Press release
UK international risk status for BSE downgraded in huge boost to farm sector
World Organisation for Animal Health (WOAH) downgrades UK’s BSE risk rating to negligible
From:
Department for Environment, Food & Rural Affairs and Daniel Zeichner MP Published
2 June 2025
The UK’s risk rating status for Bovine Spongiform Encephalopathy (BSE) has been downgraded to negligible by the World Organisation for Animal Health (WOAH).
In a major boost for the food and farm sector, more avenues will now be open for trade with other countries as our improved risk status for beef and bovine products is recognised.
The abattoir and meat processing industry will be able to take advantage of changes to control measures, which will reduce operational burden and release financial savings for the abattoir and meat processing industry.
The UK’s improved risk status is a reflection of the UK’s global reputation for having some of the highest standards in the world for biosecurity .
BSE, occasionally known as mad cow disease, was a considerable public health concern in the 1980s leading to long-standing bans on British beef exports. The downgrading risk status marks a major step forward, reflecting decades of rigorous controls and opening the door to expanded trade and renewed confidence in UK beef.
Farming Minister Zeichner said:
Today’s announcement is a major step forward and will deliver a real boost to our hard-working cattle farmers, who will now have more avenues open for trading our excellent beef products.
It is also a huge vote of confidence in this government’s commitment to rigorous animal health standards and biosecurity.
UK Chief Veterinary Officer, Christine Middlemiss said:
WOAH’s recognition of the UK as negligible risk for BSE is a significant milestone and is a testament to the UK’s strong biosecurity measures and the hard work and vigilance of farmers and livestock keepers across the country who have all played their part in managing the spread of this disease.
This is the latest example of the UK’s global reputation as a world leader in biosecurity and our new status will improve UK trade for beef and bovine products and reduce the operational burden and create financial savings for the abattoir and meat processing industry.
Natasha Smith, Deputy Director of Food Policy at the Food Standards Agency said:
This good news reflects that our strict controls in place to protect consumers such as controls on animal feed, and removal of the parts of cattle most likely to carry BSE infectivity, have helped make sure there is no food safety risk.
Although the meat industry will be now able to use more of the carcass, consumers can be reassured that strict food safety controls remain in place. Food Standards Agency Official Veterinarians and Meat Hygiene Inspectors working in all abattoirs in England and Wales will continue to ensure that the safety of consumers remains the top priority.
Nan Jones, British Meat Processors Association (BMPA) Technical Policy Manager said:
This milestone is of significant value to the industry. To illustrate, the ability to recover mesenteric fat alone could generate value of approximately £10 million per year. Given the substantial benefits this change brings to our members, we hope that the improving UK–EU relationship offers an opportunity to seek earlier EU recognition of our status.
Jonathan Eckley, Agriculture and Horticulture Development Board (AHDB) International Trade Development Director, said:
This is welcome news for the UK beef sector. It highlights the strength of our animal health and food safety systems, reinforces the UK’s reputation for high-quality beef, and supports ongoing efforts to grow our export markets.
Farmers and livestock owners are still urged to remain vigilant for BSE disease. 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.
An isolated case of classical scrapie has been confirmed in a 2-year-old Welsh Mountain Badger Face female sheep. United Kingdom
THURSDAY, MAY 22, 2025
Single case of atypical BSE confirmed on a farm in Essex
FRIDAY, MAY 23, 2025
Epidemiological investigation of a single atypical BSE case in Dumfries and Galloway, Scotland (RBSE 24/00006)
Report on the epidemiological investigation of a BSE case in Scotland (RBSE24_00003) United Kingdom October 2024
Report on the epidemiological investigation of a BSE case in Scotland (RBSE24_00003) United Kingdom October 2024
Executive summary
On 9 May 2024, Scotland’s Chief Veterinary Officer (CVO) confirmed a case of classical bovine spongiform encephalopathy (BSE) in a 7.5-year-old cow on a beef suckler farm in Ayrshire, Scotland. This was the first case of classical BSE to be confirmed in the United Kingdom (UK) since 2021, and in Scotland since 2018. This report summarises the epidemiological investigations that have been carried out to describe and understand this single case of BSE.
The index case was a Simmental cross cow, born on 18 October 2016 in a holding in Dumfries and Galloway, Scotland. It was purchased and introduced into the incident herd on 27 June 2018, where it resided until its death.
The index case died on farm on 26 April 2024. The farmer did not suspect notifiable disease and the carcass was collected by the fallen stock company on the same day. The carcass was tested for BSE as per the UK’s statutory BSE surveillance procedures due to the cow’s age and because she was fallen stock.
A preliminary positive result was received on 1 May 2024. A final positive result was confirmed on 9 May 2024 by the Animal and Plant Health Agency (APHA) Weybridge. APHA Weybridge is the UK National Reference Laboratory (NRL) for transmissible spongiform encephalopathies (TSEs). It is also the World Organisation for Animal Health (WOAH) Reference Laboratory for BSE and scrapie.
Tracing investigations identified 2 offspring born in the 24 months prior to the clinical onset of disease and death of the index case (see also appendix 2, point (f)):
• The first one had a date of birth (DOB) of 13 May 2023. It was alive at the time of confirmation and placed under restrictions following BSE confirmation in the index case. It was transported alive to the NRL for TSEs in Weybridge for clinical observation. It was then euthanised and underwent a postmortem examination and BSE testing, with negative results.
• The second one had a DOB of 21 May 2022. It was already dead (slaughtered for human consumption and not eligible for BSE testing) when traced after the BSE case was confirmed.
Tracings investigations also identified 45 cohort animals born and/or reared with the index case during the relevant risk period (12 months either side of the date of birth of this case).
Of these, 43 were restricted and humanely culled on farm at their respective locations.
The carcasses were sampled for BSE testing and then disposed of as category 1 animal by products (ABP) at an approved ABP rendering facility. All the samples returned negative results for BSE.
The remaining 2 cohort animals were already dead when traced after the BSE case was confirmed. (They were slaughtered for human consumption and not tested for BSE as they were not eligible.)
2
Epidemiological investigations were undertaken at both the holding of birth and the holding of death of the positive BSE case. Following these investigations, the most likely source of infection remains undetermined. Four potential risk pathways were identified and assessed as very low likelihood events, all with high uncertainty. These 4 potential risk pathways were:
• accidental exposure to contaminated feed (possibly feed delivered before the reinforced feed ban that had remained attached to the side walls of a feed silo decommissioned in 2017) (see also appendix 2, point (b))
• maternal transmission
• environmental source 1: exposure to previous potential presence of the BSE agent on the natal farm via birth products
• environmental source 2: exposure to previous potential presence of the BSE agent on the natal farm from on farm or local cattle burials (when it was still legal to do so before 1 May 2003) via contaminated groundwater or other pathways (see also appendix 2, point (c))
The likelihood of any other potential risk pathways has been assessed as negligible. Any identified sources of infection have been effectively controlled through the following measures:
• The positive animal died on farm and was not destined to enter the food chain. As fallen stock, the entire carcass was category 1 ABP and was appropriately disposed of.
• Rearing cohorts and offspring cohorts were traced, culled and disposed of. All those culled cohorts and offspring were tested for BSE with negative results.
• Surveillance and testing of at-risk animals and fallen stock (see appendix 2, point D).
• Elimination of animal proteins from cattle feed as primary route of transmission (reinforced feed ban in effect since August 1996, see appendix 2, point B).
• Effective disposal of specified risk material (SRM) as per legislative requirements (see appendix 2, point E).
• Ban on burying fallen stock (dead animals) on farms since 1 May 2003 (see appendix 2, point C).
• The old feed silo was decommissioned in 2017.
The implementation of these control measures ensures that the risk of BSE agents being recycled within the bovine population has remained negligible. There is no evidence or other cause for concern that statutory official BSE or feed controls have been breached at any point in relation to this case or its herd of origin.
The detection of this case is evidence that the UK surveillance system for detecting and containing BSE is robust and effective. There is no threat to food safety, to human health or to animal health as a consequence of this case.
3
Introduction
snip...
K – Spontaneous origin
According to EFSA opinion, ‘the classification of a case as spontaneous is circumstantial and may change over time subject to additional information. It does not infer that there is no external cause; just that it could not be ascertained. A case of disease is classified as spontaneous by a process of elimination, excluding all other definable possibilities.’ (Ricci and others, 2017.)
As not all other pathways have been excluded, the likelihood of spontaneous origin is assessed as negligible.
Medium uncertainty reflects that the highest likelihood of any other pathways has been assessed as ‘very low, with high uncertainty’.
Pathway assessment Negligible likelihood, medium uncertainty.
snip...
Concluding remarks
Following an epidemiological investigation, 4 potential risk pathways have been identified as most likely source of infection. Each are assessed as a very low likelihood event, with high uncertainty.
1. Potential accidental exposure to contaminated feed concentrates at natal farm (old feed remnants of potentially contaminated feed – before the total feed ban in 1996– that might have remained in silo 1 and that could have accidentally been released in 2017).
2. Potential maternal transmission.
3. Environmental source
1: Potential exposure to previous potential presence of BSE on natal farm via birth products.
4. Environmental source
2: Potential exposure to previous potential presence of BSE on natal farm from on farm or local cattle burials via contaminated groundwater or other pathways.
The likelihood of any other potential risk pathways has been assessed as negligible.
The detection of this case is evidence that the surveillance system for detecting and containing BSE is solid and effective. There is no threat to food safety, to human health or to animal health as a consequence of this case. The implementation of control measures and continuous monitoring ensures that the risk of BSE agents being recycled within the bovine population has remained negligible. There is no evidence that any TSE regulations have been breached in this case. There is every reason to believe that current actions will contain any further potential exposure to cattle or the human food chain.
Acknowledgements
The views expressed in this report are those of the National Emergency Epidemiology Group (NEEG). We would like to express our thanks to the TSE experts within APHA, members of the One Health Team and the many other APHA colleagues who have assisted with this investigation. The NEEG is comprised of staff from APHA’s Veterinary, Operations and Science Directorates.
snip...see full report;
Report on the epidemiological investigation of a BSE case in Scotland (RBSE24_00003)
News BSE Published 10 May 2024 10:30 Topic Farming and rural Disease confirmed in Ayrshire.
A case of classical Bovine Spongiform Encephalopathy (BSE) has been confirmed on a farm in Ayrshire.
Precautionary movement restrictions have been put in place at impacted premises and cover animals which have been in contact with the case. Further investigations to identify the origin of the disease are ongoing. This is standard procedure for a confirmed case of classical BSE.
The case was identified as a result of routine surveillance and stringent control measures. The animal did not enter the human food chain. Food Standards Scotland have confirmed there is no risk to human health as a result of this isolated case.
The owners of the affected animals are working with authorities on next steps.
Read more: BSE: how to spot and report the disease. Agriculture Minister Jim Fairlie said:
“Following confirmation of a case of classical BSE in Ayrshire, the Scottish Government and other agencies took swift and robust action to protect the agriculture sector. This included establishing a precautionary movement ban on the farm.
“The fact we identified this isolated case so quickly is proof that our surveillance system for detecting this type of disease is working effectively.
“I want to thank the animal’s owner for their diligence. Their decisive action has allowed us to identify and isolate the case at speed which has minimised its impact on the wider industry."
Chief Veterinary Officer Sheila Voas said:
“The fast detection of this case is proof that our surveillance system is doing its job.
“We are working closely with the Animal and Plant Health Agency, and other partners to identify where the disease came from.
“I want to reassure both farmers and the public that the risk associated with this isolated case is minimal. But, if any farmers are concerned, I would urge them to seek veterinary advice."
Ian McWatt, Deputy Chief Executive of Food Standards Scotland said:
“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 Scotland Official Veterinarians and Meat Hygiene Inspectors working in all abattoirs in Scotland will continue to ensure that in respect of BSE controls, the safety of consumers remains a priority.
“We will continue to work closely with Scottish Government, other agencies and industry at this time.”
Background
The Animal Plant and Health Agency (APHA) is investigating the source of the outbreak.
All animals over four years of age that die on farm are routinely tested for BSE under our comprehensive surveillance system. Whilst the disease is not directly transmitted from animal to animal, its cohorts, including offspring, have been traced and isolated, and will be destroyed in line with our legal requirements.
In addition to the measures we have in place for fallen stock and animal feed, there is a strict control regime to protect consumers. This includes the removal of specified risk material such as the spinal column, brain and skull from carcasses destined for human consumption.
Movement restrictions have also been put in place at three further farms – the farm of the animal’s origin and two more holdings where animals that have had access to the same feed are.
The European Union summary report on surveillance for the presence of transmissible spongiform encephalopathies (TSE) in 2023
Published: 28 November 2024
Adopted: 29 October 2024
KEYWORDS atypical, BSE, classical, CWD, scrapie, surveillance, TSE
CONTACT biohaw@efsa.europa.eu
Abstract
This report presents the results of surveillance on transmissible spongiform encephalopathies in cattle, sheep, goats, cervids and other species, and genotyping in sheep and goats, carried out in 2023 by 27 Member States (MS, EU27), the United Kingdom (in respect of Northern Ireland, (XI)) and other eight non‐EU reporting countries: Bosnia and Herzegovina, Iceland, Montenegro, North Macedonia, Norway, Serbia, Switzerland (the data reported by Switzerland include those of Liechtenstein) and Türkiye. In total, 948,165 cattle were tested by EU27 and XI (−3%, compared with 2022), with five atypical BSE cases reported (four H‐type: two in Spain, one in France and one in Ireland; one L‐type in the Netherlands); and 46,096 cattle by eight non‐EU reporting countries with two atypical BSE cases reported by Switzerland. Three additional atypical BSE cases were reported by UK (1), USA (1) and Brazil (1). In total, 284,686 sheep and 102,646 goats were tested in the EU27 and XI (−3.5% and −5.9%, respectively, compared to 2022). In the other non‐EU reporting countries 26,047 sheep and 589 goats were tested. In sheep, 538 cases of scrapie were reported by 14 MS and XI: 462 classical scrapie (CS) by 4 MS (104 index cases (IC) with genotypes of susceptible groups in 93.4% of the cases), 76 atypical scrapie (AS) (76 IC) by 12 MS. In the other non‐EU reporting countries, Iceland reported 70 cases of CS while Norway reported 7 cases of ovine AS. Ovine random genotyping was reported by six MS and genotypes of susceptible groups accounted for 6.9%. In goats, 183 cases of scrapie were reported, all from EU MS: 176 CS (47 IC) by seven MS and 7 AS (7 IC) by five MS. Three cases in Cyprus and one in Spain were reported in goats carrying heterozygous alleles at codon 146 and 222, respectively. In total, 2096 cervids were tested for chronic wasting disease by ten MS, none tested positive. Norway tested 14,224 cervids with one European moose positive.
© European Food Safety Authority
See full report;
The European Union summary report on surveillance for the presence of transmissible spongiform encephalopathies (TSE) in 2022
European Food Safety Authority (EFSA)
First published: 28 November 2023
Approved: 19 October 2023 Abstract
This report presents the results of surveillance on transmissible spongiform encephalopathies (TSE) in cattle, sheep, goats, cervids and other species, and genotyping in sheep and goats, carried out in 2022 by 27 Member States (MS, EU27), the United Kingdom (in respect of Northern Ireland [XI]) and other eight non-EU reporting countries: Bosnia and Herzegovina, Iceland, Montenegro, North Macedonia, Norway, Serbia, Switzerland and Türkiye. In total, 977,008 cattle were tested by EU27 and XI (−4.3%, compared with 2021), and 52,395 cattle by eight non-EU reporting countries, with one case of H-BSE in France. In total, 295,145 sheep and 109,074 goats were tested in the EU27 and XI (−5.2% and −7.9%, respectively, compared to 2021). In the other non-EU reporting countries, 25,535 sheep and 633 goats were tested. In sheep, 557 cases of scrapie were reported by 17 MS and XI: 480 classical scrapie (CS) by five MS (93 index cases [IC] with genotypes of susceptible groups in 97.6% of the cases), 77 atypical scrapie (AS) (76 IC) by 14 MS and XI. In the other non-EU reporting countries, Norway reported 16 cases of ovine AS. Ovine random genotyping was reported by eight MS and genotypes of susceptible groups accounted for 7.3%. In goats, 224 cases of scrapie were reported, all from EU MS: 216 CS (42 IC) by six MS, and 8 AS (8 IC) by four MS. In Cyprus, two cases of CS were reported in goats carrying the heterozygous DN146 allele. In total, 3202 cervids were tested for chronic wasting disease by 10 MS. One wild European moose tested positive in Finland. Norway tested 17,583 cervids with two European moose, one reindeer and one red deer positive. In total, 154 animals from four other species tested negative in Finland.
Monday, March 20, 2023
WAHIS, WOAH, OIE, REPORT United Kingdom Bovine Spongiform Encephalopathy Atypical H-Type
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
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.
Given that cattle have been successfully infected by the oral route, at least for L-BSE, it is reasonable to conclude that atypical BSE is potentially capable of being recycled in a cattle population if cattle are exposed to contaminated feed. In addition, based on reports of atypical BSE from several countries that have not had C-BSE, it appears likely that atypical BSE would arise as a spontaneous disease in any country, albeit at a very low incidence in old cattle. In the presence of livestock industry practices that would allow it to be recycled in the cattle feed chain, it is likely that some level of exposure and transmission may occur. As a result, since atypical BSE can be reasonably considered to pose a potential background level of risk for any country with cattle, the recycling of both classical and atypical strains in the cattle and broader ruminant populations should be avoided.
Annex 7 (contd) AHG on BSE risk assessment and surveillance/March 2019
34 Scientific Commission/September 2019
3. Atypical BSE
The Group discussed and endorsed with minor revisions an overview of relevant literature on the risk of atypical BSE being recycled in a cattle population and its zoonotic potential that had been prepared ahead of the meeting by one expert from the Group. This overview is provided as Appendix IV and its main conclusions are outlined below. With regard to the risk of recycling of atypical BSE, recently published research confirmed that the L-type BSE prion (a type of atypical BSE prion) may be orally transmitted to calves1 . In light of this evidence, and the likelihood that atypical BSE could arise as a spontaneous disease in any country, albeit at a very low incidence, the Group was of the opinion that it would be reasonable to conclude that atypical BSE is potentially capable of being recycled in a cattle population if cattle were to be exposed to contaminated feed. Therefore, the recycling of atypical strains in cattle and broader ruminant populations should be avoided.
4. Definitions of meat-and-bone meal (MBM) and greaves
Consumption of L-BSE–contaminated feed may pose a risk for oral transmission of the disease agent to cattle.
Thus, it is imperative to maintain measures that prevent the entry of tissues from cattle possibly infected with the agent of L-BSE into the food chain.
''H-TYPE BSE AGENT IS TRANSMISSIBLE BY THE ORONASAL ROUTE''
This study demonstrates that the H-type BSE agent is transmissible by the oronasal route. These results reinforce the need for ongoing surveillance for classical and atypical BSE to minimize the risk of potentially infectious tissues entering the animal or human food chains.
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.
Snip…
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.
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Acknowledgment This study was supported by the Health Labor Sciences Research Grant (H29-Shokuhin-Ippan-004, 20KA1003, and 23KA1004).
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“Those that fail to learn from history are doomed to repeat it.”
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