SCRAPIE USA

Transmissible Spongiform Encephalopathy TSE Prion PrP sheep and goats

About Me

My Photo
Name:
Location: BACLIFF, Texas, United States

My mother was murdered by what I call corporate and political homicide i.e. FOR PROFIT! she died from a rare phenotype of CJD i.e. the Heidenhain Variant of Creutzfeldt Jakob Disease i.e. sporadic, simply meaning from unknown route and source. I have simply been trying to validate her death DOD 12/14/97 with the truth. There is a route, and there is a source. There are many here in the USA. WE must make CJD and all human TSE, of all age groups 'reportable' Nationally and Internationally, with a written CJD questionnaire asking real questions pertaining to route and source of this agent. Friendly fire has the potential to play a huge role in the continued transmission of this agent via the medical, dental, and surgical arena. We must not flounder any longer. ...TSS

Wednesday, December 24, 2025

SCRAPIE TSE Prion USA RAPID RESPONSE URGENT UPDATES DECEMBER 25, 2025

 SCRAPIE TSE Prion USA RAPID RESPONSE URGENT UPDATES DECEMBER 25, 2025


Volume 31, Number 12—December 2025

Research

Oral Transmission of Classical Bovine Spongiform Encephalopathy in ARR/ARR Sheep

Alvina Huor1, Frederic Lantier1, Jean-Yves Douet, Severine Lugan, Naima Aron, Chloe Mesic, Herve Cassard, Tomás Barrio, Hugh Simmons, Isabelle Lantier, and Olivier Andreoletti

Comments to Author Author affiliation: University of Toulouse, Toulouse, France (A. Huor, J.-Y. Douet, S. Lugan, N. Aron, C. Mesic, H. Cassard, T. Barrio, O. Andreoletti); National Research Institute for Agriculture, Food and Environment, Nouzilly, France (F. Lantier, I. Lantier); Animal and Plant Health Agency, Weybridge, UK (H. Simmons)

Abstract

Selection for the A136R154R171 PRNP allele is known to curb classical scrapie in sheep, and we expected it to minimize the risk for classical bovine spongiform encephalopathy (c-BSE) propagation. We orally challenged newborn ARR/ARR and ARQ/ARQ lambs with ovine-passaged c-BSE. Contrary to our expectations, prion disease developed in all ARR/ARR lambs after markedly longer incubation times (≈50 months) than ARQ/ARQ controls (≈20 months). Tissue distribution of the abnormal isoform of prion protein (PrP) in clinically affected ARR/ARR sheep largely mirrored tissue distribution seen in ARQ/ARQ animals. Bioassays in bovine- and human-PrP transgenic mice showed that passage through ARR/ARR sheep did not increase the agent’s zoonotic potential. Transmission efficiency in human normal cellular isoform PrP-expressing mice remained similar to cattle c-BSE and lower than ARQ-passaged c-BSE. Our data reveal the limitations of breeding exclusively for ARR when the objective is to mitigate c-BSE risk and underscore the need to maintain specific-risk-material removal and surveillance programs.

Prion diseases, or transmissible spongiform encephalopathies (TSE), are fatal neurodegenerative disorders that occur naturally in various mammalian species, including sheep (scrapie), cervids (chronic wasting disease), and humans (Creutzfeldt-Jakob disease [CJD]). A key event in the pathogenesis of TSEs is the conversion of the normal cellular prion protein (PrPC), encoded by the PRNP gene, into an abnormal disease-associated isoform (PrPSc) within the tissues of those affected. PrPC is completely degraded after controlled digestion with proteinase K (PK) under nondenaturing conditions, whereas PrPSc is N terminally truncated under such conditions, leaving a PK-resistant core termed PrPres (1).

In 1985, classical bovine spongiform encephalopathy (c-BSE), a new prion disease affecting cattle, was identified in the United Kingdom (2). The number of c-BSE cases in cattle rapidly increased because of the recycling of infected carcasses into the feed chain in the form of meat and bone meal (MBM) (3). Over the next 2 decades, c-BSE disseminated to >28 countries, mostly in Europe but also in the United States, Canada, and Japan, through the export of infected live animals and contaminated MBM and livestock feed.

Experimental oral or parenteral exposure to c-BSE demonstrated its transmissibility to sheep (4). Because MBM was also distributed to small ruminants, the potential spread of c-BSE in the sheep population became a major concern for health authorities. The emergence of variant CJD (vCJD) in humans, because of dietary exposure to the c-BSE agent, further reinforced those concerns, making the prevention of any potential spread of c-BSE to small ruminants a top priority in Europe (5,6).

In sheep, susceptibility to prion diseases is determined principally by polymorphisms in the PRNP gene. The major polymorphic sites influencing susceptibility to classical scrapie are located at codons 136 (A or V), 154 (R or H), and 171 (R, Q, or H) (7,8), which also strongly influence susceptibility to BSE. Sheep with the AHQ/AHQ and ARQ/ARQ PrP genotypes are highly susceptible to c-BSE infection when exposed through intracerebral or oral routes (4).

In contrast, intracerebral inoculation of ARR/ARR sheep with cattle c-BSE resulted in an inefficient transmission of the disease (incomplete attack rate), and oral inoculation failed to transmit disease or cause detectable accumulation of prion infectivity or abnormal PrP in the peripheral tissues or central nervous system (9). Those findings led to the conclusion that the ARR/ARR PrP genotype confers strong, if not complete, resistance to c-BSE infection in sheep. Selection for the ARR allele was originally conceived as a tool to control classical scrapie in farmed sheep population, but it also appeared to protect against possible c-BSE transmission (10). In this study, we experimentally exposed ARQ/ARQ and ARR/ARR newborn lambs orally to c-BSE passaged in ARQ/ARQ sheep to determine transmission efficiency of the disease.

snip…

Discussion

The efficient transmissions observed in orally challenged ARR/ARR animals demonstrate that this genotype does not provide substantial resistance against the ovine c-BSE agent. Our results strongly contrast with those previously obtained in ARR/ARR and ARR/ARQ sheep orally challenged with cattle c-BSE, where no clinical signs and no or limited PrPSc accumulation has been evidenced, whereas positive transmission occurred in ARQ/ARQ sheep (22–24).

The inoculation doses used in this study (5 g of brain equivalent material) were similar to those used in studies that concluded the absence of cattle c-BSE transmission through the oral route in ARR/ARR sheep. However, in the absence of an endpoint titration establishing the c-BSE titer in our inoculum, the hypothesis that differences in the infectious titer in the inoculum account for, or at least contribute to, the discrepancies observed between studies cannot be ruled out.

In sheep, the age at the time of inoculation does appear to affect the efficacy of c-BSE transmission in orally exposed ARQ/ARQ sheep (25). Transmission efficiency is much higher in animals challenged before weaning (<3 weeks) than in animals inoculated after weaning (>3 months). In our study, lambs were orally challenged 24 hours after birth and at the age of 2 weeks, whereas in previous studies, where no c-BSE transmission to ARR/ARR animals was observed, the age at inoculation varied from 3–6 months (26,27) or 5–8 months (22).

Experimental oral exposure early after birth is potentially more relevant to a scenario where maternal lateral transmission (via milk and contact with placenta) would play a central role in the disease transmission, as observed in classical scrapie–infected flocks (28,29). Experimental oral challenge after weaning is certainly a relevant model to mimic a scenario where sheep would be exposed to the c-BSE agent through the ingestion of contaminated feedstuffs (meat and bone meal), as observed in cattle during the c-BSE epidemics.

The last major difference between our transmission experiment and those reported in previous studies was the use of an ovine-adapted c-BSE rather than cattle c-BSE as inoculum. The apparent higher capacity of ARQ/ARQ sheep-passaged c-BSE (when compared with cattle c-BSE) to cross transmission barriers (transmission to porcine and human PrP-expressing hosts) is a well-documented phenomenon. The use of such ovine-passaged c-BSE as inoculum could, at least partly, explain the efficient transmission of the c-BSE agent to ARR/ARR sheep.

During the past 20 years, a breeding for resistance policy relying on the progressive increase of the ARR allele frequency in sheep has been implemented by certain member states of the European Union (EU). That policy’s original objectives were to reduce the global incidence of TSEs and to prevent c-BSE emergence and spread in sheep populations. The most recent analysis of the small ruminants’ TSE epidemiologic situation in the EU confirmed that the breeding for resistance policy is an efficient means to reduce classical scrapie prevalence in sheep populations (10). However, the transmission of the c-BSE agent to ARR/ARR sheep reported in this study suggests that ARR allele selection could have a more limited effect than originally expected on the risk for c-BSE propagation in the sheep population.

At the clinical stage of the disease, the distribution and levels of c-BSE prions in the peripheral tissues of both ARR/ARR and ARQ/ARQ experimentally challenged animals were broadly similar. The main differences observed between both genotypes were a slower dissemination of the c-BSE agent in the organism and a longer incubation period in the ARR/ARR animals.

In the humanized transgenic mouse panel, both ARR/ARR- and ARQ/ARQ-derived c-BSE remained transmissible to mice expressing methionine 129 human PrPC, confirming that neither ovine genotype eliminates zoonotic potential. However, the ARR/ARR isolate exhibited modestly reduced transmission efficiency, evident as a lower primary attack rate and longer mean survival times, compared with its ARQ/ARQ counterpart. Those kinetic differences were largely lost after a single adaptation passage, however, suggesting that once the species barrier is crossed, the underlying strain behaves similarly.

In 2001, specific risk material (SRM) measures were implemented throughout the EU, consisting of the systematic removal of cattle and small ruminants’ tissues susceptible to contain critical levels of prion infectivity from the food and feed chains. The SRM measures are key for ensuring the protection of consumers against exposure to prions present in farmed animals. Current SRM measures applied to small ruminants in the EU consist of the removal of the spleen and the ileum and, in animals over 12 months of age, the skull (including the eyes and brain), spinal cord, and tonsils. Because of the large distribution of TSE infectivity in the lymphoid tissues of small ruminants, SRM measures applied to sheep and goats are considered to have a more limited effect on the protection of consumers than they have in the cattle c-BSE context (30). However, mathematical modeling of the effect of the SRM measures on the different prion diseases susceptible to occur in small ruminants (atypical scrapie, classical scrapie, and c-BSE) confirmed the strong positive effect of the SRM measures on the final consumer exposure to these different prions (31).

In conclusion, although the capacity of the c-BSE agent to propagate in ARR/ARR sheep can be considered unfortunate news, the continuation of the TSE surveillance and SRM measures currently in force for small ruminants in the EU will continue to ensure efficient protection against the risk for exposure to this zoonotic agent. c-BSE infection in ARR/ARR sheep can still pose a public-health risk, but the quantitative probability of successful cross-species transmission might be lower than transmission associated with ARQ/ARQ sheep cases.

Dr. Huor is an assistant engineer in the transmissible spongiform encephalopathies research group at the University of Toulouse. Her primary research interests are the pathogenesis of prion diseases and the evolution of prion strain properties, with special emphasis on their iatrogenic and zoonotic risks of transmission.

Acknowledgment

This work was supported by the European Union (grant no. QLK-CT 2001-309, program nos. FEDER/INTERREG EFA282/13 TRANSPRION, EFA148/16 REDPRION, and EFA031/01 NEUROCOOP).

References

https://wwwnc.cdc.gov/eid/article/31/12/25-0501_article

Volume 31, Number 12—December 2025

Research

Silent Propagation of Classical Scrapie Prions in Homozygous K222 Transgenic Mice

Abstract

Classical scrapie affects sheep and goats. To control prevalence in sheep, the European Union initiated breeding programs targeting resilient genotypes. Although certain goat polymorphisms, such as Q222K, are linked to resistance, specific breeding programs have not been implemented. Hemizygous transgenic mice carrying the goat K222 cellular prion protein (PrP) allele (K222-Tg516) exhibited resistance to several classical scrapie isolates. We inoculated homozygous K222-Tg516 and Q222-Tg501 mice with various scrapie isolates. Homozygous K222-Tg516 mice reached the end of their lifespan without exhibiting clinical signs; we observed brain proteinase K–resistant PrP accumulation in those mice that was lower than in Q222-Tg501 mice. Histologically, K222-Tg516 brains lacked prion-related lesions, except for the presence of few isolated scrapie PrP plaques in cases of isolates highly adapted to the K222-PrPC environment. Our findings caution against including that polymorphism in breeding programs, because it could lead to emergence of asymptomatic silent prion carriers of classical scrapie among goat populations.

snip…

Discussion Previous studies conducted in heterozygous Q/K222 and homozygous K222 goats (20–23), as well as in hemizygous K222-Tg516 mice (29), have highlighted the Q222K polymorphism as one of the most promising candidates for reducing prion disease transmission in goats. Although the K222 allele has been consistently reported in certain countries in Europe, such as Italy (15,16), France (10), and Greece (17,42), in other countries, such as the United Kingdom, the polymorphism has been reported as infrequent (43). However, once the supposed protective effect against prion diseases is confirmed, the frequency of the K222 allele could increase across different countries through selective breeding programs.

Transgenic mice expressing K222-PrPC in homozygosity emerge as the optimal tool for definitively testing the susceptibility or resistance that allele confers to prions. Our model enables the testing of multiple prion strains more rapidly and cost-effectively than the model using goats. In our study, classical scrapie isolates representing different classical scrapie strains circulating within Europe (40–42) were selected and used to challenge homozygous K222-Tg516 mice.

Once the expression level is increased, homozygous K222-Tg516 mice become susceptible to all tested classical scrapie isolates (Table 3). The K222-PrPC variant is capable of sustaining PrPSc replication even in the absence of the Q222-PrPC variant, which was identified as responsible for most accumulated brain PrPres in Q222K heterozygous goats (24). Furthermore, K222-Tg516 mice exhibit consistently lower brain PrPres accumulation than Q222-Tg501 mice (Figure 1). The explanation that K222-PrPres is more sensitive to proteinase K treatment and so reduced detection of brain PrPres accumulation has been ruled out (Figure 6). Therefore, we recommend careful analysis of the general features and behavior of classical scrapie K222-PrPres.

K222-Tg516 mice inoculated with classical scrapie did not develop typical prion pathology and showed no clinical signs of prion disease, which suggests that classical scrapie K222-PrPres might not be toxic or might not induce the signaling pathways leading to neuronal death. Those conclusions are not only caused by insufficient time for the onset of neuronal death pathways within the animal lifespan; second passages in K222-Tg516 yielded identical results to the first ones. However, we noted that the lower brain PrPres accumulation in K222-Tg516 animals could lead to a misinterpretation of those results. The reduced accumulation might reflect insufficient replication within the animal’s lifespan, possibly caused by consistently low replication rates, as suggested by our kinetic experiments, or by more efficient clearance of PrPres aggregates. Those factors could explain why transmission does not necessarily result in prion disease, highlighting a dissociation between infectivity and toxicity of classical scrapie K222-PrPres.

All circulating prion strains must be considered in the design of breeding selection programs. Programs aimed at controlling and reducing classical scrapie in sheep, implemented by EU member states, have identified sheep herds that are more susceptible to atypical/Nor98 scrapie (44). In our study, K222-Tg516 mice died without exhibiting overt clinical signs after inoculation with different classical scrapie isolates; we found that PrPres accumulated in their brains (Table 1). Of note, K222-derived PrPres retained infectivity when transmitted back to Q222-Tg501 mice, recovering the strain characteristics observed in the original inocula. Our findings suggest that, under the experimental conditions we established, the K222 allele does not confer full resistance to classical scrapie agents.

Of interest, the reversibility of strain features observed upon reinoculation of K222-derived PrPres into Q222-Tg501 mice is reminiscent of the phenomenon of nonadaptive prion amplification as described previously (45). In that model, PrPSc can replicate transiently in a nonpermissive host without inducing a permanent adaptation of the strain. Our data are consistent with that concept; the classical scrapie agents replicated in K222-Tg516 mice but reverted to their original biochemical and biologic properties upon passage back into a permissive Q222 context. That interpretation reinforces the view that the K222 allele may enable subclinical or low-efficiency replication of classical scrapie agents without supporting stable strain selection or adaptation.

It is important to note that the use of transgenic models with PrP overexpression may enhance prion replication efficiency, potentially uncovering low-level or subclinical conversion events that might not occur under physiologic PrP expression in goats. In addition, all animals were inoculated intracerebrally; that route does not mimic natural exposure and bypasses key peripheral barriers such as the gut and associated lymphoid tissues, which play a critical role in determining prion susceptibility and pathogenesis under field conditions. Therefore, although our results highlight the potential for silent propagation of classical scrapie strains in the context of the K222 variant, extrapolation to the natural host should be made with caution.

Interest has grown for in-depth characterization of the strains of Q/K222 heterozygous goats affected with scrapie, which are abundant in various regions of Greece. The interest lies in determining whether prions propagated under the K222 allele can act as potential silent carriers of the disease, as shown in previous studies. Furthermore, understanding whether the presence of the K222 allele induces a change in the biologic properties of the strains and their potential transmission to other animal species is crucial.

Overall, our results underscore the need for further in vivo studies using physiologically relevant models or natural hosts to fully evaluate the protective efficacy of the K222 allele. Until such evidence becomes available, the inclusion of the K222 polymorphism in breeding selection programs should be critically considered, especially in regions where classical scrapie strains with known zoonotic potential remain present. Furthermore, experiments conducted in classical BSE-inoculated Q/K222 heterozygous goats have shown at least low infectivity in goat tissues after long postinoculation periods (26), whereas heterozygous K222-Tg516 mice were already fully susceptible to goat BSE (29). In addition, at least 1 Q/K222 heterozygous goat tested positive for atypical/Nor98 scrapie (28), and homozygous K222-Tg516 mice were found to be completely susceptible to atypical/Nor98 scrapie (30). Taken together, those data suggest that the protective effect of the Q222K polymorphism may be limited, and its use in breeding programs should be carefully evaluated.

Dr. Fernández-Borges is a tenured researcher in the Laboratory of Molecular and Cellular Biology of Prions at Centro de Investigación en Sanidad Animal (CISA-INIA-CSIC). Her research interests include prion strain characterization and evolution and the pathogenesis of prion diseases and their effects on human and animal health.

Acknowledgments

https://wwwnc.cdc.gov/eid/article/31/12/25-0302_article

Scrapie typical and atypical USA

FY 2023, 16,646 from sheep and 8,726 from goats.

* There have been 491 NVSL confirmed positive animals (474 classical cases – 471 sheep and 3 goats) and

19 Nor98- like cases since the beginning of RSSS. Figure 3 depicts RSSS collection sites in FY 2023.

https://www.aphis.usda.gov/sites/default/files/scrapie-annual-report.pdf

In 2023, APHIS collected samples from more than 26,000 sheep and goats for scrapie testing. Out of the total number of animals tested in 2023, no animals tested positive for classical scrapie and

one sheep tested positive for non-classical scrapie (Nor98-like)...

https://www.usda.gov/sites/default/files/documents/22-APHIS-2025-ExNotes.pdf

In 2022, APHIS collected samples from more than 23,000 sheep and goats for scrapie testing. Out of the total number of animals tested in 2022, no animals tested positive for classical scrapie and

one sheep tested positive for non-classical scrapie (Nor98-like).

https://www.usda.gov/sites/default/files/documents/23-2024-APHIS.pdf

In FY 2021, APHIS collected samples from more than 30,000 sheep and goats for scrapie testing. Out of the total number of samples processed and reported in FY 2021,

one sheep tested positive for classical scrapie and one sheep tested positive for non-classical scrapie (Nor98-like).

https://www.usda.gov/sites/default/files/documents/23-2023-APHIS.pdf

In FY 2020, APHIS collected samples from 33,839 sheep and goats for scrapie testing. This number represents sample results reported by October 15, 2020 and is expected to slightly increase as the remaining results are processed and reported. No animals tested positive for classical scrapie.

Two sheep tested positive at slaughter for non-classical scrapie (Nor98-like).

https://www.usda.gov/sites/default/files/documents/22APHIS2022Notes.pdf

In FY 2019, APHIS collected samples from 34,730 sheep and goats for scrapie testing, detecting 7 classical scrapie positive animals. Of these animals, five sheep and one goat were from a source flock in Pennsylvania that was found in August 2018, depopulated in October 2018, and tested for scrapie in November 2018. A second goat, which was from an Indiana herd, was sampled at slaughter in June 2019. The source flock completed a cleanup plan and was placed on a 5-year monitoring plan. The source herd of the positive Indiana goat no longer contained any exposed animals and was also placed on a 5-year monitoring plan. A trace-back investigation narrowed the goat’s birth herd to two possible herds. Animals in both herds tested negative for scrapie and were placed on 5-year monitoring plans. There were no classical scrapie cases detected in slaughter sheep in FY 2019.

Also in FY 2019, two sheep tested positive at slaughter for non-classical scrapie (Nor98-like) and were traced back to Colorado flocks.

https://www.usda.gov/sites/default/files/documents/20aphis2021notes.pdf

In FY 2018, APHIS collected samples from 43,625 sheep and goats for scrapie testing, detecting three positive (0.0068%) cases. These figures are based on sample submissions and testing completed by September 30, 2018. FY 2018 values are expected to change when testing is completed for all animals sampled in FY 2018.

In October 2017, a non-classical scrapie case was detected in a sheep from Virginia sampled at slaughter. As a result, the non- classical scrapie affected flock was placed on a 5-year monitoring plan.

https://www.usda.gov/sites/default/files/documents/20aphis2020notes.pdf

In FY 2016, the program identified one flock infected with classical scrapie and one infected with Nor98-like scrapie through slaughter surveillance, and two flocks infected with classical scrapie through on-farm surveillance.

An additional 10 sheep were confirmed with classical scrapie through testing of sheep depopulated from these infected flocks as part of flock clean-up activities conducted in FY 2016.

The Nor98-like scrapie affected flock will be placed on a 5-year monitoring plan.

https://www.usda.gov/sites/default/files/documents/20aphisexnotes2018.pdf

please see

2026 USDA EXPLANATORY NOTES, APHIS, CWD, BSE, Scrapie, TSE, Prion

https://transmissiblespongiformencephalopathy.blogspot.com/2025/12/2026-usda-explanatory-notes-aphis-cwd.html

https://transmissiblespongiformencephalopathy.blogspot.com/2025/12/2026-usda-explanatory-notes-aphis-cwd.html

Classical BSE emergence from Nor98/atypical scrapie: Unraveling the shift vs. selection dichotomy in the prion field

Sara Canoyra, Alba Marín-Moreno, Juan Carlos Espinosa , and Juan María Torres

Authors Info & Affiliations Edited by Byron Caughey, National Institute of Allergy and Infectious Diseases (National Institutes of Health), Hamilton, MT; received January 17, 2025; accepted June 7, 2025 by Editorial Board Member Lila M. Gierasch

July 15, 2025

122 (29) e2501104122 https://doi.org/10.1073/pnas.2501104122

Significance

Classical bovine spongiform encephalopathy (c-BSE) is a fatal cattle prion disease transmissible to humans as variant Creutzfeldt–Jakob Disease (vCJD). Understanding how c-BSE emerges is crucial for preventing future outbreaks and protecting public health. Two main hypotheses explain prion adaptation during cross-species transmission: “conformational shift or deformed templating,” where the species barrier forces a change to a different pathological prion protein, and “conformational selection,” where the species barrier filters preexisting conformers. Our results demonstrate that the conformational shift mechanism explains the emergence of c-BSE when Nor98/atypical scrapie (AS) is transmitted to cattle. This is significant because AS, found in sheep and goats worldwide, can convert to c-BSE. Preventing AS from entering the food chain is crucial to reduce c-BSE/vCJD risks.

Abstract

Prion diseases can manifest with distinct phenotypes in a single species, a phenomenon known as prion strains. Upon cross-species transmission, alterations in the disease phenotype can occur, interpreted as the emergence of a new strain. Two main and non–mutually exclusive evolutionary hypotheses have been proposed to explain this phenomenon: the “conformational shift” or “deformed templating” and the “conformational selection.” The conformational shift hypothesis proposes that the introduction of a new host prion protein (PrPC) forces a change in the conformation of the pathological prion protein (PrPSc), causing the new prion strain emergence. On the contrary, the conformational selection model postulates that prion isolates are a conglomerate of PrPSc conformations with relative distribution frequencies, wherein the species barrier acts as a filter selecting the one fittest for the new species environment. Previous studies reported the emergence of the classical bovine spongiform encephalopathy agent (c-BSE) upon transmission of Nor98/atypical scrapie (AS) onto a bovine PrP. This study investigates the evolutionary dichotomy of this c-BSE emergence by using prion strain thermostability combined with protein misfolding cyclic amplification to distinguish between both strains. Our results suggest that the conformational shift could be the principal mechanism responsible for the c-BSE emergence. Furthermore, the selection model was dismissed as the key mechanism based on the analysis of an artificial c-BSE and AS mixture. The ability of the AS conformers to shift conformation to a c-BSE one supports the hypothesis that the epidemic c-BSE prion may have originated from the transmission of AS in cattle.

https://www.pnas.org/doi/abs/10.1073/pnas.2501104122?download=true

Published: 04 October 2023

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

Marina Betancor, Belén Marín, Alicia Otero, Carlos Hedman, Antonio Romero, Tomás Barrio, Eloisa Sevilla, Jean-Yves Douet, Alvina Huor, Juan José Badiola, Olivier Andréoletti & Rosa Bolea Veterinary Research volume 54, Article number: 89 (2023) Cite this article

Abstract

The emergence of bovine spongiform encephalopathy (BSE) prions from atypical scrapie has been recently observed upon experimental transmission to rodent and swine models. This study aimed to assess whether the inoculation of atypical scrapie could induce BSE-like disease in cattle. Four calves were intracerebrally challenged with atypical scrapie. Animals were euthanized without clinical signs of prion disease and tested negative for PrPSc accumulation by immunohistochemistry and western blotting. However, an emergence of BSE-like prion seeding activity was detected during in vitro propagation of brain samples from the inoculated animals. These findings suggest that atypical scrapie may represent a potential source of BSE infection in cattle.

Snip…

Discussion

Previous studies have demonstrated that C-BSE prions can be present as a minor variant in ovine atypical scrapie isolates and that C-BSE can emerge during the passage of these isolates to pigs and bovine PrP mice [7, 8]. These results pointed to atypical scrapie as a possible origin of C-BSE. Therefore, this study was meant to assess the link between atypical scrapie and C-BSE in the natural host of C-BSE, cattle. Although the intracerebral challenge has some limitations and does not reflect the natural transmission process of prions, bioassays using experimental prion inoculation have allowed to identify and describe the transmission mechanisms of these pathogens. Therefore, we decided to challenge cattle with an atypical scrapie isolate.

It is important to note that none of the animals in this study showed any clinical signs of TSE after inoculation with atypical scrapie, according to the results previously obtained in pigs [8]. In addition, the absence of spongiform changes in brain sections, as well as the absence of PrPSc accumulation by conventional techniques in brain areas from the atypical scrapie-inoculated cows, further highlights the need for highly sensitive techniques such as PMCA to detect low levels of prions. After the in vitro propagation of brain samples from the cows included in this study, seeding activity was detected in reactions seeded with brain material from three out of the four cows, in the areas of frontal cortex, thalamus, and/or cerebellum. Interestingly, none of the samples from the obex, which is one of the most affected areas in prion diseases [14], showed seeding activity. Importantly, the observed glycosylation pattern of the positive PMCA reactions was indistinguishable from that of C-BSE prions and PMCA products from reactions seeded with C-BSE prions. To check whether C-BSE-like prions were present in the original atypical scrapie isolate or if they emerged in the brain of the cows after the inoculation, we performed PMCA of the original inoculum in TgBov substrate, following the same conditions described above. The in vitro amplification of the atypical scrapie inoculum resulted in the propagation of BSE-like seeding activity, biochemically indistinguishable from C-BSE or positive PMCA reactions seeded with brain samples from the inoculated cows, suggesting that, as described before, certain atypical scrapie isolates contain low levels of C-BSE prions [9].

Moreover, in order to rule out a spontaneous in vitro misfolding of bovine PrP during PMCA, we included, as a control for the technique, brain samples from non-inoculated age-matching cows that were also subjected to serial in vitro propagation in TgBov substrate. No positivity was observed in PMCA reactions seeded with samples from these animals, suggesting a true C-BSE-like prion seeding activity and not a spontaneous in vitro misfolding of PrP.

All these results suggest the amplification of C-BSE-like prions during the transmission of ovine atypical scrapie to cows. It is true that, in order to confirm the presence of infectious BSE prions in the challenged cows, strain typing experiments of the PMCA products should be carried out in established mouse lines. Therefore, studies involving a bioassay in bovine and ovine PrP-expressing mice have been started.

Interestingly, the time after inoculation and the BSE-like prion seeding activity were not correlated. As previously stated, the emergence of C-BSE from atypical scrapie has been associated with the presence of low levels of C-BSE prions in the atypical scrapie isolates and our results after the in vitro amplification of the PS152 inoculum support this theory. Therefore, the number of C-BSE conformers contained in the used atypical scrapie isolates may be reduced and not homogeneously distributed, making cows receiving different amounts of C-BSE-like prions. It is true that the emergence of C-BSE-like PMCA seeding activity from the brains of cows could be related to the persistence of prions from the original atypical scrapie inoculum. Previous studies, in which prion seeding activity was detected in the brain of intracerebrally inoculated PrP0/0 mice have highlighted the capacity of prions to persist in non-replicative environments [15]. Nevertheless, cows were intracerebrally challenged in the frontal cortex, and seeding activity was detected in caudal regions of their brains but not in more rostral areas such as the frontal cortex. If these positive PMCA reactions were not a bona fide propagation of C-BSE-like prions but associated to inoculum persistence, it would be expected to detect such amplification in the most rostral areas of the brain. Although all these results support a bona fide propagation of C-BSE-like prions, the possibility of PMCA detecting remaining prions of the inoculum, would be definitely ruled out after in vivo bioassays in mouse lines, which are currently being carried out.

The lack of clinical signs of prion disease in cows after inoculation with atypical scrapie contrasts with results from a previous study in which bovine PrP mice (TgBov) were challenged with atypical scrapie isolates and displayed signs of clinical prion disease, developing neuropathological characteristics of C-BSE [7]. In addition, in the mentioned study, after the first passage, signs of clinical prion disease were only observed in a low proportion of the inoculated mice, and several of the inoculated isolates did not lead to PrPSc accumulation. Three serial passages of atypical scrapie were needed to observe complete attack rates in TgBov mice. Moreover, mice from the first passage that developed clinical signs showed long incubation periods considering the lifespan of a mouse. The cows in this study were also euthanized after a long post-inoculation period (between ~7 and ~11 years). However, the number of C-BSE-like prions present in the original atypical scrapie inoculum was probably too low to produce disease in the cows upon first passage. We also need to consider that TgBov mice overexpress ~8 times bovine PrPC, making them more susceptible to develop disease after the inoculation of C-BSE prions.

Further in vivo experiments challenging different mouse lines have been started in order to confirm the infectivity of the PMCA products obtained in this study. However, in conclusion, our findings show that the propagation of atypical scrapie in cattle leads to the emergence of BSE-like seeding activity. This is a concerning issue with far-reaching implications for public health and food safety. The possibility of interspecies transmission of prion diseases and the emergence of new prion strains highlight the critical need for continued surveillance and monitoring of these diseases in both animal and human populations. Early detection of prion diseases is crucial, and highly sensitive detection techniques such as PMCA can play an important role in this regard.

https://veterinaryresearch.biomedcentral.com/articles/10.1186/s13567-023-01225-2

Classical BSE prions emerge from asymptomatic pigs challenged with atypical/Nor98 scrapie

Belén Marín, Alicia Otero, Séverine Lugan, Juan Carlos Espinosa, Alba Marín-Moreno, Enric Vidal, Carlos Hedman, Antonio Romero, Martí Pumarola, Juan J. Badiola, Juan María Torres, Olivier Andréoletti & Rosa Bolea

Scientific Reports volume 11, Article number: 17428 (2021) Cite this article

Abstract

Pigs are susceptible to infection with the classical bovine spongiform encephalopathy (C-BSE) agent following experimental inoculation, and PrPSc accumulation was detected in porcine tissues after the inoculation of certain scrapie and chronic wasting disease isolates. However, a robust transmission barrier has been described in this species and, although they were exposed to C-BSE agent in many European countries, no cases of natural transmissible spongiform encephalopathies (TSE) infections have been reported in pigs. Transmission of atypical scrapie to bovinized mice resulted in the emergence of C-BSE prions. Here, we conducted a study to determine if pigs are susceptible to atypical scrapie. To this end, 12, 8–9-month-old minipigs were intracerebrally inoculated with two atypical scrapie sources. Animals were euthanized between 22- and 72-months post inoculation without clinical signs of TSE. All pigs tested negative for PrPSc accumulation by enzyme immunoassay, immunohistochemistry, western blotting and bioassay in porcine PrP mice. Surprisingly, in vitro protein misfolding cyclic amplification demonstrated the presence of C-BSE prions in different brain areas from seven pigs inoculated with both atypical scrapie isolates. Our results suggest that pigs exposed to atypical scrapie prions could become a reservoir for C-BSE and corroborate that C-BSE prions emerge during interspecies passage of atypical scrapie.

snip...

Discussion The outbreak of C-BSE was followed by the appearance of TSE in species that had never been diagnosed with prion diseases and the emergence in humans of vCJD16,17,18. However, no natural prion disease has been described in pigs, even though they were exposed to C-BSE contaminated feed12. Posterior experimental challenges in pigs and mice expressing porcine PrP have demonstrated that, although they are not completely resistant, pigs present a robust transmission barrier for C-BSE prions4,14,19.

However, the possible transmission of a TSE to swine is a public health concern due to the wide use of pork as a source of human food, and the increasing use of pigs as tissue donors, being reported a case of vCJD in a human patient receiving a swine dura mater graft20. Although pigs are apparently non-susceptible to C-BSE after oral challenge4,5,21, infectivity has been detected in tissues from pigs orally inoculated with classical scrapie or CWD10,11. In addition, these positive orally inoculated pigs are often subclinical, what could represent a public health concern, considering that these animals could reach the slaughterhouse without showing signs suggestive of prion disease.

In the present study, we evaluated the transmissibility of atypical scrapie to pigs. Pigs were euthanized between 22- and 72-months post inoculation (mpi), and their tissues tested for PrPSc accumulation and infectivity. We did not find evidence of transmission of atypical scrapie to any of the animals by EIA (Table 2), western blotting, or mouse bioassay (Table 3). PrPSc accumulation can be detected in BSE-challenged pigs at 34 mpi4, and at 22 mpi when inoculated with SBSE7. Although scrapie or CWD-inoculated pigs do not show clinical signs, PrPSc presence can be found in scrapie-challenged animals at 51 mpi11 and as early as 6 mpi in the case of CWD10.

Our main goal was to test the ability of atypical scrapie/Nor98 strain to propagate in swine, given that mice expressing porcine PrP (PoPrP-Tg001/tgPo mice) showed to be susceptible to atypical scrapie inoculation. One atypical scrapie isolate adapted to this transgenic line, reaching a 100% attack rate and rapid incubation periods in serial passages13, a similar adaptation to that observed with the C-BSE agent19. However, when this atypical scrapie isolate was tested for propagation in tgPo mice again, together with other atypical scrapie isolates, no positive results were obtained, in vitro nor in vivo14. These results, together with the negative transmissions showed in the present study, reinforce the conclusion that porcine species is highly resistant to atypical scrapie. However, we only performed one passage in tgPo mice, and further passages in this line and/or PMCA analysis of tgPo brains to detect any possible prion replication would be of interest.

However, it was demonstrated that C-BSE prions can be present as a minor variant in ovine atypical scrapie isolates and that C-BSE can emerge during the passage of these isolates to bovine PrP mice15. Considering that the aforementioned atypical scrapie isolate also acquired BSE-like properties when transmitted to tgPo mice13, and that C-BSE is the only prion that efficiently propagates in swine PrP4,7,14, we decided to investigate whether C-BSE prions could emerge from atypical scrapie during the ovine-porcine interspecies transmission.

Interestingly, PMCA reactions seeded with brain material from 7 pigs propagated in tgBov substrate showing PrPres with identical biochemical characteristics to those of C-BSE (Fig. 1). Positive C-BSE amplification was detected in the brain of pigs inoculated with either the PS152 or TOA3 atypical scrapie isolates, at minimum incubation periods of 28- and 35-months post inoculation, respectively. From each animal, positive reactions were not obtained from all brain areas tested (Supplementary table 1). Although PrPres amplified from the pigs showed C-BSE biochemical characteristics, further bioassays in tgBov mice are required to know whether these prions replicate the neuropathological features of C-BSE.

Altogether, our results and data obtained from transmission studies of prions to pigs, tgPo mice and in vitro studies using porcine substrate have shown that pig PrP has a very limited ability to sustain prion replication. No significant polymorphisms have been described for pig PRNP22, and it has been suggested that the conformational flexibility of pig PrP sequence is very low, limiting the number of PrPSc conformations able to produce misfolding14. No differences have been found between pig and minipig PrP sequences either23, suggesting that the conclusions obtained here could be extrapolated to domestic, non-experimental pigs. However, using tgBov substrate, we have demonstrated in vitro the presence of C-BSE seeding activity in some pig brain areas, suggesting that C-BSE prions emerged during the transmission of ovine atypical scrapie prions to pigs. Interestingly, C-BSE prions did not emerge from brain material of all the pigs, and, of those from which it did emerge, it was not detected in all brarsain areas tested. No correlation between time after inoculation and BSE emergence was found either. When the emergence of C-BSE from atypical scrapie in PMCA was described, it was associated to low levels of C-BSE prions that were present in the original atypical scrapie isolates15. It is possible that this result is related to the great resistance that pigs present to prion diseases, making the penetrance of the BSE prions that could be present in the original inoculum incomplete. In addition, considering that the amount of C-BSE conformers in the atypical scrapie inocula is probably very reduced and perhaps not homogeneously distributed throughout the isolate, it is also possible that not all the pigs received a sufficient amount of C-BSE conformers capable of being detected by PMCA. Finally, we should consider that PMCA amplification of prions is sometimes a stochastic phenomenon, which could explain why no C-BSE propagation was obtained from some of the pigs. It could be also discussed that C-BSE emergence from the pig brains could be related to persistence of the original atypical scrapie inoculum. However, C-BSE amplification was not obtained from all of the pigs and, in some of them (i.e. P-1217 and P-1231) C-BSE propagation was detected in caudal regions of the brain (cerebellum or occipital cortex) but not in more rostral areas (such as parietal cortex). If C-BSE amplification from pig brain samples were associated to inoculum persistence and not bona fide propagation of C-BSE prions it would be expected that such amplification would be detected mainly in the most rostral areas of the brain. Finally, even though the titer generated was not enough to produce disease in the pigs, these results evidence again the issue that pigs could act as subclinical reservoirs for prion diseases as observed with scrapie and CWD, and that the presence of prions can be detected in pigs short after exposure to prions7,10,11.

In conclusion, our findings suggest that, although pigs present a strong transmission barrier against the propagation of atypical scrapie, they can propagate low levels of C-BSE prions. The prevalence of atypical scrapie and the presence of infectivity in tissues from atypical scrapie infected sheep are underestimated24,25. Given that pigs have demonstrated being susceptible to other prion diseases, and to propagate prions without showing signs of disease, the measures implemented to ban the inclusion of ruminant proteins in livestock feed must not be interrupted.

https://www.nature.com/articles/s41598-021-96818-2
The prevalence of atypical scrapie and the presence of infectivity in tissues from atypical scrapie infected sheep are underestimated24,25.
Given that pigs have demonstrated being susceptible to other prion diseases, and to propagate prions without showing signs of disease, the measures implemented to ban the inclusion of ruminant proteins in livestock feed must not be interrupted.
https://nor-98.blogspot.com/2021/10/classical-bse-prions-emerge-from.html

EFSA atypical Scrapie

***> AS is considered more likely (subjective probability range 50–66%) that AS is a non-contagious, rather than a contagious, disease.

SNIP...SEE;

THURSDAY, JULY 8, 2021

EFSA Scientific report on the analysis of the 2‐year compulsory intensified monitoring of atypical scrapie

***> AS is considered more likely (subjective probability range 50–66%) that AS is a non-contagious, rather than a contagious, disease.

https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2021.6686

https://efsa.onlinelibrary.wiley.com/doi/full/10.2903/j.efsa.2021.6686

https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2021.6686

https://efsaopinionbseanimalprotein.blogspot.com/2021/07/efsa-scientific-report-on-analysis-of.html

***> Incomplete inactivation of atypical scrapie following recommended autoclave decontamination procedures <***

John Spiropoulos Richard Lockey Katy E. Beck Chris Vickery Thomas M. Holder Leigh Thorne Mark Arnold Olivier Andreoletti Marion M Simmons Linda A. Terry First published: 21 May 2019 https://doi.org/10.1111/tbed.13247 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/tbed.13247

Summary Prions are highly resistant to the decontamination procedures normally used to inactivate conventional pathogens. This is a challenging problem not only in the medical and veterinary fields for minimising the risk of transmission from potentially infective sources, but also for ensuring the safe disposal or subsequent use of animal by‐products. Specific pressure autoclaving protocols were developed for this purpose, but different strains of prions have been reported to have differing resistance patterns to established prion decontamination procedures, and as additional TSE strains are identified it is necessary to determine the effectiveness of such procedures. In this study we assessed the efficacy of sterilisation using the EU recommended autoclave procedure for prions (133o C, 3 Bar for 20 min) on the atypical or Nor98 (AS/Nor98) scrapie strain of sheep and goats. Using a highly sensitive murine mouse model (tg338) that overexpresses ovine PrPC, we determined that this method of decontamination reduced the infectivity titre by 1010. Infectivity was nonetheless still detected after applying the recommended autoclaving protocol. This shows that AS/Nor98 can survive the designated legislative decontamination conditions, albeit with a significant decrease in titre. The infectivity of a classical scrapie isolate subjected to the same decontamination conditions was reduced by 106 suggesting that the AS/Nor98 isolate is less sensitive to decontamination than the classical scrapie source. This article is protected by copyright. All rights reserved.

https://onlinelibrary.wiley.com/doi/abs/10.1111/tbed.13247

Saturday, May 2, 2009

APHIS AND WHO PLAN TO EXEMPT THE ATYPICAL SCRAPIE NOR-98 FROM REGULATIONS AT MEETING THIS MONTH

http://nor-98.blogspot.com/2009/05/aphis-and-who-plan-to-exempt-atypical.html

Monday, November 30, 2009

USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE

http://nor-98.blogspot.com/2009/11/usda-and-oie-collaborate-to-exclude.html

Thursday, December 20, 2012

OIE GROUP RECOMMENDS THAT SCRAPE PRION DISEASE BE DELISTED AND SAME OLD BSe WITH BOVINE MAD COW DISEASE

http://transmissiblespongiformencephalopathy.blogspot.com/2012/12/oie-group-recommends-that-scrape-prion.html

Experimental transmission of ovine atypical scrapie to cattle

Timm Konold, John Spiropoulos, Janet Hills, Hasina Abdul, Saira Cawthraw, Laura Phelan, Amy McKenna, Lauren Read, Sara Canoyra, Alba Marín-Moreno & Juan María Torres

Veterinary Research volume 54, Article number: 98 (2023)

Abstract

Classical bovine spongiform encephalopathy (BSE) in cattle was caused by the recycling and feeding of meat and bone meal contaminated with a transmissible spongiform encephalopathy (TSE) agent but its origin remains unknown. This study aimed to determine whether atypical scrapie could cause disease in cattle and to compare it with other known TSEs in cattle. Two groups of calves (five and two) were intracerebrally inoculated with atypical scrapie brain homogenate from two sheep with atypical scrapie. Controls were five calves intracerebrally inoculated with saline solution and one non-inoculated animal. Cattle were clinically monitored until clinical end-stage or at least 96 months post-inoculation (mpi). After euthanasia, tissues were collected for TSE diagnosis and potential transgenic mouse bioassay. One animal was culled with BSE-like clinical signs at 48 mpi. The other cattle either developed intercurrent diseases leading to cull or remained clinical unremarkable at study endpoint, including control cattle. None of the animals tested positive for TSEs by Western immunoblot and immunohistochemistry. Bioassay of brain samples from the clinical suspect in Ov-Tg338 and Bov-Tg110 mice was also negative. By contrast, protein misfolding cyclic amplification detected prions in the examined brains from atypical scrapie-challenged cattle, which had a classical BSE-like phenotype. This study demonstrates for the first time that a TSE agent with BSE-like properties can be amplified in cattle inoculated with atypical scrapie brain homogenate.

snip...

This is the first study in cattle inoculated with naturally occurring scrapie isolates that found the presence of prions resembling classical BSE in bovine brain although this was limited to detection by the ultrasensitive PMCA. The results from thermostability assay confirmed that the isolates were as thermoresistant as the BSE agent as proven in other studies [36, 48]. Previous PMCA studies with various British atypical scrapie isolates did not find any evidence of amplification [49, 50]. This may be explained by the use of ovine brain as substrate rather than brain from Bov-Tg110 mice, which may facilitate conversion to classical BSE prions.

Two hypotheses for prion strain propagation in cross-species transmission experiments have been proposed: conformational selection favours a particular strain conformation out of a mixture of conformations in a scrapie isolate whilst mutation results in the conformational shift of one conformation into another [51]. Following on from the study in mice [17], it has been subsequently suggested that classical BSE properties that arise in atypical scrapie isolates transmitted to cattle may be due to conformational mutation in a new host [52]. It does not confirm that the atypical scrapie agent is the origin of the classical BSE epidemic and further transmission studies would be required to see whether classical BSE can be generated.

Would PMCA applied to brains from cattle exposed to TSE agents other than classical BSE and atypical scrapie also produce a classical BSE-like molecular phenotype? The PMCA product obtained in the thermostability test using a thermosensitive classical scrapie control showed a profile unlike classical BSE. Atypical BSE has been linked to the origin of classical BSE because of its conversion into classical BSE following serial passages in wild-type mice (L-type BSE [11]) and bovine transgenic mice (H-type BSE [53]). Although we have not tested PMCA products of atypical BSE isolates as part of this study, there is no evidence that PMCA products from atypical BSE convert into classical BSE, at least for H-type BSE using bovine brain as substrate [54]. In fact, we were unable to propagate H-type BSE using the same methodology (S Canoyra, A Marín-Moreno, JM Torres, unpublished observation).

The study results support the decision to maintain the current ban on animal meal in feedstuffs for ruminants, particularly as atypical scrapie occurs world-wide, and eradication is unlikely for a sporadic disease.

In summary, experimental inoculation of cattle with the atypical scrapie agent may produce clinical disease indistinguishable from classical BSE, which cannot be diagnosed by conventional diagnostic tests, but prions can be amplified by ultrasensitive tests in both clinically affected and clinically unremarkable cattle, which reveal classical BSE-like characteristics. Further studies are required to assess whether a BSE-like disease can be confirmed by conventional tests, which may initially include a second passage in cattle.

https://veterinaryresearch.biomedcentral.com/articles/10.1186/s13567-023-01224-3

Volume 17, Number 5—May 2011

Research

Experimental Oral Transmission of Atypical Scrapie to Sheep

Marion M. SimmonsComments to Author , S. Jo Moore1, Timm Konold, Lisa Thurston, Linda A. Terry, Leigh Thorne, Richard Lockey, Chris Vickery, Stephen A.C. Hawkins, Melanie J. Chaplin, and John Spiropoulos

Author affiliations: Author affiliation: Veterinary Laboratories Agency–Weybridge, Addlestone, UK Cite This Article

Abstract

To investigate the possibility of oral transmission of atypical scrapie in sheep and determine the distribution of infectivity in the animals’ peripheral tissues, we challenged neonatal lambs orally with atypical scrapie; they were then killed at 12 or 24 months. Screening test results were negative for disease-specific prion protein in all but 2 recipients; they had positive results for examination of brain, but negative for peripheral tissues. Infectivity of brain, distal ileum, and spleen from all animals was assessed in mouse bioassays; positive results were obtained from tissues that had negative results on screening. These findings demonstrate that atypical scrapie can be transmitted orally and indicate that it has the potential for natural transmission and iatrogenic spread through animal feed. Detection of infectivity in tissues negative by current surveillance methods indicates that diagnostic sensitivity is suboptimal for atypical scrapie, and potentially infectious material may be able to pass into the human food chain.

Snip…

Discussion This study is still ongoing and will not be completed until 2012. However, the current interim report documents the successful oral transmission of atypical scrapie, confirms that the disease phenotype is retained following transmission by this route in AHQ/AHQ sheep, and indicates that infectivity can be demonstrated in the gut in the absence of detectable PrPSc at least as early as 12 months after exposure.

One sheep (animal 12) culled at 24 months post inoculation displayed abnormalities in behavior and movement suggestive of atypical scrapie. Signs like ataxia with head tremor and circling have been described in experimental (19) and natural (3,30) disease, which was attributed to lesions in the cerebellum and forebrain, respectively, corresponding with PrPSc accumulation in these areas (20,24).

By contrast, animal 11, which had confirmed atypical scrapie based on postmortem tests, was considered clinically normal. The less severe and limited PrPSc accumulation in the brain of this sheep than in animal 12 may explain the absence of clinical abnormalities, which is supported by our findings in goats with scrapie in which more extensive PrPSc accumulation in the brain was usually associated with a more severe clinical disease (25).

Although all TSEs are transmissible after intracerebral challenge to a susceptible host, only some are infectious under natural conditions. Therefore, it was important from a pathogenesis and disease control perspective to establish whether or not oral transmission can be successful. However, the challenge model in this study exposed animals as neonates, when the esophageal groove is operational and the lambs are physiologically monogastric. Exposure of 3-month-old ruminating animals to similar amounts of positive brain by the oral route have so far not resulted in any clinical disease, with all animals still alive >1,500 days post challenge (M.M. Simmons, unpub. data), but most natural cases have been recorded in animals older than this, so these animals may still progress to disease in the next few years. Since this challenge study in older animals has no time-kill component, and no losses caused by unrelated disease have occurred, whether any of these sheep are in a preclinical phase of disease is unknown. Unfortunately, the absence of detectable PrPSc in lymphoreticular tissues of sheep with atypical scrapie precludes the use of biopsies to ascertain early infection in these animals.

Transmission may be more efficient in newborn animals; the incubation periods of sheep orally infected with classical scrapie were significantly shorter in sheep challenged at 14 days of age than those challenged at 6 months of age (31). If, however, oral transmission is only effective in such young animals, then field exposure would most likely have to be through milk, which is known to be a highly effective route of transmission for classical scrapie (32). No data are currently available on the potential infectivity of milk from animals with atypical scrapie.

Successful oral transmission also raises questions regarding the pathogenesis of this form of disease. There must be passage of the infectious agent from the alimentary canal to the brain through one of several possible routes, most likely those that have been suggested and discussed in detail for other TSEs, for example, retrograde neuronal transportation either directly (33–35) or through lymphoid structures or hematogenously (36). Infectivity in the absence of readily demonstrable PrPSc has been reported (37–39), and although the mouse bioassay may detect evidence of disease in other tissues, these data may not be available for at least another 2 years. More protease-sensitive forms of PrPSc may be broken down more efficiently within cells and thus do not accumulate in peripheral tissues (19), enabling atypical PrPSc to transit the digestive tract and disseminate through other systems in small amounts before accumulating detectably in the central nervous system.

Although we do not have epidemiologic evidence that supports the efficient spread of disease in the field, these data imply that disease is potentially transmissible under field situations and that spread through animal feed may be possible if the current feed restrictions were to be relaxed. Additionally, almost no data are available on the potential for atypical scrapie to transmit to other food animal species, certainly by the oral route. However, work with transgenic mice has demonstrated the potential susceptibility of pigs, with the disturbing finding that the biochemical properties of the resulting PrPSc have changed on transmission (40). The implications of this observation for subsequent transmission and host target range are currently unknown.

How reassuring is this absence of detectable PrPSc from a public health perspective? The bioassays performed in this study are not titrations, so the infectious load of the positive gut tissues cannot be quantified, although infectivity has been shown unequivocally. No experimental data are currently available on the zoonotic potential of atypical scrapie, either through experimental challenge of humanized mice or any meaningful epidemiologic correlation with human forms of TSE. However, the detection of infectivity in the distal ileum of animals as young as 12 months, in which all the tissues tested were negative for PrPSc by the currently available screening and confirmatory diagnostic tests, indicates that the diagnostic sensitivity of current surveillance methods is suboptimal for detecting atypical scrapie and that potentially infectious material may be able to pass into the human food chain undetected.

https://wwwnc.cdc.gov/eid/article/17/5/10-1654_article

See updated studies on AS

Meeting-book-final-version prion 2023 Prion 2023 Congress Organizing Committee and the NeuroPrion Association, we invite you to join us for the International Conference Prion2023 from 16-20 October 2023 in Faro, Portugal.

https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf

https://web.archive.org/web/20250828201533/https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf

https://www.researchgate.net/profile/Syed-Zahid-Shah/publication/378314391_Meeting-book-final-version_prion_2023/links/65d44dad28b7720cecdca95f/Meeting-book-final-version-prion-2023.pdf

AS

https://intcwdsympo.wordpress.com/wp-content/uploads/2023/06/final-agenda-with-abstracts.pdf

Abstract for Prion 2023

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

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

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

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

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

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

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

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

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

Presentation Type: Oral Presentation

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

Research Institute

Grant Number: ALMA/APRI: 201400006, HC 414250

Abstract for Prion 2023

Acknowledgement: TSE unit NCAD, Lethbridge (Jianmin Yang, Sarah Bogart, Rachana Muley, Yuanmu Fang, Keri Colwell, Renee Anderson, John Gray, Rakhi Katoch) (CFIA, Canada), Dr. Catherine Graham (NSDA, Canada), Dr. Michel Levy (UCVM, Canada), Dr. Martin Groschup (FLI, Germany), Dr. Christine Fast (FLI, Germany), Dr. Bob Hills (Health Canada, Canada)

Meeting-book-final-version prion 2023 Prion 2023 Congress Organizing Committee and the NeuroPrion Association, we invite you to join us for the International Conference Prion2023 from 16-20 October 2023 in Faro, Portugal.

https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf

https://web.archive.org/web/20250828201533/https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf

https://www.researchgate.net/profile/Syed-Zahid-Shah/publication/378314391_Meeting-book-final-version_prion_2023/links/65d44dad28b7720cecdca95f/Meeting-book-final-version-prion-2023.pdf

Final rule on the Importation of Sheep, Goats, and Certain Other Ruminants (APHIS-2009-0095) Scrapie, BSE, CWD, TSE Prion Singeltary Submission

https://scrapie-usa.blogspot.com/2021/12/final-rule-on-importation-of-sheep.html

MAD SHEEP OF MAD RIVER VALLEY

DECLARATION OF EXTRAORDINARY EMERGENCY BECAUSE OF AN ATYPICAL T.S.E. (PRION DISEASE) OF FOREIGN ORIGIN IN THE UNITED STATES [No. 00-072-1] August 15, 2000 OIG case # NY-3399-56 REDACTED, VT

History my 10 year plus FOIA requests and investigation into the truth of infamous Mad Sheep of Mad River Valley!

''Enclosed is OIG's notification that they have scheduled an investigation of the following individual. REDACTED is alleged to have provided possibly inaccurate test results involving diseased sheep. However, because the results were determined to be inconclusive, no actual violation was actually committed.''

https://foiamadsheepmadrivervalley.blogspot.com/

''However, because the results were determined to be inconclusive, no actual violation was actually committed.'' ...confused

Friday, February 20, 2015 

***APHIS Freedom of Information Act (FOIA) Appeal Mouse Bio-Assays 2007-00030-A Sheep Imported From Belgium and the Presence of TSE Prion Disease Kevin Shea to Singeltary 2015



i don't make this stuff up...

IN SHORT ;

August 15, 2000

OIG case # NY-3399-56 REDACTED, VT

''Enclosed is OIG's notification that they have scheduled an investigation of the following individual. REDACTED is alleged to have provided possibly inaccurate test results involving diseased sheep. However, because the results were determined to be inconclusive, no actual violation was actually committed.''

snip...

[only bush et al could have interpreted it that way. don't all criminals wish this is the way the system worked. ...tss]

JULY, 28, 2000

Case Opening Memorandum

snip...

An investigation regarding the subject identified below will be conduced and a report submitted at the conclusion of the investigation. If you have or should later receive additional information concerning this matter, please forward it to this office.

If you believe that administrative action should be taken before all criminal and other legal matters are completed, please coordinate that action with this office in order not to jeopardize the ongoing investigation.

The fact that this subject is under investigation should not be discussed with anyone who does not have a need to know and all inquiries on the investigation should be referred to the office of Inspector General.

snip...end

FOR OFFICIAL USE ONLY FEBRUARY 7, 2002

SUBJECT OIG CASE NY-3399-56 REDACTED VT HEALTH/SANITATION VIOLATION

TO: William Buisch, Regional Director Eastern Region, VS Raleigh, NC

Enclosed is the official investigation report on REDACTED. If you will recall, REDACTED is alleged to have provided possible inaccurate test results involving diseased sheep.

OIG is closing their file upon issuance of the Report of Investigation (copy enclosed). We are, therefore, also closing our case file.

REDACTED

Resource Management Systems and Evaluation Staff

Enclosure

cc:

REDACTED IES, Riverdale, MD (w/cy of incoming)

APHIS:RMSES: REDACTED 2/7/02 "NY-3399-56-REDACTED Closure''

END...TSS

NOW, the question is, who screwed those test up, and was it done on purpose, just to cover someone's ass for letting those sheep in here in the first place ???

WHICH tests were compromised, one of them, all of them, and, can we trust the outcome of any of these test under the circumstances here ???

i.e.

"It is significant that four of the sheep which first tested positive on REDACTED Western blot tests, thereby providing the type of confirmation the plaintiffs argue is lacking on the current record."

UNDER what circumstances were these test compromised ???

MY basic, simple question, was not answered in layman term, i.e. exactly what strain of TSE did those sheep have ???

IS this the best we can do ???
"REDACTED is alleged to have provided possibly inaccurate test results involving diseased sheep. However, because the results were determined to be inconclusive, no actual violation was actually committed.''<<<
Saturday, February 27, 2010

*** FINAL REPORT OF THE TESTING OF THE BELGIAN (VERMONT) SHEEP February 27, 2010 IN SHORT ; August 15, 2000 OIG case # NY-3399-56 REDACTED, VT ''Enclosed is OIG's notification that they have scheduled an investigation of the following individual. REDACTED is alleged to have provided possibly inaccurate test results involving diseased sheep. However, because the results were determined to be inconclusive, no actual violation was actually committed.''

FINAL REPORT OF THE TESTING OF THE BELGIAN (VERMONT) SHEEP February 27, 2010

(10 YEARS LATER, FOIA, none of the sheep had any TSE at all...tss)

http://foiamadsheepmadrivervalley.blogspot.com/2010/02/final-report-of-testing-of-belgian.html

Thursday, April 24, 2008

RE-FOIA OF DECLARATION OF EXTRAORDINARY EMERGENCY BECAUSE OF AN ATYPICAL T.S.E. OF FOREIGN ORIGIN IN THE UNITED STATES [Docket No. 00-072-1]

http://foiamadsheepmadrivervalley.blogspot.com/2008/04/re-foia-of-declaration-of-extraordinary.html

FOIA MAD SHEEP MAD RIVER VALLEY

Tuesday, November 13, 2007

DECLARATION OF EXTRAORDINARY EMERGENCY BECAUSE OF AN ATYPICAL T.S.E. (PRION DISEASE) OF FOREIGN ORIGIN IN THE UNITED STATES [Docket No. 00-072-1]

To: Garfield.O.Daley@aphis.usda.gov

CC: phyllis.Fong@usda.gov; bse-L@aegee.org;

Re: FOIA APPEAL 07-566 DECLARATION OF EXTRAORDINARY EMERGENCY BECAUSE OF AN ATYPICAL T.S.E. (PRION DISEASE) OF FOREIGN ORIGIN IN THE UNITED STATES [Docket No. 00-072-1]

November 13, 2007

Greetings Garfield O. Daley, Acting FOIA Director, and USDA et al,

SNIP

for those interested, please see full text answer below received from USDA et al below on latest appeal ;

http://foiamadsheepmadrivervalley.blogspot.com/2007/11/declaration-of-extraordinary-emergency.html

http://foiamadsheepmadrivervalley.blogspot.com/

Owens, Julie

From: Terry S. Singeltary Sr. [flounder9@verizon.net]

Sent: Monday. July 24. 2006 1:09 PM

To: FSIS Regulations Comments

Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)

Greetings FSIS,

I would kindly like to comment on the following :

[Federal Register: July 12, 2006 (Volume 71, Number 133)] (Notices) [Page 39282-39283] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr12jy06-35] DEPARTMENT OF AGRICULTURE Food Safety and Inspection Service [Docket No. FSIS-2006-0011]

Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)

Update; Notice of Availability and Technical Meeting

AGENCY: Food Safety and Inspection Service, USDA.

ACTION: Notice of availability and announcement of technical meeting. SUMMARY: The Food Safety and Inspection Service (FSIS) is announcing

the availability of an updated risk assessment model and report for BSE. The previous risk assessment, released in October 2003, was revised to incorporate information available through December 2003, including the discovery of a BSE-infected cow in Washington State. The revised risk assessment model evaluates the impact of measures implemented after the discovery of the BSE-positive cow and recommendations made by an international BSE panel. FSIS will also hold a technical meeting to discuss the updated risk assessment model and report.

DATES: The public meeting will be held on July 25, 2006, from 1 p.m. to

https://web.archive.org/web/20060925205531/http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf

Scrapie, Humans, Zoonotic, what if?

=====

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

***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

https://www.ars.usda.gov/research/publications/publication/?seqNo115=361032

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

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

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

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

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

==============

PRION 2015 CONFERENCE

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019500/

PRION 2016 TOKYO

Saturday, April 23, 2016

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

Prion. 10:S15-S21. 2016 ISSN: 1933-68961933-690X

WS-01: Prion diseases in animals and zoonotic potential

***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

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

Ru G1 ., Pocchiari M2 ., Bertolini S. 1, Pite L.1 , Puopolo M.2 , Ladogana A.2 , Perrotta M.G.3 , Meloni D 1 . (1) National reference center for the study and research on animal encephalopathies and comparative neuropathologies (CEA). Experimental Zooprophylactic Institute of Piemonte, Liguria and Valle d'Aosta, Torino, Italy.

(2) Department of Cellular Biology and Neuroscience, Istituto Superiore di Sanità, Roma, Italy. (3) Office 3 National center for the fight and emergency against animal diseases. Ministry of Health, Roma, Italy.

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

Materials and Methods: National data from prion disease surveillance in humans (sporadic CJD) and small ruminants (CS) in Italy were utilized. A descriptive geographic analysis was conducted for each disease individually. Subsequently, an ecological study was performed to compare the occurrence of both diseases at the district and regional levels. Standardized incidence ratios (SIR), adjusted for confounders, were calculated for CJD and CS by district and region, respectively, representing the outcome and proxy of exposure. Considering a possible long incubation period of CJD, two study periods were analysed: 2010-2014 for CJD and 2002-2006 for CS. Eight alternative linear regression models were developed using SIR in humans as the dependent variable and SIR in sheep as the independent variable. These models varied in the scale of SIR data (continuous vs. categorical), geographical level (district vs. region), and the potential past exposure of sheep in specific areas to a known source of infection (via a contaminated vaccine).

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

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

Funded by: Italian Ministry of Health Grant number: Realizzazione del programma epidemiologico finalizzato a dare evidenza del potenziale zoonotico delle TSE animali diverse dalla BSE. Prot. N. 0018730-17/07/2015-DGSAFCOD_UO-P

''Nevertheless, these findings provide valuable evidence to formulate a hypothesis regarding the zoonotic potential of classical scrapie. Further investigations are necessary, employing specific designs such as analytical epidemiology studies, to test this hypothesis effectively.''

Meeting-book-final-version prion 2023 Prion 2023 Congress Organizing Committee and the NeuroPrion Association, we invite you to join us for the International Conference Prion2023 from 16-20 October 2023 in Faro, Portugal.

https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf

https://web.archive.org/web/20250828201533/https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf

https://www.researchgate.net/profile/Syed-Zahid-Shah/publication/378314391_Meeting-book-final-version_prion_2023/links/65d44dad28b7720cecdca95f/Meeting-book-final-version-prion-2023.pdf

=====

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

Enric Vidal1,2, Samanta Giler1,2, Montse Ordóñez1,2, Hasier Eraña3,4, Jorge M. Charco3,4, Guillermo Cantero1,2, Juan C. Espinosa5 , Juan M. Torres5 , Vincent Béringue6 , Martí Pumarola7 and Joaquín Castilla3,8,9

Aims: About 90% of Creutzfeldt-Jakob disease cases are classified as sporadic (sCJD), that is, occur infrequently, randomly and without a known cause. It is a fatal neurodegenerative disease with an incidence of 1-1.5 cases per million per year. Epidemiological studies have been so far unable to establish a causal relationship between sCJD and prion diseases in animals.

The zoonotic potential of sheep scrapie was demonstrated in 2014 (Cassard et al., Nature Communications) through inoculation of transgenic mice overexpressing the human prion protein with scrapie isolates. The resulting prion disease was indistinguishable from that occurring after sCJD inoculation in the same model and, while these results do not demonstrate that sCJD is caused by scrapie prions, they do show that the transmission barrier between ovine and human prions is not absolute. Our aim is to further assess this zoonotic risk.

Materials and methods: we have prepared inocula from 3 sCJD cases (MM1, MV2 and VV2) and 2 VPSPr cases (MM and MV) to verify if it is possible to recover the scrapie phenotype upon inoculation in Tg338 and Tg501 ovinized mouse models. Additionally, two different inocula gCJD (E200K) and GSS (A117V) have been also included in the bioassays as controls for classical and atypical genetic human prions, respectively.

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

Funded by: MINECO grant number AGL2017-88535-P and PID2021-1222010B-C22 and by Interreg POCTEFA grant number EFA148/16 (RedPRION)

''but on second passage, 4/10 Tg338 mice succumbed to CJDMM1 (40% attack rate after 645 dpi) and 1/12 Tg501 mice (519dpi, 10 still alive). The remaining 2nd passages are still ongoing. Conclusions: In this poster, the neuropathological features of the resulting strain are discussed.''

Meeting-book-final-version prion 2023 Prion 2023 Congress Organizing Committee and the NeuroPrion Association, we invite you to join us for the International Conference Prion2023 from 16-20 October 2023 in Faro, Portugal.

https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf

https://web.archive.org/web/20250828201533/https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf

https://www.researchgate.net/profile/Syed-Zahid-Shah/publication/378314391_Meeting-book-final-version_prion_2023/links/65d44dad28b7720cecdca95f/Meeting-book-final-version-prion-2023.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

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

***>“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.”<***

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, +8, and Jean-Philippe DeslysAuthors Info & Affiliations

March 20, 2001

98 (7) 4142-4147

https://doi.org/10.1073/pnas.041490898

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.

snip...

Discussion

One aim of this study was to determine the risk of secondary transmission to humans of vCJD, which is caused not by a primarily human strain of TSE agent but by the BSE strain having passed the species barrier to humans. This risk is tightly linked to the capacity of the BSE agent to adapt to primates and harbor enhanced virulence (i.e., induce disease after a short incubation period and provoke disease even if highly diluted) and to its pathogenicity after inoculation by the peripheral route. With respect to the latter, there are huge variations between different TSE agent strains and hosts. For example, the BSE agent is pathogenic to pigs after i.c. inoculation but not after oral administration (23). Thus, we wanted to know to what extent the BSE/vCJD agent is pathogenic to humans by the i.c. and i.v. routes. To achieve this, we used the macaque model. To monitor the evolution of the BSE agent in primates, but also to verify the identity of French vCJD, we conducted parallel transmission to C57BL/6 mice, allowing strain-typing. The experimental scheme is depicted in Fig. 1.

Characterization of the BSE Agent in Primates.

The identity of the lesion profiles obtained from the brains of the French patient with vCJD, two British patients with vCJD, and nonhuman primates infected with BSE provides experimental demonstration of the fact that the BSE agent strain has been transmitted to humans both in the U.K. and in France. Further, it lends support to the validity of the macaque model as a powerful tool for the study of vCJD. As far as the evolution of the BSE agent in primates is concerned, we observed an interesting phenomenon: at first passage of BSE in macaques and with vCJD, there was a polymorphism of the lesion profile in mice in the hippocampal region, with about half of them harboring much more severe vacuolation than the mice inoculated with cattle BSE. At second passage, the polymorphism tended to disappear, with all mice showing higher vacuolation scores in the hippocampus than cattle BSE mice. This observation suggests the appearance of a variant of the BSE agent at first passage in primates and its clonal selection during second passage in primates. The lesion profiles showed that it was still the BSE agent, but the progressive appearance of a “hippocampal signature” hallmarked the evolution toward a variant by essence more virulent to primates.

Characterization of the CJD and Scrapie Strains.

Controls were set up by transmitting one French and one U.S. scrapie isolate from ruminants as well as French sCJD and iCJD cases from humans. None of these revealed a lesion profile or transmission characteristics similar or close to those of BSE or vCJD, respectively, thus extending to the present French scrapie isolate the previous observation that the BSE agent was different from all known natural scrapie strains (4, 24).

The lesion profiles of sCJD and iCJD differed only slightly in severity of the lesions, but not in shape of the profile, revealing the identity of the causative agents. One of us reported the absence of similarity between sCJD (six cases) and U.K. scrapie (eight cases) in transmission characteristics in mice (4). Herein, we made the striking observation that the French natural scrapie strain (but not the U.S. scrapie strain) has the same lesion profile and transmission times in C57BL/6 mice as do the two human TSE strains studied. This strain “affiliation” was confirmed biochemically. There is no epidemiological evidence for a link between sheep scrapie and the occurrence of CJD in humans (25). However, such a link, if it is not a general rule, would be extremely difficult to establish because of the very low incidence of CJD as well as the existence of different isolates in humans and multiple strains in scrapie. Moreover, scrapie is transmissible to nonhuman primates (26). Thus, there is still a possibility that in some instances TSE strains infecting humans do share a common origin with scrapie, as pointed out by our findings.

Transmission of vCJD and BSE to Nonhuman Primates.

vCJD transmitted readily to the cynomolgus macaque after 2 years of incubation, which was comparable to the transmission obtained from first-passaged macaque BSE and much shorter than the interspecies transmission of BSE. Starting with 100 mg of BSE–macaque brain material, dilutions up to 4 μg still provoked disease. These data suggest that the BSE agent rapidly adapts to primates accompanied by enhanced virulence.

Examination of macaque brain inoculated with vCJD revealed a similar pathology to that with second-passage BSE. The distribution of vacuolation and gliosis, as well as the pattern of PrP deposition, including the dense, sometimes florid plaques, were similar to the human vCJD and the BSE hallmarks of the first passage (1, 2). These data show that the phenotype of BSE in primates is conserved over two passages. Moreover, they confirm that the BSE agent behaves similarly in humans and macaques, a precious finding that will prove useful in the near future for the design of pathogenesis or therapeutic studies. Because of the number of macaques examined in this study, we can now reliably state that the pathology, in particular the PrP deposition pattern provoked by BSE, is similar in older and very young animals. However, plaque deposition is greater, and mature florid plaques were more numerous, in the young, which may be correlated with a longer duration of the clinical phase observed in this animal (2). This is important with regard to the fact that vCJD has been diagnosed mainly in teenagers and young adults, which raises the concern that older patients may have been misdiagnosed because of an alternative phenotype of the disease.

One should bear in mind, however, that cynomolgus macaques are all homozygotes for methionine at codon 129 of the PrP gene. Thus, our observations may not be relevant to humans carrying one or both valine alleles; however, all patients with vCJD reported to date have been M/M at this position (27). Intravenous Transmissions to Nonhuman Primates.

Brain pathology was identical in macaques inoculated i.c. and i.v. The i.v. route proved to be very efficient for the transmission of BSE, as shown by the 2-year survival of the animals, which is only 5 months longer than that obtained after inoculating the same amount of agent i.c. As the i.v. injection of the infectious agent implies per se a delayed neuroinvasion compared with a direct inoculation in the brain, this slight lengthening of the incubation period cannot, at this stage, be interpreted as a lower efficiency of infection as regards the i.c. route. These data should be taken into account in the risk assessment of iatrogenic vCJD transmission by i.v. administration of biological products of human origin. They also constitute an incentive for a complete i.v. titration.

Conclusions

From BSE and vCJD transmissions in nonhuman primates, a number of conclusions can be drawn that are of major importance for human health: (i) human-adapted BSE appears to be a variant of the BSE agent that is more virulent for humans than cattle BSE and is efficiently transmitted by the peripheral route; (ii) the detection of vCJD in unusually young patients is probably not because of a lack of diagnosis of cases in older patients, thus raising the question of the source of human contamination with BSE early in life; and (iii) iatrogenic transmissions from patients with vCJD would be readily recognized by using the same diagnostic criteria as those applied to vCJD [clinical and pathological criteria (27) comprising neuronal loss and gliosis in the thalamus correlated with high MRI signal (28, 29)], whether such contaminations had occurred by the central or i.v. route. Primary and iatrogenic cases of vCJD could be distinguished on the basis of the patient's clinical history.

The risk assessment of biological products of human origin, notably those derived from blood, has been deeply modified by the appearance of vCJD. We confirm that the BSE agent has contaminated humans not only in the U.K. and the Republic of Ireland but also in France, and we show that its pathogenic properties for primates are being enhanced by a primary passage in humans. Considering the flow of potentially contaminated bovine-derived products between 1980 and 1996, it is obvious that further vCJD cases may occur outside the U.K. Thus, and in the light of the present study, it is necessary to sustain worldwide CJD surveillance regardless of national BSE incidence and to take all precautionary measures to avoid iatrogenic transmissions from vCJD.

https://www.pnas.org/doi/10.1073/pnas.041490898

Scrapie and CJD, Suspect Symptoms, Like Lambs To the Slaughter, a review 2022

2001

Suspect symptoms

What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?

28 Mar 01

Like lambs to the slaughter

31 March 2001

by Debora MacKenzie Magazine issue 2284.

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 in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.

Deslys and colleagues were originally studying vCJD, not sCJD. They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.

As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain. As expected, they all affected the brain in a different way from BSE and vCJD. But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology.

"The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys. "You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie." In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar.

But there are more than 20 strains of scrapie, and six of sCJD. "You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys. Bruce is cautious about the mouse results, but agrees they require further investigation. Other trials of scrapie and sCJD in mice, she says, are in progress.

People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD.

But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD. "If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection."

There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain. Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.

Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.

https://www.newscientist.com/article/mg16922840-300-like-lambs-to-the-slaughter/

Atypical Scrapie

***> “The WOAH and APHIS determined that it is not a disease of trade concern.” <***

Remember That!

2025 USDA EXPLANATORY NOTES – ANIMAL AND PLANT HEALTH INSPECTION SERVICEIn 2023, APHIS collected samples from more than 26,000 sheep and goats for scrapie testing. Out of the total number of animals tested in 2023, no animals tested positive for classical scrapie and one sheep tested positive for non-classical scrapie (Nor98-like). Unlike classical scrapie, non-classical scrapie is either not laterally transmissible or is transmissible at a very low rate. The WOAH and APHIS determined that it is not a disease of trade concern.

USDA National Scrapie Program History and Bovine Spongiform Encephalopathy BSE TSE Update 2025 October 2025

https://www.usda.gov/sites/default/files/documents/22-APHIS-2025-ExNotes.pdf

https://www.researchgate.net/publication/396084947_USDA_National_Scrapie_Program_History_and_Bovine_Spongiform_Encephalopathy_BSE_TSE0AUpdate_2025

Atypical Scrapie

***> “The WOAH and APHIS determined that it is not a disease of trade concern.” <***

Remember That!…terry

I remember what “deep throat” told me about Scrapie back around 2001, during early days of my BSE investigation, after my Mom died from hvCJD, I never forgot, and it seems it’s come to pass;

***> Confidential!!!!

***> As early as 1992-3 there had been long studies conducted on small pastures containing scrapie infected sheep at the sheep research station associated with the Neuropathogenesis Unit in Edinburgh, Scotland. Whether these are documented...I don't know. But personal recounts both heard and recorded in a daily journal indicate that leaving the pastures free and replacing the topsoil completely at least 2 feet of thickness each year for SEVEN years....and then when very clean (proven scrapie free) sheep were placed on these small pastures.... the new sheep also broke out with scrapie and passed it to offspring. I am not sure that TSE contaminated ground could ever be free of the agent!! A very frightening revelation!!!

---end personal email---end...tss

and so it seems…

so, this is what we leave our children and grandchildren?

Rapid recontamination of a farm building occurs after attempted prion removal

First published: 19 January 2019 https://doi.org/10.1136/vr.105054

The data illustrates the difficulty in decontaminating farm buildings from scrapie, and demonstrates the likely contribution of farm dust to the recontamination of these environments to levels that are capable of causing disease.

snip...

This study clearly demonstrates the difficulty in removing scrapie infectivity from the farm environment. Practical and effective prion decontamination methods are still urgently required for decontamination of scrapie infectivity from farms that have had cases of scrapie and this is particularly relevant for scrapie positive goatherds, which currently have limited genetic resistance to scrapie within commercial breeds.24 This is very likely to have parallels with control efforts for CWD in cervids.

https://bvajournals.onlinelibrary.wiley.com/doi/abs/10.1136/vr.105054

***>This is very likely to have parallels with control efforts for CWD in cervids.

https://pubmed.ncbi.nlm.nih.gov/30602491/

Front. Vet. Sci., 14 September 2015 | https://doi.org/10.3389/fvets.2015.00032

Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission

In conclusion, the results in the current study indicate that removal of furniture that had been in contact with scrapie-infected animals should be recommended, particularly since cleaning and decontamination may not effectively remove scrapie infectivity (31), even though infectivity declines considerably if the pasture and the field furniture have not been in contact with scrapie-infected sheep for several months. As sPMCA failed to detect PrPSc in furniture that was subjected to weathering, even though exposure led to infection in sheep, this method may not always be reliable in predicting the risk of scrapie infection through environmental contamination.

http://journal.frontiersin.org/article/10.3389/fvets.2015.00032/full

"Additionally, we have determined that prion seeding activity is retained for at least fifteen years at a contaminated site following attempted remediation."

15 YEARS!

Detection of prions in soils contaminated by multiple routes

Results: We are able to detect prion seeding activity at multiple types of environmental hotspots, including carcass sites, contaminated captive facilities, and scrapes (i.e. urine and saliva). Differences in relative prion concentration vary depending on the nature and source of the contamination. Additionally, we have determined that prion seeding activity is retained for at least fifteen years at a contaminated site following attempted remediation.

Conclusions: Detection of prions in the environment is of the utmost importance for controlling chronic wasting disease spread. Here, we have demonstrated a viable method for detection of prions in complex environmental matrices. However, it is quite likely that this method underestimates the total infectious prion load in a contaminated sample, due to incomplete recovery of infectious prions. Further refinements are necessary for accurate quantification of prions in such samples, and to account for the intrinsic heterogeneities found in the broader environment.

Funded by: Wisconsin Department of Natural Resources

Prion 2023 Abstracts

Meeting-book-final-version prion 2023 Prion 2023 Congress Organizing Committee and the NeuroPrion Association, we invite you to join us for the International Conference Prion2023 from 16-20 October 2023 in Faro, Portugal.

https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf

https://web.archive.org/web/20250828201533/https://prion2023.org/wp-content/uploads/2023/10/Meeting-book-final-version2.pdf

https://www.researchgate.net/profile/Syed-Zahid-Shah/publication/378314391_Meeting-book-final-version_prion_2023/links/65d44dad28b7720cecdca95f/Meeting-book-final-version-prion-2023.pdf

FRIDAY, NOVEMBER 21, 2025

While no one was watching: Tenuous status of CDC prion unit, risk of CWD to people worry scientists

https://chronic-wasting-disease.blogspot.com/2025/11/while-no-one-was-watching-tenuous.html

Scrapie Field Trial was developed at Mission, Texas, on 450 acres of pastureland, part of the former Moore Air Force Base

EPIDEMIOLOGY OF SCRAPIE IN THE UNITED STATES

Academic Preg

James Hourriganl, Albert Klingsporn2, Edited by » Peast

W. W. Clark3, and M, de Camp4

United States Department of Agriculture, Animal and Plant Health Inspection Service, Veterinary Services

snip...

METHODS

A Scrapie Field Trial was developed at Mission, Texas, to provide additional information for the eradication program on the epidemiology of natural scrapie. The Mission Field Trial Station is located on 450 acres of pastureland, part of the former Moore Air Force Base, near Mission,

Texas. It was designed to bring previously exposed, and later also unexposed, sheep or goats to the Station and maintain and breed them under close observation for extended periods

to determine which animals would develop scrapie and define more closely the natural spread and other epidemiological aspects of the disease.

The 547 previously exposed sheep brought to the Mission Station beginning in 1964 were of the Cheviot, Hampshire, Montadale, or Suffolk breeds. They were purchased as field outbreaks occurred, and represented 21 bloodlines in which scrapie had been diagnosed. Upon arrival at the Station, the sheep were maintained on pasture, with supplemental feeding as necessary. The station was divided into 2 areas:

snip...

RESULTS

Table 1 indicated that previously exposed sheep brought to the Station at various times and ages (1 to 89 months old) included 333 Suffolks at risk. Of these, 98 (29%) developed scrapie. This demonstrated the necessity to slaughter such sheep to prevent further Spread of the disease, These pre- viously exposed Suffolks were bred at the Station and produced 446 progeny at risk. Of these 153 (34%) developed scrapie.

Although the minimum and average ages when scnapied were similar for both groups, some of the previously exposed Suffolks brought to the Station developed scrapie when much older--ewes 60 to 142 months old and rams 67 to 102 months old. O£ the 153 Suffolks born at the Station, only 3 were more than 60 months of age (65, 66, and 69 months old).

This difference in age scrapied was attributed to the fact that the Suffolks born at the Station may have been sub- ject to a greater exposure from birth.

It was also observed that when both dam and progeny were scrapied, the progeny nearly always developed clinical disease at a younger age than their respective dam. Thirty- two dams were scrapied at an average of 60 months of age. Forty-six of their progeny developed the disease at an average of 38 months (range 25 to 53 months). Thirty-seven of the 46 progeny were younger than the dam (average 20 months younger, range 2 to 99 months younger). Two were scrapied at the same age as their dams, and 8 were older (average 5 months, range 1 to 13 months older).

++. Although the incidence of scrapie was considerably Greater in the progeny of scrapied compared to free dams, the progeny of either scrapied or free dams manifested scrapie at the typical age and irrespective of the age their respective dams were scrapied. The differences in ages that dams and progeny were scrapied was believed due to difference of exposure, particularly whether they were exposed at an early age,

Table 2 summarized the data on exposed Suffolks and was Prepared so as to show scrapie incidence in the progeny of dams and sires of known Scrapie status. The scrapie incidence in the progeny of Free X Free parents was 25%, progeny of scrapied Sires 39%, and scrapied dams 42%. When both sire and dam were scrapied, the scrapie incidence in 18 Progeny at risk was 78%.

When the scrapie status of the sire was ignored, scrapie incidence in th- progeny of free dams was 34% and in pre y of scrapied da as 62%. When the scrapie status of the dam was ignored, scrapie incidence in the progeny of free sires was 26% and in the progeny of scrapied sires was 452.

Although the scrapie incidence was nearly double in the progeny of scrapied compared to free dams, the latter con- tributed a greater number of scrapied progeny, 116, compared to only 51 cases which had scrapied dams. This was because free dams made a considerably heavier contribution to the progeny at risk4-342 compared to 82. It was felt that in farm flocks a similar situation could exist.

It was possible that free dams could have been mis- classified; however, this was unlikely to have been significant, unless "nonclinical or carrier" dams exist. In this Suffolk group, the ages of 100 free dams of scrapied progeny ranged from 25 to 160 (average 97) months. These free dams did not show clinical signs of scrapie,”and there were no histopathological lesions suggesting scrapie in those which died, If one cannot classify as free, ewes which have reached 97 months (average) and did not develop the disease, from a practical standpoint, it is not possible to classify sheep as free, at least on the basis of clinical signs and histology. The free dams of 50% of the scrapied progeny were more than 100 months of age, averaging 126 months.

Upon arrival at the Mission Station at 3 to 9 months of age, the 140 previously unexposed sheep and goats were placed in infected pastures and corrals and were subjected to con- tact with a succession of natural cases of scrapie in sheep, and eventually also in goats. These animals were bred only within their respective groups and were not crossbred to other breeds of sheep or those brought to the Station from infected flocks or their progeny. The male or female animals mixed freely with animals of their respective sex of the infected Flock and were similarly identified and subjected to similar flock management and diagnostic procedures.

Table 3 indicated that natural scrapie had occurred in 5 of the 140 previously unexposed sheep. One case each occurred in Rambouillet, Targhee, and Hampshire ewes at 88, 89, and 89 months of age and in % Suffolk ewes at 73 and 102 months of age, and 85, 82, 80, 64, and 93 months following initial natural exposure. This represented a natural situation involving lateral spread, under the circumstances involved, when sheep were not exposed when very young. Scrapie was not detected clinicaliy or histologically in any of the dairy or Angora goats brought to the Station. The disease occurred in an average of 27% of the progeny of previously unexposed sheep or goats born at the Station and included cases in progeny of all breeds of sheep or goats taken there, The incidence in the progeny ranged from 14% in Rambouillet sheep to 61% in dairy goats. ~

These data showed that scrapie spread laterally, by contact exposure, from scrapied te previously free animals, but at an apparently lower rate when exposure was first received at the age of 3 to 9 months. These animals were presumed to be susceptible to the disease, as their progeny developed scrapie at rates and ages similar (on the average) to the progeny, pf previously exposed Suffolk sheep born and reared in the same environment.

It was suggested that the progeny of previously unexposed animals developed scrapie at a much higher rate than their parents, and at a younger age, because they were subjected to exposure from birth. The data did not rule out the possibility that the animals born at the Station could have also received the virus from their dams "vertically" prior te, at, or following birth.

Table 4 summarized the scrapie incidence in #he progeny, born at the Station, of previously unexposed dairy goats.

The data were prepared so as to show scrapie incidence in the progeny of dams and sires of known scrapie status.

The 58% incidence in the progeny (24 at risk) of Free X Free parents was more than twice the 25% seen in the Suffolk group (Table 2). Scrapied sires did not increase the incidence in goat progeny (it was 44%); scrapied dams increased the incidence to 71%. When both sire and dam were scrapied the incidence was 89%, with only 9 goat progeny at risk.

When the scrapie status of the sire was ignored, the scrapie incidence in the progeny of free dams was 56% and in the progeny of scrapied dams it was 74%.

Free dams contributed 34 progeny at risk and scrapied dams 31 progeny.

When the scrapie status of the dam was ignored, scrapie incidence was 64% in the progeny of free sires and a similar 66% in the progeny of scrapied sires.

A total of 244 sheep (127 Suffolk, 59 Rambouillet, and 58 Targhee) were removed from scrapie exposure within a few hours of birth or at 4, 9, or 20 months of age and placed in isolation pens. Removal of sheep from exposure at these ages was selected as being representative of usual flock operations when sheep might be sold from an infected flock at weaning, the first fall or the second fall after their birth.

Table 5 reflected the fate of such animals. Four of the 6 scrapied sheep which had been isolated at birth were Suffolks and the 2 older animals were Targhees. The first case in the group isolated at birth was a Targhee, progeny of a ewe that did not develop clinical scrapie. The scrapie incidence in 36 at risk Suffolks removed from exposure at birth was 11%, con- siderably less -“en that expected had these animals remz d in an infected en ment.

Table 6 reflected the status of 51 goats isolated from scrapie exposure at birth, and at 6, 8 to 10, 20, 32 to 59 and 60 to 82 months of age.

None of the goats removed at birth developed scrapie, although all 5 of those alive at 5 years of age had scrapied dams and 1 also had a scrapied sire. The sire of the remaining 4 had sired 7 scrapied progeny. Under such circumstances, had they remained in an infected environment nearly all of these goats would have been expected to develop scrapie. With the exception of the 20 month group, scrapie occurred at an incidence of 25 to 100% in ali other groups and at the expected age. A further observation was that 4 of the progeny of these dairy goats, born and kept apart from any sheep, developed scrapie which suggested that goats were not "dead- end hosts" insofar as scrapie was concerned.

Table 7 recorded the fate of progeny of certain selected scrapied or free Suffolk sheep or dairy goat dams.’

Suffolk ewe G298 was scrapied at 46 months of age. She had twin lambs in 1969 and 1 lamb in 1970. All 3 lambs developed scrapie. Suffolk ewe G27a was scrapied at 39 months. Her lamb born in 1966 was scrapied at 53 months; however, her lambs born in 1967 and 1968 remained free--lived to 102 months of age.

Suffolk ewe G25a died at 131] months of age and was nega- tive clinically and histologically. Mice remained negative following intracerebral inoculation of brain, spleen, and lymph nodes from this ewe. This ewe had 9 progeny at risk, of which 4 developed scrapie and 5 did not. There was no dis- cernible pattern to the cases. In two instances, 1 twin was scrapied and 1 remained free.

Goat B259 was scrapied when 43 months old. All of her 6 progeny at risk developed scrapie.

Goat B14a remained free and died at 101 months of age. Of her 11 progeny at risk, 7 were scrapied and 4 were not.

It was observed at the Station that when scrapied dams had several progeny at risk, 1 or more progeny usually developed the disease. However, many such scrapied dams also had progeny which lived, or are living, considerably beyond the age of their dams and beyond the age animals born at the Station manifested the disease.

It was also observed that individual free dams had free progeny in earlier years followed by scrapied progeny when they were older, or had scrapied progeny when young followed by free progeny when older, or scrapie and free progeny dis- persed throughout the dam's breeding life. The same situation occurred in progeny of scrapied dams; however, the pattern was less irregular due to the smaller number of progeny from each scrapied dam and the higher incidence of scrapie in such progeny. Circumstances prevented breeding all ewes ary year and, thus, many had only 1 progeny at risk. Scrapie developed in 100% of the single progeny at risk of 11 scrapied and 15 free dams. The 26 scrapied progeny were equally divided between ewes and rams.

Table 8 reflected the difference in age scrapied of - sheep brought to the Station compared to the age scrapied of those born there. Although the average age of previously exposed sheep (Suffolks) brought to the Station did not differ greatly from the overall average, several animals brought to the Station developed the disease at quite advanced ages. The previously unexposed scrapied animals brought to the Station were also considerably older than animals born there. Progeny of scrapied dams developed the disease at a slightly younger age than did progeny of free dams. The average age was nearly the same for males and females.

DISCUSSION

snip...see full text;

http://web.archive.org/web/20030513212324/http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf

https://scrapie-usa.blogspot.com/2023/01/epidemiology-of-scrapie-in-united-states.html

TUESDAY, SEPTEMBER 30, 2025

USDA National Scrapie Program History and Bovine Spongiform Encephalopathy BSE TSE Update 2025

USDA National Scrapie Program FY 2025 Third Quarter Progress Report: July 2025

https://www.aphis.usda.gov/sites/default/files/scrapie-quarterly-report.pdf

https://scrapie-usa.blogspot.com/2025/09/usda-national-scrapie-program-history.html

https://bovineprp.blogspot.com/2025/09/usda-national-scrapie-program-history.html

WEDNESDAY, AUGUST 13, 2025

Revised Bovine Spongiform Encephalopathy BSE TSE Prion Standards

https://bovineprp.blogspot.com/2025/08/revised-bovine-spongiform.html

https://prpsc.proboards.com/thread/177/revised-bovine-spongiform-encephalopathy-standards

WEDNESDAY, OCTOBER 15, 2025

US NATIONAL PRION DISEASE PATHOLOGY SURVEILLANCE CENTER CJD TSE REPORT 2025

https://prionunitusaupdate.blogspot.com/2025/10/us-national-prion-disease-pathology.html

terry

posted by Terry S. Singeltary Sr. | 9:54 PM | 0 Comments