Malta - Scrapie - Immediate notification [FINAL]
GENERAL INFORMATIONCOUNTRY/TERRITORY OR ZONE
ZONE ANIMAL TYPE
TERRESTRIAL DISEASE CATEGORY
Listed disease EVENT ID
6365 DISEASE
Scrapie CAUSAL AGENT
Scrapie prion protein GENOTYPE / SEROTYPE / SUBTYPE
- START DATE
2025/01/26 REASON FOR NOTIFICATION
First occurrence in the country DATE OF LAST OCCURRENCE
- CONFIRMATION DATE
2025/03/26 EVENT STATUS
Resolved END DATE
2025/01/26 SELF-DECLARATION
NO REPORT INFORMATION REPORT NUMBER
Immediate notification REPORT ID
IN_173310 REPORT REFERENCE
MT_TSE_OVI_01 REPORT DATE
2025/03/29 REPORT STATUS
Validated NO EVOLUTION REPORT
- EPIDEMIOLOGY SOURCE OF EVENT OR ORIGIN OF INFECTION
Atypical occurrence EPIDEMIOLOGICAL COMMENTS
A brain sample was submitted for analysis on 29th January 2025 after a sheep died on 26th January showing neurological signs on a farm. The National Reference Laboratory in Malta got positive results on 13th February and on 24th February. On 10th March, the sample was sent for confirmatory analysis to the EURL-TSE Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d`Aosta. A confirmatory analysis by Western blot was finalised on 24th March and the official result was sent by e-mail on 26th March. Since it is an atypical case, the date of start and of end of the outbreak is considered to be the date of death (26th January)…
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Malta - Scrapie - Immediate notification [FINAL]
https://wahis.woah.org/#/in-review/6365
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) 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.
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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.
Detection of classical BSE prions in asymptomatic cows after inoculation with atypical/Nor98 scrapie
This is a concerning issue with far-reaching implications for public health and food safety.
https://veterinaryresearch.biomedcentral.com/articles/10.1186/s13567-023-01225-2
Atypical Nor98 Scrapie, Atypical BSE, CWD, Can Emerge As Different TSE PrP In Cross Species Transmission, A Volatile Situation For Human and Animal Health
Research Project: Genetic Impact and Improved Diagnostics for Sheep and Goat Transmissible Spongiform Encephalopathies Location: Animal Disease Research
Title: PrP-res in placental tissue following experimental transmission of atypical scrapie in ARR/ARR sheep is not infectious by Tg338 mouse bioassay
Author item Piel Iii, Robert item MCELLIOTT, VALERIE - University Of Georgia item STANTON, JAMES - University Of Georgia item ZHUANG, DONGYUE - Retired ARS Employee item MADSEN-BOUTERSE, SALLY - Washington State University item Hamburg, Linda item HARRINGTON, ROBERT - Retired ARS Employee item Schneider, David Submitted to: PLoS ONE Publication Type: Peer Reviewed Journal Publication Acceptance Date: 1/4/2022 Publication Date: 1/21/2022 Citation: Piel Iii, R., Mcelliott, V.R., Stanton, J.B., Zhuang, D., Madsen-Bouterse, S.A., Hamburg, L.K., Harrington, R.D., Schneider, D.A. 2022. PrP-res in placental tissue following experimental transmission of atypical scrapie in ARR/ARR sheep is not infectious by Tg338 mouse bioassay. PLoS ONE. PLoS ONE 17(1): e0262766. https://doi.org/10.1371/journal.pone.0262766. DOI: https://doi.org/10.1371/journal.pone.0262766
Interpretive Summary: Transmissible spongiform encephalopathies or prion diseases in sheep and goats are classified into two main categories: classical scrapie and Nor98-like/atypical scrapie. Classical scrapie is naturally transmissible and, along with surveillance and depopulation, breeding programs selecting for genetic resistance have been a major strategy for the control of classical scrapie in domestic ruminants. Nor98-like scrapie is generally considered non-transmissible in natural conditions and is currently exempt from control measures. Genotypes that confer resistance to classical scrapie remain susceptible to Nor98-like scrapie. ARR/ARR is a primary genotype target for resistance breeding programs and represents an increasing proportion of domestic sheep in the US. This study reports the experimental transmission of Nor98-like scrapie between ARR/ARR sheep, examines the pattern of disease in the recipient animals, and evaluates the potential for natural transmission from the recipient ewes to lambs. Inoculation of breeding ewes with Nor98-like scrapie was successful. Surprisingly, some protein with characteristics similar to prions was observed to accumulate in the placentas as recipient ewes aged; however, this material was determined to be non-infectious in a transgenic mouse model susceptible to scrapie.
Technical Abstract: Nor98-like atypical scrapie, isolated from a US sheep with the classical scrapie resistant ARR/ARR genotype, was transmitted to four ARR/ARR ewes via intracerebral inoculation of brain homogenate. These ewes were followed and observed to 8 years of age, remained non-clinical but exhibited progression of infection broadly consistent with Nor98-like scrapie, including characteristic patterns of PrP-Sc accumulation in the brain and a lack of accumulation in peripheral lymphoid tissues as detected by conventional methods. Immunoblots of placental tissues from the infected ewes revealed accumulation of a distinct conformation of PrP-res, particularly as the animals aged. These tissues showed no infectivity when analyzed via ovinized mouse bioassay. Taken together, these results support a low risk for natural transmission of Nor98-like scrapie in ARR/ARR sheep.
https://www.ars.usda.gov/research/publications/publication/?seqNo115=388184
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.
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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.
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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
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.
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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.
USA, AS of 2023, A total of 491 NVSL confirmed positive animals have been identified, including 474 classical cases (471 sheep and 3 goats) and 19 Nor98-like cases.
https://www.aphis.usda.gov/sites/default/files/scrapie-annual-report.pdf
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