Subject: IRL 24-01-17 OIE Alert - Alerta - Alerte - Bovine spongiform encephalopathy - Encéphalopathie spongiforme bovine - Encefalopatía espongiforme bovina English	PDF reports
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Bovine spongiform encephalopathy ,Ireland

Information received on 23/01/2017 from Dr Martin Blake, Chief Veterinary Officer, Department of Agriculture, Food and the Marine, Agriculture House, Dublin, Ireland

Summary

Report type	Immediate notification
Date of start of the event	13/01/2017
Date of confirmation of the event	14/01/2017
Report date	23/01/2017
Date submitted to OIE	24/01/2017
Reason for notification	Reoccurrence of a listed disease
Date of previous occurrence	25/06/2015
Manifestation of disease	Clinical disease
Causal agent	BSE prion
Nature of diagnosis	Laboratory (advanced)
This event pertains to	the whole country

New outbreaks

Summary of outbreaks

Total outbreaks: 1

Outbreak Location

GALWAY ( Loughrea )

Total animals affected

Species	Susceptible	Cases	Deaths	Destroyed	Slaughtered
Cattle	3	1	0	3	0

Outbreak statistics

Species	Apparent morbidity rate	Apparent mortality rate	Apparent case fatality rate	Proportion susceptible animals lost*
Cattle	33.33%	0.00%	0.00%	100.00%

* Removed from the susceptible population through death, destruction and/or slaughter;

Epidemiology

Source of the outbreak(s) or origin of infection

Unknown or inconclusive

Epidemiological comments

On 14th January, the Department of Agriculture, Food and the Marine (DAFM) was advised of a positive result to a rapid screening test (Idexx HerdChek BSE/Scrapie Antigen Test Kit using the Ultra-Short protocol) carried out by an accredited private laboratory approved by the competent authority. The suspect animal was sampled by DAFM staff at a knackery as part of the on-going official sampling of all fallen (died on farm) animals of 48 months and older. The sample material and the brain were subsequently forwarded to the National Reference Laboratory (NRL) where samples from different brain areas were subject to confirmatory testing using an OIE-approved confirmatory Western blot method, a two-blot protocol for the classification of BSE isolates. All the samples had an identical molecular pattern indicating atypical L Type BSE. In accordance with NRL protocols, samples from the animal were then sent for histopathology and immunohistochemistry on the medulla of the brain. These are further OIE confirmatory testing methods for BSE. Results of these tests are due this week.
Final confirmatory test results were received from the NRL on 18th January 2017 confirming the case to be atypical L type BSE.
The animal was an Aberdeen Angus female, born on 5 March 1998. The animal was born in a herd in County Cork and it moved early in its life to the herd in Galway where it remained for the rest of its life. The farmer reported that the animal had appeared stiff for 2 weeks prior to death. On 11th January the animal was recumbent but it recovered and it became recumbent again on the morning of January 13th. The decision was taken to euthanize the animal then. The animal remained eating and drinking at all times.

Control measures

Measures applied	Movement control inside the country Official disposal of carcasses, by-products and waste Vaccination permitted (if a vaccine exists) No treatment of affected animals
Measures to be applied	No other measures

Diagnostic test results

Laboratory name and type

Central Veterinary Research Laboratory ( National laboratory )

Tests and results

Species	Test	Test date	Result
Cattle	histopathological examination		Pending
Cattle	immunohistochemical test		Pending
Cattle	western blot	18/01/2017	Positive

Laboratory name and type

Enfer laboratories ( Private Laboratory )

Tests and results

Species	Test	Test date	Result
Cattle	rapid tests	14/01/2017	Positive

Future Reporting

The event is continuing. Weekly follow-up reports will be submitted.

Encéphalopathie spongiforme bovine ,Irlande

Information reçue le 23/01/2017 de Dr Martin Blake, Chief Veterinary Officer, Department of Agriculture, Food and the Marine, Agriculture House, Dublin, Irlande

Résumé

Type de rapport	Notification immédiate
Date de début de l’événement	13/01/2017
Date de confirmation de l´événement	14/01/2017
Date du rapport	23/01/2017
Date d'envoi à l'OIE	24/01/2017
Raison de notification	Réapparition d’une maladie listée par l'OIE
Date de la précédente apparition de la maladie	25/06/2015
Manifestation de la maladie	Maladie clinique
Agent causal	Prion de l'ESB
Nature du diagnostic	Tests approfondis en laboratoire (i.e. virologie, microscopie électronique, biologie moléculaire, immunologie)
Cet événement se rapporte à	tout le pays

Nouveaux foyers

Récapitulatif des foyers

Nombre total de foyers : 1

Localisation du foyer

GALWAY ( Loughrea )

Nombre total d'animaux atteints

Espèce(s)	Sensibles	Cas	Morts	Détruits	Abattus
Bovins	3	1	0	3	0

Statistiques sur le foyer

Espèce(s)	Taux de morbidité apparent	Taux de mortalité apparent	Taux de létalité apparent	Proportion d'animaux sensibles perdus*
Bovins	33.33%	0.00%	0.00%	100.00%

* Soustraits de la population sensible suite à la mort, à l´abattage et/ou à la destruction;

Epidémiologie

Source du/des foyer(s) ou origine de l´infection

Inconnue ou incertaine

Autres renseignements épidémiologiques / Commentaires

Le 14 janvier, le Ministère de l’agriculture, de l’alimentation et de la marine (DAFM) a été informé d’un résultat positif à un test de dépistage rapide (HerdChek BSE/Scrapie Antigen Test Kit d'Idexx en utilisant un protocole ultra-court) effectué par un laboratoire privé accrédité approuvé par l’autorité compétente. L’animal suspecté a été échantillonné par le personnel du DAFM dans une usine d’équarrissage dans le cadre de l’échantillonnage officiel en cours de tous les animaux de 48 mois et plus trouvés morts ou moribonds à la ferme. Le matériau de l’échantillon et le cerveau ont ensuite été transmis au Laboratoire national de référence, où des échantillons provenant de différentes zones du cerveau ont été soumis à des tests de confirmation en utilisant une méthode western blot approuvée par l’OIE, un protocole de deux transferts pour la classification des souches de l’ESB. Tous les échantillons avaient un motif moléculaire identique indiquant l’ESB atypique de type L. En conformité avec les protocoles du Laboratoire national de référence, des échantillons de l’animal ont été ensuite envoyés pour histopathologie et immunohistochimie du bulbe rachidien. Il s’agit d’autres méthodes de test de confirmation de l’OIE pour l’ESB. Les résultats de ces tests se recevront cette semaine.
Les résultats définitifs des tests de confirmation ont été reçus du Laboratoire national de référence le 18 janvier 2017 confirmant le cas comme un cas d’ESB atypique de type L.
L’animal était une femelle de race Aberdeen Angus née le 5 mars 1998. L’animal était né dans un troupeau dans le comté de Cork et il a été transféré jeune à un troupeau à Galway, où il a passé le reste de sa vie. L’éleveur a indiqué que l’animal semblait raide deux semaines avant sa mort. Le 11 janvier l’animal restait couché puis il s’est récupéré puis il est tombé malade à nouveau le 13 janvier au matin. L’éleveur avait pris la décision de l’euthanasier. A tout moment, il a continué à manger et à boire.

Mesures de lutte

Mesures de lutte appliquées	Restriction des déplacements à l'intérieur du pays Destruction officielle des cadavres, des produits dérivés et des déchets Vaccination autorisée (si un vaccin existe) Aucun traitement des animaux atteints
Mesures à appliquer	Aucune autre mesure

Résultats des tests de diagnostics

Nom du laboratoire et type

Laboratoire central de recherche vétérinaire ( Laboratoire national )

Tests et résultats

Espèce(s)	Test	Date du test	Résultat
Bovins	examen histopathologique		En attente
Bovins	examen immunohistochimique		En attente
Bovins	western blot	18/01/2017	Positif

Nom du laboratoire et type

Enfer laboratories ( Laboratoire privé )

Tests et résultats

Espèce(s)	Test	Date du test	Résultat
Bovins	test de détection rapide	14/01/2017	Positif

Rapports futurs

Cet événement se poursuit. Des rapports de suivi hebdomadaires devront être envoyés.

Encefalopatía espongiforme bovina ,Irlanda

Información recibida el 23/01/2017 desde Dr Martin Blake, Chief Veterinary Officer, Department of Agriculture, Food and the Marine, Agriculture House, Dublin, Irlanda

Resumen

Tipo de informe	Notificación inmediata
Fecha del inicio del evento	13/01/2017
Fecha de confirmación del evento	14/01/2017
Fecha del informe	23/01/2017
Fecha de envio del informe a la OIE	24/01/2017
Motivo de la notificación	Reaparición de una enfermedad de la Lista de la OIE
Fecha de la anterior aparición de la enfermedad	25/06/2015
Manifestación de la enfermedad	Enfermedad clínica
Agente causal	Prión de la EEB
Naturaleza del diagnóstico	Pruebas de diagnóstico de laboratorio avanzadas (ej. virología, microscopía electrónica, biología molecular e inmunología)
Este evento concierne	todo el país

Nuevos focos

Resumen de los focos

Número total de focos: 1

Localización del foco

GALWAY ( Loughrea )

Número total de animales afectados

Especies	Susceptibles	Casos	Muertos	Destruidos	Sacrificados
Bovinos	3	1	0	3	0

Estadística del foco

Especies	Tasa de morbilidad aparente	Tasa de mortalidad aparente	Tasa de letalidad aparente	Proporción de animales susceptibles perdidos*
Bovinos	33.33%	0.00%	0.00%	100.00%

* Descontados de la población susceptible a raíz de su muerte, destrucción o sacrificio;

Epidemiología

Fuente del o de los focos u origen de la infección

Desconocida o no concluyente

Otros detalles epidemiológicos / comentarios

El 14 de enero, el Departamento de agricultura, alimentación y medio marino (DAFM) fue informado de un resultado positivo en una prueba de detección rápida (HerdChek BSE/Scrapie Antigen Test Kit de Idexx con un protocolo ultra-corto) llevada a cabo por un laboratorio privado acreditado aprobado por la autoridad competente. El personal del DAFM tomó muestras del animal sospechoso en una planta de destrucción de reses muertas o moribundas en el marco de la toma de muestras oficial en curso de todos los animales de 48 meses de edad o más hallados muertos o moribundos en las granjas. El material de la muestra y el cerebro fueron posteriormente remitidos al Laboratorio nacional de referencia, donde muestras de diferentes áreas del cerebro fueron sometidas a pruebas de confirmación mediante un método western blot aprobado por la OIE, un protocolo de dos transferencias para la clasificación de las cepas de la EEB. Todas las muestras tenían un patrón molecular idéntico que indicaba EEB atípica de tipo L. Según los protocolos del Laboratorio nacional de referencia, las muestras del animal fueron enviadas entonces para histopatología e inmunohistoquímica del bulbo raquídeo. Éstos son otros métodos de pruebas confirmatorias de la OIE para la EEB. Se recibirán los resultados esta semana.
Se recibieron los resultados de las pruebas confirmatorias finales del Laboratorio nacional de referencia el 18 de enero de 2017, confirmando el caso como EEB atípica de tipo L.
El animal era una hembra de raza Aberdeen Angus nacida el 5 de marzo de 1998. El animal nació en una manada en el condado de Cork y fue transferido joven a una manada en Galway, donde pasó el resto de su vida. El ganadero informó de que el animal estaba rígido dos semanas antes de la muerte. El 11 de enero permanecía echado pero luego se había recuperado, después volvió a caer enfermo el 13 de enero por la mañana. El ganadero tomó la decisión de eutanasiarlo. No dejó de comer y beber.

Medidas de Control

Medidas implementadas	Restricción de los movimientos en el interior del país Eliminación oficial de canales, subproductos y desechos de origen animal Vacunación autorizada (si existe vacuna) Ningún tratamiento de los animales afectados
Medidas para implementar	Ninguna otra medida

Resultados de las pruebas diagnósticas

Nombre y tipo de laboratorio

Laboratorio central de investigación veterinaria ( Laboratorio nacional )

Pruebas y resultados

Especies	Prueba	Fecha de la prueba	Resultados
Bovinos	examen histopatológico		Pendiente
Bovinos	examen inmunohistoquímico		Pendiente
Bovinos	western blot	18/01/2017	Positivo

Nombre y tipo de laboratorio

Enfer laboratories ( Laboratorio privado )

Pruebas y resultados

Especies	Prueba	Fecha de la prueba	Resultados
Bovinos	prueba rápida	14/01/2017	Positivo

Informes futuros

El episodio continúa. Informes de seguimiento semanales serán enviados

http://www.oie.int/wahis_2/temp/reports/en_imm_0000022493_20170124_184939.pdf

WEDNESDAY, JANUARY 18, 2017

Ireland Department of Agriculture confirmed a case of Atypical BSE 18 year old cow

http://bse-atypical.blogspot.com/2017/01/ireland-department-of-agriculture.html

SUNDAY, JANUARY 15, 2017

US lifts French beef MAD COW BSE import embargo, France says… LOL!

http://bovineprp.blogspot.com/2017/01/us-lifts-french-beef-mad-cow-bse-import.html

WEDNESDAY, JANUARY 18, 2017

EU-approved rapid tests might underestimate bovine spongiform encephalopathy infection in goats

http://bovineprp.blogspot.com/2017/01/eu-approved-rapid-tests-might.html

Variant Creutzfeldt–Jakob Disease in a Patient with Heterozygosity at PRNP Codon 129

N Engl J Med 2017; 376:292-294January 19, 2017DOI: 10.1056/NEJMc1610003

Share: ArticleMetrics To the Editor:

Prions cause lethal neurodegenerative diseases in mammals and are composed of multichain assemblies of misfolded host-encoded cellular prion protein (PrP). A common polymorphism at codon 129 of the PrP gene (PRNP), where either methionine (M) or valine (V) is encoded, affects the susceptibility to prion disease, as well as the incubation period1 and clinical phenotype of prion disease. Human infection with the epizootic prion disease bovine spongiform encephalopathy resulted in variant Creutzfeldt–Jakob disease, which provoked a public health crisis in the United Kingdom and other regions. All definite cases of variant Creutzfeldt–Jakob disease to date have occurred in patients with the MM genotype at PRNP codon 129.1

A 36-year-old man was referred to the United Kingdom National Prion Clinic in August 2015 with personality change. Over a period of 9 months, he had become uncharacteristically irascible and had progressive episodic memory impairment, gait ataxia, and myoclonus. His score on the Mini–Mental State Examination was 25 (with scores ranging from 0 to 30 and higher scores indicating less impairment); clinical examination revealed extraocular eye-movement abnormalities, pyramidal and cerebellar signs, and multifocal myoclonus. Magnetic resonance imaging of the brain (Figure 1FIGURE 1 MRI of the Brain.) revealed restricted diffusion in the basal ganglia, hypothalami, insular cortexes, and medial thalami but not in the pulvinar nuclei.2 Examination of the cerebrospinal fluid for protein 14-3-3 was negative, as was a real-time quaking-induced conversion assay, although these two tests are known to have low sensitivity for variant Creutzfeldt–Jakob disease.3 His genotype at PRNP codon 129 was MV. During the following 6 months, the patient’s condition declined progressively, and severe dysphagia and agitation occurred shortly before his death in February 2016.

At autopsy, histologic examination of the brain revealed frequent florid and cluster plaques in cerebral and cerebellar cortexes, microvacuolar degeneration in neuropil, and immunostaining for abnormal PrP in a stellate pericellular and perivascular distribution. Minute amounts of protease-resistant PrP (PrPSc) were seen in lymphoid tissue of the spleen. Immunoblotting of brain homogenate revealed type 4 PrPSc (according to the London classification system), which is pathognomonic of variant Creutzfeldt–Jakob disease.4 (For more details, see the Supplementary Appendix, available with the full text of this letter at NEJM.org.)

This patient’s clinical features differed from those of typical variant Creutzfeldt–Jakob disease, and his neuroimaging features suggested a diagnosis of sporadic Creutzfeldt–Jakob disease. He did not meet the epidemiologic diagnostic criteria for probable or possible variant Creutzfeldt–Jakob disease,5 yet the results of the neuropathological examination and molecular strain typing were consistent with variant Creutzfeldt–Jakob disease. It remains uncertain whether this case marks the start of a second wave of variant Creutzfeldt–Jakob disease in persons with the MV genotype at PRNP codon 129 (the most common genotype in the United Kingdom), mirroring the long incubation periods seen in persons with the MV genotype who have other acquired prion diseases, notably kuru.1 This case emphasizes the importance of performing an autopsy and molecular strain typing in cases of prion disease to ascertain the prevalence of human prion disease related to bovine spongiform encephalopathy.

snip...see full text ;

http://www.nejm.org/doi/full/10.1056/NEJMc1610003#t=article

>>> This patient’s clinical features differed from those of typical variant Creutzfeldt–Jakob disease, and his neuroimaging features suggested a diagnosis of sporadic Creutzfeldt–Jakob disease. He did not meet the epidemiologic diagnostic criteria for probable or possible variant Creutzfeldt–Jakob disease,5 yet the results of the neuropathological examination and molecular strain typing were consistent with variant Creutzfeldt–Jakob disease. <<<

Many more people could still die from mad cow disease in the UK

SHORT SHARP SCIENCE

By Debora MacKenzie

18 January 2017

It’s finally happened. Until now, vCJD – the deadly disease caused by infection with BSE, or “mad cow disease” – has struck only people with a certain genetic makeup. Now, for the first time, researchers have confirmed a case in someone with different genes – a finding that could mean we have been misdiagnosing a new wave of cases.

https://www.newscientist.com/article/2118418-many-more-people-could-still-die-from-mad-cow-disease-in-the-uk/

FRIDAY, JANUARY 20, 2017

Many more people could still die from mad cow disease in the UK

http://creutzfeldt-jakob-disease.blogspot.com/2017/01/many-more-people-could-still-die-from.html

> Many more people could still die from mad cow disease in the UK

and elsewhere in the world...tss

31 March 2001

Like lambs to the slaughter

By Debora MacKenzie

FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer’s, but Singeltary was suspicious. The diagnosis didn’t fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.

Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.

Now scientists in France have stumbled across new evidence that adds weight to the campaigners’ fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.

“This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie,” says team member Jean-Philippe Deslys of the French Atomic Energy Commission’s medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.

Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. But if the French finding means that scrapie can cause sCJD...

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

http://www.newscientist.com/article.ns?id=mg16922840.300

Neurobiology Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt- Jakob disease: Implications for human health

Corinne Ida Lasmézas*,, Jean-Guy Fournier*, Virginie Nouvel*, Hermann Boe*, Domíníque Marcé*, François Lamoury*, Nicolas Kopp, Jean-Jacques Hauw§, James Ironside¶, Moira Bruce, Dominique Dormont*, and Jean-Philippe Deslys* * Commissariat à l'Energie Atomique, Service de Neurovirologie, Direction des Sciences du Vivant/Département de Recherche Medicale, Centre de Recherches du Service de Santé des Armées 60-68, Avenue du Général Leclerc, BP 6, 92 265 Fontenay-aux-Roses Cedex, France; Hôpital Neurologique Pierre Wertheimer, 59, Boulevard Pinel, 69003 Lyon, France; § Laboratoire de Neuropathologie, Hôpital de la Salpêtrière, 83, Boulevard de l'Hôpital, 75013 Paris, France; ¶ Creutzfeldt-Jakob Disease Surveillance Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; and Institute for Animal Health, Neuropathogenesis Unit, West Mains Road, Edinburgh EH9 3JF, United Kingdom

Edited by D. Carleton Gajdusek, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France, and approved December 7, 2000 (received for review October 16, 2000)

Abstract

There is substantial scientific evidence to support the notion that bovine spongiform encephalopathy (BSE) has contaminated human beings, causing variant Creutzfeldt-Jakob disease (vCJD). This disease has raised concerns about the possibility of an iatrogenic secondary transmission to humans, because the biological properties of the primate-adapted BSE agent are unknown. We show that (i) BSE can be transmitted from primate to primate by intravenous route in 25 months, and (ii) an iatrogenic transmission of vCJD to humans could be readily recognized pathologically, whether it occurs by the central or peripheral route. Strain typing in mice demonstrates that the BSE agent adapts to macaques in the same way as it does to humans and confirms that the BSE agent is responsible for vCJD not only in the United Kingdom but also in France. The agent responsible for French iatrogenic growth hormone-linked CJD taken as a control is very different from vCJD but is similar to that found in one case of sporadic CJD and one sheep scrapie isolate. These data will be key in identifying the origin of human cases of prion disease, including accidental vCJD transmission, and could provide bases for vCJD risk assessment.

http://www.pnas.org/cgi/content/full/041490898v1

THURSDAY, JANUARY 19, 2017

Variant Creutzfeldt–Jakob Disease in a Patient with Heterozygosity at PRNP Codon 129

http://vcjd.blogspot.com/2017/01/variant-creutzfeldtjakob-disease-in.html

PRICE OF PRION POKER GOES UP

*** SPONTANEOUS ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY ***

***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.***

http://www.nature.com/articles/srep11573

Primate Biol., 3, 47–50, 2016 www.primate-biol.net/3/47/2016/ doi:10.5194/pb-3-47-2016 © Author(s) 2016. CC

Attribution 3.0 License.

Prions

Walter Bodemer German Primate Center, Kellnerweg 4, 37077 Göttingen, Germany Correspondence to: Walter Bodemer (wbodemer@dpz.eu)

Received: 15 June 2016 – Revised: 24 August 2016 – Accepted: 30 August 2016 – Published: 7 September 2016

Abstract.

Prions gained widespread public and scientiﬁc interest in the year 2000. At that time, the human neurological Creutzfeldt–Jakob disease (CJD) was known. However, new CJD cases were diagnosed but they could not be ascribed to one of the classical CJD categories i.e. sporadic (sCJD), hereditary or acquired. Hence, they were classiﬁed as variant CJD (vCJD). Later on, experimental evidence suggested that vCJD was caused by prions postulated as unique novel infectious agents and, for example, responsible for bovine spongiform encephalopathy (BSE) also known as mad cow disease. The infection of humans by transmission of BSE prions also deﬁned vCJD as a zoonotic disease. Prions, especially those associated with scrapie in sheep had been known for quite some time and misleadingly discussed as a slow virus. Therefore, this enigmatic pathogen and the transmission of this unusual infectious agent was a matter of a controversial scientiﬁc debate. An agent without nucleic acid did not follow the current dogma postulating DNA or RNA as inheritable information encoding molecules. Although numerous experimental results clearly demonstrated the infectious capacity of prions in several animal species, a model close to human was not readily available. Therefore, the use of rhesus monkeys (Macaca mulatta) served as a non-human primate model to elucidate prion infection under controlled experimental conditions. Not the least, transmission of BSE, human vCJD, and sCJD prions could be conﬁrmed in our study. Any prion infection concomitant with progression of disease in humans, especially vCJD, could be analyzed only retrospectively and at late stages of disease. In contrast, the prion-infected rhesus monkeys were accessible before and after infection; the progression from early stage to late clinical stages – and eventually death of the animal–could be traced. Because of the phylogenetic proximity to humans, the rhesus monkey was superior to any rodent or other animal model. For these reasons an experimental approach had been conceived by J. Collinge in London and A. Aguzzi in Zurich and performed in a cooperative study with both research groups in the pathology unit of the German Primate Center (DPZ). The study in the DPZ lasted from 2001 until 2012. Our research in the pathology unit provided a temporal monitoring of how an initial prion infection develops eventually into disease; an approach that would have never been possible in humans since the time point of infection with prions from, for example, BSE is always unknown. Telemetry revealed a shift in sleep– wake cycles early on, long before behavioral changes or clinical symptoms appeared. Pathology conﬁrmed nonneuronal tissue as hidden places where prions exist. The rhesus model also allowed ﬁrst comparative studies of epigenetic modiﬁcations on RNA in peripheral blood and brain tissue collected from uninfected and prion infected animals. To conclude, our studies clearly demonstrated that this model is valid since progression to disease is almost identical to human CJD.

Published by Copernicus Publications on behalf of the Deutsches Primatenzentrum GmbH (DPZ).

SNIP...

2 Methods and results

2.1 Animals The reason to perform prion research in rhesus monkeys was to monitor infection and the temporal progression of prion infection in the rhesus monkey. In contrast to studies of human CJD cases, we could decide on the infectious dose. We also could control behavior immediately after prion inoculation and during the rather long time until animals died from the prion infection. Hidden places where prions might exist were found. Even epigenetic modiﬁcations on RNA could be detected. Taken together, these experimental approaches depended on animals. Using rhesus monkeys as a model system required thorough ethic reasoning and consultation with authorities before we actually turned to conduct the experiments. The Number of animals was limited just to fulﬁll statistical conditions. The individual health status was obtained and health care was provided throughout the study. The animals underwent daily inspection to monitor any changes in health and behavior. The experiments were conceived with the aim of reducing pain, suffering, and harm. Groups of animals were preferred in order to keep them in a social environment. The animals were originally kept in Vienna at Baxter and transferred to the German Primate Center (DPZ) in 2001. J. Collinge, A. Aguzzi, and C. Weissmann were the scientists who recommended this well-controlled prion infection study, and ﬁnancial support was provided by an EU grant.To ensure statistical signiﬁcance four groups consisting of four rhesus macaques each were formed: one uninfected control group, one group infected with BSE prions, one with vCJD prions, and one with sCJD prions. Health of animals, infection, and progression to disease was looked at in our pathology department and in cooperation with W. Schulz-Schaeffer at the UMG (University Medicine, Göttingen). Besides, neurologists from the UMG also observed the animals whenever clinical symptoms seemed to appear. This close observation and comparison with human CJD cases demonstrated how close clinical progression of human disease resembles the experimental infection in the non-human primate.

2.2 Infection Infectious prions from brain tissue of one sCJD and one vCJD case (provided by J. Collinge) as well as BSE prions (from a “German” madcow case and provided by W. Schulz Schaeffer) were intraperitoneally administered into the rhesus monkeys.

2.3 Monitoring of behavior and telemetry Early behavioral monitoring was carried out by the ethologists I. Machatschke and J. Dittami from Vienna University. Transmitters were used to record changes in the circadian rhythms. Body temperature, sleep–wake cycles, and activity proﬁles could be obtained over a time span of 2 years. Up to half a year after infection animals did not show any signs of prion infection. However, after 6 months and persisting for another few months some animals had some disturbances in circadian rhythms which disappeared and then never appeared again(I. Machatschke, personal communication,2006).For a rather long time of about 4–5 years animals seemed to be healthy. But then, almost all animals rapidly progressed to symptoms. Symptoms were highly similar or even identical to those seen in human CJD.

2.4 Pathology Blood and necropsy specimens from the animals served as a valuable source to detect pathologically associated prion protein even in non-neuronal skeletal and cardiac tissue. These “hidden places” of prion pathology and replication were clearly demonstrated and extended our view where prions might spread within an organism. Not only leukocytes and neuronal tissue harbor abnormal prion protein isoforms but also other tissues can propagate prion protein isoforms leading to toxicity, cell degeneration, and eventually transmissible prions (Krasemann et al., 2010, 2013).

SNIP...

3 Conclusion

Most importantly, early signs of an altered circadian rhythm, sleep–wake cycle, and activity and body temperature were recorded in prion-infected animals. This experimental approach would have never been feasible in studies with human CJD cases. After 4–6 years animals developed clinical symptoms highly similar to those typical for CJD. Clinicians conﬁrmed how close the animal model and the human disease matched. Non-neuronal tissue like cardiac muscle and peripheral blood with abnormal, disease-related prion protein were detected in rhesus monkey tissues.

Molecular changes in RNA from repetitive Alu and BC200 DNA elements were identiﬁed and found to be targets of epigenetic editing mechanisms active in prion disease. To conclude, our results with the rhesus monkey model for prion disease proved to be a valid model and increased our knowledge of pathogenic processes that are distinctive to prion disease.

SEE FULL TEXT ;

http://www.primate-biol.net/3/47/2016/pb-3-47-2016.pdf

*** WDA 2016 NEW YORK ***

We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species. We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions.

Student Presentations Session 2

The species barriers and public health threat of CWD and BSE prions

Ms. Kristen Davenport1, Dr. Davin Henderson1, Dr. Candace Mathiason1, Dr. Edward Hoover1 1Colorado State University

Chronic wasting disease (CWD) is spreading rapidly through cervid populations in the USA. Bovine spongiform encephalopathy (BSE, mad cow disease) arose in the 1980s because cattle were fed recycled animal protein. These and other prion diseases are caused by abnormal folding of the normal prion protein (PrP) into a disease causing form (PrPd), which is pathogenic to nervous system cells and can cause subsequent PrP to misfold. CWD spreads among cervids very efficiently, but it has not yet infected humans. On the other hand, BSE was spread only when cattle consumed infected bovine or ovine tissue, but did infect humans and other species. The objective of this research is to understand the role of PrP structure in cross-species infection by CWD and BSE. To study the propensity of each species’ PrP to be induced to misfold by the presence of PrPd from verious species, we have used an in vitro system that permits detection of PrPd in real-time. We measured the conversion efficiency of various combinations of PrPd seeds and PrP substrate combinations. We observed the cross-species behavior of CWD and BSE, in addition to feline-adapted CWD and BSE. We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species. We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions. CWD is unique among prion diseases in its rapid spread in natural populations. BSE prions are essentially unaltered upon passage to a new species, while CWD adapts to the new species. This adaptation has consequences for surveillance of humans exposed to CWD.

Wildlife Disease Risk Communication Research Contributes to Wildlife Trust Administration Exploring perceptions about chronic wasting disease risks among wildlife and agriculture professionals and stakeholders

http://www.wda2016.org/uploads/5/8/6/1/58613359/wda_2016_conference_proceedings_low_res.pdf

PRION 2016 TOKYO

Zoonotic Potential of CWD Prions: An Update

Ignazio Cali1, Liuting Qing1, Jue Yuan1, Shenghai Huang2, Diane Kofskey1,3, Nicholas Maurer1, Debbie McKenzie4, Jiri Safar1,3,5, Wenquan Zou1,3,5,6, Pierluigi Gambetti1, Qingzhong Kong1,5,6 1Department of Pathology, 3National Prion Disease Pathology Surveillance Center, 5Department of Neurology, 6National Center for Regenerative Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. 4Department of Biological Sciences and Center for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada, 2Encore Health Resources, 1331 Lamar St, Houston, TX 77010

Chronic wasting disease (CWD) is a widespread and highly transmissible prion disease in free-ranging and captive cervid species in North America. The zoonotic potential of CWD prions is a serious public health concern, but the susceptibility of human CNS and peripheral organs to CWD prions remains largely unresolved. We reported earlier that peripheral and CNS infections were detected in transgenic mice expressing human PrP129M or PrP129V. Here we will present an update on this project, including evidence for strain dependence and influence of cervid PrP polymorphisms on CWD zoonosis as well as the characteristics of experimental human CWD prions.

PRION 2016 TOKYO In Conjunction with Asia Pacific Prion Symposium 2016 PRION 2016 Tokyo Prion 2016

http://prion2016.org/dl/newsletter_03.pdf

http://grantome.com/grant/NIH/R01-NS088604-01A1

Monday, May 02, 2016

*** Zoonotic Potential of CWD Prions: An Update Prion 2016 Tokyo ***

http://chronic-wasting-disease.blogspot.com/2016/05/zoonotic-potential-of-cwd-prions-update.html

Saturday, April 23, 2016

PRION 2016 TOKYO

Saturday, April 23, 2016

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

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,

Natalia Fernandez-Borges a. and Alba Marin-Moreno a

"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France

Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion. Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.

To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.

These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.

Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with ef?ciency comparable to that of cattle BSE. While the ef?ciency 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

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

Title: Transmission of scrapie prions to primate after an extended silent incubation period)

*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.

*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.

*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.

http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160

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

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online

http://scrapie-usa.blogspot.com/2016/04/scrapie-ws-01-prion-diseases-in-animals.html

http://wwwnc.cdc.gov/eid/article/22/12/16-0635_article

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

Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France

Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.

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

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

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

***thus questioning the origin of human sporadic cases. We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.

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

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

***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.

https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf

LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$

*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***

https://www.landesbioscience.com/journals/prion/article/28124/?nocache=112223249

*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies.

http://cdmrp.army.mil/prevfunded/nprp/NPRP_Summit_Final_Report.pdf

WEDNESDAY, JANUARY 18, 2017

Ireland Department of Agriculture confirmed a case of Atypical BSE 18 year old cow

http://bse-atypical.blogspot.com/2017/01/ireland-department-of-agriculture.html

SUNDAY, JANUARY 15, 2017

US lifts French beef MAD COW BSE import embargo, France says… LOL!

http://bovineprp.blogspot.com/2017/01/us-lifts-french-beef-mad-cow-bse-import.html

SATURDAY, JANUARY 14, 2017

CHRONIC WASTING DISEASE CWD TSE PRION GLOBAL UPDATE JANUARY 14, 2017

http://chronic-wasting-disease.blogspot.com/2017/01/chronic-wasting-disease-cwd-tse-prion.html

Monday, April 04, 2016

*** Limited amplification of chronic wasting disease prions in the peripheral tissues of intracerebrally inoculated cattle ***