Thursday, May 29, 2025

Animal feed company convicted at Ballymena court EU Regulation No.999/2001 TSE Regulations

 Animal feed company convicted at Ballymena court EU Regulation No.999/2001 TSE Regulations


Animal feed company convicted at Ballymena court

Date published: 28 May 2025 

Robin Rainey & Sons Limited, Portglenone Road, Randalstown were convicted today at Ballymena Court in relation to one charge of failure to comply with animal feeding requirements.

Green image with the word News in the centre

This contravenes EU Regulation No.999/2001, the Transmissible Spongiform Encephalopathies Regulations (Northern Ireland) 2018 and the Animal By-Products (Enforcement) Regulations 2015 (as amended).

Robin Rainey & Sons Limited pleaded guilty and fined £350 plus £15 offender levy.

The case was brought to the attention of DAERA following routine sampling on a sample of calf meal which tested positive for bone fragments and terrestrial muscle fibres. 

Notes to editors:

Robin Rainey & Sons Limited was convicted on one charge of failed to comply with animal feeding requirements, in contravention of Article 7 of EU Regulation No.999/2001 and the Transmissible Spongiform Encephalopathies and Animal By-Products (Amendment etc.) (EU Exit) Regulations 2019, contrary to Regulation 5(5) of the Transmissible Spongiform Encephalopathies Regulations (Northern Ireland) 2018

Assuring food safety in Northern Ireland is essential to uphold public health standards, food production standards and is crucial for the commercial viability of the agri-food sector. All Food and Feed Business Operators should rightly employ all reasonable and practical steps to reduce the risk of any potential contaminants entering the food chain and all operators need to be fully aware of the consequences of not managing risks effectively.

Food safety scares undermine consumer confidence in the output of the agri-food sector. Contamination incidents early in the food chain can have a huge impact in terms of consumer confidence, public health and financial implications. The Feed sector works with supply chain partners, farmers processors, towards the common goal of assuring supply chain integrity. Under EU TSE Regulation (EC) No. 999/2001, the feeding of animal protein to ruminants is prohibited. The controls are implemented in Northern Ireland by the TSE Regulations (Northern Ireland) 2018. TSEs are caused by pathogens known as prions, which are responsible for a range of fatal brain diseases. The diseases include BSE in cattle, Scrapie in sheep and goats and Creutzfeldt-Jakob disease (CJD) and Kuru in humans.

In the UK, the first feed ban of this nature was introduced in 1988. In addition, it has been illegal to feed ruminants with all forms of mammalian protein since November 1994 and to feed any farmed livestock, including fish and horses, with mammalian meat and bone meal since 4 April 1996.

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All media queries should be directed to the DAERA Press Office: pressoffice.group@daera-ni.gov.uk or telephone: 028 9052 4619.

The Executive Information Service operates an out of hours’ service for media enquiries only between 1800hrs and 0800hrs Monday to Friday and at weekends and public holidays. The duty press officer can be contacted on 028 9037 8110.

https://www.daera-ni.gov.uk/news/animal-feed-company-convicted-ballymena-court

Abstract for Prion 2023

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

Authors: Sandor Dudas'

1, Samuel James Sharpe', Kristina Santiago-Mateo', Stefanie Czub', Waqas Tahirl,2, *

Affiliation: National and WOAH reference Laboratory for Bovine Spongiform Encephalopathy, Canadian Food inspection Agency, Lethbridge Laboratory, Lethbridge, Canada. ?Department 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 (C-BSE) 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 Prpso 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 Prps 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 Prps 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


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 Prps in C-BSE, suggesting atypical BSE as a possible origin of C-BSE in UK.

Previous studies have demonstrated that L-BSE can be orally transmitted to cattle (7) and might have caused prion disease in farm-raised minks (6), indicating that L-BSE could naturally affect various animal species. Our findings suggest that L-BSE can also be orally transmitted to macaques. Therefore, current control measures aimed at preventing primary C-BSE in cattle and humans may also need to consider the potential risk of spontaneous L-BSE transmission.

Volume 31, Number 5—May 2025

Dispatch

Administration of L-Type Bovine Spongiform Encephalopathy to Macaques to Evaluate Zoonotic Potential

Morikazu Imamura1Comments to Author , Ken’ichi Hagiwara, Minoru Tobiume, Minako Ohno, Hiromi Iguchi, Hanae Takatsuki, Tsuyoshi Mori, Ryuichiro Atarashi, Hiroaki Shibata, and Fumiko Ono1 Author affiliation: University of Miyazaki, Miyazaki, Japan (M. Imamura, M. Ohno, H. Iguchi, H. Takatsuki, T. Mori, R. Atarashi); National Institute of Infectious Diseases, Tokyo, Japan (K. Hagiwara, M. Tobiume); The Corporation for Production and Research of Laboratory Primates, Tsukuba, Japan (H. Shibata); Okayama University of Science, Imabari, Japan (F. Ono) Cite This Article

Abstract

We administered L-type bovine spongiform encephalopathy prions to macaques to determine their potential for transmission to humans. After 75 months, no clinical symptoms appeared, and prions were undetectable in any tissue by Western blot or immunohistochemistry. Protein misfolding cyclic amplification, however, revealed prions in the nerve and lymphoid tissues.

Worldwide emergence of classical bovine spongiform encephalopathy (C-BSE) is associated with variant Creutzfeldt-Jakob disease in humans (1). Two other naturally occurring BSE variants have been identified, L-type (L-BSE) and H-type. Studies using transgenic mice expressing human normal prion protein (PrPC) (2) and primates (3–5) have demonstrated that L-BSE is more virulent than C-BSE. Although L-BSE is orally transmissible to minks (6), cattle (7), and mouse lemurs (5), transmissibility to cynomolgus macaques, a suitable model for investigating human susceptibility to prions, remains unclear. We orally inoculated cynomolgus macaques with L-BSE prions and explored the presence of abnormal prion proteins (PrPSc) in tissues using protein misfolding cyclic amplification (PMCA) along with Western blot (WB) and immunohistochemistry (IHC). PMCA markedly accelerates prion replication in vitro, and its products retain the biochemical properties and transmissibility of seed prion strains (8).

The Study

Two macaques orally inoculated with L-BSE prions remained asymptomatic and healthy but were euthanized and autopsied at 75 months postinoculation. WB showed no PrPSc accumulation in any tissue (Table), IHC revealed no PrPSc accumulation, hematoxylin and eosin staining revealed no spongiform changes in brain sections, and pathologic examination revealed no abnormalities.

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Conclusion We noted no detectable evidence of PrPSc by WB or IHC in any tissues of L-BSE orally inoculated macaques. Nevertheless, PMCA successfully amplified PrPres from lymphatic and neural tissues. The PrPres exhibited electrophoretic patterns distinct from those detected by PMCA using L-BSE–affected cattle BH as the seed (Figure 3, panel C), indicating that the PrPSc used as the template for PrPres amplification in orally inoculated macaques did not originate from the bovine L-BSE prions used as inoculum. Instead, PrPSc were newly generated by the conversion of macaque PrPC by bovine L-BSE prions. Our results provide strong evidence that L-BSE can infect macaques via the oral route.

We found no evidence that PrPSc reached the brain in orally inoculated macaques; however, the macaques euthanized 6 years postinoculation might have been in the preclinical period. At low infection levels, lymph nodes play a vital role in prion spread to the central nervous system (11). Therefore, had the macaques been maintained for a longer period, they might have developed prion disease. Retrospective surveillance studies using the appendix and tonsil tissues suggested a considerable number of humans harboring vCJD in a carrier state (12). Thus, we cannot exclude that L-BSE orally inoculated macaques could similarly remain in a potentially infectious state.

The brain of L-BSE intracerebrally inoculated macaque accumulated prions with biochemical properties resembling bovine L-BSE prions (Figure 3, panel C; Appendix Figure 2); however, we observed no PrPSc accumulation in lymphoid tissues by WB or IHC (4). In contrast, macaques orally inoculated with C-BSE prions showed PrPSc accumulation in lymphoid tissues, including the spleen, tonsils, and mesenteric lymph nodes by WB and IHC (13). In our study, L-BSE orally inoculated macaques harbored C-BSE–like prions in their lymphoid and neural tissues. Interspecies transmission of L-BSE prions to ovine PrP transgenic mice can result in a shift toward C-BSE–like properties (14,15). Our data suggest that L-BSE prions may alter biophysical and biochemical properties, depending on interspecies transmission and inoculation route, acquiring traits similar to those of C-BSE prions. This transformation might result from structural changes in the L-BSE prion to C-BSE–like prions and other lymphotropic prions within lymphoid tissues or from the selective propagation of low-level lymphotropic substrains within the L-BSE prion population.

The first limitation of our study is that the oral inoculation experiment involved only 2 macaques and tissues collected at 6 years postinoculation, before disease onset. Consequently, subsequent progression of prion disease symptoms remains speculative. A larger sample size and extended observation periods are required to conclusively establish infection in orally inoculated macaques. Furthermore, we performed no bioassays for PMCA-positive samples, leaving the relationship between PMCA results and infectious titers undefined. Considering that PrPres amplifications from tissues from the orally inoculated macaque tissues required 2 rounds of PMCA, the PrPSc levels in positive tissues might have been extremely low and undetectable in the bioassay.

Previous studies have demonstrated that L-BSE can be orally transmitted to cattle (7) and might have caused prion disease in farm-raised minks (6), indicating that L-BSE could naturally affect various animal species. Our findings suggest that L-BSE can also be orally transmitted to macaques. Therefore, current control measures aimed at preventing primary C-BSE in cattle and humans may also need to consider the potential risk of spontaneous L-BSE transmission.

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Dr. Imamura is an associate professor in the Division of Microbiology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. His research interests are focused on elucidating the mechanisms underlying prion formation.

TopExternal Link

Acknowledgment This study was supported by the Health Labor Sciences Research Grant (H29-Shokuhin-Ippan-004, 20KA1003, and 23KA1004).

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References…snip…end

https://wwwnc.cdc.gov/eid/article/31/5/24-1257_article#r5

Single case of atypical BSE confirmed on a farm in Essex

Press release

Single case of atypical BSE confirmed on a farm in Essex

A single case of atypical Bovine Spongiform Encephalopathy (BSE) has been confirmed on a farm in Essex, the Animal and Plant Health Agency (APHA) confirmed today (Tuesday 20 May).

From: Department for Environment, Food & Rural Affairs and Animal and Plant Health Agency Published 20 May 2025

The animal showed some clinical signs of BSE and was humanely culled on farm and tested as part of Defra’s routine surveillance programme. There is no risk to public health or food safety from this case and the animal, as fallen stock, was not destined to enter the food chain.

Atypical BSE is a naturally occurring, non-contagious disease in cattle which occurs spontaneously. It is distinct from classical BSE which is linked to contaminated feed.

Chief Veterinary Officer Christine Middlemiss said:   “A single case of atypical BSE has been confirmed on a farm in Essex. The animal died on farm and was tested as part of our strict routine controls and surveillance regime. 

“Atypical BSE is distinct from classical BSE and is a spontaneously and sporadically occurring, non-contagious disease which is believed to occur at a very low level in all cattle populations. This is proof that our surveillance system for detecting and containing this type of disease is working.”

Dr James Cooper, Deputy Director of Food Policy at the Food Standards Agency said:   “There is no food safety risk. There are strict controls in place to protect consumers from the risk of BSE, including controls on animal feed, and removal of the parts of cattle most likely to carry BSE infectivity.

“Consumers can be reassured that these important protection measures remain in place and that Food Standards Agency Official Veterinarians and Meat Hygiene Inspectors working in all abattoirs in England will continue to ensure that the safety of consumers remains the top priority.” 

Great Britain’s overall risk status for BSE remains at ‘controlled’ and there is no risk to food safety or public health.

The World Organisation for Animal Health and trading partners have been informed of the case. This does not affect the UK’s ability to export beef to other countries.

BSE is a notifiable animal disease. If you suspect it, you must report it immediately by calling the Defra Rural Services Helpline on 03000 200 301. In Wales, contact 0300 303 8268. In Scotland, contact your local Field Services Office. Failure to do so is an offence. This applies to pet and small holder animals as well as commercial cattle.

ENDS

Notes to editors:   Bovine Spongiform Encephalopathy is a chronic degenerative disease affecting the central nervous system of cattle. It is not contagious, so it does not spread from animal to animal or between holdings.

Classical BSE was first diagnosed in the United Kingdom in 1986.

Atypical BSE is distinct from classical BSE and occurs at a very low level in all cattle populations. It is reported occasionally in countries with active BSE surveillance programmes.

The last case of atypical BSE in the UK was in December 2024 in Scotland. There has been a total of 4 cases since 2015 (including this latest case).

[The case was identified as a result of strict control measures we have in place. It was not destined for the human food chain and the Food Standards Agency have confirmed there is no risk to human health as a result of this isolated case.]

Published 20 May 2025

https://www.gov.uk/government/news/single-case-of-atypical-bseconfirmed-on-a-farm-in-essex

THURSDAY, MAY 22, 2025 

Single case of atypical BSE confirmed on a farm in Essex 

https://bse-atypical.blogspot.com/2025/05/single-case-of-atypical-bseconfirmed-on.html

Atypical BSE in cattle

THE recent diagnosis of two atypical bovine spongiform encephalopathy (BSE) cases in Great Britain (March 2023 in Cornwall and December 2024 in Dumfries and Galloway) and one in the Republic of Ireland (in November 2023) warrants a reminder about this notifiable disease.

Since 2005, a total of 17 cases have been detected in Great Britain.1 Unlike classical BSE, which resulted in over 180,000 cases in Great Britain and was predominantly associated with the consumption of feed contaminated with the BSE agent, and where the last case was confirmed in Ayrshire in May 2024, atypical BSE is believed to be a spontaneous disease in cattle found in approximately one in 1,000,000 tested cattle based on French data,2 similar to the sporadic Creutzfeldt- Jakob disease in people. There is currently no evidence that atypical BSE causes a disease in people, although it can be transmitted experimentally to other species by intracerebral inoculation, including primates.3–5 The World Organisation for Animal Health does not include atypical BSE in its geographical BSE risk status assessment.

Despite differences in terms of epidemiological, molecular and biological phenotype compared with classical BSE, atypical BSE is currently treated as if it were classical BSE in accordance with EU and UK legislation: once a case is identified, all cohort animals born and reared with the affected animal during the first 12 months of its life, and all offspring born within 24 months of its clinical onset, are culled and tested for BSE, which does seem to be at odds with the hypothesis that it is a spontaneous disease. This is more a precautionary measure to maintain confidence in the beef trade and protect consumers while more knowledge about this disease is obtained.

Almost all current knowledge on atypical BSE is based on experimental infection because this spontaneous

VET RECORD | 29 March–12 April 2025

disease has generally only been found in aged downer cows, which is difficult to replicate experimentally in the host species. Intracerebral inoculation of brain tissue from an affected cow causes disease in cattle in less than two years, unlike the natural disease that usually occurs in animals over eight years of age.

The vast majority of cases have been identified by active monitoring of fallen stock or emergency slaughter of cattle, where only the brain sample of various stages of autolysis is generally available. Little is known of where the atypical BSE agent can be found in natural disease, other than in the brain, because all the cases confirmed have been identified after death through active surveillance, by which time most peripheral tissue has been disposed of. Limited material from a single case of a naturally affected cow was tested in Italy by mouse bioassay, which found infectivity in muscle.6 In experimental disease generated by intracerebral inoculation of cattle, infectivity can be detected in the brain and spinal cord, ganglia, peripheral nerves and skeletal muscles, similar to classical BSE, but not in peripheral lymphoid tissue.6–8

Early reporting of clinical suspects is needed so that the live animal or the whole carcase can be delivered to an APHA regional laboratory for tissue sampling. This is made more difficult due to the subtlety of clinical signs based on experimental disease. Clinical cases may not be as over- reactive or nervous as classical BSE cases; some may, in fact, be dull, but what most cases have in common is that they have difficulty getting up and eventually end up as downer cows, and only the clinical history may reveal some prior behavioural or locomotor changes. High creatinine kinase serum levels and nibbling in response to scratching the tail head or back were some features in experimental disease,8, 9 but it is not known whether this is also seen in natural disease.

In general, BSE should be considered as a differential diagnosis in all downer cows that do not respond to treatment, where the blood results do not support the presence of a metabolic disease and where the cause cannot be determined with confidence.

Since BSE is a notifiable disease, suspected cases of BSE in Great Britain must be reported to the local APHA office.

Changes are imminent in the reporting of fallen stock cattle, which will require the owner to state whether the animal displayed signs of changes in behaviour, sensation or locomotion before death, in addition to the likely cause of death or disease. This is to obtain a better profile of the clinical history, if cattle are retrospectively diagnosed as BSE cases, which has happened in all BSE cases confirmed since 2010: none has been reported as a clinical suspect.

“BSE should be considered as a differential diagnosis in all downer cows that do not respond to treatment”

Timm Konold, TSE lead scientist

Brenda Rajanayagam, workgroup leader for the data systems group

APHA Weybridge, New Haw, Addlestone, Surrey KT15 3NB email: timm.konold@apha.gov.uk

Keith Meldrum, former chief veterinary officer The Orchard, Swaynes Lane, Guildford, Surrey GU1 2XX

References

1 APHA. Cattle: TSE surveillance statistics. Overview of Great Britain statistics. 2025. https://bit.ly/4ho5Nds (accessed 19 March 2025)

Atypical BSE In Cattle

https://bvajournals.onlinelibrary.wiley.com/doi/abs/10.1002/vetr.5400?campaign=woletoc

FRIDAY, MAY 23, 2025 

Epidemiological investigation of a single atypical BSE case in Dumfries and Galloway, Scotland (RBSE 24/00006

https://bse-atypical.blogspot.com/2025/05/epidemiological-investigation-of-single.html

terry

Sunday, January 19, 2025

Experimental Bovine Spongiform Encephalopathy in Squirrel Monkeys: The Same Complex Proteinopathy Appearing after Very Different Incubation Times

Pathogens. 2022 May 20;11(5):597. doi: 10.3390/pathogens11050597

Experimental Bovine Spongiform Encephalopathy in Squirrel Monkeys: The Same Complex Proteinopathy Appearing after Very Different Incubation Times

Pedro Piccardo 1,2,3, Juraj Cervenak 1, Wilfred Goldmann 2,†, Paula Stewart 2, Kitty L Pomeroy 1,‡, Luisa Gregori 1, Oksana Yakovleva 1, David M Asher 1,*,† Editor: Pawel P Liberski

PMCID: PMC9144249 PMID: 35631118

Abstract

Incubation periods in humans infected with transmissible spongiform encephalopathy (TSE) agents can exceed 50 years. In humans infected with bovine spongiform encephalopathy (BSE) agents, the effects of a “species barrier,” often observed when TSE infections are transmitted from one species to another, would be expected to increase incubation periods compared with transmissions of same infectious agents within the same species. As part of a long-term study investigating the susceptibility to BSE of cell cultures used to produce vaccines, we inoculated squirrel monkeys (Saimiri sp., here designated SQ) with serial dilutions of a bovine brain suspension containing the BSE agent and monitored them for as long as ten years. Previously, we showed that SQ infected with the original “classical” BSE agent (SQ-BSE) developed a neurological disease resembling that seen in humans with variant CJD (vCJD). Here, we report the final characterization of the SQ-BSE model. We observed an unexpectedly marked difference in incubation times between two animals inoculated with the same dilution and volume of the same C-BSE bovine brain extract on the same day. SQ-BSE developed, in addition to spongiform changes and astrogliosis typical of TSEs, a complex proteinopathy with severe accumulations of protease-resistant prion protein (PrPTSE), hyperphosphorylated tau (p-tau), ubiquitin, and α-synuclein, but without any amyloid plaques or β-amyloid protein (Aβ) typical of Alzheimer’s disease. These results suggest that PrPTSE enhanced the accumulation of several key proteins characteristically seen in human neurodegenerative diseases. The marked variation in incubation periods in the same experimental TSE should be taken into account when modeling the epidemiology of human TSEs.

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The epidemic of BSE in UK cattle in the 1980s and 90s was followed by a relatively modest number of diagnosed cases of vCJD (233 total cases worldwide—all but 55 in the UK—as of May 2022, reported by the UK CJD Research and Surveillance Unit, Edinburgh [www.cjd.ed/uk], accessed on 12 May 2022), among tens of millions of people probably exposed to the agent. That observation raised questions about the overall transmissibility of the agent to humans and the possible existence of some unknown number of latent or asymptomatic cases of vCJD [2]. Experiments in monkeys—large long-lived animals genetically more closely related to humans than are rodents and ruminants—might help to address some of those issues. Studies in monkeys might also help to elucidate the possible role that aggregates of brain proteins other than PrP play in pathology and pathogenesis of various human TSEs [10]. As part of a long-term study investigating susceptibility of several widely used cell cultures to BSE infection, we inoculated squirrel monkeys (SQ) with serial dilutions of a bovine brain suspension containing the C-BSE agent and monitored them for ten years. In a preliminary study, we showed that SQ infected with C-BSE (SQ-BSE) developed a spongiform encephalopathy resembling that seen in humans with vCJD [10,11], albeit without PrP plaques. Here, we report the final characterization of this experimental model after observation over ten years. We observed an unexpected extreme difference in incubation times between two animals inoculated with the same dilution and volume of a C-BSE brain suspension on the same day. SQ-BSE developed, in addition to spongiform changes and astrogliosis, a complex proteinopathy with severe accumulations of PrPTSE, hyperphosphorylated tau (p-tau), ubiquitin, and α-synuclein but without the beta-amyloid (Aβ) protein typical of Alzheimer’s disease.

2. Results

2.1. Seven Squirrel Monkeys Inoculated with Material Containing BSE Agent Developed a Similar Neurological Disease (SQ-BSE) after Significantly Different Incubation Times Compared to Four Uninfected Squirrel Monkeys (SQ-Uninfected)

We previously showed that transgenic mice expressing bovine PrP (TgBo) inoculated with a bacteria-free filtrate of the same 1% C-BSE-infected brain suspension used to inoculate SQ developed neurological signs confirmed neuropathologically as TSE [11]. Those preliminary studies demonstrated that the original C-BSE brain extract used in the experiments described here contained infectivity (5 log10 IC ID50 per 0.03 mL). SQ were inoculated with serial dilutions of the same material used to inoculate TgBo mice. Ten years after inoculation the experiment was terminated.

Seven monkeys, designated SQ-BSE, developed neurologic signs typical of TSE, including loss of normal responsiveness (withdrawal), tremor, bradykinesia, jerky uncoordinated movements, and generalized weakness. No monkeys became noticeably irritable or aggressive and none lost weight. Three animals inoculated with 10−1 (10%) unfiltered low-speed clarified C-BSE agent were euthanized ~3.2 years (~38.4 months) after inoculation. Two animals inoculated with 10−2 unfiltered, low-speed clarified C-BSE suspension were euthanized 3.7 years (44.4 months) after inoculation. Two animals inoculated with the 0.45-µm-filtered bacteria-free 10−2 C-BSE-infected brain suspension also developed TSE. One of those animals (SQ-BSE 735) was euthanized with signs of TSE 3.3 years (39.6 months) after inoculation. SQ-BSE 735’s cage mate (736) had been inoculated by the same investigator with the same dilution and volume of C-BSE inoculum, on the same day and in the same facility used to inoculate all other animals described here; SQ-BSE 736 developed similar signs of neurological illness including weakness and ataxia, but almost five years (60 months) later (a total of 7.9 years [94.8 months] after inoculation). SQ-BSE 736’s neurological disease progressed over a period of 50 days until the animal was euthanized. Both SQ-BSE 735 and SQ-BSE 736 showed similar neurological signs and durations of overt illness (Table 1). All other animals inoculated with dilutions of BSE brain extract diluted > 10−2 remained asymptomatic until the experiment was terminated.

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3. Discussion Although squirrel monkeys have long been recognized as susceptible to infection with several TSE agents [2,14] transmission of BSE into this species has not been reported by other research groups [15]. The results presented here, after a ten-year observation period, show that intracerebral and peripheral inoculation of C-BSE agent into SQ transmitted a neurological disease with progressive behavioral, motor and cerebellar signs typical of TSEs. Neuropathologic examinations of brains from all seven animals with experimental BSE showed similar severe spongiform degeneration in the cerebrum, cerebellum and brainstem. Abundant PrPTSE deposits were present in most brain areas analyzed, closely correlated with severity of spongiform degeneration and astrogliosis. However, no obvious spongiform degeneration or PrP accumulation occurred in the temporal cortex; the hippocampus showed only minimal PrPTSE accumulation in the CA1 area. Brains of all animals with BSE showed severe tauopathy (in cerebral cortex, basal ganglia, cerebellum and brainstem) in the same areas with spongiform degeneration, PrPTSE, and astrogliosis, suggesting a correlation between neurodegeneration and complex protein accumulation in SQ-BSE. The morphology and distribution of p-tau deposits differ from those seen in humans with Alzheimer’s disease and with primary tauopathies [16]. However, p-tau rods similar to those described here have been described in other experimental TSEs, in humans with vCJD [16,17,18,19] and in a non-transmitted encephalopathy of UK cattle [20]. Our findings suggest that p-tau probably accumulated as a secondary event following appearance of spongiform encephalopathy and accumulation of PrPTSE. While it would have been interesting to study early development of the several histopathologic changes and accumulation of proteins during the silent incubation period of experimental BSE, especially the temporal relationship in appearance and accumulation of PrPTSE and p-tau, the study was not designed for that purpose and it was not feasible. Although p-tau is considered a neuropathologic hallmark in several degenerative diseases of the central nervous system, tau protein displays other post-translational modifications (e.g., glycosylation, acetylation), raising a possibility that other tau species might also participate in the disease process [21]. No obvious differences in distribution of PrPTSE and p-tau deposits or in astrogliosis were observed in SQ-BSE after incubation periods ranging from 29 to 98.6 months or in those with different durations of clinical signs ranging from two to five months. We did find larger amounts of PrPTSE, astrogliosis, p-tau, and α-synuclein in the brain of SQ-BSE 736 compared with SQ-BSE 735, suggesting that more post-translationally modified proteins accumulated during the longer asymptomatic phase of BSE. The extended incubation period in SQ-BSE 736 underscores one limitation of rodent models expressing human PrP to assess pathogenesis of human later-onset TSEs—that most mice rarely live much longer than two years. The severe pathology seen in the brainstem and the cerebellum of SQ-BSE is of special interest. Most patients become demented in the terminal stages of many neurodegenerative diseases; consequently, postmortem studies of their brains have usually directed special attention to lesions in the telencephalon (supratentorial) while rather neglecting degenerative changes in brainstem and cerebellum. Further studies should explore whether loss of cortical neurons in TSEs causes secondary infratentorial pathology or if infratentorial regions are also a primary target of disease. Additional studies might also determine to what extent the nuclei of the brainstem (essential to maintain vital neurological functions) affected by neurodegenerative processes in TSEs contribute to the rapid clinical decline typical of TSEs. Recent studies of early AD and PD also found considerable unexpected involvement of brainstem nuclei, findings that might profoundly change present concepts on origin, anatomical spread, and early clinical diagnosis of these diseases [22]. Previous studies suggest that a disturbed insulin signaling cascade may be implicated in the pathways through which soluble Aβ protein induces tau protein to phosphorylate [23]. Vasconcelos concluded that Aβ induced heterotypic seeding of tau filaments by spread of abnormal tau isoforms [24], possibly because hyperphosphorylation of tau, leads to self-assembly [25]. Here, we report that both p-tau and α-synuclein accumulated in all the same brain areas with neurodegeneration, but without forming detectable Aβ-amyloid plaques. Those findings suggest that subfibrillary PrPTSE aggregates might have stimulated a complex proteinopathy involving both tau and α-synuclein proteins that actively contributed to pathogenesis, perhaps resulting from loss of some function of PrPC. An incidental finding of significance in the study is that differences in incubation times of BSE in SQ cannot be attributed to variation in the open reading frames of PRNP genes because those sequences were identical in all monkeys tested; any genetic differences influencing incubation times must reside elsewhere in the genome. Furthermore, these results suggest caution before relying on similarities or differences in PrPTSE glycotype to infer that a TSE infection in one species was acquired from a TSE agent originating in the same or another species, because PrP of three species infected with the classical C-BSE agent in our study displayed different glycotypes. In any case, results with the SQ-BSE model presented here affirm that primate models can improve our understanding of the pathogenesis of human neurodegenerative diseases.

Keywords: prion, TSE, bovine spongiform encephalopathy, squirrel monkey

https://pmc.ncbi.nlm.nih.gov/articles/PMC9144249/

why do we not want to do TSE transmission studies on chimpanzees $ 5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.

snip... R. BRADLEY

http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf

Transmission Studies

Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculum (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in ALL of these species with the shortest incubation period in the ferret.

snip...


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

Subject: Re: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY

Date: Fri, 18 Oct 2002 23:12:22 +0100

From: Steve Dealler

Reply-To: Bovine Spongiform Encephalopathy Organization: Netscape Online member

To: BSE-L@ References:

Dear Terry,

An excellent piece of review as this literature is desperately difficult to get back from Government sites.

What happened with the deer was that an association between deer meat eating and sporadic CJD was found in about 1993. The evidence was not great but did not disappear after several years of asking CJD cases what they had eaten. I think that the work into deer disease largely stopped because it was not helpful to the UK industry...and no specific cases were reported. Well, if you dont look adequately like they are in USA currently then you wont find any!

Steve Dealler

====

''The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).''

CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE UNITED KINGDOM THIRD ANNUAL REPORT AUGUST 1994

Consumption of venison and veal was much less widespread among both cases and controls. For both of these meats there was evidence of a trend with increasing frequency of consumption being associated with increasing risk of CJD. (not nvCJD, but sporadic CJD...tss) These associations were largely unchanged when attention was restricted to pairs with data obtained from relatives. ...

Table 9 presents the results of an analysis of these data.

There is STRONG evidence of an association between ‘’regular’’ veal eating and risk of CJD (p = .0.01).

Individuals reported to eat veal on average at least once a year appear to be at 13 TIMES THE RISK of individuals who have never eaten veal.

There is, however, a very wide confidence interval around this estimate. There is no strong evidence that eating veal less than once per year is associated with increased risk of CJD (p = 0.51).

The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).

There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY OF LAMB EATING (p = 0.02).

The evidence for such an association between beef eating and CJD is weaker (p = 0.14). When only controls for whom a relative was interviewed are included, this evidence becomes a little STRONGER (p = 0.08).

snip...

It was found that when veal was included in the model with another exposure, the association between veal and CJD remained statistically significant (p = < 0.05 for all exposures), while the other exposures ceased to be statistically significant (p = > 0.05).

snip...

In conclusion, an analysis of dietary histories revealed statistical associations between various meats/animal products and INCREASED RISK OF CJD. When some account was taken of possible confounding, the association between VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS STATISTICALLY. ...

snip...

In the study in the USA, a range of foodstuffs were associated with an increased risk of CJD, including liver consumption which was associated with an apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3 studies in relation to this particular dietary factor, the risk of liver consumption became non-significant with an odds ratio of 1.2 (PERSONAL COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS)

snip...see full report ;

http://web.archive.org/web/20090506050043/http://www.bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf

http://web.archive.org/web/20090506050007/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf

http://web.archive.org/web/20090506050244/http://www.bseinquiry.gov.uk/files/yb/1994/07/00001001.pdf

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

***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

***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: 1933-6896 1933-690X

WS-01: Prion diseases in animals and zoonotic potential

Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.

These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

Tuesday, December 16, 2014

Evidence for zoonotic potential of ovine scrapie prions

Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier Andréoletti1, Affiliations Contributions Corresponding author Journal name: Nature Communications

Volume: 5, Article number: 5821 DOI: doi:10.1038/ncomms6821 Received 07 August 2014 Accepted 10 November 2014 Published 16 December 2014

Abstract

Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie prions remains unknown. Mice genetically engineered to overexpress the human​prion protein (tgHu) have emerged as highly relevant models for gauging the capacity of prions to transmit to humans. These models can propagate human prions without any apparent transmission barrier and have been used used to confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie prions transmit to several tgHu mice models with an efficiency comparable to that of cattle BSE.

***The serial transmission of different scrapie isolates in these mice led to the propagation of prions that are phenotypically identical to those causing sporadic CJD (sCJD) in humans.

***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

Subject terms: Biological sciences• Medical research At a glance

http://www.nature.com/ncomms/2014/141216/ncomms6821/full/ncomms6821.html


SUNDAY, JANUARY 19, 2025 

Scrapie Field Trial was developed at Mission, Texas, what if? Epidemiology of Scrapie in the United States 

https://chronic-wasting-disease.blogspot.com/2025/01/scrapie-field-trial-was-developed-at.html

Terry S. Singeltary Sr.