National Scrapie Eradication Program May 2017 Monthly Report Fiscal Year 2017
U.S. Department of Agriculture
Animal and Plant Health Inspection Service
Veterinary Services
Surveillance, Response and Preparedness Services
Sheep and Goat Health Program
June 15, 2017
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Positive Cases and Infected/Source Flocks
Positive Scrapie Cases*
No classical scrapie cases have been reported in FY 2017. The last classical case was reported in April 2016.
Since 2002, the total number of positive cases in goats is 41; the last goat case was reported in February 2015. Figure 1 shows the number of positive cases by State and by fiscal year of last reported case.
Infected and Source Flocks
As of May 31, 2017, there were two open infected and source flock statuses for classical scrapie
Figure 2). One flock was designated as a Nor98-like source flock in October 2016 as a result of a sheep sampled in September 2016 that tested positive.
* Samples collected between October 1, 2016 and May 31, 2017 and confirmed by June 15, 2017.
Program Summary
At the end of FY 2016, the percent of cull black face sheep found positive at slaughter was 0.01 percent (Chart 1) a 99 percent decrease compared to FY 2003. At the end of FY 2016, the percent of cull sheep found positive at slaughter and adjusted for face color* was 0.001 percent (Chart 2). As of May 31, 2017, no animals have tested positive for classical scrapie in FY 2017.
Two infected and three source flocks were designated in FY 2016 (Chart 3). No classical scrapie infected or source flocks have been designated in FY 2017. One flock was designated as a Nor98-like source flock in October 2016 based on a sample submitted at the end of FY 2016.
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.
Only one positive goat (FY 2015) has been found through RSSS since the start of RSSS in 2003. Based on all goats sampled at slaughter, the prevalence of scrapie in U.S. cull goats is 0.002 percent with an upper 95 percent confidence limit of 0.004 percent. * See slide 4 for an explanation of adjusted weights. Note: The number of animals sampled annually only allows accurate measurement to about 0.01 percent for the overall rate and about 0.03 percent for when face color is broken out separately, so the changes in the prevalence values smaller than 0.01 or 0.03 percent respectively are within the error of the measure.
''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.''
LMAO! 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
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
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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 ???
Terry S. Singeltary Sr.
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