
During the 1990s, at the peak of the BSE epidemic in the UK, the possibility that the disease might have spread into the small ruminant population led to renewed attention to surveillance for scrapie. Although scrapie had been known since the 18th century, the real distribution of the disease was not clear. Therefore, throughout Europe, passive surveillance targeting sheep …
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Due to limitations in the ability to detect field cases, it has been suggested that the available figures of prevalence and circulation of AS are likely underestimated (Andreoletti et al., 2011, Simmons et al., 2011) as is the potential for its recycling e.g. into feed and food chains. Therefore, investigations of AS, such as that published in this issue, are of the utmost importance for identifying still unknown risk factors, and to inform effective preventive strategies - without surrendering to the idea of “bad luck”.
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Due to limitations in the ability to detect field cases, it has been suggested that the available figures of prevalence and circulation of AS are likely underestimated (Andreoletti et al., 2011, Simmons et al., 2011) as is the potential for its recycling e.g. into feed and food chains. Therefore, investigations of AS, such as that published in this issue, are of the utmost importance for identifying still unknown risk factors, and to inform effective preventive strategies - without surrendering to the idea of “bad luck”.
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Determinants
Determinant: any factor, whether event, characteristic, or other definable entity, that brings about a change in a health condition or other defined characteristic.
Epidemiology is also used to search for determinants, which are the causes and other factors that influence the occurrence of disease and other health-related events. Epidemiologists assume that illness does not occur randomly in a population, but happens only when the right accumulation of risk factors or determinants exists in an individual. To search for these determinants, epidemiologists use analytic epidemiology or epidemiologic studies to provide the “Why” and “How” of such events. They assess whether groups with different rates of disease differ in their demographic characteristics, genetic or immunologic make-up, behaviors, environmental exposures, or other so-called potential risk factors. Ideally, the findings provide sufficient evidence to direct prompt and effective public health control and prevention measures.
> Do we need to explain the occurrence of atypical scrapie?
ABSOLUTELY !!!
what the OIE and the USDA et al did by deregulating atypical scrapie and making it a legal trading commodity knowing that it was transmissible should be criminal in my opinion.
not having access to the full text paper is difficult for me to reply, but here are my reasons why the atypical scrapie i.e. Nor-98 or any other atypical scrapie should be in the same risk category as all the rest of the TSE Prion disease...
HERE'S WHY;
''Epidemiological studies indicate that Nor98-like scrapie is either not transmissible or poorly transmissible under natural conditions. Further, the World Organization for Animal Health (OIE) has determined that Nor98-like scrapie is distinct from classical scrapie and is not a listed disease of trade concern. Animals in Nor98-like scrapie infected flocks are not removed and are free to move once they have been officially identified.''
CAN YOU SAY USDA, OIE, TRADE AND MONEY $$$
J Vet Med Sci. 2016 Oct; 78(10): 1619–1624. Published online 2016 Jun 20. doi: 10.1292/jvms.16-0259 PMCID: PMC5095634
Transmission of atypical scrapie to homozygous ARQ sheep
Hiroyuki OKADA,1,* Kohtaro MIYAZAWA,1 Morikazu IMAMURA,1 Yoshifumi IWAMARU,1 Kentaro MASUJIN,1 Yuichi MATSUURA,1 and Takashi YOKOYAMA1
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In this study, the estimated infectivity level in skeletal muscle and lymphoid tissues from animals (n = 4) affected with two different classical scrapie isolates did reach up to 1/10 (weight/weight) of the infectivity found in the CNS from terminally affected sheep. These values are higher than those expected from previous work. This could be explained by the fact that previously available data on prion quantities in peripheral tissues of small ruminants (in particular those related to striated muscle) relied on biochemical measurement of PrPScamount [26] and the cell types accumulating PrPSc and the composition of these tissues may have impact on the PrPSc recovery yield. Also, if in some classical scrapie cases a 3–4 log10 infectivity difference was reported between CNS and some lymphoid tissues using bioassay in conventional mice, in other classical scrapie cases, the same study reported that infectivity in lymphoid tissue was only 1 to 10 fold lower than in CNS [27].
The classical scrapie cases that were investigated in this work cannot be assumed to be representative of all field diversity as only four animal cases of highly susceptible genotypes were used. However, the results indicate that exposure risk to such TSE agents through the unrestricted entry in the food chain of potentially infectious tissues would be significantly higher than previously thought.
In most countries, the identification of Atypical/Nor98 scrapie was a consequence of the implementation of an active surveillance for TSE consisting in random testing for PrPScpresence in brainstem of a fraction of fallen or healthy culled small ruminants [10]. In Atypical/Nor98 scrapie cases, the sensitivity of PrPSc detection tests that are used for initial field screening or confirmation of TSE cases is debated. Several authors reported failure to detect PrPSc in some CNS areas like the obex area [5], [6], [20] from known affected animals or discrepancies in results when applying different diagnostic tests to a same sample [6], [10].
The results obtained in this study by comparing the analytical sensitivity of biochemical PrPScdetection (using an OIE registered WB method and a validated rapid screening test for TSE detection, in small ruminants) and bioassay indicated that CNS samples that would contain up to 107.4.–107.7 ID50/g of Atypical/Nor98 scrapie (according to tg338 IC bioassay) could remain negative for PrPSc detection. In field, Atypical/Nor98 scrapie cases (Table 1) PrPSc positive WB was observed in CNS samples in which infectious titre was estimated (on the basis of incubation period) to be higher than 105.8 ID50/g IC in tg338. Such discrepancies might reflect an individual variability of the PrPSc WB detection limits between atypical scrapie cases. It might alternatively be the consequence of a relative imprecision in estimating the titre of low infectious doses by the incubation period bioassay method.
In contrast to Atypical/Nor98 scrapie cases, using two different classical agents the WB PrPScdetection sensitivity limit was about 102 ID50 IC in tg338 (ie a tissue with a titre of 103.7 ID50/g IC in tg338). These differences strongly support the contention that diagnostic assays based on PrPSc detection have lower performance for identifying Atypical/Nor98 scrapie cases than classical scrapie cases. It is consequently highly probable that a significant number of Atypical/Nor98 cases remain undetected by field testing, leading to an underestimation of Atypical/Nor98 scrapie prevalence in the small ruminant population. It is however not possible on the sole basis of this study to evaluate the importance of such underestimation.
The under detection of Atypical/Nor98 scrapie in the field due to the sensitivity of the current PrPSc based approach would also impact on understanding of the biology of this TSE agent.
While under natural conditions, classical scrapie is known to transmit between individuals, the analysis of data collected through the active TSE surveillance program seemed to indicate that Atypical/Nor98 scrapie could be poorly or not transmissible at all. This is based on the lack of statistical difference of the observed Atypical/Nor98 frequencies between the general population and the flocks where a positive case had been identified [38], [39]. The lower ability to detect Atypical Scrapie incubating animals using the PrPSc based methodologies means that this conclusion should be considered with caution.
Atypical/Nor98 cases are identified in older animals in comparison to classical scrapie [6], [40]. The lack of PrPSc detection in peripheral tissues of reported cases suggested that Atypical/Nor98 scrapie agent could be restricted to CNS. This is supportive of the hypothesis that Atypical/Nor98 scrapie could be a spontaneous disorder of PrP folding and metabolism occurring in aged animals without external cause [6], [38].
However, this hypothesis is questioned by the evidence reported here that a negative PrPSctesting result could be observed in animals harbouring high infectious titre in their brain and that the infectious agent can be present in peripheral tissues of Atypical/Nor98 scrapie incubating sheep. TSE are considered to be transmitted following oral exposure; initial uptake is followed by a peripheral replication phase which is generally associated with a dissemination of the agent in the lymphoid system and the deposition of large amounts of PrPSc. This peripheral replication phase is later followed by the entry of the infectious agent into the CNS through the autonomic nervous system [25], [27], [35], [36]. However, in several situations, like BSE in cattle [41], [42], [43] or classical scrapie in ARR heterozygote sheep [44], [45], the involvement of secondary lymphoid system is marginal, which does not preclude central neuro-invasion through the autonomic nervous system [46]. It could be proposed that Atypical Scrapie/Nor98 might occur following oral exposure to a TSE agent, which would spread marginally in lymphoid tissues before neuro-invasion. The slow propagation of Atypical Scrapie/Nor98 in its host (long incubation period) and the impaired detection sensitivity level of PrPSc based assays would explain the apparent old age of detected cases.
The results presented here are insufficient to rule out the hypothesis of a spontaneous/non contagious disorder or to consider this alternative scenario as a plausible hypothesis. Indeed, the presence of Atypical scrapie/Nor98 infectivity in peripheral tissues could be alternatively due to the centripetal spreading of the agent from the CNS. However, our findings point out that further clarifications on Atypical/Nor98 scrapie agent biology are needed before accepting that this TSE is a spontaneous and non contagious disorder of small ruminants. Assessing Atypical/Nor98 scrapie transmissibility through oral route in natural host and presence in placenta and in colostrum/milk (which are considered as major sources for TSE transmission between small ruminants) [28], [32] will provide crucial data.
The presence of infectivity in peripheral tissues that enter the food chain clearly indicates that the risk of dietary exposure to Atypical/Nor98 scrapie cannot be disregarded. However, according to our observations, in comparison to the brain, the infectious titres in the peripheral tissues were five log10 lower in Atypical/Nor98 scrapie than in classical scrapie. Therefore, the reduction of the relative exposure risk following SRM removal (CNS, head, spleen and ileum) is probably significantly higher in Atypical/Nor98 scrapie cases than in classical scrapie cases. However, considering the currently estimated prevalence of Atypical/Nor98 scrapie in healthy slaughtered EU population [10], it is probable that atypical scrapie infectivity enters in the food chain despite the prevention measures in force.
Finally, the capacity of Atypical/Nor98 scrapie agent (and more generally of small ruminants TSE agents) to cross species barrier that naturally limits the transmission risk is insufficiently documented. Recently, the transmission of an Atypical/Nor98 scrapie isolate was reported into transgenic mice over-expressing the porcine PrP [47]. Such results cannot directly be extrapolated to natural exposure conditions and natural hosts. However, they underline the urgent need for further investigations on the potential capacity of Atypical/Nor98 scrapie to propagate in other species than small ruminants.
Porcine prion protein amyloid and Nor-98 atypical Scrapie
Porcine prion protein amyloid
Per Hammarström & Sofie Nyström Pages 266-277 | Received 01 Jun 2015, Accepted 17 Jun 2015, Accepted author version posted online: 28 Jul 2015, Published online: 28 Jul 2015
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On the other hand, Nor98 scrapie (Atypical scrapie) as well as BSE from both cattle and BoTg mouse model resulted in clinical disease in the PoTg001 mice. However, in the first generation, disease progression was FIGURE 3. Schematic model of prion strain adaptation. (Model adapted from Collinge and Clarke 2007 and Sandberg et al 2011, 2013.31,49,50) The red horizontal line indicates the tolerance threshold for prion toxicity for the respective model, the green vertical line indicates normal lifespan/experimental termination for the mice. The black curves indicate increase in prion titer over time upon prion inoculation. (a) BSE and classical scrapie in wild type mice according to Bruce et al.23 (b) BSE, classical scrapie and Nor98 scarpie in PoTg001 mice according to Espinosa, Torres et al. (2009, 2014).25,26 270 Hammarstrom and Nystr € om€ slow. Incubation time until death was as long as 600 d and the hit rate was low. This indicates that disease has barely developed by the time the mice reach their natural life span limit which in this study was set to 650 d Already in the second passage the hit rate was 100 % and the incubation time was cut in half (Fig. 3b). No further shortening of incubation time was observed upon third passage. This shows that PoPrP is capable of forming infectious and neurotoxic prions in vivo if triggered by a compatible prion strain and if given enough time to develop. Both BSE and Nor98 rapidly adapts to the PoPrP host sequence, resulting in higher penetrance as well as in markedly shorter life span already in the second passage, well within the limits of normal life span for a mouse.
It is known that prion strains need time and serial passages to adapt. Knowing that pigs in modern farming are rarely kept for enough time for clinical signs to emerge in prion infected pigs it is important to be vigilant if there is a sporadic porcine spongiform encephalopathy (PSE) as has been seen in cattle (BASE) and sheep (Nor98). Hypothetically such a sporadic and then infectious event could further adapt and over a few generations have reached the point where clinical PSE is established within the time frame where pigs are being slaughtered for human consumption (Fig. 4). USE OF MATERIALS DERIVED FROM PIG IN VIEW OF PORCINE PrP AMYLOID The pig is the most versatile species used by humans for food and other applications. Over 1,5 billion pigs are slaughtered each year worldwide for human use.32 Besides juicy pork sirloin other parts from pig are used for making remarkably diverse things such as musical instruments, china, leather, explosives, lubricants etc. Pig offal is used for human medicine, e.g., hormone preparations such as insulin and cerebrolysin, in xenographs, sutures, heparin and in gelatin for drug capsules.33,34
http:// http://www.tandfonline.com/doi/full/10.1080/19336896.2015.1065373
indeed, the spontaneous/sporadic is a term used to deceive sometimes. if you look at pubmed and search sporadic or spontaneous, you get many hits;
indeed, the spontaneous/sporadic is a term used to deceive sometimes. if you look at pubmed and search sporadic or spontaneous, you get many hits;
spontaneous 301466 hits for different disease and reasons...
sporadic
49879 hits for different disease and reasons...
85%+ of all human prion disease i.e. sporadic, do not happen spontaneously or sporadically in terms corporate and officials use them. i know, you know, but many folks take that to the bank as fact, and it's just 'fake news'.
fact is, they don't know, and that's the bottom line. same with atypical scrapie, atypical bse, atypical cwd, and atypical human tse prion, and there is a wide variety of names they are tying to pawn off the simple fact they are Transmissible Spongiform Encephalopathy TSE Prion disease. and now we know that science have linked all of the above to sporadic CJD. to continue this charade of the sporadic, sporadic, nvCJD only theory, will only continue to deceive the public further, it will never change the science, and the people will eventually find out, they always do, science will prevail in the end...
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.
Title: 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.
SPONTANEOUS ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY
***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.***
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.
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R. BRADLEY
Like lambs to the slaughter
* 31 March 2001 * Debora MacKenzie * Magazine issue 2284
Suspect symptoms
What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?
Exclusive from New Scientist magazine
Four years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.
Photo: Murdo McLeod
Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise.
He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris.
Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.
Brain damage
Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.
Deslys and colleagues were originally studying vCJD, not sCJD. They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.
As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain.
As expected, they all affected the brain in a different way from BSE and vCJD. But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology.
Multiple strains
"The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys.
"You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie," she says. In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar.
But there are more than 20 strains of scrapie, and six of sCJD. "You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys. Bruce is cautious about the mouse results, but agrees they require further investigation. Other trials of scrapie and sCJD in mice, she says, are in progress.
Deformed proteins
People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD.
But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD. "If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection."
There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain.
Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.
Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.
More at: Proceedings of the National Academy of Sciences (vol 98, p 4142)
http://www.pnas.org/cgi/content/full/041490898v1
Correspondence about this story should be directed to letters@newscientist.com
1900 GMT, 28 March 2001
* New Scientist http://www.newscientist.com/dailynews/news.jsp?id=ns9999560
http://www.newscientist.com/article.ns?id=mg16922840.300
FSA 06/06/03 AGENDA 3.1, 15 JUNE 2006
ATYPICAL SCRAPIE IN SMALL RUMINANTS: CONSIDERATION OF THE
CURRENT PRECAUTIONARY RISK MANAGEMENT MEASURES
Executive Summary
1. This paper provides information on atypical scrapie (a transmissible spongiform
encephalopathy (TSE)) in sheep and goats and the precautionary measures
currently in place to protect consumers from the possible risks from TSEs in
these species. There are a great many unknowns about atypical scrapie,
including the potential implications, if any, for human health.
2. It also reports on the views of stakeholders and consumer focus groups who
were asked whether, in the light of this uncertainty, additional precautionary
measures were needed and for their views on the Agency’s advice on this
subject.
3. The Board is asked to:
• note that the Agency’s advice has been reworded to take account of the views
of stakeholders and the consumer focus groups and will be tested further
• note that the background information on sheep TSEs on the Agency’s website
will be reviewed
• note that the agricultural departments are planning to review the Ram
Genotyping Scheme
• note that surveillance for atypical scrapie will be maintained in order to detect
any changes in prevalence.
• agree that the Agency’s advice and recommendations on precautionary
measures should be kept under review and be brought back to the Board if
there are significant changes in the understanding of the risk.
• agree that developments on atypical scrapie be kept under review to enable
contingency policy to be refined as new information emerges.
• agree that the Agency should open discussions with the European
Commission on the issue of the identification of meat from older sheep or
goats and natural sausage casings made from sheep intestines to enable
consumer choice.
2
TSE DIVISION
Contacts:
Alison Gleadle Tel: 020 7276 8303
Email: alison.gleadle@foodstandards.gsi.gov.uk
Irene Hill Tel: 020 7276 8324
Email: irene.hill@foodstandards.gsi.gov.uk
3
FSA 06/06/03 AGENDA ITEM 3.1, 15 JUNE 2006
ATYPICAL SCRAPIE IN SHEEP AND GOATS: CONSIDERATION OF THE
CURRENT PRECAUTIONARY RISK MANAGEMENT MEASURES
Issue
1. To consider whether the Agency should recommend, on the basis of current
evidence, that additional precautionary measures are needed to reduce the
possible risk to consumers from atypical scrapie.......
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Conclusions
27. Atypical scrapie is definitely present in the UK flock, and in the flocks of other
Member States (MS), and animals with atypical scrapie have, and will be,
entering the food supply. However it is not known if this constitutes any risk to
human health. Unlike the situation when BSE was first discovered in cattle,
precautionary measures are already in place. Based on the limited knowledge of
the distribution of infectivity in atypical scrapie, the SEAC Subgroup concluded
that the SRM requirements that were put in place on a precautionary basis for
BSE in sheep may provide at least a similar level of protection against the
possible risk from atypical scrapie.
28. The consideration of the proportionality of any additional precautionary measures
is very difficult when the human health risk is unknown, and, as reported by
SEAC, there is insufficient data to carry out a risk assessment.
29. Any additional precautionary measures that could be put in place have a high
economic cost, are currently highly impractical (see Annex 1 for details) and
would impose a cost on industry that would, according to industry stakeholders,
be likely to bring into question the economic viability of sheep farming. ...
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full text ;
http://www.food.gov.uk/multimedia/pdfs/fsa060603.pdf
FSA 06/06/04 AGENDA ITEM 3.2, 15 JUNE 2006
BSE AND SHEEP CONTINGENCY POLICY
Executive Summary
1. This paper asks the Board to agree, for purposes of contingency planning, a
possible approach to a graduated strengthening of measures to protect
consumers in response to one or more findings of BSE in the current UK sheep
flock.
2. The paper also notes the high level of uncertainty around estimates of the
possible risk from BSE in sheep and that, if BSE were ever found in a UK sheep,
the estimate of the risk to consumers would depend on the accumulated results
of surveillance for BSE in sheep up to that time. It therefore recommends that the
policy be kept under review and that any policy agreed now on a contingency
basis should urgently be reconfirmed taking into account the circumstances at the
time of any finding of BSE in a UK sheep.
3. The Board is invited to:
• note that, in the event of confirmation of BSE in a sheep, targeted testing of
animals in the affected flock or flocks would be carried out to assist in
determining the potential spread of the disease and whether it may have
entered the food supply (paragraph 9).
• agree that an expert group be set up to advise on what additional surveillance
should be put in place, if BSE were to be found in a UK sheep, to improve
estimates of prevalence of BSE in UK sheep (paragraph 13).
• agree that, on current knowledge, it would advise the following graduated
response to one or more findings of BSE in the current UK sheep flock:
• one finding of BSE in sheep - remove additional SRM;
• two findings of BSE in unrelated flocks - exclude sheep aged over 12
months from the food supply and remove the additional SRM from the
remaining sheep;
• three findings of BSE in unrelated flocks - allow into the food supply only
sheep that were either genetically resistant to BSE or semi-resistant and
aged under 12 months and remove the additional SRM from those sheep
(paragraph 20).
2
• agree that its contingency policy for a finding of BSE in sheep should be kept
under review and be urgently reconfirmed should BSE actually be found in a
UK sheep (paragraph 22).
• comment on the outline handling plan at Annex F and the strategy for the
external communication that would be needed (paragraph 30).
TSE Division
Contacts:
Alison Gleadle Tel: 020 7276 8303 (GTN 7276 8303)
Email: alison.gleadle@foodstandards.gsi.gov.uk
David Carruthers Tel: 020 7276 8305 (GTN 7276 8305)
Email: david.carruthers@foodstandards.gsi.gov.uk
snip...
http://www.food.gov.uk/multimedia/pdfs/fsa060604.pdf
EFSA provides update on plans to assess the safety of goat meat and goat meat products with regard to BSE/TSE Last updated: 31 January 2005
The European Food Safety Authority s (EFSA) Scientific Panel on Biological Hazards (BIOHAZ) provided an update today on its plans to assess possible risks associated with the consumption of goat meat. The BIOHAZ Panel has undertaken this work following findings of a research group in France concerning a suspected case of Bovine Spongiform Encephalopathy (BSE) infection in a goat, confirmed today by the Community Reference Laboratory (CRL). On 26 November 2004, EFSA published a statement on the safety of goat milk and derived products with regard to possible risks from BSE/TSE (Transmissible Spongiform Encephalopathy).
* 35 kB Press release
http://www.efsa.eu.int/press_room/press_release/790/efsapr_bsegoat_28012005_en3.pdf
EFSA provides update on plans to assess the safety of
goat meat and goat meat products with regard to BSE/TSE
The European Food Safety Authority s (EFSA) Scientific Panel on Biological Hazards (BIOHAZ) provided an update today on its plans to assess possible risks associated with the consumption of goat meat. The BIOHAZ Panel has undertaken this work following findings of a research group in Franceconcerning a suspected case of Bovine Spongiform Encephalopathy (BSE) infection in a goat, confirmed today by the Community Reference Laboratory (CRL)[1] . On 26 November 2004, EFSA published a statement on the safety of goat milk and derived products with regard to possible risks from BSE/TSE (Transmissible Spongiform Encephalopathy)[2] . The BIOHAZ Panel reaffirmed today that important information gaps do not allow, at this stage, the quantification of BSE-related risks with regard to the consumption of goat meat. The Panel stresses that the significance of this single case of BSE infection in a goat in Franceis yet to be assessed. In order to do so, the results of the increased monitoring of TSEs in goats as proposed by the European Commission[3] will be essential. The BIOHAZ Panel s ability to carry out a quantitative risk assessment will be determined by the availability of the monitoring results and further experimental and epidemiological data. The success of its work will also depend on access to unpublished findings from MemberStatesand third countries. EFSA will review progress with members of its Advisory Forum at a meeting scheduled next week following a call for data launched in November 2004. The BIOHAZ Panel expects to provide further advice relating to the safety of goat meat and goat meat products by July 2005.
The full text of the statement of the BIOHAZ Panel on the assessment of safety with respect to the consumption of goat meat and goat meat products in relation to BSE/TSE is available on the EFSA website at:
http://www.efsa.eu.int/science/biohaz/biohaz_documents/787_en.html
http://www.efsa.eu.int/science/biohaz/biohaz_documents/787/statement25-01-2005bsegoatfinal2.pdf
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[1] http://europa.eu.int/comm/food/food/biosafety/bse/crl_statement_tse_goats_28-01-05_en.pdf
[2] Statement of the EFSA Scientific Expert Working Group on BSE/TSE of the Scientific Panel on Biological Hazards on the health risks of the consumption of milk and milk derived products from goats. http://www.efsa.eu.int/science/biohaz/biohaz_documents/709/bdoc_statement_goatsmilk_en1.pdf
[3] http://europa.eu.int/rapid/pressRel...format=HTML&aged=0&language=EN&guiLanguage=en
Publication date: 28 January 2005
http://www.efsa.eu.int/press_room/press_release/790_en.html
Subject: Case of BSE in a goat confirmed: Commission extends testing programme Date: January 28, 2005 at 7:49 am PST
Référence:
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IP/05/105 Brussels, 28 January 2005
Case of BSE in a goat confirmed: Commission extends testing programme
A suspected case of BSE in a goat slaughtered in France in 2002 has been confirmed today by a panel of European scientists (http://europa.eu.int/comm/food/food/biosafety/bse/crl_statement_tse_goats_28-01-05_en.pdf). The European Commission proposes to step up testing to determine if this is an isolated incident. Although this is the first time that BSE has been found in a goat under natural conditions, precautionary measures to protect consumers from this eventuality have been applied in the EU for several years. The level of TSE infection in goats seems however to be extremely low and any possible risk to consumers is minimal. The European Commission asked the French authorities to submit their preliminary findings to the Community Reference Laboratory (CRL) for TSEs based in Weybridge, UK (see IP/04/1324 ). TSEs are transmissible spongiform encephalopathies, namely BSE affecting cattle and scrapie affecting goats and sheep.
Markos Kyprianou, EU Commissioner responsible for Health and Consumer Protection, said “I want to reassure consumers that existing safety measures in the EU offer a very high level of protection. This case was discovered thanks to the EU testing system in place in France. The testing programme has shown us that there is a very low incidence rate of TSEs in goats and allowed us to detect suspect animals so that they can be taken out of the food chain, as was done with this goat and its entire herd. I am proposing to extend testing further to determine whether this is an isolated incident.”
Existing safety measures
For many years, safety measures have been applied to all farmed ruminants (cattle, goats, sheep) to offer maximum public health protection in case BSE in goats was ever confirmed. These safety measures include the ban on feeding animal proteins in the form of meat-and-bone meal (MBM), the removal of specified risk materials (i.e. the removal of tissues such as brain, spinal cord, part of the intestines) from the food and feed chain, the slaughtering of herds affected by scrapie (a disease of goats and sheep similar to BSE but not infectious for humans), and a TSE monitoring and testing programme in all Member States. Over 140,000 goats have been tested since April 2002, including random testing of healthy animals, sick animals and those that die on the farm.
Extension of testing regime
Following this confirmation, the Commission is proposing increased testing for BSE among goats for at least 6 months (200 000 tests of healthy goats in the EU) to determine if this is an isolated incident. The extent of the monitoring programme will be based on the goat population in each Member State and will focus primarily on Member States where BSE is present in the cattle population. All confirmed TSE cases will be subjected to a three-step testing scheme, already in use, which will make it possible to differentiate between scrapie and BSE. These additional measures will be submitted for Member States approval at the next meeting of the Standing Committee on the Food Chain and Animal Health scheduled on 2-3 February 2005..
Does this BSE case indicate a widespread problem?
The conditions that existed when the affected goat was born in 2000 no longer exist and available evidence would suggest that even if the infection still exists in goats, the level would be extremely low. The feeding of meat-and-bone meal (MBM) to ruminants is generally considered to be the transmission route of BSE. In January 2001 the existing ban on feeding MBM to all ruminants was extended to a total ban on feeding MBM to all farmed animals. Goats in the EU generally only live for a few years, which means that the majority of goats in the EU today were born after the total feed ban was put in place.
Are goat milk, cheese and meat safe?
The European Food Safety Authority has advised that based on current scientific knowledge, goat milk and derived products are unlikely to present any risk of TSE contamination if the milk comes from healthy animals: http://www.efsa.eu.int/science/biohaz/biohaz_documents/709/bdoc_statement_goatsmilk_en1.pdf
Currently, as a precautionary measure and following scientific advice, milk and meat from goats which are affected by TSE cannot be used. These rules were in place before the case of BSE in a goat was discovered. As for cattle and sheep, specified risk materials (the tissues most likely to carry infectivity if the disease is present) are also removed from all goats even if there is no infection detected. While it is not possible to say that there is absolutely no risk, any potential risk will be mitigated by the safety measures put in place.
In light of the above, the European Commission advises no change in current consumption of goat milk, cheese and meat. The European Commission has asked EFSA to carry out a quantitative risk assessment for goat meat and goat meat products, which is expected to be ready by July 2005.
Background
Following the findings by a research group in France of a suspected BSE infection in a goat, the European Commission immediately made the findings public on 28 October 2004 (see IP/04/1324 ). The supporting data were submitted on 5 November, as foreseen by the EU procedure, by the French authorities to the Community Reference Laboratory (CRL) for TSEs based in Weybridge (UK), for an evaluation by an expert panel. The CRL expert panel reported their findings today (http://europa.eu.int/comm/food/food/biosafety/bse/crl_statement_tse_goats_28-01-05_en.pdf).
The infected goat was born in March 2000 and slaughtered in France in October 2002. The results are only now becoming available as the series of confirmatory tests included testing on mice (a so-called “mouse bioassay”), which takes two years to complete.
The goat and its herd were disposed in accordance with EU rules and did not enter either the food or feed chain, and therefore do not represent a risk to public health. This goat was detected as part of the EU wide surveillance programme designed to detect suspicious TSE strains in small ruminants, and was the only one in its herd of 300 goats to develop BSE. Over 140,000 goats have been tested across Europe since April 2002.
See also MEMO/05/29 http://europa.eu.int/rapid/pressReleasesAction.do?reference=MEMO/05/29&format=HTML&aged=0&language=EN&guiLanguage=en.
http://europa.eu.int/rapid/pressReleasesAction.do?reference=IP/05/105&format=HTML&aged=0&language=EN&guiLanguage=fr
Isolation of Prion with BSE Properties from Farmed Goat
John Spiropoulos, Richard Lockey, Rosemary E. Sallis, Linda A. Terry, Leigh Thorne, Thomas M. Holder, Katy E. Beck, and Marion M. Simmons
Transmissible spongiform encephalopathies are fatal neurodegenerative diseases that include variant Creutzfeldt-Jakob disease in humans, scrapie in small ruminants, and bovine spongiform encephalopathy (BSE) in cattle. Scrapie is not considered a public health risk, but BSE has been linked to variant Creutzfeldt-Jakob disease. Small ruminants are susceptible to BSE, and in 2005 BSE was identified in a farmed goat in France. We confi rm another BSE case in a goat in which scrapie was originally diagnosed and retrospectively identified as suspected BSE. The prion strain in this case was further characterized by mouse bioassay after extraction from formaldehyde-fixed brain tissue embedded in paraffi n blocks. Our data show that BSE can infect small ruminants under natural conditions and could be misdiagnosed as scrapie. Surveillance should continue so that another outbreak of this zoonotic transmissible spongiform encephalopathy can be prevented and public health safeguarded.
The 2 cases of naturally occurring BSE in small ruminants—the 1 reported here and the 1 identifi ed in France (15)—occurred in different countries, during different time periods, and before strict BSE control measures were fully implemented. Therefore, the most likely origin of these 2 cases would be exposure to BSE-contaminated food supplements. ...
GOAT BSE
Sheep-Passaged Bovine Spongiform Encephalopathy Agent Exhibits Altered Pathobiological Properties in Bovine-PrP Transgenic Mice▿
Juan Carlos Espinosa1, Olivier Andréoletti2, Joaquín Castilla1, María Eugenia Herva1, Mónica Morales1, Elia Alamillo1, Fayna Díaz San-Segundo1, Caroline Lacroux2, Séverine Lugan2, Francisco Javier Salguero1, Jan Langeveld3, and Juan María Torres1,* + Author Affiliations
1Centro de Investigación en Sanidad Animal, INIA, 28130 Valdeolmos, Madrid, Spain 2UMR INRA-ENVT 1225, Interactions Hôte Agent Pathogène, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France 3CIDC-Lelystad, 8203 AA Lelystad, The Netherlands Next Section ABSTRACT
Sheep can be experimentally infected with bovine spongiform encephalopathy (BSE), and the ensuing disease is similar to scrapie in terms of pathogenesis and clinical signs. BSE infection in sheep is an animal and human health concern. In this study, the transmission in BoPrP-Tg110 mice of prions from BSE-infected sheep was examined and compared to the transmission of original cattle BSE in cattle and sheep scrapie prions. Our results indicate no transmission barrier for sheep BSE prions to infect BoPrP-Tg110 mice, but the course of the disease is accelerated compared to the effects of the original BSE isolate. The shortened incubation period of sheep BSE in the model was conserved in subsequent passage in BoPrP-Tg110 mice, indicating that it is not related to infectious titer differences. Biochemical signature, lesion profile, and PrPSc deposition pattern of both cattle and sheep BSE were similar. In contrast, all three sheep scrapie isolates tested showed an evident transmission barrier and further adaptation in subsequent passage. Taken together, those data indicate that BSE agent can be altered by crossing a species barrier, raising concerns about the virulence of this new prion towards other species, including humans. The BoPrP-Tg110 mouse bioassay should be considered as a valuable tool for discriminating scrapie and BSE in sheep.
Transmission of sheep-bovine spongiform encephalopathy to pigs
Carlos Hedman, Rosa BoleaEmail author, Belén Marín, Fabien Cobrière, Hicham Filali, Francisco Vazquez, José Luis Pitarch, Antonia Vargas, Cristina Acín, Bernardino Moreno, Martí Pumarola, Olivier Andreoletti and Juan José Badiola Veterinary Research201647:14 https://doi.org/10.1186/s13567-015-0295-8© Hedman et al. 2016 Received: 15 May 2015Accepted: 21 September 2015Published: 7 January 2016
Abstract
Experimental transmission of the bovine spongiform encephalopathy (BSE) agent has been successfully reported in pigs inoculated via three simultaneous distinct routes (intracerebral, intraperitoneal and intravenous). Sheep derived BSE (Sh-BSE) is transmitted more efficiently than the original cattle-BSE isolate in a transgenic mouse model expressing porcine prion protein. However, the neuropathology and distribution of Sh-BSE in pigs as natural hosts, and susceptibility to this agent, is unknown. In the present study, seven pigs were intracerebrally inoculated with Sh-BSE prions. One pig was euthanized for analysis in the preclinical disease stage. The remaining six pigs developed neurological signs and histopathology revealed severe spongiform changes accompanied by astrogliosis and microgliosis throughout the central nervous system. Intracellular and neuropil-associated pathological prion protein (PrPSc) deposition was consistently observed in different brain sections and corroborated by Western blot. PrPSc was detected by immunohistochemistry and enzyme immunoassay in the following tissues in at least one animal: lymphoid tissues, peripheral nerves, gastrointestinal tract, skeletal muscle, adrenal gland and pancreas. PrPSc deposition was revealed by immunohistochemistry alone in the retina, optic nerve and kidney. These results demonstrate the efficient transmission of Sh-BSE in pigs and show for the first time that in this species propagation of bovine PrPSc in a wide range of peripheral tissues is possible. These results provide important insight into the distribution and detection of prions in non-ruminant animals.
Research Editorial Controlling scrapie and bovine spongiform encephalopathy in goats Cristina Acín, BVet, PhD and José Luis Pitarch, BVet, PhD Author affiliations
http://dx.doi.org/10.1136/vr.i702
Statistics from Altmetric.com Article has an altmetric score of 2 See more details
Tweeted by 3 8 readers on Mendeley TRANSMISSIBLE spongiform encephalopathies (TSEs) are a group of neurodegenerative diseases caused by the accumulation in the central nervous system (CNS) of an anomalous isoform called prion protein (Prusiner 1982). Bovine spongiform encephalopathy (BSE) represents one of the most important food crises of past decades in Europe. BSE started in the UK, due to cattle consumption of feedstuff contaminated with prions (Wilesmith and others 1992). In Europe, efforts have focused on eradicating the disease in the bovine population. However, since sheep and goats are susceptible to prion diseases, eradication efforts in these species have to be considered; in fact, in 2005 the first case of natural BSE in a goat from France was diagnosed (Eloit and others 2005). These findings imply that BSE in small ruminants (particularly goats) could represent a danger for human health and therefore various strategies must be considered to avoid infection.
It has been recognised that polymorphisms of the PRNP gene are responsible for some element of susceptibility or resistance to prion diseases. Studies in sheep have shown that the haplotype …
Sheep and Goat BSE Propagate More Efficiently than Cattle BSE in Human PrP Transgenic Mice
Danielle Padilla1., Vincent Be´ ringue2., Juan Carlos Espinosa1 , Olivier Andreoletti3 , Emilie Jaumain2 , Fabienne Reine2 , Laetitia Herzog2 , Alfonso Gutierrez-Adan4 , Belen Pintado4 , Hubert Laude2 , Juan Maria Torres1
* 1 Centro de Investigacio´n en Sanidad Animal (CISA-INIA), Madrid, Spain, 2 INRA, UR892, Virologie Immunologie Mole´culaires, Jouy-en-Josas, France, 3 UMR INRA-ENVT 1225, Interactions Hoˆte Agent Pathoge`ne, Ecole Nationale Ve´te´rinaire de Toulouse, Toulouse, France, 4Departamento de Reproduccio´n Animal-INIA, Madrid, Spain
Abstract
A new variant of Creutzfeldt Jacob Disease (vCJD) was identified in humans and linked to the consumption of Bovine Spongiform Encephalopathy (BSE)-infected meat products. Recycling of ruminant tissue in meat and bone meal (MBM) has been proposed as origin of the BSE epidemic. During this epidemic, sheep and goats have been exposed to BSEcontaminated MBM. It is well known that sheep can be experimentally infected with BSE and two field BSE-like cases have been reported in goats. In this work we evaluated the human susceptibility to small ruminants-passaged BSE prions by inoculating two different transgenic mouse lines expressing the methionine (Met) allele of human PrP at codon 129 (tg650 and tg340) with several sheep and goat BSE isolates and compared their transmission characteristics with those of cattle BSE. While the molecular and neuropathological transmission features were undistinguishable and similar to those obtained after transmission of vCJD in both transgenic mouse lines, sheep and goat BSE isolates showed higher transmission efficiency on serial passaging compared to cattle BSE. We found that this higher transmission efficiency was strongly influenced by the ovine PrP sequence, rather than by other host species-specific factors. Although extrapolation of results from prion transmission studies by using transgenic mice has to be done very carefully, especially when human susceptibility to prions is analyzed, our results clearly indicate that Met129 homozygous individuals might be susceptible to a sheep or goat BSE agent at a higher degree than to cattle BSE, and that these agents might transmit with molecular and neuropathological properties indistinguishable from those of vCJD. Our results suggest that the possibility of a small ruminant BSE prion as vCJD causal agent could not be ruled out, and that the risk for humans of a potential goat and/or sheep BSE agent should not be underestimated.
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Taken all together, our results suggest that the possibility of a small ruminant BSE prion as vCJD causal agent could not be ruled out, which has important implications on public and animal health policies. On one hand, although the exact magnitude and characteristic of the vCJD epidemic is still unclear, its link with cattle BSE is supported by strong epidemiological ground and several experimental data. On the other hand, the molecular typing performed in our studies, indicates that the biochemical characteristics of the PrPres detected in brains of our sheep and goat BSEinoculated mice seem to be indistinguishable from that observed in vCJD. Considering the similarity in clinical manifestation of BSEand scrapie-affected sheep [48], a masker effect of scrapie over BSE, as well as a potential adaptation of the BSE agent through subsequent passages, could not be ruled out. As BSE infected sheep PrPSc have been detected in many peripheral organs, small ruminant-passaged BSE prions might be a more widespread source of BSE infectivity compared to cattle [19,49,50]. This fact is even more worrying since our transmission studies suggest that apparently Met129 human PrP favours a BSE agent with ovine rather than a bovine sequence. Finally, it is evident that, although few natural cases have been described and so far we cannot draw any definitive conclusion about the origin of vCJD, we can not underestimate the risk of a potential goat and/or sheep BSE agent.
P-160: Rapid tests might overlook bovine spongiform encephalopathy infection in goats
Daniela Meloni
Elena Bozzetta
Jan P. M. Lageveld
Martin H. Groschup
Wilfred Goldmann
Olivier Andreoletti
Isabelle Lantier
Lucien Van Keulen
Alex Bossers
Romolo Nonno
Francesco Ingravalle
Elsa Manzardo
Maria C. Cavarretta
Daniela Loprevite
Pier Luigi Acutis
CEA, Istituto Zooprofilattico Sperimentale dl Piemonte, Liguria e Valle d'Aosta, Turin, Italy
Central Veterinary Institute, Wageningen UR, Lelystad, the Netherlands
Friedrich-Loeffler Institut, Federal Research Institute for Animal Health, Insel Riems, Germany
Roslin Institute and R(D)SVS University of Edinburgh, Roslin, Midlothian, United Kingdom
UMR INRA ENVT 1225 Interactions Hotes Agents Pathogenes, ENVT, Toulouse, France
INRA IASP, Center INRA de Tours, Nouzilly, France
Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanita, Rome, Italy
Scrapie disease of sheep and goats has been endemic in Europe for more than 200 years, but has never been convincingly associated with any form of human TSE disease, though recent data based on experimental transmission of scrapie to humanized mice or non-human primates have re-opened this issue. On the other hand, the epidemic of bovine spongiform encephalopathy (BSE) in the UK and other European cattle population has been unequivocally linked to the appearance of variant Creutzfeldt-Jakob disease. A specific investigation on the suitability of EU approved rapid methods for the detection of TSE diseases in goats was never performed. The aim of this study was to compare the performance of IDEXX HerdChek® BSE-scrapie (IDEXX), Bio-Rad® TeSeE SAP (BIORAD-SAP) and Bio-Rad® TeSeE Sheep/Goat (BIORAD-SG) tests on brain samples from goats with natural scrapie, experimental scrapie or BSE. Thirty-one of these samples were sourced from goats with natural scrapie from 7 different EU countries: 7 from clinically affected goats and 24 from clinically healthy animals. Other samples (n = 32) from goats with experimentally induced scrapie or BSE were provided by the CVI, FLI, Roslin, INRA, and CEA institutes. Different PRNP genotypes characterized the positive samples. Overall, the 3 rapid tests showed 100% specificity and over 80% sensitivity, being the IDEXX significantly more sensitive than the Bio-Rad tests. All tests recognized 100% of samples from goats with clinical scrapie, either experimentally or naturally infected. In contrast, the sensitivity was lower in goats with pre-clinical scrapie, where IDEXX missed about 7% of samples, BIORAD-SAP 14%, and BIORAD-SG up to 24%. Finally, IDEXX picked up all the samples from clinical BSE-infected goats, while the other 2 rapid tests missed the 15% (BIORAD-SG) to the 25% (BIORAD-SAP). Overall, 2 concerns come from these results: i) that pre-clinical scrapie infections may be missed by EU surveillance, with sensitivity of detection strongly dependent on the rapid test used, and most importantly ii) that a significant proportion of clinical BSE infections may be overlooked when using BIORAD rapid tests. Assuming that the same sensitivity on pre-clinical goats would also occur in BSE-infected goats, our data show that only the IDEXX test would be possibly suitable for detecting eventual preclinical field case of BSE infection in goats, though with a disappointing 7% failure. Our results cast some concerns in relation to the reliability of current figures on BSE infections in goats deriving from EU surveillance.
APPROVED: 9 November 2016 doi: 10.2903/j.efsa.2016.4643
The European Union summary report on data of the surveillance of ruminants for the presence of transmissible spongiform encephalopathies (TSEs) in 2015 European Food Safety Authority (EFSA),
Frank Boelaert, Marta Hugas, Angel Ortiz Pelaez, Valentina Rizzi, Pietro Stella and Yves Van Der Stede
Abstract
This report of EFSA presents the results of surveillance activities on transmissible spongiform encephalopathies (TSEs) in bovine animals, sheep and goats as well as genotyping data in sheep, carried out in 2015 in the EU and in three non-Member States (non-MS). Since 2001, approximately 114 million cattle in the EU have been tested for bovine spongiform encephalopathy (BSE) according Regulation (EC) 999/2001. In 2015, 1.4 million bovine animals were tested and five cases were detected in four MS (Ireland: one case; Slovenia: one case; Spain: one case; and the United Kingdom: two cases) and one case was detected in Norway. Two cases (in Ireland and the United Kingdom) were affected by classical BSE and both cases were born after the EU-wide feed ban enforced in 2001. The remaining four cases were atypical BSE cases (three H-BSE type and one L-BSE type). Since 2002, approximately 8.4 million small ruminants have been tested during the EU-wide surveillance for scrapie. In 2015, 319,638 sheep and 135,857 goats were tested. In total, 641 scrapie cases in sheep were detected in 18 MS while 1,052 scrapie cases in goats were detected in nine MS, respectively. In two non-MS (Iceland and Norway), 40 scrapie cases in sheep were detected. Although in a number of MS the decrease in classical scrapie is clear, at the EU level there is no clear decreasing trend in the occurrence of scrapie in small ruminants. Results obtained from genotyping in sheep confirm that cases of classical scrapie are clustered among certain genotypes, and animals with these genotypes seem to account for less than 20% of the European randomly sampled sheep population. In total, 580 samples from species other than domestic ruminants were tested for TSE in three MS, all with negative results.
© 2016 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.
Keywords: transmissible spongiform encephalopathies (TSE), bovine spongiform encephalopathy (BSE), scrapie, zoonosis, surveillance
Requestor: European Commission Question number: EFSA-Q-2015-00653 Correspondence: zoonoses@efsa.europa.eu
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Location: Virus and Prion Research
Title: Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease
Author item Moore, Sarah item Kunkle, Robert item Kondru, Naveen item Manne, Sireesha item Smith, Jodi item Kanthasamy, Anumantha item West Greenlee, M item Greenlee, Justin
Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 3/15/2017 Publication Date: N/A Citation: N/A Interpretive Summary:
Technical Abstract: Aims: Chronic wasting disease (CWD) is a naturally-occurring, fatal neurodegenerative disease of cervids. We previously demonstrated that disease-associated prion protein (PrPSc) can be detected in the brain and retina from pigs challenged intracranially or orally with the CWD agent. In that study, neurological signs consistent with prion disease were observed only in one pig: an intracranially challenged pig that was euthanized at 64 months post-challenge. The purpose of this study was to use an antigen-capture immunoassay (EIA) and real-time quaking-induced conversion (QuIC) to determine whether PrPSc is present in lymphoid tissues from pigs challenged with the CWD agent.
Methods: At two months of age, crossbred pigs were challenged by the intracranial route (n=20), oral route (n=19), or were left unchallenged (n=9). At approximately 6 months of age, the time at which commercial pigs reach market weight, half of the pigs in each group were culled (<6 challenge="" groups="" month="" pigs="" remaining="" the="">6 month challenge groups) were allowed to incubate for up to 73 months post challenge (mpc). The retropharyngeal lymph node (RPLN) was screened for the presence of PrPSc by EIA and immunohistochemistry (IHC). The RPLN, palatine tonsil, and mesenteric lymph node (MLN) from 6-7 pigs per challenge group were also tested using EIA and QuIC.
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 5="" 6="" at="" by="" detected="" eia.="" examined="" group="" in="" intracranial="" least="" lymphoid="" month="" months="" of="" one="" pigs="" positive="" prpsc="" quic="" the="" tissues="" was="">6 months group, 5/6 pigs in the oral <6 4="" and="" group="" months="" 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.
CONFIDENTIAL
EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY
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.
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.....
snip...see much more here ;
WEDNESDAY, APRIL 05, 2017
Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease
spontaneous atypical BSE or spontaneous atypical Nor98 Scrapie, the spontaneous part, or sporadic, no cause, that dog does not hunt anymore. that old folks and old cow disease is BSe at it's finest, just like sporadic CJD, a spontaneous event from nothing in 85%+ of all humans, that's bull shit as well.
AS with atypical BSE type h, type L, and look at France, if atypical BSE was spontaneous, why then does France have an overly abundant cases of atypical BSE in both L type and H type?
must be an epidemic of spontaneous BSE in one given area? i don't think so.
Table 10: Number and proportion of BSE cases subject to discriminatory testing, by case type for the period 2003–2015 in the EU and other reporting countries
see chart page 25;
Table 10: Number and proportion of BSE cases subject to discriminato ry testing, by case type for the period2003–2015 in the EU and other repo rting countries
SAME with atypical scrapie, why then does Portugal of the Russian Federation have an outbreak of the highest documented atypical scrapie cases, if then atypical scrapie is a spontaneous event? look at the chart on page 35, see atypical scrapie cases by country, and someone please tell me why a few of these countries have way over what other countries have of the atypical Scrapie. if it was a spontaneous event, you would think these spontaneous events would be uniform, ...unless there were causes, then they would not be so uniform. look at the chart on page 35
The European Union summary report on data of the surveillance of ruminants for the presence of transmissible spongiform encephalopathies (TSEs) in 2015
European Food Safety Authority (EFSA),Frank Boelaert, Marta Hugas, Angel Ortiz Pelaez, Valentina Rizzi, Pietro Stella andYves Van Der Stede
AND FINALLY, THIS CHART HAS ALL THE PROOF YOU NEED THAT ATYPICAL SCRAPIE IS _NOT_ SPONTANEOUS. IF IT IS, THERE ARE A FEW COUNTRIES WITH AN EPIDEMIC OF ATYPCIAL NOR98 SCRAPIE, THAT OTHER COUNTRIES DON'T HAVE.
Table 14: Annual TSE cases by country, species and case type in 2002–2015 in the EU and other reporting countries
Case type Atypical Classical Year 2002 2003 2004 2005 20062007 2008 2009 2010 2011 2012 2013 2014 2015 Total 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Total Sheep
Country
SNIP...SEE FIGURES PAGE 40;
SPONTANEOUS ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY
***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.***
Experimental transmission of atypical scrapie to sheep
Marion M SimmonsEmail author, Timm Konold, Hugh A Simmons, Yvonne I Spencer, Richard Lockey, John Spiropoulos, Sharon Everitt and Derek Clifford BMC Veterinary Research20073:20 DOI: 10.1186/1746-6148-3-20© Crown copyright; licensee BioMed Central Ltd. 2007 Received: 26 March 2007Accepted: 28 August 2007Published: 28 August 2007 Abstract
Background Active surveillance for transmissible spongiform encephalopathies in small ruminants has been an EU regulatory requirement since 2002. A number of European countries have subsequently reported cases of atypical scrapie, similar to previously published cases from Norway, which have pathological and molecular features distinct from classical scrapie. Most cases have occurred singly in flocks, associated with genotypes considered to be more resistant to classical disease. Experimental transmissibility of such isolates has been reported in certain ovinised transgenic mice, but has not previously been reported in the natural host. Information on the transmissibility of this agent is vital to ensuring that disease control measures are effective and proportionate.
Results This report presents the successful experimental transmission, in 378 days, of atypical scrapie to a recipient sheep of homologous genotype with preservation of the pathological and molecular characteristics of the donor. This isolate also transmitted to ovinised transgenic mice (Tg338) with a murine phenotype indistinguishable from that of Nor 98.
Conclusion This result strengthens the opinion that these cases result from a distinct strain of scrapie agent, which is potentially transmissible in the natural host under field conditions.
Conclusion
At present the significance of this result, in terms of the transmissibility or pathogenicity under 'field conditions' of this agent strain in any species remains speculative, but it supports the need for appropriate control measures protecting both the animal and the human food chain to encompass atypical scrapie cases specifically.
The European Unio n sum mary report on data of thesurveillance of ruminants for the presence of transmissiblespongiform encephalopathies (TSEs) in 2015European Food Safety Authority (EFSA),Frank Boelaert, Marta Hugas, Angel Ortiz Pelaez, Valentina Rizzi, Pietro Stella andYves Van Der Stede
MONDAY, APRIL 25, 2011 Experimental Oral Transmission of Atypical Scrapie to Sheep
Volume 17, Number 5–May 2011
Research
Experimental Oral Transmission of Atypical Scrapie to Sheep
Marion M. Simmons, S. Jo Moore,1 Timm Konold, Lisa Thurston, Linda A. Terry, Leigh Thorne, Richard Lockey, Chris Vickery, Stephen A.C. Hawkins, Melanie J. Chaplin, and John Spiropoulos –Weybridge, Addlestone, UK
Suggested citation for this article
Abstract To investigate the possibility of oral transmission of atypical scrapie in sheep and determine the distribution of infectivity in the animals' peripheral tissues, we challenged neonatal lambs orally with atypical scrapie; they were then killed at 12 or 24 months. Screening test results were negative for disease-specific prion protein in all but 2 recipients; they had positive results for examination of brain, but negative for peripheral tissues. Infectivity of brain, distal ileum, and spleen from all animals was assessed in mouse bioassays; positive results were obtained from tissues that had negative results on screening. These findings demonstrate that atypical scrapie can be transmitted orally and indicate that it has the potential for natural transmission and iatrogenic spread through animal feed. Detection of infectivity in tissues negative by current surveillance methods indicates that diagnostic sensitivity is suboptimal for atypical scrapie, and potentially infectious material may be able to pass into the human food chain.
SNIP...
Discussion This study is still ongoing and will not be completed until 2012. However, the current interim report documents the successful oral transmission of atypical scrapie, confirms that the disease phenotype is retained following transmission by this route in AHQ/AHQ sheep, and indicates that infectivity can be demonstrated in the gut in the absence of detectable PrPSc at least as early as 12 months after exposure.
One sheep (animal 12) culled at 24 months post inoculation displayed abnormalities in behavior and movement suggestive of atypical scrapie. Signs like ataxia with head tremor and circling have been described in experimental (19) and natural (3,30) disease, which was attributed to lesions in the cerebellum and forebrain, respectively, corresponding with PrPSc accumulation in these areas (20,24).
By contrast, animal 11, which had confirmed atypical scrapie based on postmortem tests, was considered clinically normal. The less severe and limited PrPSc accumulation in the brain of this sheep than in animal 12 may explain the absence of clinical abnormalities, which is supported by our findings in goats with scrapie in which more extensive PrPSc accumulation in the brain was usually associated with a more severe clinical disease (25).
Although all TSEs are transmissible after intracerebral challenge to a susceptible host, only some are infectious under natural conditions. Therefore, it was important from a pathogenesis and disease control perspective to establish whether or not oral transmission can be successful. However, the challenge model in this study exposed animals as neonates, when the esophageal groove is operational and the lambs are physiologically monogastric. Exposure of 3-month-old ruminating animals to similar amounts of positive brain by the oral route have so far not resulted in any clinical disease, with all animals still alive >1,500 days post challenge (M.M. Simmons, unpub. data), but most natural cases have been recorded in animals older than this, so these animals may still progress to disease in the next few years. Since this challenge study in older animals has no time-kill component, and no losses caused by unrelated disease have occurred, whether any of these sheep are in a preclinical phase of disease is unknown. Unfortunately, the absence of detectable PrPSc in lymphoreticular tissues of sheep with atypical scrapie precludes the use of biopsies to ascertain early infection in these animals.
Transmission may be more efficient in newborn animals; the incubation periods of sheep orally infected with classical scrapie were significantly shorter in sheep challenged at 14 days of age than those challenged at 6 months of age (31). If, however, oral transmission is only effective in such young animals, then field exposure would most likely have to be through milk, which is known to be a highly effective route of transmission for classical scrapie (32). No data are currently available on the potential infectivity of milk from animals with atypical scrapie.
Successful oral transmission also raises questions regarding the pathogenesis of this form of disease. There must be passage of the infectious agent from the alimentary canal to the brain through one of several possible routes, most likely those that have been suggested and discussed in detail for other TSEs, for example, retrograde neuronal transportation either directly (33–35) or through lymphoid structures or hematogenously (36). Infectivity in the absence of readily demonstrable PrPSc has been reported (37–39), and although the mouse bioassay may detect evidence of disease in other tissues, these data may not be available for at least another 2 years. More protease-sensitive forms of PrPSc may be broken down more efficiently within cells and thus do not accumulate in peripheral tissues (19), enabling atypical PrPSc to transit the digestive tract and disseminate through other systems in small amounts before accumulating detectably in the central nervous system.
Although we do not have epidemiologic evidence that supports the efficient spread of disease in the field, these data imply that disease is potentially transmissible under field situations and that spread through animal feed may be possible if the current feed restrictions were to be relaxed. Additionally, almost no data are available on the potential for atypical scrapie to transmit to other food animal species, certainly by the oral route. However, work with transgenic mice has demonstrated the potential susceptibility of pigs, with the disturbing finding that the biochemical properties of the resulting PrPSc have changed on transmission (40). The implications of this observation for subsequent transmission and host target range are currently unknown.
How reassuring is this absence of detectable PrPSc from a public health perspective? The bioassays performed in this study are not titrations, so the infectious load of the positive gut tissues cannot be quantified, although infectivity has been shown unequivocally. No experimental data are currently available on the zoonotic potential of atypical scrapie, either through experimental challenge of humanized mice or any meaningful epidemiologic correlation with human forms of TSE. However, the detection of infectivity in the distal ileum of animals as young as 12 months, in which all the tissues tested were negative for PrPSc by the currently available screening and confirmatory diagnostic tests, indicates that the diagnostic sensitivity of current surveillance methods is suboptimal for detecting atypical scrapie and that potentially infectious material may be able to pass into the human food chain undetected.
Increased Atypical Scrapie Detections
Press reports indicate that increased surveillance is catching what otherwise would have been unreported findings of atypical scrapie in sheep. In 2009, five new cases have been reported in Quebec, Ontario, Alberta, and Saskatchewan. With the exception of Quebec, all cases have been diagnosed as being the atypical form found in older animals. Canada encourages producers to join its voluntary surveillance program in order to gain scrapie-free status. The World Animal Health will not classify Canada as scrapie-free until no new cases are reported for seven years. The Canadian Sheep Federation is calling on the government to fund a wider surveillance program in order to establish the level of prevalence prior to setting an eradication date. Besides long-term testing, industry is calling for a compensation program for farmers who report unusual deaths in their flocks.
Friday, February 11, 2011
Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
snip...
The presence of infectivity in peripheral tissues that enter the food chain clearly indicates that the risk of dietary exposure to Atypical/Nor98 scrapie cannot be disregarded. However, according to our observations, in comparison to the brain, the infectious titres in the peripheral tissues were five log10 lower in Atypical/Nor98 scrapie than in classical scrapie. Therefore, the reduction of the relative exposure risk following SRM removal (CNS, head, spleen and ileum) is probably significantly higher in Atypical/Nor98 scrapie cases than in classical scrapie cases. However, considering the currently estimated prevalence of Atypical/Nor98 scrapie in healthy slaughtered EU population [10], it is probable that atypical scrapie infectivity enters in the food chain despite the prevention measures in force.
Finally, the capacity of Atypical/Nor98 scrapie agent (and more generally of small ruminants TSE agents) to cross species barrier that naturally limits the transmission risk is insufficiently documented. Recently, the transmission of an Atypical/Nor98 scrapie isolate was reported into transgenic mice over-expressing the porcine PrP [47]. Such results cannot directly be extrapolated to natural exposure conditions and natural hosts. However, they underline the urgent need for further investigations on the potential capacity of Atypical/Nor98 scrapie to propagate in other species than small ruminants.
snip...please see full text thanks to the Authors and plospathogens.org/
PR-26
NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS
R. Nonno1, E. Esposito1, G. Vaccari1, E. Bandino2, M. Conte1, B. Chiappini1, S. Marcon1, M. Di Bari1, S.L. Benestad3, U. Agrimi1 1 Istituto Superiore di Sanità, Department of Food Safety and Veterinary Public Health, Rome, Italy (romolo.nonno@iss.it); 2 Istituto Zooprofilattico della Sardegna, Sassari, Italy; 3 National Veterinary Institute, Department of Pathology, Oslo, Norway
Molecular variants of PrPSc are being increasingly investigated in sheep scrapie and are generally referred to as “atypical” scrapie, as opposed to “classical scrapie”. Among the atypical group, Nor98 seems to be the best identified. We studied the molecular properties of Italian and Norwegian Nor98 samples by WB analysis of brain homogenates, either untreated, digested with different concentrations of proteinase K, or subjected to enzymatic deglycosylation. The identity of PrP fragments was inferred by means of antibodies spanning the full PrP sequence. We found that undigested brain homogenates contain a Nor98-specific PrP fragment migrating at 11 kDa (PrP11), truncated at both the C-terminus and the N-terminus, and not N-glycosylated. After mild PK digestion, Nor98 displayed full-length PrP (FL-PrP) and N-glycosylated C-terminal fragments (CTF), along with increased levels of PrP11. Proteinase K digestion curves (0,006-6,4 mg/ml) showed that FL-PrP and CTF are mainly digested above 0,01 mg/ml, while PrP11 is not entirely digested even at the highest concentrations, similarly to PrP27-30 associated with classical scrapie. Above 0,2 mg/ml PK, most Nor98 samples showed only PrP11 and a fragment of 17 kDa with the same properties of PrP11, that was tentatively identified as a dimer of PrP11. Detergent solubility studies showed that PrP11 is insoluble in 2% sodium laurylsorcosine and is mainly produced from detergentsoluble, full-length PrPSc. Furthermore, among Italian scrapie isolates, we found that a sample with molecular and pathological properties consistent with Nor98 showed plaque-like deposits of PrPSc in the thalamus when the brain was analysed by PrPSc immunohistochemistry. Taken together, our results show that the distinctive pathological feature of Nor98 is a PrP fragment spanning amino acids ~ 90-155. This fragment is produced by successive N-terminal and C-terminal cleavages from a full-length and largely detergent-soluble PrPSc, is produced in vivo and is extremely resistant to PK digestion. Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.
119
P03.141
Aspects of the Cerebellar Neuropathology in Nor98
Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute,
Norway Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.
A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes
Annick Le Dur*,?, Vincent Béringue*,?, Olivier Andréoletti?, Fabienne Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶, Jean-Luc Vilotte?, Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,?? +Author Affiliations
*Virologie Immunologie Moléculaires and ?Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France; ?Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066 Toulouse, France; §Agence Française de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon, France; **Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway
Edited by Stanley B. Prusiner, University of California, San Francisco, CA (received for review March 21, 2005)
Abstract Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.
Monday, December 1, 2008
When Atypical Scrapie cross species barriers
Authors
Andreoletti O., Herva M. H., Cassard H., Espinosa J. C., Lacroux C., Simon S., Padilla D., Benestad S. L., Lantier F., Schelcher F., Grassi J., Torres, J. M., UMR INRA ENVT 1225, Ecole Nationale Veterinaire de Toulouse.France; ICISA-INlA, Madrid, Spain; CEA, IBiTec-5, DSV, CEA/Saclay, Gif sur Yvette cedex, France; National Veterinary Institute, Postboks 750 Sentrum, 0106 Oslo, Norway, INRA IASP, Centre INRA de Tours, 3738O Nouzilly, France.
Content
Atypical scrapie is a TSE occurring in small ruminants and harbouring peculiar clinical, epidemiological and biochemical properties. Currently this form of disease is identified in a large number of countries. In this study we report the transmission of an atypical scrapie isolate through different species barriers as modeled by transgenic mice (Tg) expressing different species PRP sequence.
The donor isolate was collected in 1995 in a French commercial sheep flock. inoculation into AHQ/AHQ sheep induced a disease which had all neuro-pathological and biochemical characteristics of atypical scrapie. Transmitted into Transgenic mice expressing either ovine or PrPc, the isolate retained all the described characteristics of atypical scrapie.
Surprisingly the TSE agent characteristics were dramatically different v/hen passaged into Tg bovine mice. The recovered TSE agent had biological and biochemical characteristics similar to those of atypical BSE L in the same mouse model. Moreover, whereas no other TSE agent than BSE were shown to transmit into Tg porcine mice, atypical scrapie was able to develop into this model, albeit with low attack rate on first passage.
Furthermore, after adaptation in the porcine mouse model this prion showed similar biological and biochemical characteristics than BSE adapted to this porcine mouse model. Altogether these data indicate.
(i) the unsuspected potential abilities of atypical scrapie to cross species barriers
(ii) the possible capacity of this agent to acquire new characteristics when crossing species barrier
These findings raise some interrogation on the concept of TSE strain and on the origin of the diversity of the TSE agents and could have consequences on field TSE control measures.
Sunday, March 28, 2010
Nor-98 atypical Scrapie, atypical BSE, spontaneous TSE, trade policy, sound science ?
Monday, December 14, 2009
Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types
(hmmm, this is getting interesting now...TSS) Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine (reticular) deposits, see also ; All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.
see full text ;
Monday, December 14, 2009
Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types
THURSDAY, MARCH 29, 2012
atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012
THURSDAY, DECEMBER 08, 2016
USDA APHIS National Scrapie Eradication Program October 2016 Monthly Report Fiscal Year 2017 atypical NOR-98 Scrapie
At the time of this writing, the macaque exposed to the atypical (Nor98) scrapie isolate remains asymptomatic (>7 years post-inoculation). Similarly, we have not observed clinical signs in three macaques exposed to CWD isolates derived from naturally infected white-tailed deer or experimentally infected cattle (7 years post-inoculation).
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress
Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1
University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen
This is a progress report of a project which started in 2009. 21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves.
Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice.
At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation.
PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS
Subject: PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS VIDEO
PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS
PRION 2017 CONFERENCE VIDEO
Chronic Wasting Disease CWD TSE Prion to Humans, who makes that final call, when, or, has it already happened?
TUESDAY, JUNE 13, 2017
PRION 2017 CONFERENCE ABSTRACT First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress
TUESDAY, JUNE 13, 2017
PRION 2017 CONFERENCE ABSTRACT Chronic Wasting Disease in European moose is associated with PrPSc features different from North American CWD
TUESDAY, JULY 04, 2017
*** PRION 2017 CONFERENCE ABSTRACTS ON CHRONIC WASTING DISEASE CWD TSE PRION ***
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Location: Virus and Prion Research
Title: Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease
Author item Moore, Sarah item Kunkle, Robert item Kondru, Naveen item Manne, Sireesha item Smith, Jodi item Kanthasamy, Anumantha item West Greenlee, M item Greenlee, Justin
Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 3/15/2017 Publication Date: N/A Citation: N/A Interpretive Summary:
Technical Abstract: Aims: Chronic wasting disease (CWD) is a naturally-occurring, fatal neurodegenerative disease of cervids. We previously demonstrated that disease-associated prion protein (PrPSc) can be detected in the brain and retina from pigs challenged intracranially or orally with the CWD agent. In that study, neurological signs consistent with prion disease were observed only in one pig: an intracranially challenged pig that was euthanized at 64 months post-challenge. The purpose of this study was to use an antigen-capture immunoassay (EIA) and real-time quaking-induced conversion (QuIC) to determine whether PrPSc is present in lymphoid tissues from pigs challenged with the CWD agent.
Methods: At two months of age, crossbred pigs were challenged by the intracranial route (n=20), oral route (n=19), or were left unchallenged (n=9). At approximately 6 months of age, the time at which commercial pigs reach market weight, half of the pigs in each group were culled (<6 challenge="" groups="" month="" pigs="" remaining="" the="">6 month challenge groups) were allowed to incubate for up to 73 months post challenge (mpc). The retropharyngeal lymph node (RPLN) was screened for the presence of PrPSc by EIA and immunohistochemistry (IHC). The RPLN, palatine tonsil, and mesenteric lymph node (MLN) from 6-7 pigs per challenge group were also tested using EIA and QuIC.
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 5="" 6="" at="" by="" detected="" eia.="" examined="" group="" in="" intracranial="" least="" lymphoid="" month="" months="" of="" one="" pigs="" positive="" prpsc="" quic="" the="" tissues="" was="">6 months group, 5/6 pigs in the oral <6 4="" and="" group="" months="" 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.
CONFIDENTIAL
EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY
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.
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.....
snip...see much more here ;
WEDNESDAY, APRIL 05, 2017
Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease
TUESDAY, APRIL 18, 2017
*** EXTREME USA FDA PART 589 TSE PRION FEED LOOP HOLE STILL EXIST, AND PRICE OF POKER GOES UP ***
TUESDAY, MARCH 28, 2017
*** Passage of scrapie to deer results in a new phenotype upon return passage to sheep ***
Atypical scrapie in Australia
RW Cook,a* J Bingham,bAS Besier,cCL Bayley,dM Hawes,ePL Shearer,fM Yamada,bJ Bergfeld,bDT Williamsband DJ Middletonb Background Since its initial detection in Norway in 1998, atypical scrapie (‘atypical/Nor98 scrapie’) has been reported in sheep in the majority of European countries (including in regions free of classical scrapie) and in the Falkland Islands, the USA, Canada,New Zealand and Australia.
Case series The diagnosis in Australia of atypical scrapie in four Merino and one Merino-cross sheep showing clinical signs of neurological disease was based on the detection of grey matter neuropil vacuolation (spongiform change) in the brain (particularly inthe molecular layer of the cerebellar cortex) and associated abnormal prion protein (PrPSc) deposition in both grey and white matter. Changes were minimal in the caudal brainstem, the predilection site for lesions of classical scrapie.Conclusion The distinctive lesion profile of atypical scrapie in these five sheep highlights the diagnostic importance of routine histological evaluation of the cerebellum for evidence of neuropil vacuolation and associated PrPSc deposition in adult sheep with suspected neurological disease.
Keywords atypical scrapie; prion disease; sheep; transmissible spongiform encephalopathy
Abbreviations ANZSDP, Australian and New Zealand StandardDiagnostic Procedure; CNS, central nervous system; DMNV, dorsalmotor nucleus of the vagus nerve; H&E, haematoxylin and eosin;IHC, immunohistochemistry; NTSESP, National TSE SurveillanceProgram; PrPSc, abnormal prion protein isomer; TSE, transmissiblespongiform encephalopathy. Aust Vet J 2016;94:452–455 doi: 10.1111/avj.12529
SUNDAY, JULY 16, 2017
*** Temporal patterns of chronic wasting disease prion excretion in three cervid species ***
O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France
Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.
*** 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. We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.
===============
***thus questioning the origin of human sporadic cases***
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
Saturday, April 23, 2016
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 printl 1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France
Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion. Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.
To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.
These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.
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.
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
Title: 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.
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
MONDAY, NOVEMBER 30, 2009
*** USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE ***
THURSDAY, JUNE 22, 2017
World Organisation for Animal Health (OIE) to establish liaison office in College Station, Texas
THURSDAY, JULY 13, 2017
EFSA BSE Sixty cases of mad cow disease since 2001 breached feed ban likely the cause
Scientists investigate origin of isolated BSE cases
National Prion Center could lose all funding just as concern about CWD jumping to humans rises
SATURDAY, JULY 15, 2017
National Prion Center could lose all funding just as concern about CWD jumping to humans rises
TO THE USDA AND OIE ET AL, you can't lie your way out of this tse prion nightmare, you can't wish your way out of this tse prion nightmare, and you can't buy your way out of this tse prion nightmare, by assuming it's a spontaneous entity it's not, and science has proven this time and time again. money, greed, and political science is why we are in this mess, and the science used by the oie and usda et al on the atypical nor98 scrapie, and their decision to classify atypical Nor98 Scrapie as a safe TSE prion disease to consume and import and export all around the world (putting the cart before the horse) while having the information above, will come back to haunt them once again, more humans exposed, and potentially more humans will die needlessly once again, because of the negligence of the OIE and USDA et al. it is criminal negligence in my opinion. ...nothing new$$$
p.s. hmmm, i am thinking about the cwd strain or strains in cervid species in Norway, the Nor98 atypical Scrapie in Norway, and the atypical BSE in Norway, interesting no ???
MONDAY, JULY 17, 2017
National Scrapie Eradication Program May 2017 Monthly Report Fiscal Year 2017
TUESDAY, JULY 18, 2017
USDA announces Alabama case of Bovine Spongiform Encephalopathy Alabama
THURSDAY, JULY 20, 2017
USDA OIE Alabama Atypical L-type BASE Bovine Spongiform Encephalopathy BSE animal feeds for ruminants rule, 21 CFR 589.200
SUNDAY, JULY 23, 2017
atypical L-type BASE Bovine Amyloidotic Spongiform Encephalopathy BSE TSE PRION
SUNDAY, JULY 23, 2017
Experimental Infection of Cattle With a Novel Prion Derived From Atypical H-Type Bovine Spongiform Encephalopathy
Saturday, July 23, 2016
BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING, AND SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016
Tuesday, July 26, 2016
Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016
Monday, June 20, 2016
Specified Risk Materials SRMs BSE TSE Prion Program
THURSDAY, JULY 13, 2017
EFSA BSE Sixty cases of mad cow disease since 2001 breached feed ban likely the cause
Scientists investigate origin of isolated BSE cases
SUNDAY, JULY 30, 2017
PRION2017 Low levels of classical BSE infectivity in rendered fat tissue
SATURDAY, JULY 29, 2017
Risk Advisory Opinion: Potential Human Health Risks from Chronic Wasting Disease CFIA, PHAC, HC (HPFB and FNIHB), INAC, Parks Canada, ECCC and AAFC
PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS
Subject: PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS VIDEO
PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS
PRION 2017 CONFERENCE VIDEO
Chronic Wasting Disease CWD TSE Prion to Humans, who makes that final call, when, or, has it already happened?
TUESDAY, JUNE 13, 2017
PRION 2017 CONFERENCE ABSTRACT First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress
TUESDAY, JULY 04, 2017
*** PRION 2017 CONFERENCE ABSTRACTS ON CHRONIC WASTING DISEASE CWD TSE PRION ***
TUESDAY, JUNE 13, 2017
PRION 2017 CONFERENCE ABSTRACT Chronic Wasting Disease in European moose is associated with PrPSc features different from North American CWD
URINE
SUNDAY, JULY 16, 2017
*** Temporal patterns of chronic wasting disease prion excretion in three cervid species ***
WEDNESDAY, JULY 26, 2017
Chronic wasting disease continues to spread Disease of cervids causing local population declines
TUESDAY, JULY 18, 2017
MINK FARMING USA TRANSMISSIBLE MINK ENCEPHALOPATHY TSE PRION DISEASE SURVEILLANCE AND TESTING
WEDNESDAY, APRIL 05, 2017
Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease
TUESDAY, APRIL 18, 2017
*** EXTREME USA FDA PART 589 TSE PRION FEED LOOP HOLE STILL EXIST, AND PRICE OF POKER GOES UP ***
TUESDAY, MARCH 28, 2017
*** Passage of scrapie to deer results in a new phenotype upon return passage to sheep ***
SPONTANEOUS ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY
***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.***
MONDAY, JULY 17, 2017
National Scrapie Eradication Program May 2017 Monthly Report Fiscal Year 2017
2001 FDA CJD TSE Prion Singeltary Submission
*** U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL
Jan. 9, 2001
THURSDAY, JUNE 22, 2017
World Organisation for Animal Health (OIE) to establish liaison office in College Station, Texas
NEEDLESS CONFLICT
WEDNESDAY, JULY 26, 2017
APHIS USDA Emerging Animal Disease Preparedness and Response Plan July 2017
O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France
Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.
*** 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. We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.
===============
***thus questioning the origin of human sporadic cases***
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
-------- Original Message --------
Subject: re-BSE prions propagate as either variant CJD-like or sporadic CJD
Date: Thu, 28 Nov 2002 10:23:43 -0000 From: "Asante, Emmanuel A" e.asante@ic.ac.uk
To: "'flounder@wt.net'" flounder@wt.net
Dear Terry,
I have been asked by Professor Collinge to respond to your request. I am a Senior Scientist in the MRC Prion Unit and the lead author on the paper. I have attached a pdf copy of the paper for your attention.
Thank you for your interest in the paper. In respect of your first question, the simple answer is, ***yes.
As you will find in the paper, we have managed to associate the alternate phenotype to type 2 PrPSc, the commonest sporadic CJD.
It is too early to be able to claim any further sub-classification in respect of Heidenhain variant CJD or Vicky Rimmer's version.
It will take further studies, which are on-going, to establish if there are sub-types to our initial finding which we are now reporting.
The main point of the paper is that, as well as leading to the expected new variant CJD phenotype, BSE transmission to the 129-methionine genotype can lead to an alternate phenotype which is indistinguishable from type 2 PrPSc.
I hope reading the paper will enlighten you more on the subject. If I can be of any further assistance please to not hesitate to ask.
Best wishes. Emmanuel Asante <>
____________________________________
Dr. Emmanuel A Asante MRC Prion Unit & Neurogenetics Dept. Imperial College School of Medicine (St. Mary's) Norfolk Place, LONDON W2 1PG Tel: +44 (0)20 7594 3794 Fax: +44 (0)20 7706 3272 email: e.asante@ic.ac.uk (until 9/12/02) New e-mail: e.asante@prion.ucl.ac.uk (active from now) _________
end...TSS
___________________
***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67 PrPsc was not detected using rapid tests for BSE.
***Subsequent testing resulted in the detection of pathologic lesion in unusual brain location and PrPsc detection by PMCA only.
IBNC Tauopathy or TSE Prion disease, it appears, no one is sure Posted by flounder on 03 Jul 2015 at 16:53 GMT
2014
***Moreover, L-BSE has been transmitted more easily to transgenic mice overexpressing a human PrP [13,14] or to primates [15,16] than C-BSE.
***It has been suggested that some sporadic CJD subtypes in humans may result from an exposure to the L-BSE agent.
*** Lending support to this hypothesis, pathological and biochemical similarities have been observed between L-BSE and an sCJD subtype (MV genotype at codon 129 of PRNP) [17], and between L-BSE infected non-human primate and another sCJD subtype (MM genotype) [15].
snip...
Saturday, April 23, 2016
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 printl 1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France
Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion. Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.
To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.
These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.
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.
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
Title: 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.
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Friday, January 10, 2014
vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???
THURSDAY, JULY 13, 2017
TEXAS CREUTZFELDT JAKOB DISEASE CJD TSE PRION
National Prion Center could lose all funding just as concern about CWD jumping to humans rises
SATURDAY, JULY 15, 2017
*** National Prion Center could lose all funding just as concern about CWD jumping to humans rises
SATURDAY, JULY 22, 2017
Why the U.S. Needs to Continue Prion Disease Surveillance, instead of reducing funding to zero
Terry S. Singeltary Sr.
