Transmission of CH1641 in cattle
Jemma K. Thorne, Janet Hills, M. Carmen Garcia-Pelayo, Timm Konold, and John Spiropoulos
Pathology and Animal Sciences Department, Animal and Plant Health Agency, Addlestone, UK
Aims: Classical BSE (C-BSE) was first identified in UK in the 1980s and is the only TSE that has proven zoonotic potential. The emergence of C-BSE was associated with a change in rendering practices implying that prions were able to escape inactivation. However, the exact origin of C-BSE remains unknown to this date although several theories have been proposed. CH1641 is a type of scrapie that biochemically is most akin to BSE. In addition CH1641 is the only scrapie type that can transmit as efficiently as C-BSE to bovinised mice (tg110) suggesting that the agent can propagate with ease on a bovine PrP background in contrast to other scrapie strains. This study was designed to investigate the transmissibility of CH1641 into cattle and characterise the resulting phenotype.
Material and Methods: To examine the ability of CH1641 to transmit to cattle, 5 animals were inoculated intracerebrally with an ovine CH1641 source. The clinical status of the animals was monitored and when they developed neurological signs they were euthanised on welfare grounds. Another 5 cattle were inoculated intracerebrally with saline solution to serve as negative, age-matched controls. Disease status was confirmed postmortem by statutory testing (Immunohistochemistry and Western blot).
Results: All CH1641 inoculated animals succumbed to clinical TSE with incubation periods 609–654 days post inoculation (dpi). One negative control died at 37 dpi and was excluded from the analysis as an intercurrent death. The remaining negative controls were killed at predetermined points to age match the CH1641 challenged cattle; they all were TSE negative. Western blot analysis revealed that in some animals the agent retained a CH1641 signature whilst in others the molecular profile acquired properties resembling C-BSE. Immunohistochemical analysis showed a similar phenotypic spectrum.
Conclusions: These preliminary data suggest that transmission of CH1641 in cattle is efficient and it results in a variable disease phenotype. Further studies are currently ongoing and include inoculation of bovinised and ovinised mice to identify if the CH1641 agent changed biological properties upon transmission to cattle. Secondary passages in cattle to investigate if intraspecies transmission can alter further the properties of the agent forcing it to converge towards C-BSE are also under consideration.
Funded by: Defra
Grant number: SE1962
Acknowledgement: Pathology and Animal Science Department staff members for technical excellence
PRION 2022 ABSTRACTS, AND A BIG THANK YOU TO;
On behalf of the Prion2020/2022 Congress Organizing Committee and the NeuroPrion Association, we heartily invite you to join us for the International Conference Prion2020/2022 from 13.-16. September 2022 in Göttingen.
Prion 2022 Conference abstracts: pushing the boundaries
***> In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q (AAQQ) and the disease phenotype is similar to that seen with experimental strain CH1641. <***
Title: ASSESSMENT OF THE GENETIC RISK AND IMPACT OF LATERAL TRANSMISSION IN A VALINE-ASSOCIATED SCRAPIE OUTBREAK IN SHEEP
Author item EVONIUK, J item STOLTENOW, C item O'Rourke, Katherine item MOORE, B item REDMER, DSubmitted to: American Journal of Veterinary ResearchPublication Type: Peer Reviewed JournalPublication Acceptance Date: 6/8/2005Publication Date: 8/1/2005
Citation: Evoniuk, J.M., Stoltenow, C.L., O'Rourke, K.I., Moore, B.L., Redmer, D.A. 2005. Assessment of the genetic risk and impact of lateral transmission in a valine-associated scrapie outbreak in sheep. American Journal of Veterinary Research. 66(8):1-6.
Interpretive Summary: Scrapie is a fatal neurologic disease of sheep, endemic in the US but the subject of a vigorous eradication program. Scrapie is associated with accumulation of a misfolded form of the sheep prion protein. Control measures in an infected flock include removal of all genetically susceptible sheep. Susceptibility is controlled by naturally occurring differences in the prion protein, designated 171Q (susceptible) or 171R (generally resistant). The resistance of sheep with the 171R form of the gene occurs with one scrapie strain, the most US strain, but these sheep are not protected from the alternative strain, identified as valine associated scrapie. Anecdotal reports have shown that the strain probably occurs in the US but is relatively rare. In this publication, the presence of the valine associated strain was demonstrated through epidemiology and genetic analysis of a large flock of sheep. The study demonstrated that this scrapie strain can infect sheep as adults and is spread efficiently among related and unrelated sheep housed together during lambing seasons. The results suggest that the outbreak was due to the relatively high number of sheep with the susceptible form of the gene, probably introduced through the use of highly prolific rams carrying the gene. Further, transmission of the disease among adults, the prolonged incubation time, the unsuitability of some susceptible sheep to live animal testing, and susceptibility of sheep with the 171R gene suggest that removal of sheep with the genotype AVQR from infected flocks would be prudent.
Technical Abstract: Scrapie is a member of the heterogenous family of transmissible spongiform encephalopathies. Although these disorders appear to be related to misfolding of a host protein rather than an exogenous organism, two distinct disease phenotypes or strains are noted in sheep. Characterization of the scrapie strains in experimental and field settings in the United Kingdom and Europe have included differences in incubation time, survival rates, lateral transmission efficiency and most importantly, genetic susceptibility. Sheep of the prototype strain SSPB/1 are susceptible only if the PRNP (prion protein precursor gene) encodes valine (V) at codon 136; a polymorphism (encoding glutamine to arginine) at codon 171 apparently reduces disease prevalence but increases incubation time and limits tissue distribution to the brain. Sheep with the prototype valine-independent strain CH1641 are susceptible only if homozygous for glutamine (Q) at codon 171. In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q (AAQQ) and the disease phenotype is similar to that seen with experimental strain CH1641. The only genotype useful for strain discrimination is the relatively rare 136AV/171QR. In this study, a flock of sheep with a large number of infected sheep was analyzed. The presence of at least one V136 allele was identified in all but 2 sheep in the study, incubation times were very short in V136 homozygous sheep, probable lateral transmission was demonstrated in 15 sheep, and at least one AVQR sheep was identified. Therefore, this outbreak was probably due to a valine-associated (SSBP/1-like) strain and this report is the first full description of the epidemiology of this strain in US sheep. The high rate of lateral transmission and the susceptibility of 136AV/171QR sheep to scrapie suggest that genotyping for codon 136 may assist management decisions following a scrapie diagnosis and that it may be prudent to remove sheep of the 136AV/171QR genotype from infected flocks.
OPII-1
Disease incidence and incubation period of BSE and CH1641 in sheep is associated with PrP gene polymorphisms.
Goldman W., Hunter N., Benson G., Foster J. and Hope J. | F 4 5 AFRC&MRC Neuropathogenesis Unit, Institute for Animal Health, - CO West Mains Rd. Edinburgh EH9 3JF, U.K.
The relative survival periods of mice with different Sinc genotype have long been used for scrapie strain typing. The PrP protein, a key molecule in the pathogenesis of scrapie and related diseases, is a product of the Sinc locus and homologous proteins are also linked to disease-incidence loci in sheep and man. In sheep alleles of this locus (Sip) encode several PrP protein variants, of which one has been associated with short incubation periods of Cheviot sheep infected with SSBP/1 scrapie. Other isolates, i.e. BSE or CH1641, cause a different pattern of incubation periods and a lower disease incidence in the same flock of Cheviot sheep. Using transmission to sheep of known PrP genotype as our criterion for agent strain typing, we have found a link between BSE and CH1641, a C-group strain of scrapie. Disease susceptibility of sheep to these isolates is associated with different PrP genotypes compared to SSBP/1 scrapie.
OPII-2
Transmission of Bovine Spongiform Encephalopathy in sheep, goats and mice.
Foster J., Hope J., McConnell I. and Fraser H.
Institute for Animal Health, AFRC and MRC Neuropathogenesis Unit, Kings Buildings, West - Mains Road, Edinburgh EH9 3JF
Bovine Spongiform Encephalopathy (BSE) has been transmitted in two lines of genetically selected sheep {differing in their susceptibilities to the SSBP/1 source of scrapie}, and to goats by intracerebral injection and by oral dosing. Incubation periods in sheep for both routes of challenge ranged from 440-994 days. In goats this range was 506-1508 days. Both routes of infection in sheep and goats were almost equally efficient. In mice, primary transmission of BSE identified a sinc-independant genetic control of incubation period. Also, intermediate passage of BSE in sheep or goats did not alter these primary transmission properties. Hamsters were susceptible to BSE only after intervening passage through mice.
Title: ASSESSMENT OF THE GENETIC RISK AND IMPACT OF LATERAL TRANSMISSION IN A VALINE-ASSOCIATED SCRAPIE OUTBREAK IN SHEEP
Author item EVONIUK, J item STOLTENOW, C item O'Rourke, Katherine item MOORE, B item REDMER, D
Submitted to: American Journal of Veterinary Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/8/2005
Publication Date: 8/1/2005
Citation: Evoniuk, J.M., Stoltenow, C.L., O'Rourke, K.I., Moore, B.L., Redmer, D.A. 2005. Assessment of the genetic risk and impact of lateral transmission in a valine-associated scrapie outbreak in sheep. American Journal of Veterinary Research. 66(8):1-6.
Interpretive Summary: Scrapie is a fatal neurologic disease of sheep, endemic in the US but the subject of a vigorous eradication program. Scrapie is associated with accumulation of a misfolded form of the sheep prion protein. Control measures in an infected flock include removal of all genetically susceptible sheep. Susceptibility is controlled by naturally occurring differences in the prion protein, designated 171Q (susceptible) or 171R (generally resistant). The resistance of sheep with the 171R form of the gene occurs with one scrapie strain, the most US strain, but these sheep are not protected from the alternative strain, identified as valine associated scrapie. Anecdotal reports have shown that the strain probably occurs in the US but is relatively rare. In this publication, the presence of the valine associated strain was demonstrated through epidemiology and genetic analysis of a large flock of sheep. The study demonstrated that this scrapie strain can infect sheep as adults and is spread efficiently among related and unrelated sheep housed together during lambing seasons. The results suggest that the outbreak was due to the relatively high number of sheep with the susceptible form of the gene, probably introduced through the use of highly prolific rams carrying the gene. Further, transmission of the disease among adults, the prolonged incubation time, the unsuitability of some susceptible sheep to live animal testing, and susceptibility of sheep with the 171R gene suggest that removal of sheep with the genotype AVQR from infected flocks would be prudent.
Technical Abstract: Scrapie is a member of the heterogenous family of transmissible spongiform encephalopathies. Although these disorders appear to be related to misfolding of a host protein rather than an exogenous organism, two distinct disease phenotypes or strains are noted in sheep. Characterization of the scrapie strains in experimental and field settings in the United Kingdom and Europe have included differences in incubation time, survival rates, lateral transmission efficiency and most importantly, genetic susceptibility. Sheep of the prototype strain SSPB/1 are susceptible only if the PRNP (prion protein precursor gene) encodes valine (V) at codon 136; a polymorphism (encoding glutamine to arginine) at codon 171 apparently reduces disease prevalence but increases incubation time and limits tissue distribution to the brain. Sheep with the prototype valine-independent strain CH1641 are susceptible only if homozygous for glutamine (Q) at codon 171. In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q (AAQQ) and the disease phenotype is similar to that seen with experimental strain CH1641. The only genotype useful for strain discrimination is the relatively rare 136AV/171QR. In this study, a flock of sheep with a large number of infected sheep was analyzed. The presence of at least one V136 allele was identified in all but 2 sheep in the study, incubation times were very short in V136 homozygous sheep, probable lateral transmission was demonstrated in 15 sheep, and at least one AVQR sheep was identified. Therefore, this outbreak was probably due to a valine-associated (SSBP/1-like) strain and this report is the first full description of the epidemiology of this strain in US sheep. The high rate of lateral transmission and the susceptibility of 136AV/171QR sheep to scrapie suggest that genotyping for codon 136 may assist management decisions following a scrapie diagnosis and that it may be prudent to remove sheep of the 136AV/171QR genotype from infected flocks.
OPII-1
Disease incidence and incubation period of BSE and CH1641 in sheep is associated with PrP gene polymorphisms.
Goldman W., Hunter N., Benson G., Foster J. and Hope J. | F 4 5 AFRC&MRC Neuropathogenesis Unit, Institute for Animal Health, - CO West Mains Rd. Edinburgh EH9 3JF, U.K.
The relative survival periods of mice with different Sinc genotype have long been used for scrapie strain typing. The PrP protein, a key molecule in the pathogenesis of scrapie and related diseases, is a product of the Sinc locus and homologous proteins are also linked to disease-incidence loci in sheep and man. In sheep alleles of this locus (Sip) encode several PrP protein variants, of which one has been associated with short incubation periods of Cheviot sheep infected with SSBP/1 scrapie. Other isolates, i.e. BSE or CH1641, cause a different pattern of incubation periods and a lower disease incidence in the same flock of Cheviot sheep. Using transmission to sheep of known PrP genotype as our criterion for agent strain typing, we have found a link between BSE and CH1641, a C-group strain of scrapie. Disease susceptibility of sheep to these isolates is associated with different PrP genotypes compared to SSBP/1 scrapie.
OPII-2
Transmission of Bovine Spongiform Encephalopathy in sheep, goats and mice.
Foster J., Hope J., McConnell I. and Fraser H.
Institute for Animal Health, AFRC and MRC Neuropathogenesis Unit, Kings Buildings, West - Mains Road, Edinburgh EH9 3JF
Bovine Spongiform Encephalopathy (BSE) has been transmitted in two lines of genetically selected sheep {differing in their susceptibilities to the SSBP/1 source of scrapie}, and to goats by intracerebral injection and by oral dosing. Incubation periods in sheep for both routes of challenge ranged from 440-994 days. In goats this range was 506-1508 days. Both routes of infection in sheep and goats were almost equally efficient. In mice, primary transmission of BSE identified a sinc-independant genetic control of incubation period. Also, intermediate passage of BSE in sheep or goats did not alter these primary transmission properties. Hamsters were susceptible to BSE only after intervening passage through mice.
***> Our transmission study demonstrates that CH 1641-like scrapie is likely to be more virulent than classical scrapie in cattle.
In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q (AAQQ) and the disease phenotype is similar to that seen with experimental strain CH1641.
***> Our transmission study demonstrates that CH 1641-like scrapie is likely to be more virulent than classical scrapie in cattle.
P-088 Transmission of experimental CH1641-like scrapie to bovine PrP overexpression mice
Kohtaro Miyazawa1, Kentaro Masujin1, Hiroyuki Okada1, Yuichi Matsuura1, Takashi Yokoyama2
1Influenza and Prion Disease Research Center, National Institute of Animal Health, NARO, Japan; 2Department of Planning and General Administration, National Institute of Animal Health, NARO
Introduction: Scrapie is a prion disease in sheep and goats. CH1641-lke scrapie is characterized by a lower molecular mass of the unglycosylated form of abnormal prion protein (PrpSc) compared to that of classical scrapie. It is worthy of attention because of the biochemical similarities of the Prpsc from CH1641-like and BSE affected sheep. We have reported that experimental CH1641-like scrapie is transmissible to bovine PrP overexpression (TgBoPrP) mice (Yokoyama et al. 2010). We report here the further details of this transmission study and compare the biological and biochemical properties to those of classical scrapie affected TgBoPrP mice.
Methods: The details of sheep brain homogenates used in this study are described in our previous report (Yokoyama et al. 2010). TgBoPrP mice were intracerebrally inoculated with a 10% brain homogenate of each scrapie strain. The brains of mice were subjected to histopathological and biochemical analyses.
Results: Prpsc banding pattern of CH1641-like scrapie affected TgBoPrP mice was similar to that of classical scrapie affected mice. Mean survival period of CH1641-like scrapie affected TgBoPrP mice was 170 days at the 3rd passage and it was significantly shorter than that of classical scrapie affected mice (439 days). Lesion profiles and Prpsc distributions in the brains also differed between CH1641-like and classical scrapie affected mice.
Conclusion: We succeeded in stable transmission of CH1641-like scrapie to TgBoPrP mice. Our transmission study demonstrates that CH 1641-like scrapie is likely to be more virulent than classical scrapie in cattle.
snip...
In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q (AAQQ) and the disease phenotype is similar to that seen with experimental strain CH1641.
CH1641
Thursday, July 14, 2011
Histopathological Studies of "CH1641-Like" Scrapie Sources Versus Classical Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/histopathological-studies-of-ch1641.html
Histopathological Studies of "CH1641-Like" Scrapie Sources Versus Classical Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/histopathological-studies-of-ch1641.html
SHEEP AND BSE
A. The experimental transmission of BSE to sheep.
Studies have shown that the ''negative'' line NPU flock of Cheviots can be experimentally infected with BSE by intracerebral (ic) or oral challenge (the latter being equivalent to 0.5 gram of a pool of four cow brains from animals confirmed to have BSE).
A. The experimental transmission of BSE to sheep.
Studies have shown that the ''negative'' line NPU flock of Cheviots can be experimentally infected with BSE by intracerebral (ic) or oral challenge (the latter being equivalent to 0.5 gram of a pool of four cow brains from animals confirmed to have BSE).
RISK OF BSE TO SHEEP VIA FEED
http://web.archive.org/web/20010614054402/http://www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf
IN CONFIDENCE
EXPERIMENTAL TRANSMISSION OF BSE TO SHEEP
PERSONAL AND CONFIDENTIAL
SHEEP AND BSE
PERSONAL AND CONFIDENTIAL
SHEEP AND BSE
A. The experimental transmission of BSE to sheep.
Studies have shown that the ''negative'' line NPU flock of Cheviots can be experimentally infected with BSE by intracerebral (ic) or oral challenge (the latter being equivalent to 0.5 gram of a pool of four cow brains from animals confirmed to have BSE).
PERSONAL AND CONFIDENTIAL
SHEEP AND BSE
A. The experimental transmission of BSE to sheep.
Studies have shown that the ''negative'' line NPU flock of Cheviots can be experimentally infected with BSE by intracerebral (ic) or oral challenge (the latter being equivalent to 0.5 gram of a pool of four cow brains from animals confirmed to have BSE).
BSE-TRANSMISSION STUDIES 1991
IN CONFIDENCE
http://web.archive.org/web/20090506041605/http://www.bseinquiry.gov.uk/files/yb/1990/09/26003001.pdf
http://web.archive.org/web/20090506035759/http://www.bseinquiry.gov.uk/files/yb/1990/11/01005001.pdf
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
12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY
snip...
A The Present Position with respect to Scrapie A] The Problem Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries. The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep. It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible. Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates.
One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias" Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.
snip...
76/10.12/4.6
http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf
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).
http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.html
Epidemiology of Scrapie in the United States 1977
http://web.archive.org/web/20030513212324/http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf
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
12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY
snip...
A The Present Position with respect to Scrapie A] The Problem Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries. The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep. It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible. Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates.
One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias" Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.
snip...
76/10.12/4.6
http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf
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).
http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.html
Epidemiology of Scrapie in the United States 1977
http://web.archive.org/web/20030513212324/http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf
Monday, March 21, 2011
Sheep and Goat BSE Propagate More Efficiently than Cattle BSE in Human PrP Transgenic Mice
snip...
On the other hand, this component would not be distinguishable from bovine-passaged BSE prions due to the current limits of the standard biological methods and/or the molecular tools employed here to characterize prion strains. Whatever the mechanism, the notion that a passage through an intermediate species can profoundly alter prion virulence for the human species has important public-health issues, regarding emerging and/or expanding TSEs, like atypical scrapie or CWD.
snip...
Taken all together, our results suggest that the possibility of a small ruminant BSE prion as vCJD causal agent could not be ruled out, which has important implications on public and animal health policies. On one hand, although the exact magnitude and characteristic of the vCJD epidemic is still unclear, its link with cattle BSE is supported by strong epidemiological ground and several experimental data. On the other hand, the molecular typing performed in our studies, indicates that the biochemical characteristics of the PrPres detected in brains of our sheep and goat BSE-inoculated mice seem to be indistinguishable from that observed in vCJD. Considering the similarity in clinical manifestation of BSE- and scrapie-affected sheep [48], a masker effect of scrapie over BSE, as well as a potential adaptation of the BSE agent through subsequent passages, could not be ruled out. As BSE infected sheep PrPSc have been detected in many peripheral organs, small ruminant-passaged BSE prions might be a more widespread source of BSE infectivity compared to cattle [19], [49], [50]. This fact is even more worrying since our transmission studies suggest that apparently Met129 human PrP favours a BSE agent with ovine rather than a bovine sequence. Finally, it is evident that, although few natural cases have been described and so far we cannot draw any definitive conclusion about the origin of vCJD, we can not underestimate the risk of a potential goat and/or sheep BSE agent.
snip...
http://nor-98.blogspot.com/2011/03/sheep-and-goat-bse-propagate-more.html
Sheep and Goat BSE Propagate More Efficiently than Cattle BSE in Human PrP Transgenic Mice
snip...
On the other hand, this component would not be distinguishable from bovine-passaged BSE prions due to the current limits of the standard biological methods and/or the molecular tools employed here to characterize prion strains. Whatever the mechanism, the notion that a passage through an intermediate species can profoundly alter prion virulence for the human species has important public-health issues, regarding emerging and/or expanding TSEs, like atypical scrapie or CWD.
snip...
Taken all together, our results suggest that the possibility of a small ruminant BSE prion as vCJD causal agent could not be ruled out, which has important implications on public and animal health policies. On one hand, although the exact magnitude and characteristic of the vCJD epidemic is still unclear, its link with cattle BSE is supported by strong epidemiological ground and several experimental data. On the other hand, the molecular typing performed in our studies, indicates that the biochemical characteristics of the PrPres detected in brains of our sheep and goat BSE-inoculated mice seem to be indistinguishable from that observed in vCJD. Considering the similarity in clinical manifestation of BSE- and scrapie-affected sheep [48], a masker effect of scrapie over BSE, as well as a potential adaptation of the BSE agent through subsequent passages, could not be ruled out. As BSE infected sheep PrPSc have been detected in many peripheral organs, small ruminant-passaged BSE prions might be a more widespread source of BSE infectivity compared to cattle [19], [49], [50]. This fact is even more worrying since our transmission studies suggest that apparently Met129 human PrP favours a BSE agent with ovine rather than a bovine sequence. Finally, it is evident that, although few natural cases have been described and so far we cannot draw any definitive conclusion about the origin of vCJD, we can not underestimate the risk of a potential goat and/or sheep BSE agent.
snip...
http://nor-98.blogspot.com/2011/03/sheep-and-goat-bse-propagate-more.html
IN CONFIDENCE
SCRAPIE TRANSMISSION TO CHIMPANZEES
IN CONFIDENCE
reference...
RB3.20
TRANSMISSION TO CHIMPANZEES
1. Kuru and CJD have been successfully transmitted to chimpanzees but scrapie and TME have not.
2. We cannot say that scrapie will not transmit to chimpanzees. There are several scrapie strains and I am not aware that all have been tried (that would have to be from mouse passaged material). Nor has a wide enough range of field isolates subsequently strain typed in mice been inoculated by the appropriate routes (i/c, ilp and i/v) :
3. I believe the proposed experiment to determine transmissibility, if conducted, would only show the susceptibility or resistance of the chimpanzee to infection/disease by the routes used and the result could not be interpreted for the predictability of the susceptibility for man. Proposals for prolonged oral exposure of chimpanzees to milk from cattle were suggested a long while ago and rejected.
4. In view of Dr Gibbs' probable use of chimpazees Mr Wells' comments (enclosed) are pertinent. I have yet to receive a direct communication from Dr Schellekers but before any collaboration or provision of material we should identify the Gibbs' proposals and objectives.
5. A positive result from a chimpanzee challenged severely 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.
6. A negative result would take a lifetime to determine but that would be a shorter period than might be available for human exposure and it would still not answer the question regarding mans' susceptibility. In the meantime no doubt the negativity would be used defensively. It would however be counterproductive if the experiment finally became positive. We may learn more about public reactions following next Monday' s meeting.
R. Bradley
23 September 1990
CVO (+Mr Wells' comments)
Dr T W A Little
Dr B J Shreeve
90/9.23/1.1.
http://web.archive.org/web/20090506041740/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf
IN CONFIDENCE CHIMPANZEES
CODE 18-77 Reference RB3.46
Some further information that may assist in decision making has been gained by discussion with Dr Rosalind Ridley.
She says that careful study of Gajdusek's work shows no increased susceptibility of chimpanzees over New World Monkeys such as Squirrel Monkeys. She does not think it would tell you anything about the susceptibility to man. Also Gajdusek did not, she believes, challenge chimpanzees with scrapie as severely as we did pigs and we know little of that source of scrapie. Comparisons would be difficult. She also would not expect the Home Office to sanction such experiments here unless there was a very clear and important objective that would be important for human health protection. She doubted such a case could be made. If this is the case she thought it would be unethical to do an experiment abroad because we could not do it in our own country.
Retrospectively she feels they should have put up more marmosets than they did. They all remain healthy. They would normally regard the transmission as negative if no disease resulted in five years.
We are not being asked for a decision but I think that before we made one we should gain as much knowledge as we can. If we decided to proceed we would have to bear any criticisms for many years if there was an adverse view by scientists or media. This should not be undertaken lightly. There is already some adverse comment here, I gather, on the pig experiment though that will subside.
The Gibbs' (as' distinct from Schellekers') study is somewhat different. We are merely supplying material for comparative studies in a laboratory with the greatest experience of human SEs in the world and it has been sanctioned by USDA (though we do not know for certain yet if chimpanzees specifically will be used). This would keep it at a lower profile than if we conducted such an experiment in the UK or Europe.
I consider we must have very powerful and defendable objectives to go beyond Gibbs' proposed experiments and should not initiate others just because an offer has been made.
Scientists have a responsibility to seek other methods of investigative research other than animal experimentation. At present no objective has convinced me we need to do research using Chimpanzees - a species in need of protection. Resisting such proposals would enable us to communicate that information to the scientist and the public should the need arise. A line would have been drawn.
CVO cc Dr T Dr B W A Little Dr B J Shreeve
R Bradley
26 September 1990
90/9.26/3.2
http://web.archive.org/web/20090506041605/http://www.bseinquiry.gov.uk/files/yb/1990/09/26003001.pdf
this is tse prion political theater here, i.e. what i call TSE PRION POKER...tss
3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs.
snip...
PAGE 26
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.
The occurrence of CWD must be viewed against the contest of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite its subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA viewed it as a wildlife problem and consequently not their province! ...page 26.
snip...see;
IN CONFIDENCE
PERCEPTIONS OF UNCONVENTIONAL SLOW VIRUS DISEASE OF ANIMALS IN THE USA
GAH WELLS
REPORT OF A VISIT TO THE USA
APRIL-MAY 1989
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...
***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***
Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.
https://www.nature.com/articles/srep11573
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.
==============
https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf
***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.
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
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.
==============
https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf
***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.
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
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
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.
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
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.
http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160
IBNC Tauopathy or TSE Prion disease, it appears, no one is sure
Terry S. Singeltary Sr., 03 Jul 2015 at 16:53 GMT
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 ***
WEDNESDAY, DECEMBER 23, 2020
Idiopathic Brainstem Neuronal Chromatolysis IBNC BSE TSE Prion a Review 2020
MONDAY, SEPTEMBER 19, 2022
589.2001 BSE TSE regulations which prohibits the use of high-risk cattle material in feed for all animal species 2022
FRIDAY, SEPTEMBER 23, 2022
SPILLOVER CWD TSE PRION INTO DIFFERENT SPECIES, pigs, sheep, cattle, camel, and humans, what if?
Terry S. Singeltary Sr.
