Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice
Emerg Infect Dis. 2020 Jun; 26(6): 1130–1139.
doi: 10.3201/eid2606.181790
PMCID: PMC7258450
PMID: 32441630
Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice
Alba Marín-Moreno,1 Alvina Huor,1 Juan Carlos Espinosa, Jean Yves Douet, Patricia Aguilar-Calvo,2 Naima Aron, Juan Píquer, Sévérine Lugan, Patricia Lorenzo, Cecile Tillier, Hervé Cassard, Olivier Andreoletti, and Juan María Torrescorresponding author
Author information Copyright and License information Disclaimer
Abstract
Classical bovine spongiform encephalopathy (BSE) is the only zoonotic prion disease described to date. Although the zoonotic potential of atypical BSE prions have been partially studied, an extensive analysis is still needed. We conducted a systematic study by inoculating atypical BSE isolates from different countries in Europe into transgenic mice overexpressing human prion protein (PrP): TgMet129, TgMet/Val129, and TgVal129. L-type BSE showed a higher zoonotic potential in TgMet129 mice than classical BSE, whereas Val129-PrP variant was a strong molecular protector against L-type BSE prions, even in heterozygosis. H-type BSE could not be transmitted to any of the mice. We also adapted 1 H- and 1 L-type BSE isolate to sheep-PrP transgenic mice and inoculated them into human-PrP transgenic mice. Atypical BSE prions showed a modification in their zoonotic ability after adaptation to sheep-PrP producing agents able to infect TgMet129 and TgVal129, bearing features that make them indistinguishable of sporadic Creutzfeldt-Jakob disease prions.
snip...
Discussion The zoonotic potential of atypical BSE prions has been partially studied by using both PrP-overexpressing animals and gene-targeted mice (10,27–29). All evidence converges to indicate a higher capacity of L-BSE than of C-BSE to transmit in human-PrP–expressing hosts and a high transmission barrier for H-BSE. Absence of a transmission barrier for L-BSE in TgMet129 has already been reported (10). Our study (using other transgenic mice with a different PrPC expression level) expands the investigation to other genotypes. Lack of prion propagation in TgMet/Val129 and TgVal129 indicates that Val129 variant is a strong molecular protector against L-BSE zoonotic transmission even in heterozygosis, as previously reported for C-BSE and related C-BSE prions (18). Finally, H-BSE clearly has a robust transmission barrier with respect to the human-PrP sequence, independent of the codon 129 polymorphism.
Once adapted to TgMet129, L-BSE did not propagate in TgMet/Val129 and TgVal129, which precludes secondary infections between persons. In contrast, C-BSE propagated in Val129 genotypes once adapted to the Met129 human-PrP sequence, even when Val129 also protected against primary infection (18). However, Met/Val129 genotypes might be naturally affected by vCJD because a definite vCJD case of a subject heterozygous for codon 129 has already been reported (16). Moreover, evidence of potential prion propagation in Val129-homozygous persons has been indicated in examinations of tonsils and appendices (30–32). These observations are in contrast with our finding of a lack of transmission of C-BSE in Val129 genotypes. However, only 1 vCJD case has been reported in a Met/Val-heterozygous person, which might mean that the event is very rare. Moreover, whether the PrPres positivity detected in lymphoid tissues (tonsils and appendix) of Val129-homozygous persons would eventually extend to their central nervous system is still unknown. As a consequence, the risk for L-BSE secondary transmission once adapted to human-PrP sequence should be assessed carefully.
A complete assessment of the zoonotic potential of atypical BSE prions should include the evaluation of zoonotic potential after adaptation to the sheep-PrP sequence given that C-BSE virulence toward human-PrP transgenic mouse models increased after passage in ovine-PrP transgenic mice. Thus, we propagated 1 H-BSE and 1 L-BSE isolate into ovine-PrP transgenic mice. L-BSE has already been transmitted into sheep (13), whereas no H-BSE propagation into this host has been reported. Thus, we decided to perform the adaptation to the sheep sequence by using sheep-PrP transgenic mice, although overexpression of PrPC reportedly could render changes on prion strains features (33). The absence of divergent PrPres profiles among the animals and the uniformity of the incubation times after 2 passages into sheep-PrP transgenic mice argue against the occurrence of mutation events attributable to PrPC overexpression in our study. In addition, previously reported strain features of L-BSE propagated in sheep (13) were similar to those reported in this study using sheep-PrP transgenic mice, which also validates use of these animal models. Our results suggest a moderate but surmountable transmission barrier for L-BSE in the 2 analyzed sheep genotypes, whereas for H-BSE a high transmission barrier exists when transmitted into an ARQ sheep sequence. The polymorphism Ala/Val136 present in the sheep-PrP sequence seems to be responsible for the different behavior of the obtained prion agents. Once proved that these isolates could be propagated on sheep-PrP sequence, determining whether they can be differentiated from classical scrapie and C-BSE will be important.
Our results and those provided by other studies indicate that L-BSE adapted to a VRQ sheep sequence resemble C-BSE in its molecular features (14). Moreover, L-BSE adapted to ARQ sheep sequence and H-BSE adapted to VRQ sheep sequence generate prions similar to classical scrapie, at least in terms of PrPres glycoprofile. Therefore, in the supposed case of atypical BSE transmission to sheep, early differentiation of both atypical BSE agents from other sheep prions like classical scrapie would be difficult. Nevertheless, the combination of the low incidence of atypical BSE (because of its supposed sporadic nature) and the continued prohibition of meat and bone meal recycling ameliorates the risk for transmission to sheep.
The transmission of atypical BSEs into sheep resulted in the emergence of prions similar to types 1 and 2 sCJD in terms of mean survival times, attack rates, PrPres profile, and PrPres deposition pattern in the brain of human-PrP transgenic mice. The similarities between the sheep-adapted atypical BSE prions propagated into our human-PrP transgenic mouse lines and sCJD prions could suggest a link between them. The well-established dogma that sCJD is a spontaneous disorder unrelated to animal prion disease has been questioned in a previous study given the resemblance of scrapie prions transmitted into human transgenic mouse models to sCJD strains (26); however, the data from that study do not unequivocally establish a causative link between exposure to sheep scrapie and the subsequent appearance of sCJD in humans, and the same could apply to our findings. An alternative explanation that cannot be ruled out is that, although being different strains, only a limited number of phenotypes could be generated for the human-PrP, indicating phenotypic convergence. Updates to old epidemiologic research is needed to reconsider all these results involving a possible infectious origin of sCJD. In any case, continuing the characterization of this newly emerged prion strain would be useful to finally discarding or refuting a link with sCJD prions.
Extrapolation of results from prion transmission studies based on transgenic mice should be done with caution, especially when human susceptibility to prions is analyzed. However, our results clearly indicate that atypical BSE adaptation to an ovine-PrP sequence could modify the prion agent to potentially infect humans, showing strain features indistinguishable from those of classic sCJD prions, even though they might or might not be different agents. The supposed sporadic nature of atypical BSE makes its transmission to sheep and later to humans unlikely. However, the expanding range of TSE agents displaying the capacity to transmit in human-PrP–expressing hosts warrants the continuation of the ban on meat and bone meal recycling and underscores the ongoing need for active surveillance.
Keywords: transmissible spongiform encephalopathies, prion, atypical bovine spongiform encephalopathy, BSE, Val129-PrP, transmission barrier, Creutzfeldt-Jakob disease, CJD, zoonoses
Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice
Atypical BSE prions showed a modification in their zoonotic ability after adaptation to sheep-PrP producing agents able to infect TgMet129 and TgVal129, bearing features that make them indistinguishable of sporadic Creutzfeldt-Jakob disease prions.
our results clearly indicate that atypical BSE adaptation to an ovine-PrP sequence could modify the prion agent to potentially infect humans, showing strain features indistinguishable from those of classic sCJD prions, even though they might or might not be different agents.
However, the expanding range of TSE agents displaying the capacity to transmit in human-PrP–expressing hosts warrants the continuation of the ban on meat and bone meal recycling and underscores the ongoing need for active surveillance
A REVIEW of facts and science on scrapie zoonosis potential/likelihood and the USA incredible failure of the BSE 589.2001 FEED REGULATIONS (another colossal failure, and proven to be a sham)
1st up BSE 589.2001 FEED REGULATIONS
cwd scrapie pigs oral routes
***> However, at 51 months of incubation or greater, 5 animals were positive by one or more diagnostic methods. Furthermore, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study) suggesting that swine are potential hosts for the agent of scrapie. <***
>*** Although the current U.S. feed ban is based on keeping tissues from TSE infected cattle from contaminating animal feed, swine rations in the U.S. could contain animal derived components including materials from scrapie infected sheep and goats. These results indicating the susceptibility of pigs to sheep scrapie, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health. <***
***> Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 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.
***> In summary, our results establish aerosols as a surprisingly efficient modality of prion transmission. This novel pathway of prion transmission is not only conceptually relevant for the field of prion research, but also highlights a hitherto unappreciated risk factor for laboratory personnel and personnel of the meat processing industry. In the light of these findings, it may be appropriate to revise current prion-related biosafety guidelines and health standards in diagnostic and scientific laboratories being potentially confronted with prion infected materials. While we did not investigate whether production of prion aerosols in nature suffices to cause horizontal prion transmission, the finding of prions in biological fluids such as saliva, urine and blood suggests that it may be worth testing this possibility in future studies.
Adriano Aguzzi ''We even showed that a prion AEROSOL will infect 100% of mice within 10 seconds of exposure''
7. TRUCKING TRANSPORTING CERVID CHRONIC WASTING DISEASE TSE PRION VIOLATING THE LACEY ACT
***> PLEASE SEE HISTORY OF TEXAS TRUCKING CWD TSE PRION DISEASE AT THE BOTTOM OF MY SUBMISSION, TOO LONG TO POST HERE.
8.CONSIDERING RECENT SCIENCE THAT CWD TSE PRION WILL TRANSMIT ORALLY TO PIGS AND ALSO SCRAPIE TO PIGS BY ORAL ROUTES, CONSIDERING CWD TRANSMIT EASILY TO CERVID BY ORAL ROUTE, CONSIDERING A NEW TSE PRION OUTBREAK IN A NEW LIVESTOCK SPECIES, THE CAMEL, CONSIDERING THE FACT THE USA THAT THE 1997 BSE feed regulation at 589.2000, which remains in effect but which applies only to feed for cattle and other ruminants, and specifically, the new section 589.2001, WAS AND STILL IS A TOTAL AND COLOSSAL FAILURE, AND PROVEN TO BE SO BY RECENT COMMENTS COMING FROM THE FDA, BUT FIRST, COMMENTS FROM DEFRA;
In the USA, under the Food and Drug Administration's BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system. However, this recommendation is guidance and not a requirement by law.
Animals considered at high risk for CWD include:
1) animals from areas declared to be endemic for CWD and/or to be CWD eradication zones and
2) deer and elk that at some time during the 60-month period prior to slaughter were in a captive herd that contained a CWD-positive animal.
Therefore, in the USA, materials from cervids other than CWD positive animals may be used in animal feed and feed ingredients for non-ruminants.
The amount of animal PAP that is of deer and/or elk origin imported from the USA to GB can not be determined, however, as it is not specified in TRACES. It may constitute a small percentage of the 8412 kilos of non-fish origin processed animal proteins that were imported from US into GB in 2011.
Overall, therefore, it is considered there is a __greater than negligible risk___ that (nonruminant) animal feed and pet food containing deer and/or elk protein is imported into GB.
There is uncertainty associated with this estimate given the lack of data on the amount of deer and/or elk protein possibly being imported in these products.
snip.....
PLOS ONE Journal
IBNC Tauopathy or TSE Prion disease, it appears, no one is sure
Terry S. Singeltary Sr., 03 Jul 2015 at 16:53 GMT
***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 ***
http://www.plosone.org/annotation/listThread.action?root=86610
***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 ***
http://www.plosone.org/annotation/listThread.action?root=86610
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply
FDA's FAILED MAD COW FEED POLICY, IN LIVING COLOR!
***> cattle, pigs, sheep, cwd, tse, prion, oh my!
***> In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006).
Sheep and cattle may be exposed to CWD via common grazing areas with affected deer but so far, appear to be poorly susceptible to mule deer CWD (Sigurdson, 2008). In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006). It is not known how susceptible humans are to CWD but given that the prion can be present in muscle, it is likely that humans have been exposed to the agent via consumption of venison (Sigurdson, 2008). Initial experimental research suggests that human susceptibility to CWD is low and there may be a robust species barrier for CWD transmission to humans (Sigurdson, 2008), however the risk appetite for a public health threat may still find this level unacceptable.
***> READ THIS VERY, VERY, CAREFULLY, AUGUST 1997 MAD COW FEED BAN WAS A SHAM, AS I HAVE STATED SINCE 1997! 3 FAILSAFES THE FDA ET AL PREACHED AS IF IT WERE THE GOSPEL, IN TERMS OF MAD COW BSE DISEASE IN USA, AND WHY IT IS/WAS/NOT A PROBLEM FOR THE USA, and those are;
BSE TESTING (failed terribly and proven to be a sham)
BSE SURVEILLANCE (failed terribly and proven to be a sham)
BSE 589.2001 FEED REGULATIONS (another colossal failure, and proven to be a sham)
these are facts folks. trump et al just admitted it with the feed ban.
see;
FDA Reports on VFD Compliance
John Maday
August 30, 2019 09:46 AM VFD-Form 007 (640x427)
Before and after the current Veterinary Feed Directive rules took full effect in January, 2017, the FDA focused primarily on education and outreach. ( John Maday ) Before and after the current Veterinary Feed Directive (VFD) rules took full effect in January, 2017, the FDA focused primarily on education and outreach to help feed mills, veterinarians and producers understand and comply with the requirements. Since then, FDA has gradually increased the number of VFD inspections and initiated enforcement actions when necessary. On August 29, FDA released its first report on inspection and compliance activities. The report, titled “Summary Assessment of Veterinary Feed Directive Compliance Activities Conducted in Fiscal Years 2016 – 2018,” is available online.
SUNDAY, SEPTEMBER 1, 2019
***> FDA Reports on VFD Compliance
10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN COMMERCE USA 2007
Date: March 21, 2007 at 2:27 pm PST
RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II
___________________________________
PRODUCT
Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007
CODE
Cattle feed delivered between 01/12/2007 and 01/26/2007
RECALLING FIRM/MANUFACTURER
Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.
Firm initiated recall is ongoing. REASON
Blood meal used to make cattle feed was recalled because it was cross- contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement.
VOLUME OF PRODUCT IN COMMERCE
42,090 lbs.
DISTRIBUTION
WI
___________________________________
PRODUCT
Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007 CODE
The firm does not utilize a code - only shipping documentation with commodity and weights identified.
RECALLING FIRM/MANUFACTURER
Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete. REASON
Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement.
VOLUME OF PRODUCT IN COMMERCE
9,997,976 lbs.
DISTRIBUTION
ID and NV
END OF ENFORCEMENT REPORT FOR MARCH 21, 2007
http://www.fda.gov/Safety/Recalls/EnforcementReports/2007/ucm120446.htm
Saturday, August 14, 2010 BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY
*** (see mad cow feed in COMMERCE IN ALABAMA...TSS)
BANNED MAD COW FEED IN COMMERCE IN ALABAMA
Date: September 6, 2006 at 7:58 am PST PRODUCT
a) EVSRC Custom dairy feed, Recall # V-130-6;
b) Performance Chick Starter, Recall # V-131-6;
c) Performance Quail Grower, Recall # V-132-6;
d) Performance Pheasant Finisher, Recall # V-133-6.
CODE None RECALLING FIRM/MANUFACTURER Donaldson & Hasenbein/dba J&R Feed Service, Inc., Cullman, AL, by telephone on June 23, 2006 and by letter dated July 19, 2006. Firm initiated recall is complete.
REASON Dairy and poultry feeds were possibly contaminated with ruminant based protein.
VOLUME OF PRODUCT IN COMMERCE 477.72 tons
DISTRIBUTION AL
______________________________
http://www.fda.gov/bbs/topics/enforce/2006/ENF00968.html
PRODUCT Bulk custom dairy pre-mixes,
Recall # V-120-6 CODE None RECALLING FIRM/MANUFACTURER Ware Milling Inc., Houston, MS, by telephone on June 23, 2006. Firm initiated recall is complete.
REASON Possible contamination of dairy animal feeds with ruminant derived meat and bone meal.
VOLUME OF PRODUCT IN COMMERCE 350 tons
DISTRIBUTION AL and MS
______________________________
PRODUCT
a) Tucker Milling, LLC Tm 32% Sinking Fish Grower, #2680-Pellet, 50 lb. bags, Recall # V-121-6;
b) Tucker Milling, LLC #31120, Game Bird Breeder Pellet, 50 lb. bags, Recall # V-122-6;
c) Tucker Milling, LLC #31232 Game Bird Grower, 50 lb. bags, Recall # V-123-6;
d) Tucker Milling, LLC 31227-Crumble, Game Bird Starter, BMD Medicated, 50 lb bags, Recall # V-124-6;
e) Tucker Milling, LLC #31120, Game Bird Breeder, 50 lb bags, Recall # V-125-6;
f) Tucker Milling, LLC #30230, 30 % Turkey Starter, 50 lb bags, Recall # V-126-6;
g) Tucker Milling, LLC #30116, TM Broiler Finisher, 50 lb bags, Recall # V-127-6
CODE All products manufactured from 02/01/2005 until 06/20/2006 RECALLING FIRM/MANUFACTURER Recalling Firm: Tucker Milling LLC, Guntersville, AL, by telephone and visit on June 20, 2006, and by letter on June 23, 2006. Manufacturer: H. J. Baker and Brothers Inc., Stamford, CT. Firm initiated recall is ongoing.
REASON Poultry and fish feeds which were possibly contaminated with ruminant based protein were not labeled as "Do not feed to ruminants".
VOLUME OF PRODUCT IN COMMERCE 7,541-50 lb bags
DISTRIBUTION AL, GA, MS, and TN
END OF ENFORCEMENT REPORT FOR AUGUST 9, 2006
###
http://www.fda.gov/bbs/topics/ENFORCE/2006/ENF00964.html
Subject: MAD COW FEED RECALL AL AND FL VOLUME OF PRODUCT IN COMMERCE 125 TONS Products manufactured from 02/01/2005 until 06/06/2006
Date: August 6, 2006 at 6:16 pm PST PRODUCT
a) CO-OP 32% Sinking Catfish, Recall # V-100-6;
b) Performance Sheep Pell W/Decox/A/N, medicated, net wt. 50 lbs, Recall # V-101-6;
c) Pro 40% Swine Conc Meal -- 50 lb, Recall # V-102-6;
d) CO-OP 32% Sinking Catfish Food Medicated, Recall # V-103-6;
e) "Big Jim's" BBB Deer Ration, Big Buck Blend, Recall # V-104-6;
f) CO-OP 40% Hog Supplement Medicated Pelleted, Tylosin 100 grams/ton, 50 lb. bag, Recall # V-105-6;
g) Pig Starter Pell II, 18% W/MCDX Medicated 282020, Carbadox -- 0.0055%, Recall # V-106-6;
h) CO-OP STARTER-GROWER CRUMBLES, Complete Feed for Chickens from Hatch to 20 Weeks, Medicated, Bacitracin Methylene Disalicylate, 25 and 50 Lbs, Recall # V-107-6;
i) CO-OP LAYING PELLETS, Complete Feed for Laying Chickens, Recall # 108-6;
j) CO-OP LAYING CRUMBLES, Recall # V-109-6;
k) CO-OP QUAIL FLIGHT CONDITIONER MEDICATED, net wt 50 Lbs, Recall # V-110-6;
l) CO-OP QUAIL STARTER MEDICATED, Net Wt. 50 Lbs, Recall # V-111-6;
m) CO-OP QUAIL GROWER MEDICATED, 50 Lbs, Recall # V-112-6 CODE
Product manufactured from 02/01/2005 until 06/06/2006
RECALLING FIRM/MANUFACTURER Alabama Farmers Cooperative, Inc., Decatur, AL, by telephone, fax, email and visit on June 9, 2006. FDA initiated recall is complete.
REASON Animal and fish feeds which were possibly contaminated with ruminant based protein not labeled as "Do not feed to ruminants".
VOLUME OF PRODUCT IN COMMERCE 125 tons
DISTRIBUTION AL and FL
END OF ENFORCEMENT REPORT FOR AUGUST 2, 2006
###
http://www.fda.gov/bbs/topics/enforce/2006/ENF00963.html
MAD COW FEED RECALL USA EQUALS 10,878.06 TONS NATIONWIDE Sun Jul 16, 2006 09:22 71.248.128.67
RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINE -- CLASS II
______________________________
PRODUCT
a) PRO-LAK, bulk weight, Protein Concentrate for Lactating Dairy Animals, Recall # V-079-6;
b) ProAmino II, FOR PREFRESH AND LACTATING COWS, net weight 50lb (22.6 kg), Recall # V-080-6;
c) PRO-PAK, MARINE & ANIMAL PROTEIN CONCENTRATE FOR USE IN ANIMAL FEED, Recall # V-081-6;
d) Feather Meal, Recall # V-082-6 CODE
a) Bulk
b) None
c) Bulk
d) Bulk
RECALLING FIRM/MANUFACTURER H. J. Baker & Bro., Inc., Albertville, AL, by telephone on June 15, 2006 and by press release on June 16, 2006. Firm initiated recall is ongoing. REASON
Possible contamination of animal feeds with ruminent derived meat and bone meal.
VOLUME OF PRODUCT IN COMMERCE 10,878.06 tons
DISTRIBUTION Nationwide
END OF ENFORCEMENT REPORT FOR July 12, 2006
###
http://www.fda.gov/bbs/topics/enforce/2006/ENF00960.html SPECIFIED RISK MATERIAL SRM BREACHES USA
snip...see;
TUESDAY, APRIL 18, 2017
*** EXTREME USA FDA PART 589 TSE PRION FEED LOOP HOLE STILL EXIST, AND PRICE OF POKER GOES UP ***
2nd up, Scrapie zoonosis potential/likelihood
ZOONOSIS OF SCRAPIE TSE PRION
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.
==============
***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.
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.
PRION 2018 CONFERENCE
P98 The agent of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism transmits after oronasal challenge
Greenlee JJ (1), Moore SJ (1), and West Greenlee MH (2) (1) United States Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Virus and Prion Research Unit, Ames, IA, United States (2) Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, IA, United States.
reading up on this study from Prion 2018 Conference, very important findings ;
***> This study demonstrates that the H-type BSE agent is transmissible by the oronasal route.
***> These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains.
PRION 2018 CONFERENCE ABSTRACT
WEDNESDAY, OCTOBER 24, 2018
Experimental Infection of Cattle With a Novel Prion Derived From Atypical H-Type Bovine Spongiform Encephalopathy
WEDNESDAY, APRIL 24, 2019
***> USDA Announces Atypical Bovine Spongiform Encephalopathy Detection Aug 29, 2018 A Review of Science 2019 <***
MONDAY, JANUARY 09, 2017
Oral Transmission of L-Type Bovine Spongiform Encephalopathy Agent among Cattle
CDC Volume 23, Number 2—February 2017
*** Consumption of L-BSE–contaminated feed may pose a risk for oral transmission of the disease agent to cattle.
*** Consumption of L-BSE–contaminated feed may pose a risk for oral transmission of the disease agent to cattle.
TUESDAY, AUGUST 28, 2018
USDA finds BSE infection in Florida cow 08/28/18 6:43 PM
http://animalhealthreportpriontse..blogspot.com/2018/08/usda-finds-bse-infection-in-florida-cow.html
WEDNESDAY, AUGUST 29, 2018
USDA Announces Atypical Bovine Spongiform Encephalopathy Detection USDA 08/29/2018 10:00 AM EDT
WEDNESDAY, AUGUST 29, 2018
Transmissible Spongiform Encephalopathy TSE Prion Atypical BSE Confirmed Florida Update USA August 28, 2018
***> P.108: Successful oral challenge of adult cattle with classical BSE
Sandor Dudas1,*, Kristina Santiago-Mateo1, Tammy Pickles1, Catherine Graham2, and Stefanie Czub1 1Canadian Food Inspection Agency; NCAD Lethbridge; Lethbridge, Alberta, Canada; 2Nova Scotia Department of Agriculture; Pathology Laboratory; Truro, Nova Scotia, Canada
Classical Bovine spongiform encephalopathy (C-type BSE) is a feed- and food-borne fatal neurological disease which can be orally transmitted to cattle and humans. Due to the presence of contaminated milk replacer, it is generally assumed that cattle become infected early in life as calves and then succumb to disease as adults. Here we challenged three 14 months old cattle per-orally with 100 grams of C-type BSE brain to investigate age-related susceptibility or resistance. During incubation, the animals were sampled monthly for blood and feces and subjected to standardized testing to identify changes related to neurological disease. At 53 months post exposure, progressive signs of central nervous system disease were observed in these 3 animals, and they were euthanized. Two of the C-BSE animals tested strongly positive using standard BSE rapid tests, 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.
***Our study demonstrates susceptibility of adult cattle to oral transmission of classical BSE.
We are further examining explanations for the unusual disease presentation in the third challenged animal.
***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.
P.86: Estimating the risk of transmission of BSE and scrapie to ruminants and humans by protein misfolding cyclic amplification
Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama
National Institute of Animal Health; Tsukuba, Japan
To assess the risk of the transmission of ruminant prions to ruminants and humans at the molecular level, we investigated the ability of abnormal prion protein (PrPSc) of typical and atypical BSEs (L-type and H-type) and typical scrapie to convert normal prion protein (PrPC) from bovine, ovine, and human to proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding cyclic amplification (PMCA).
Six rounds of serial PMCA was performed using 10% brain homogenates from transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc seed from typical and atypical BSE- or typical scrapie-infected brain homogenates from native host species. In the conventional PMCA, the conversion of PrPC to PrPres was observed only when the species of PrPC source and PrPSc seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA and heparin), both bovine and ovine PrPC were converted by PrPSc from all tested prion strains. On the other hand, human PrPC was converted by PrPSc from typical and H-type BSE in this PMCA condition.
Although these results were not compatible with the previous reports describing the lack of transmissibility of H-type BSE to ovine and human transgenic mice, 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.
***> 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.
***> 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. <***
Transmission of scrapie prions to primate after an extended silent incubation period
Emmanuel E. Comoy, Jacqueline Mikol, Sophie Luccantoni-Freire, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Valérie Durand, Capucine Dehen, Olivier Andreoletti, Cristina Casalone, Juergen A. Richt, Justin J. Greenlee, Thierry Baron, Sylvie L. Benestad, Paul Brown & Jean-Philippe Deslys Scientific Reports volume 5, Article number: 11573 (2015) | Download Citation
Abstract
Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans and having guided protective measures for animal and human health against animal prion diseases. Recently, partial transmissions to humanized mice showed that the zoonotic potential of scrapie might be similar to c-BSE. We here report the direct transmission of a natural classical scrapie isolate to cynomolgus macaque, a highly relevant model for human prion diseases, after a 10-year silent incubation period, with features similar to those reported for human cases of sporadic CJD. Scrapie is thus actually transmissible to primates with incubation periods compatible with their life expectancy, although fourfold longer than BSE. Long-term experimental transmission studies are necessary to better assess the zoonotic potential of other prion diseases with high prevalence, notably Chronic Wasting Disease of deer and elk and atypical/Nor98 scrapie.
SNIP...
Discussion We describe the transmission of spongiform encephalopathy in a non-human primate inoculated 10 years earlier with a strain of sheep c-scrapie. Because of this extended incubation period in a facility in which other prion diseases are under study, we are obliged to consider two alternative possibilities that might explain its occurrence. We first considered the possibility of a sporadic origin (like CJD in humans). Such an event is extremely improbable because the inoculated animal was 14 years old when the clinical signs appeared, i.e. about 40% through the expected natural lifetime of this species, compared to a peak age incidence of 60–65 years in human sporadic CJD, or about 80% through their expected lifetimes. 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.
The second possibility is a laboratory cross-contamination. Three facts make this possibility equally unlikely. First, handling of specimens in our laboratory is performed with fastidious attention to the avoidance of any such cross-contamination. Second, no laboratory cross-contamination has ever been documented in other primate laboratories, including the NIH, even between infected and uninfected animals housed in the same or adjacent cages with daily intimate contact (P. Brown, personal communication). Third, the cerebral lesion profile is different from all the other prion diseases we have studied in this model19, with a correlation between cerebellar lesions (massive spongiform change of Purkinje cells, intense PrPres staining and reactive gliosis26) and ataxia. The iron deposits present in the globus pallidus are a non specific finding that have been reported previously in neurodegenerative diseases and aging27. Conversely, the thalamic lesion was reminiscent of a metabolic disease due to thiamine deficiency28 but blood thiamine levels were within normal limits (data not shown). The preferential distribution of spongiform change in cortex associated with a limited distribution in the brainstem is reminiscent of the lesion profile in MM2c and VV1 sCJD patients29, but interspecies comparison of lesion profiles should be interpreted with caution. It is of note that the same classical scrapie isolate induced TSE in C57Bl/6 mice with similar incubation periods and lesional profiles as a sample derived from a MM1 sCJD patient30.
We are therefore confident that the illness in this cynomolgus macaque represents a true transmission of a sheep c-scrapie isolate directly to an old-world monkey, which taxonomically resides in the primate subdivision (parvorder of catarrhini) that includes humans. With an homology of its PrP protein with humans of 96.4%31, cynomolgus macaque constitutes a highly relevant model for assessing zoonotic risk of prion diseases. Since our initial aim was to show the absence of transmission of scrapie to macaques in the worst-case scenario, we obtained materials from a flock of naturally-infected sheep, affecting animals with different genotypes32. This c-scrapie isolate exhibited complete transmission in ARQ/ARQ sheep (332 ± 56 days) and Tg338 transgenic mice expressing ovine VRQ/VRQ prion protein (220 ± 5 days) (O. Andreoletti, personal communication). From the standpoint of zoonotic risk, it is important to note that sheep with c-scrapie (including the isolate used in our study) have demonstrable infectivity throughout their lymphoreticular system early in the incubation period of the disease (3 months-old for all the lymphoid organs, and as early as 2 months-old in gut-associated lymph nodes)33. In addition, scrapie infectivity has been identified in blood34, milk35 and skeletal muscle36 from asymptomatic but scrapie infected small ruminants which implies a potential dietary exposure for consumers.
Two earlier studies have reported the occurrence of clinical TSE in cynomolgus macaques after exposures to scrapie isolates. In the first study, the “Compton” scrapie isolate (derived from an English sheep) and serially propagated for 9 passages in goats did not transmit TSE in cynomolgus macaque, rhesus macaque or chimpanzee within 7 years following intracerebral challenge1; conversely, after 8 supplementary passages in conventional mice, this “Compton” isolate induced TSE in a cynomolgus macaque 5 years after intracerebral challenge, but rhesus macaques and chimpanzee remained asymptomatic 8.5 years post-exposure8. However, multiple successive passages that are classically used to select laboratory-adapted prion strains can significantly modify the initial properties of a scrapie isolate, thus questioning the relevance of zoonotic potential for the initial sheep-derived isolate. The same isolate had also induced disease into squirrel monkeys (new-world monkey)9. A second historical observation reported that a cynomolgus macaque developed TSE 6 years post-inoculation with brain homogenate from a scrapie-infected Suffolk ewe (derived from USA), whereas a rhesus macaque and a chimpanzee exposed to the same inoculum remained healthy 9 years post-exposure1. This inoculum also induced TSE in squirrel monkeys after 4 passages in mice. Other scrapie transmission attempts in macaque failed but had more shorter periods of observation in comparison to the current study. Further, it is possible that there are differences in the zoonotic potential of different scrapie strains.
The most striking observation in our study is the extended incubation period of scrapie in the macaque model, which has several implications. Firstly, our observations constitute experimental evidence in favor of the zoonotic potential of c-scrapie, at least for this isolate that has been extensively studied32,33,34,35,36. The cross-species zoonotic ability of this isolate should be confirmed by performing duplicate intracerebral exposures and assessing the transmissibility by the oral route (a successful transmission of prion strains through the intracerebral route may not necessarily indicate the potential for oral transmission37). However, such confirmatory experiments may require more than one decade, which is hardly compatible with current general management and support of scientific projects; thus this study should be rather considered as a case report.
Secondly, transmission of c-BSE to primates occurred within 8 years post exposure for the lowest doses able to transmit the disease (the survival period after inoculation is inversely proportional to the initial amount of infectious inoculum). The occurrence of scrapie 10 years after exposure to a high dose (25 mg) of scrapie-infected sheep brain suggests that the macaque has a higher species barrier for sheep c-scrapie than c-BSE, although it is notable that previous studies based on in vitro conversion of PrP suggested that BSE and scrapie prions would have a similar conversion potential for human PrP38.
Thirdly, prion diseases typically have longer incubation periods after oral exposure than after intracerebral inoculations: since humans can develop Kuru 47 years after oral exposure39, an incubation time of several decades after oral exposure to scrapie would therefore be expected, leading the disease to occur in older adults, i.e. the peak age for cases considered to be sporadic disease, and making a distinction between scrapie-associated and truly sporadic disease extremely difficult to appreciate.
Fourthly, epidemiologic evidence is necessary to confirm the zoonotic potential of an animal disease suggested by experimental studies. A relatively short incubation period and a peculiar epidemiological situation (e.g., all the first vCJD cases occurring in the country with the most important ongoing c-BSE epizootic) led to a high degree of suspicion that c-BSE was the cause of vCJD. Sporadic CJD are considered spontaneous diseases with an almost stable and constant worldwide prevalence (0.5–2 cases per million inhabitants per year), and previous epidemiological studies were unable to draw a link between sCJD and classical scrapie6,7,40,41, even though external causes were hypothesized to explain the occurrence of some sCJD clusters42,43,44. However, extended incubation periods exceeding several decades would impair the predictive values of epidemiological surveillance for prion diseases, already weakened by a limited prevalence of prion diseases and the multiplicity of isolates gathered under the phenotypes of “scrapie” and “sporadic CJD”.
Fifthly, considering this 10 year-long incubation period, together with both laboratory and epidemiological evidence of decade or longer intervals between infection and clinical onset of disease, no premature conclusions should be drawn from negative transmission studies in cynomolgus macaques with less than a decade of observation, as in the aforementioned historical transmission studies of scrapie to primates1,8,9. Our observations and those of others45,46 to date are unable to provide definitive evidence regarding the zoonotic potential of CWD, atypical/Nor98 scrapie or H-type BSE. The extended incubation period of the scrapie-affected macaque in the current study also underscores the limitations of rodent models expressing human PrP for assessing the zoonotic potential of some prion diseases since their lifespan remains limited to approximately two years21,47,48. This point is illustrated by the fact that the recently reported transmission of scrapie to humanized mice was not associated with clinical signs for up to 750 days and occurred in an extreme minority of mice with only a marginal increase in attack rate upon second passage13. The low attack rate in these studies is certainly linked to the limited lifespan of mice compared to the very long periods of observation necessary to demonstrate the development of scrapie. Alternatively, one could estimate that a successful second passage is the result of strain adaptation to the species barrier, thus poorly relevant of the real zoonotic potential of the original scrapie isolate of sheep origin49. The development of scrapie in this primate after an incubation period compatible with its lifespan complements the study conducted in transgenic (humanized) mice; taken together these studies suggest that some isolates of sheep scrapie can promote misfolding of the human prion protein and that scrapie can develop within the lifespan of some primate species.
In addition to previous studies on scrapie transmission to primate1,8,9 and the recently published study on transgenic humanized mice13, our results constitute new evidence for recommending that the potential risk of scrapie for human health should not be dismissed. Indeed, human PrP transgenic mice and primates are the most relevant models for investigating the human transmission barrier. To what extent such models are informative for measuring the zoonotic potential of an animal TSE under field exposure conditions is unknown. During the past decades, many protective measures have been successfully implemented to protect cattle from the spread of c-BSE, and some of these measures have been extended to sheep and goats to protect from scrapie according to the principle of precaution. Since cases of c-BSE have greatly reduced in number, those protective measures are currently being challenged and relaxed in the absence of other known zoonotic animal prion disease. We recommend that risk managers should be aware of the long term potential risk to human health of at least certain scrapie isolates, notably for lymphotropic strains like the classical scrapie strain used in the current study. Relatively high amounts of infectivity in peripheral lymphoid organs in animals infected with these strains could lead to contamination of food products produced for human consumption. Efforts should also be maintained to further assess the zoonotic potential of other animal prion strains in long-term studies, notably lymphotropic strains with high prevalence like CWD, which is spreading across North America, and atypical/Nor98 scrapie (Nor98)50 that was first detected in the past two decades and now represents approximately half of all reported cases of prion diseases in small ruminants worldwide, including territories previously considered as scrapie free... Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.
snip...
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"
Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.
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76/10.12/4.6
Nature. 1972 Mar 10;236(5341):73-4.
Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek DC.
Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0
Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)
C. J. GIBBS jun. & D. C. GAJDUSEK
National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland
SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).
Wednesday, February 16, 2011
IN CONFIDENCE
SCRAPIE TRANSMISSION TO CHIMPANZEES
IN CONFIDENCE
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.
OR
***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.
OR
*** Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.
OR here;
*** The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE ...price of prion poker goes up again $
OR-10: Variably protease-sensitive prionopathy is transmissible in bank voles
Romolo Nonno,1 Michele Di Bari,1 Laura Pirisinu,1 Claudia D’Agostino,1 Stefano Marcon,1 Geraldina Riccardi,1 Gabriele Vaccari,1 Piero Parchi,2 Wenquan Zou,3 Pierluigi Gambetti,3 Umberto Agrimi1 1Istituto Superiore di Sanità; Rome, Italy; 2Dipartimento di Scienze Neurologiche, Università di Bologna; Bologna, Italy; 3Case Western Reserve University; Cleveland, OH USA
Background. Variably protease-sensitive prionopathy (VPSPr) is a recently described “sporadic”neurodegenerative disease involving prion protein aggregation, which has clinical similarities with non-Alzheimer dementias, such as fronto-temporal dementia. Currently, 30 cases of VPSPr have been reported in Europe and USA, of which 19 cases were homozygous for valine at codon 129 of the prion protein (VV), 8 were MV and 3 were MM. A distinctive feature of VPSPr is the electrophoretic pattern of PrPSc after digestion with proteinase K (PK). After PK-treatment, PrP from VPSPr forms a ladder-like electrophoretic pattern similar to that described in GSS cases. The clinical and pathological features of VPSPr raised the question of the correct classification of VPSPr among prion diseases or other forms of neurodegenerative disorders. Here we report preliminary data on the transmissibility and pathological features of VPSPr cases in bank voles.
Materials and Methods. Seven VPSPr cases were inoculated in two genetic lines of bank voles, carrying either methionine or isoleucine at codon 109 of the prion protein (named BvM109 and BvI109, respectively). Among the VPSPr cases selected, 2 were VV at PrP codon 129, 3 were MV and 2 were MM. Clinical diagnosis in voles was confirmed by brain pathological assessment and western blot for PK-resistant PrPSc (PrPres) with mAbs SAF32, SAF84, 12B2 and 9A2.
Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission in BvM109. Overall, 3 voles were positive with survival time between 290 and 588 d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form of the typical PrP27–30, which was indistinguishable to that previously observed in BvM109 inoculated with sCJDMM1 cases.
In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission until now. Overall, 5 voles were positive with survival time between 281 and 596 d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like PrPSc electrophoretic pattern, characterized by low molecular weight PrPres. These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus and the N-terminus. Second passages are in progress from these first successful transmissions.
Conclusions. Preliminary results from transmission studies in bank voles strongly support the notion that VPSPr is a transmissible prion disease. Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of voles, with sCJD-like features in BvM109 and GSS-like properties in BvI109.
The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.
31 March 2001
Like lambs to the slaughter
By Debora MacKenzie
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.
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.
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...
Neurobiology Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt- Jakob disease: Implications for human health
Corinne Ida Lasmézas*,, Jean-Guy Fournier*, Virginie Nouvel*, Hermann Boe*, Domíníque Marcé*, François Lamoury*, Nicolas Kopp, Jean-Jacques Hauw§, James Ironside¶, Moira Bruce, Dominique Dormont*, and Jean-Philippe Deslys* * Commissariat à l'Energie Atomique, Service de Neurovirologie, Direction des Sciences du Vivant/Département de Recherche Medicale, Centre de Recherches du Service de Santé des Armées 60-68, Avenue du Général Leclerc, BP 6, 92 265 Fontenay-aux-Roses Cedex, France; Hôpital Neurologique Pierre Wertheimer, 59, Boulevard Pinel, 69003 Lyon, France; § Laboratoire de Neuropathologie, Hôpital de la Salpêtrière, 83, Boulevard de l'Hôpital, 75013 Paris, France; ¶ Creutzfeldt-Jakob Disease Surveillance Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; and Institute for Animal Health, Neuropathogenesis Unit, West Mains Road, Edinburgh EH9 3JF, United Kingdom
Edited by D. Carleton Gajdusek, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France, and approved December 7, 2000 (received for review October 16, 2000)
Abstract
There is substantial scientific evidence to support the notion that bovine spongiform encephalopathy (BSE) has contaminated human beings, causing variant Creutzfeldt-Jakob disease (vCJD). This disease has raised concerns about the possibility of an iatrogenic secondary transmission to humans, because the biological properties of the primate-adapted BSE agent are unknown. We show that (i) BSE can be transmitted from primate to primate by intravenous route in 25 months, and (ii) an iatrogenic transmission of vCJD to humans could be readily recognized pathologically, whether it occurs by the central or peripheral route. Strain typing in mice demonstrates that the BSE agent adapts to macaques in the same way as it does to humans and confirms that the BSE agent is responsible for vCJD not only in the United Kingdom but also in France. The agent responsible for French iatrogenic growth hormone-linked CJD taken as a control is very different from vCJD but is similar to that found in one case of sporadic CJD and one sheep scrapie isolate. These data will be key in identifying the origin of human cases of prion disease, including accidental vCJD transmission, and could provide bases for vCJD risk assessment.
Diagnosis and Reporting of Creutzfeldt-Jakob Disease Singeltary, Sr et al.
JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001
JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.
Terry S. Singeltary, Sr Bacliff, Tex 1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.
Variant Creutzfeldt–Jakob Disease in a Patient with Heterozygosity at PRNP Codon 129
N Engl J Med 2017; 376:292-294January 19, 2017DOI: 10.1056/NEJMc1610003
Share: ArticleMetrics To the Editor:
Prions cause lethal neurodegenerative diseases in mammals and are composed of multichain assemblies of misfolded host-encoded cellular prion protein (PrP). A common polymorphism at codon 129 of the PrP gene (PRNP), where either methionine (M) or valine (V) is encoded, affects the susceptibility to prion disease, as well as the incubation period1 and clinical phenotype of prion disease. Human infection with the epizootic prion disease bovine spongiform encephalopathy resulted in variant Creutzfeldt–Jakob disease, which provoked a public health crisis in the United Kingdom and other regions. All definite cases of variant Creutzfeldt–Jakob disease to date have occurred in patients with the MM genotype at PRNP codon 129.1
A 36-year-old man was referred to the United Kingdom National Prion Clinic in August 2015 with personality change. Over a period of 9 months, he had become uncharacteristically irascible and had progressive episodic memory impairment, gait ataxia, and myoclonus. His score on the Mini–Mental State Examination was 25 (with scores ranging from 0 to 30 and higher scores indicating less impairment); clinical examination revealed extraocular eye-movement abnormalities, pyramidal and cerebellar signs, and multifocal myoclonus. Magnetic resonance imaging of the brain (Figure 1FIGURE 1 MRI of the Brain.) revealed restricted diffusion in the basal ganglia, hypothalami, insular cortexes, and medial thalami but not in the pulvinar nuclei.2 Examination of the cerebrospinal fluid for protein 14-3-3 was negative, as was a real-time quaking-induced conversion assay, although these two tests are known to have low sensitivity for variant Creutzfeldt–Jakob disease.3 His genotype at PRNP codon 129 was MV. During the following 6 months, the patient’s condition declined progressively, and severe dysphagia and agitation occurred shortly before his death in February 2016.
At autopsy, histologic examination of the brain revealed frequent florid and cluster plaques in cerebral and cerebellar cortexes, microvacuolar degeneration in neuropil, and immunostaining for abnormal PrP in a stellate pericellular and perivascular distribution. Minute amounts of protease-resistant PrP (PrPSc) were seen in lymphoid tissue of the spleen. Immunoblotting of brain homogenate revealed type 4 PrPSc (according to the London classification system), which is pathognomonic of variant Creutzfeldt–Jakob disease.4 (For more details, see the Supplementary Appendix, available with the full text of this letter at NEJM.org.)
This patient’s clinical features differed from those of typical variant Creutzfeldt–Jakob disease, and his neuroimaging features suggested a diagnosis of sporadic Creutzfeldt–Jakob disease. He did not meet the epidemiologic diagnostic criteria for probable or possible variant Creutzfeldt–Jakob disease,5 yet the results of the neuropathological examination and molecular strain typing were consistent with variant Creutzfeldt–Jakob disease. It remains uncertain whether this case marks the start of a second wave of variant Creutzfeldt–Jakob disease in persons with the MV genotype at PRNP codon 129 (the most common genotype in the United Kingdom), mirroring the long incubation periods seen in persons with the MV genotype who have other acquired prion diseases, notably kuru.1 This case emphasizes the importance of performing an autopsy and molecular strain typing in cases of prion disease to ascertain the prevalence of human prion disease related to bovine spongiform encephalopathy.
snip...see full text ;
>>> This patient’s clinical features differed from those of typical variant Creutzfeldt–Jakob disease, and his neuroimaging features suggested a diagnosis of sporadic Creutzfeldt–Jakob disease. He did not meet the epidemiologic diagnostic criteria for probable or possible variant Creutzfeldt–Jakob disease,5 yet the results of the neuropathological examination and molecular strain typing were consistent with variant Creutzfeldt–Jakob disease. <<<
Many more people could still die from mad cow disease in the UK
SHORT SHARP SCIENCE
By Debora MacKenzie
18 January 2017
It’s finally happened. Until now, vCJD – the deadly disease caused by infection with BSE, or “mad cow disease” – has struck only people with a certain genetic makeup. Now, for the first time, researchers have confirmed a case in someone with different genes – a finding that could mean we have been misdiagnosing a new wave of cases.
SATURDAY, JUNE 23, 2018
CDC
***> Diagnosis of Methionine/Valine Variant Creutzfeldt-Jakob Disease by Protein Misfolding Cyclic Amplification
Volume 24, Number 7—July 2018 Dispatch
THURSDAY, JANUARY 19, 2017
Variant Creutzfeldt–Jakob Disease in a Patient with Heterozygosity at PRNP Codon 129
Monday, April 20, 2020
PRION2020 POSTPONED TO 2021 – DUE TO CORONAVIRUS (COVID-19)
MONDAY, AUGUST 26, 2019
Creutzfeldt Jakob Disease CJD, TSE, Prion, Surveillance Update August 2019
SUNDAY, MARCH 10, 2019
National Prion Disease Pathology Surveillance Center Cases Examined¹ Updated Feb 1, 2019 Variably protease-sensitive prionopathy VPSPr
***> In conclusion, sensory symptoms and loss of reflexes in Gerstmann-Sträussler-Scheinker syndrome can be explained by neuropathological changes in the spinal cord. We conclude that the sensory symptoms and loss of lower limb reflexes in Gerstmann-Sträussler-Scheinker syndrome is due to pathology in the caudal spinal cord. <***
***> The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.<***
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***
***> 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.<***
***> In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids.'' Scientific opinion on chronic wasting disease (II) <***
THURSDAY, JANUARY 30, 2020
Docket Number: FDA-2012-D-0307 Recommendations to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Components; Draft Guidance for Industry Draft Guidance for Industry Singeltary Submission
FRIDAY, JANUARY 31, 2020
CJD TSE Prion Blood Products, iatrogenic transmission, Confucius is confused again, WHAT IF? Docket Number: FDA-2012-D-0307
Updated April 3, 2020
Year Total Referrals² Prion Disease Sporadic Familial Iatrogenic vCJD
1999 & earlier 381 230 200 27 3 0
2000 145 102 90 12 0 0
2001 209 118 110 8 0 0
2002 241 144 124 18 2 0
2003 259 160 137 21 2 0
2004 316 181 164 16 0 1³
2005 327 178 156 21 1 0
2006 365 179 159 17 1 2⁴
2007 374 210 191 19 0 0
2008 384 221 205 16 0 0
2009 397 231 210 20 1 0
2010 401 246 218 28 0 0
2011 392 238 214 24 0 0
2012 413 244 221 23 0 0
2013 416 258 223 34 1 0
2014 355 208 185 21 1 1⁵
2015 401 263 243 20 0 0
2016 396 277 248 29 0 0
2017 375 266 247 19 0 0
2018 309 223 204 18 1 0
2019 416 270 240 21 0 0
2020 84 56 21 2 0 0
TOTAL 73566 45037 40108 4349 13 4
1Listed based on the year of death or, if not available, on the year of referral;
2Cases with suspected prion disease for which brain tissue was submitted;
3Disease acquired in the United Kingdom;
4Disease acquired in the United Kingdom in one case and in Saudi Arabia in the other;
5Disease possibly acquired in a Middle Eastern or Eastern European country;
6Includes 14 cases in which the diagnosis is pending, and 19 inconclusive cases;
7Includes 42 (9 from 2019, 33 from 2020) cases with type determination pending in which the diagnosis of vCJD has been excluded.
8The sporadic cases include 3906 cases of sporadic Creutzfeldt-Jakob disease (sCJD), 69 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 35 cases of sporadic Fatal Insomnia (sFI).
9Total does not include 272 Familial cases diagnosed by blood test only.
Monday, February 3, 2020
Informing Patient Contacts About Iatrogenic Creutzfeldt Jakob Disease
Creutzfeldt Jakob Disease CJD
U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
Subject: BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001
Date: Tue, 9 Jan 2001 16:49:00 -0800
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
snip...
[host Richard Barns] and now a question from Terry S. Singeltary of CJD Watch.
[TSS] yes, thank you, U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?
[no answer, you could hear in the back ground, mumbling and 'we can't. have him ask the question again.]
[host Richard] could you repeat the question?
[TSS] U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?
[not sure whom ask this] what group are you with?
[TSS] CJD Watch, my Mom died from hvCJD and we are tracking CJD world-wide.
[not sure who is speaking] could you please disconnect Mr. Singeltary
[TSS] you are not going to answer my question?
[not sure whom speaking] NO
snip...see full archive and more of this;
Scientific Advisors and Consultants Staff 2001 Advisory Committee TSE PRION Singeltary Submission Freas Monday, January 08,2001 3:03 PM FDA Singeltary submission 2001
Greetings again Dr. Freas and Committee Members,
I wish to submit the following information to the Scientific Advisors and Consultants Staff 2001 Advisory Committee (short version). I understand the reason of having to shorten my submission, but only hope that you add it to a copy of the long version, for members to take and read at their pleasure, (if cost is problem, bill me, address below). So when they realize some time in the near future of the 'real' risks i speak of from human/animal TSEs and blood/surgical products. I cannot explain the 'real' risk of this in 5 or 10 minutes at some meeting, or on 2 or 3 pages, but will attempt here:
snip...see full text ;
Subject: Prion Scientific Advisors and Consultants Staff Meeting Singeltary Submission Freas Monday, January 08,2001 3:03 PM
PLEASE be aware, my submission here has now been removed from the www, or changed to a different url that no one knows now, and does not come up in search engines anymore, after 17 years...wonder why that could be, i guess the truth just hurt to much$$$
Freas, William
From: Terry S. Singeltary Sr. [flounder@wt.net]
Sent: Monday, January 08,2001 3:03 PM
Subject: CJD/BSE (aka madcow) Human/Animal TSE’s--U.S.--Submission To Scientific Advisors and Consultants Staff January 2001 Meeting (short version)
CJD/BSE (aka madcow) Human/Animal TSE’s--U.S.--Submission To Scientific Advisors and Consultants Staff January 2001 Meeting (short version)
Greetings again Dr. Freas and Committee Members,
I wish to submit the following information to the Scientific Advisors and Consultants Staff 2001 Advisory Committee (short version).
I understand the reason of having to shorten my submission, but only hope that you add it to a copy of the long version, for members to take and read at their pleasure, (if cost is problem, bill me, address below). So when they realize some time in the near future of the 'real' risks i speak of from human/animal TSEs and blood/surgical products. I cannot explain the 'real' risk of this in 5 or 10 minutes at some meeting, or on 2 or 3 pages, but will attempt here:
remember AIDS/HIV, 'no problem to heterosexuals in the U.S.? no need to go into that, you know of this blunder:
DO NOT make these same stupid mistakes again with human/animal TSE's aka MADCOW DISEASE. I lost my Mom to hvCJD, and my neighbor lost his Mother to sCJD as well (both cases confirmed). I have seen many deaths, from many diseases. I have never seen anything as CJD, I still see my Mom laying helpless, jerking tremendously, and screaming "God, what's wrong with me, why can't I stop this". I still see this, and will never forget. Approximately 10 weeks from 1st of symptoms to death. This is what drives me. I have learned more in 3 years about not only human/animal TSE's but the cattle/rendering/feeding industry/government than i ever wished to.
I think you are all aware of CJD vs vCJD, but i don't think you all know the facts of human/animal TSE's as a whole, they are all very very similar, and are all tied to the same thing, GREED and MAN.
I am beginning to think that the endless attempt to track down and ban, potential victims from known BSE Countries from giving blood will be futile. You would have to ban everyone on the Globe eventually? AS well, I think we MUST ACT SWIFTLY to find blood test for TSE's, whether it be blood test, urine test, .eyelid test, anything at whatever cost, we need a test FAST.
DO NOT let the incubation time period of these TSEs fool you.
To think of Scrapie as the prime agent to compare CJD, but yet overlook the Louping-ill vaccine event in 1930's of which 1000's of sheep where infected by scrapie from a vaccine made of scrapie infected sheep brains, would be foolish. I acquired this full text version of the event which was recorded in the Annual Congress of 1946 National Vet. Med. Ass. of Great Britain and Ireland. from the BVA and the URL is posted in my (long version).
U.S.A. should make all human/animal TSE's notifiable at all ages, with requirements for a thorough surveillance and post-mortem examinations free of charge, if you are serious about eradicating this horrible disease in man and animal.
There is histopathology reports describing o florid plaques" in CJD victims in the USA and some of these victims are getting younger. I have copies of such autopsies, there has to be more. PLUS, sub-clinical human TSE's will most definitely be a problem.
THEN think of vaccineCJD in children and the bovine tissues used in the manufacturing process, think of the FACT that this agent surviving 6OO*C. PNAS -- Brown et al. 97 (7): 3418 scrapie agent live at 600*C
Then think of the CONFIDENTIAL documents of what was known of human/animal TSE and vaccines in the mid to late 80s, it was all about depletion of stock, to hell with the kids, BUT yet they knew. To think of the recall and worry of TSE's from the polio vaccine, (one taken orally i think?), but yet neglect to act on the other potential TSE vaccines (inoculations, the most effective mode to transmit TSEs) of which thousands of doses were kept and used, to deplete stockpile, again would be foolish.
--Oral polio; up to 1988, foetal calf serum was used from UK and New Zealand (pooled); since 1988 foetal calf serum only from New Zealand. Large stocks are held.
--Rubella; bulk was made before 1979 from foetal calf serum from UK and New Zealand. None has been made as there are some 15 years stock.
--Diphtheria; UK bovine beef muscle and ox heart is used but since the end of 1988 this has been sourced from Eire. There are 1,250 litres of stock.
--Tetanus; this involves bovine material from the UK mainly Scottish. There are 21,000 litres of stock.
--Pertussis; uses bovine material from the UK. There are 63,000 litres of stock. --They consider that to switch to a non-UK source will take a minimum of 6-18 months and to switch to a non-bovine source will take a minimum of five years.
3. XXXXXXXXXXX have measles, mumps, MMR, rubella vaccines. These are sourced from the USA and the company believes that US material only is used.
89/2.14/2.1
============
BSE3/1 0251
4. XXXXXXXXXXX have a measles vaccine using bovine serum from the UK. there are 440,000 units of stock. They have also got MMR using bovine serum from the UK.
5. XXXXXXXXXXX have influenza, rubella, measles,' MMR vaccines likely to be used in children. Of those they think that only MMR contains bovine material which is probably a French origin.
6. XXXXXXXXXXX have diphtheria/tetanus and potasses on clinical trial. hese use veal material, some of which has come from the UK and has been ade by XXXXXXXXXXX (see above).
I have documents of imports from known BSE Countries, of ferments, whole blood, antiallergenic preparations,
2
human blood plasma, normal human blood sera, human immune blood sera, fetal bovine serum, and other blood fractions not elsewhere specified or included, imported glands, catgut, vaccines for both human/animal, as late as 1998. Let us not forget about PITUITARY EXTRACT. This was used to help COWS super ovulate. This tissue was considered to be of greatest risk of containing BSE and consequently transmitting the disease.
ANNEX 6
MEETING HELD ON 8 JUNE 1988 TO DISCUSS THE IMPLICATIONS OF BSE TO BIOLOGICAL PRODUCTS CONTAINING BOVINE - EXTRACTED MATERIAL
How much of this was used in the U.S.?
Please do not keep making the same mistakes; 'Absence of evidence is not evidence of absence'.
What are the U.S. rules for importing and manufacturing vaccines, medicines and medical devices?
Does the U.S.A. allow sourcing of raw material of ruminants from the U.S.A.?
U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds? . The U.S. rendering system would easily amplify T.S.E.'s:
Have we increased the stability of the system (improved heat treatments) since the EU SSC report on the U.S.A. was published in july 2000?
What is done to avoid cross-contaminations in the U.S.A.?
How can the U.S. control absence of cross-contaminations of animal TSE's when pig and horse MBM and even deer and elk are allowed in ruminant feed, as well as bovine blood? I sadly think of the rendering and feeding policy before the Aug. 4, 1997 'partial' feed ban, where anything went, from the city police horse, to the circus elephant, i will not mention all the scrapie infected sheep. I am surprised that we have not included man 'aka soyent green'. It is a disgusting industry and nothing more than greed fuels it.
When will the U.S.. start real surveillance of the U.S. bovine population (not passive, this will not work)?
When will U.S. start removing SRMs?
Have they stopped the use of pneumatic stunners in the U.S.?
If so, will we stop it in all U.S. abattoirs or only in those abattoirs exporting to Europe?
If not, WHY NOT?
same questions for removal of SRM in the U.S.A., or just for export?
If not, WHY NOT?
How do we now sterilize surgical/dental instruments in the U.S.A.?
Where have we been sourcing surgical catgut?
(i have copies of imports to U.S., and it would floor you) hen will re-usable surgical instruments be banned?
'Unregulated "foods" such as 'nutritional supplements' containing various extracts from ruminants, whether imported or derived from
3
US cattle/sheep/cervids ("antler velvet" extracts!) should be forbidden or at least very seriously regulated. (neighbors Mom, whom also died from CJD, had been taking bovine based supplement, which contained brain, eye, and many other bovine/ovine tissues for years, 'IPLEX').
What is the use of banning blood or tissue donors from Germany, France, etc... when the U.S.A. continues exposing cattle, sheep and people to SRM, refuses to have a serious feed ban, refuses to do systematic BSE-surveillance?
The FDA should feel responsible for the safety of what people eat, prohibit the most dangerous foods, not only prohibit a few more donors - the FDA should be responsible for the safe sourcing of medical devices, not only rely on banning donors "from Europe", The 'real' risks are here in the U.S. as well, and nave been for some time.
We must not forget the studies that have proven infectivity in blood from TSE's.
The Lancet, November 9, 1985
Sir, --Professor Manuelidis and his colleagues (Oct 19, p896) report transmission to animals of Creutzfeldt-Jakob disease (CJD) from the buffy coat from two patients. We also transmitted the disease from, whole blood samples of a patient (and of mice) infected with CJD.l Brain, Cornea, and urine from this patient were also infectious, and the clinicopathological findings2 are summarised as follows.
snip...
Samples,were taken aseptically at necropsy. 10% crude homogenates of brain and cornea in saline, whole blood (after crushing a clot), and untreated CSF and urine were innoculated intracerebrally into CFl strain mice (20 ul per animal). Some mice showed emaciation, bradykinesia, rigidity of the body and tail, and sometimes tremor after long incubation periods. Tissues obtained after the animal died (or was killed) were studied histologically (table). Animals infected by various inocula showed common pathological changes, consisting of severe spongiform changes, glial proliferation, and a moderate loss of nerve cells. A few mice inoculated with brain tissue or urine had the same amyloid plaques found in patients and animals with CJD.3
snip...
Department of Neuropathology,. Neurological Institute, Faculty of Medicine, Kyushu University, Fukuoka812, Japan JUN TATEISHI
(full text-long version)
and
CWD and transmission to man will be no different than other TSE's.
"Clearly, it is premature to draw firm conclusions about CWD passing naturally into humans, cattle and sheep, but the present results suggest that CWD transmissions to humans would be as limited by PrP incompatibility as transmissions of BSE or sheep scrapie to humans. Although there is no evidence that sheep scrapie has affected humans, it is likely that BSE has
4
caused variant CJD in 74 people (definite and probable variant CJD cases to date according to the UK CJD Surveillance Unit). Given the presumably large number of people exposed to BSE infectivity, the susceptibility of humans may still be very low compared with cattle, which would be consistent with the relatively inefficient conversion of human PrP-sen by PrPBSE. Nonetheless, since humans have apparently been infected by BSE, it would seem prudent to take reasonable measures to limit exposure of humans (as well as sheep and cattle) to CWD infectivity as has been recommended for other animal TSEs,"
G.J. Raymond1, A. Bossers2, L.D. Raymond1, K.I. O'Rourke3, L.E. McHolland4, P.K. Bryant III4, M.W. Miller5, E.S. Williams6, M. Smits2 and B. Caughey1,7
or more recently transmission of BSE to sheep via whole blood Research letters Volume 356, Number 9234 16 September 2000
Transmission of BSE by blood transfusion in sheep
Lancet 2000; 356: 999 – 1000
F Houston, J D Foster, Angela Chong, N Hunter, C J Bostock
See Commentary
"We have shown that it is possible to transmit bovine spongiform encephalopathy (BSE) to a sheep by transfusion with whole blood taken from another sheep during the symptom-free phase of an experimental BSE infection. BSE and variant Creutzfeldt-Jakob disease (vCJD) in human beings are caused by the same infectious agent, and the sheep-BSE experimental model has a similar pathogenesis to that of human vCJD. Although UK blood transfusions are leucodepleted--a possible protective measure against any risk from blood transmission-- this report suggests that blood donated by symptom-free vCJD-infected human beings may represent a risk of spread of vCJD infection among the human population of the UK."
"The demonstration that the new variant of Creutzfeldt-Jakob disease (vCJD) is caused by the same agent that causes bovine spongiform encephalopathy (BSE) in cattle1 has raised concerns that blood from human beings in the symptom-free stages of vCJD could transmit infection to recipients of blood transfusions (full text long version)"
and...
"The large number of cases (1040), temporal clustering of the outbreaks (15 in the first 6 months of 1997), the high in-flock incidence, and the exceptional involvement of goats (390 cases), suggested an accidental infection. The source of the epidemic might have been TSE-contaminated meat and bonemeal, but eight flocks had never been fed any commercial feedstuff. Infection might have risen from the use of a formol-inactivated vaccine against contagious agalactia prepared by a single laboratory with brain and mammary gland homogenates of sheep infected with Mycoplasma agalactiae. Although clinical signs of TSE in the donor sheep have not been found, it is possible that one or more of them were harbouring the
5
infectious agent. Between 1995 and 1996, this vaccine was given subcutaneously to 15 of the affected flocks (to one flock in 1994) ; in these animals the disease appeared between 23 and 35 months after vaccination. No information is available for herd 13 because it was made up of stolen animals. Sheep from the remaining three flocks (1-3, figure) did not receive the vaccine, thus suggesting a naturally occurring disease.’’ (again, full text long version).
IN SHORT, please do under estimate this data and or human/animal TSE's including CWD in the U.S.A.
A few last words, please.
The cattle industry would love to have us turn our focus to CWD and forget about our own home grown TSE in Bovines. This would be easy to do. Marsh's work was from downer cattle feed, NOT downer deer/elk feed. This has been proven.
DO NOT MAKE THAT MISTAKE.
There should be NO LESS THAN 1,000,000 tests for BSE/TSE ' in 2001 for U.S.A. French are testing 20,000 a week. The tests are available. Why wait until we stumble across a case from passive surveillance, by then it is to late. IF we want the truth, this is a must???
United States Total ,Bovine Brain Submissions by State,
May 10 ,1990 thru October 31, 2000
Total 11,700
FROM 1.5 BILLION HEAD OF CATTLE since 1990 ???
with same feeding and rendering practices as that of U.K. for years and years, same scrapie infected sheep used in feed, for years and years, 950 scrapie infect FLOCKS in the U.S. and over 20 different strains of scrapie known to date. (hmmm, i am thinking why there is not a variant scrapie, that is totally different than all the rest)? just being sarcastic.
with only PARTIAL FEED BAN implemented on Aug. 4, 1997??? (you really need to reconsider that blood meal etc. 'TOTAL BAN')
AND PLEASE FOR GODS SAKE, STOP saying vCJD victims are the only ones tied to this environmental death sentence. "PROVE IT". It's just not true. The 'CHOSEN ONES' are not the only ones dying because of this man-made death sentence. When making regulations for human health from human/animal TSEs, you had better include ALL human TSE's, not just vCJD. Do NOT underestimate sporadic CJD with the 'prehistoric' testing available to date. This could be a deadly mistake. Remember, sCJD kills much faster from 1st onset of symptoms to death, and hvCJD is the fastest. Could it just be a higher titre of infectivity, or route or source, or all three?
Last, but not least. The illegal/legal harvesting of body parts and tissues will come back to haunt you. Maybe not morally, but due to NO background checks and human TSEs, again it will continue to spread.
Stupidity, Ignorance and Greed is what fuels this disease. You must stop all of this, and ACT AT ONCE...
Sent: Monday, January 08,2001 3:03 PM
FDA CJD BSE TSE Prion Scientific Advisors and Consultants Staff January 2001 Meeting Singeltary Submission
2001 FDA CJD TSE Prion Singeltary Submission
THURSDAY, DECEMBER 19, 2019
TSE surveillance statistics exotic species and domestic cats Update December 2019
MONDAY, DECEMBER 16, 2019
Chronic Wasting Disease CWD TSE Prion aka mad cow type disease in cervid Zoonosis Update
***> ''In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids.'' Scientific opinion on chronic wasting disease (II) <***
What if?
> However, to date, no CWD infections have been reported in people.
key word here is ‘reported’. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can’t, and it’s as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it’s being misdiagnosed as sporadic CJD. …terry
*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***
*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***
Chronic Wasting Disease CWD TSE Prion aka mad deer disease zoonosis
We hypothesize that:
(1) The classic CWD prion strain can infect humans at low levels in the brain and peripheral lymphoid tissues;
(2) The cervid-to-human transmission barrier is dependent on the cervid prion strain and influenced by the host (human) prion protein (PrP) primary sequence;
(3) Reliable essays can be established to detect CWD infection in humans; and
(4) CWD transmission to humans has already occurred. We will test these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in vitro approaches.
ZOONOTIC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE
Prion 2017 Conference
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
PRION 2018 CONFERENCE
Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice
Hermann M. Schatzl, Samia Hannaoui, Yo-Ching Cheng, Sabine Gilch (Calgary Prion Research Unit, University of Calgary, Calgary, Canada) Michael Beekes (RKI Berlin), Walter Schulz-Schaeffer (University of Homburg/Saar, Germany), Christiane Stahl-Hennig (German Primate Center) & Stefanie Czub (CFIA Lethbridge).
To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years.
After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were detected in spinal cord and brain of some euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and pre-clinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles.
Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate.
The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.
Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP.
Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP.
The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD..
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***
READING OVER THE PRION 2018 ABSTRACT BOOK, LOOKS LIKE THEY FOUND THAT from this study ;
P190 Human prion disease mortality rates by occurrence of chronic wasting disease in freeranging cervids, United States
Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1) (1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA..
SEEMS THAT THEY FOUND Highly endemic states had a higher rate of prion disease mortality compared to non-CWD
states.
states.
AND ANOTHER STUDY;
P172 Peripheral Neuropathy in Patients with Prion Disease
Wang H(1), Cohen M(1), Appleby BS(1,2) (1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio..
IN THIS STUDY, THERE WERE autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017,
AND
included 104 patients. SEEMS THEY FOUND THAT The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%),
AND
THAT The Majority of cases were male (60%), AND half of them had exposure to wild game.
snip…
see more on Prion 2017 Macaque study from Prion 2017 Conference and other updated science on cwd tse prion zoonosis below…terry
PRION 2019 ABSTRACTS
1. Interspecies transmission of the chronic wasting disease agent
Justin Greenlee
Virus and Prion Research Unit, National Animal Disease Center, USDA Agriculture Research Service
ABSTRACT
The presentation will summarize the results of various studies conducted at our research center that assess the transmissibility of the chronic wasting disease (CWD) agent to cattle, pigs, raccoons, goats, and sheep. This will include specifics of the relative attack rates, clinical signs, and microscopic lesions with emphasis on how to differentiate cross-species transmission of the CWD agent from the prion diseases that naturally occur in hosts such as cattle or sheep. Briefly, the relative difficulty of transmitting the CWD agent to sheep and goats will be contrasted with the relative ease of transmitting the scrapie agent to white-tailed deer.
53. Evaluation of the inter-species transmission potential of different CWD isolates
Rodrigo Moralesa, Carlos Kramma,b, Paulina Sotoa, Adam Lyona, Sandra Pritzkowa, Claudio Sotoa
aMitchell Center for Alzheimer’s disease and Related Brain Disorders, Dept. of Neurology, McGovern School of Medicine University of Texas Health Science Center at Houston, TX, USA; bFacultad de Medicina, Universidad de los Andes, Santiago, Chile
ABSTRACT
Chronic Wasting Disease (CWD) has reached epidemic proportions in North America and has been identified in South Korea and Northern Europe. CWD-susceptible cervid species are known to share habitats with humans and other animals entering the human food chain. At present, the potential of CWD to infect humans and other animal species is not completely clear. The exploration of this issue acquires further complexity considering the differences in the prion protein sequence due to species-specific variations and polymorphic changes within species. While several species of cervids are naturally affected by CWD, white-tailed deer (WTD) is perhaps the most relevant due to its extensive use in hunting and as a source of food. Evaluation of inter-species prion infections using animals or mouse models is costly and time consuming. We and others have shown that the Protein Misfolding Cyclic Amplification (PMCA) technology reproduces, in an accelerated and inexpensive manner, the inter-species transmission of prions while preserving the strain features of the input PrPSc. In this work, we tested the potential of different WTD-derived CWD isolates to transmit to humans and other animal species relevant for human consumption using PMCA. For these experiments, CWD isolates homozygous for the most common WTD-PrP polymorphic changes (G96S) were used (96SS variant obtained from a pre-symptomatic prion infected WTD). Briefly, 96GG and 96SS CWD prions were adapted in homologous or heterologous substrate by PMCA through several (15) rounds. End products, as well as intermediates across the process, were tested for their inter-species transmission potentials. A similar process was followed to assess seed-templated misfolding of ovine, porcine, and bovine PrPC. Our results show differences on the inter-species transmission potentials of the four adapted materials generated (PrPC/PrPSc polymorphic combinations), being the homologous combinations of seed/substrate the ones with the greater apparent zoonotic potential. Surprisingly, 96SS prions adapted in homologous substrate were the ones showing the easiest potential to template PrPC misfolding from other animal species. In summary, our results show that a plethora of different CWD isolates, each comprising different potentials for inter-species transmission, may exist in the environment. These experiments may help to clarify an uncertain and potentially worrisome public health issue. Additional research in this area may be useful to advise on the design of regulations intended to stop the spread of CWD and predict unwanted zoonotic events.
56. Understanding chronic wasting disease spread potential for at-risk species
Catherine I. Cullingham, Anh Dao, Debbie McKenzie and David W. Coltman
Department of Biological Sciences, University of Alberta, Edmonton AB, Canada
CONTACT Catherine I. Cullingham cathy.cullingham@ualberta.ca
ABSTRACT
Genetic variation can be linked to susceptibility or resistance to a disease, and this information can help to better understand spread-risk in a population. Wildlife disease incidence is increasing, and this is resulting in negative impacts on the economy, biodiversity, and in some instances, human health. If we can find genetic variation that helps to inform which individuals are susceptible, then we can use this information on at-risk populations to better manage negative consequences. Chronic wasting disease, a fatal, transmissible spongiform encephalopathy of cervids (both wild and captive), continues to spread geographically, which has resulted in an increasing host-range. The disease agent (PrPCWD) is a misfolded conformer of native cellular protein (PrPC). In Canada, the disease is endemic in Alberta and Saskatchewan, infecting primarily mule deer and white-tail deer, with a smaller impact on elk and moose populations. As the extent of the endemic area continues to expand, additional species will be exposed to this disease, including bison, bighorn sheep, mountain goat, and pronghorn antelope. To better understand the potential spread-risk among these species, we reviewed the current literature on species that have been orally exposed to CWD to identify susceptible and resistant species. We then compared the amino acid polymorphisms of PrPC among these species to determine whether any sites were linked to susceptibility or resistance to CWD infection. We sequenced the entire PrP coding region in 578 individuals across at-risk populations to evaluate their potential susceptibility. Three amino acid sites (97, 170, and 174; human numbering) were significantly associated with susceptibility, but these were not fully discriminating. All but one species among the resistant group shared the same haplotype, and the same for the susceptible species. For the at-risk species, bison had the resistant haplotype, while bighorn sheep and mountain goats were closely associated with the resistant type. Pronghorn antelope and a newly identified haplotype in moose differed from the susceptible haplotype, but were still closely associated with it. These data suggest pronghorn antelope will be susceptible to CWD while bison are likely to be resistant. Based on this data, recommendations can be made regarding species to be monitored for possible CWD infection.
KEYWORDS: Chronic wasting disease; Prnp; wildlife disease; population genetics; ungulates
Thursday, May 23, 2019
Prion 2019 Emerging Concepts CWD, BSE, SCRAPIE, CJD, SCIENTIFIC PROGRAM Schedule and Abstracts
see full Prion 2019 Conference Abstracts
THURSDAY, OCTOBER 04, 2018
Cervid to human prion transmission 5R01NS088604-04 Update
snip…full text;
SATURDAY, FEBRUARY 09, 2019
Experts: Yes, chronic wasting disease in deer is a public health issue — for people
SATURDAY, FEBRUARY 23, 2019
Chronic Wasting Disease CWD TSE Prion and THE FEAST 2003 CDC an updated review of the science 2019
TUESDAY, NOVEMBER 04, 2014
Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: risk behaviours and health outcomes 2005–2011
Authors, though, acknowledged the study was limited in geography and sample size and so it couldn't draw a conclusion about the risk to humans. They recommended more study. Dr. Ermias Belay was the report's principal author but he said New York and Oneida County officials are following the proper course by not launching a study. "There's really nothing to monitor presently. No one's sick," Belay said, noting the disease's incubation period in deer and elk is measured in years. "
Transmission Studies
Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases {the following was written but with a single line marked through it ''first passage (by this route)}....TSS
resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculum (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in ALL of these species with the shortest incubation period in the ferret.
snip....
Prion Infectivity in Fat of Deer with Chronic Wasting Disease▿
Brent Race#, Kimberly Meade-White#, Richard Race and Bruce Chesebro* + Author Affiliations
In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species.
Prions in Skeletal Muscles of Deer with Chronic Wasting Disease
Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure.
*** now, let’s see what the authors said about this casual link, personal communications years ago, and then the latest on the zoonotic potential from CWD to humans from the TOKYO PRION 2016 CONFERENCE.
see where it is stated NO STRONG evidence. so, does this mean there IS casual evidence ???? “Our conclusion stating that we found no strong evidence of CWD transmission to humans”
From: TSS
Subject: CWD aka MAD DEER/ELK TO HUMANS ???
Date: September 30, 2002 at 7:06 am PST
From: "Belay, Ermias"
To: Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"
Sent: Monday, September 30, 2002 9:22 AM
Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Dear Sir/Madam,
In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD.. That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091). Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.
Ermias Belay, M.D. Centers for Disease Control and Prevention
-----Original Message-----
From: Sent: Sunday, September 29, 2002 10:15 AM
Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Sunday, November 10, 2002 6:26 PM .......snip........end..............TSS
Thursday, April 03, 2008
A prion disease of cervids: Chronic wasting disease 2008 1: Vet Res. 2008 Apr 3;39(4):41 A prion disease of cervids: Chronic wasting disease Sigurdson CJ.
snip...
*** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,
snip... full text ;
> However, to date, no CWD infections have been reported in people.
sporadic, spontaneous CJD, 85%+ of all human TSE, just not just happen. never in scientific literature has this been proven.
if one looks up the word sporadic or spontaneous at pubmed, you will get a laundry list of disease that are classified in such a way;
sporadic = 54,983 hits https://www.ncbi.nlm.nih.gov/pubmed/?term=sporadic
spontaneous = 325,650 hits https://www.ncbi.nlm.nih.gov/pubmed/?term=spontaneous
key word here is 'reported'. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can't, and it's as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it's being misdiagnosed as sporadic CJD. ...terry
*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***
*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***
FRIDAY, JULY 26, 2019
Chronic Wasting Disease in Cervids: Implications for Prion Transmission to Humans and Other Animal Species
TUESDAY, JUNE 09, 2020
Wisconsin Trempealeau County Deer Farm Tests Positive for CWD Release Date: June 9, 2020
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. at
3:51 PM
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