High prevalence of scrapie in a dairy goat herd: tissue distribution of disease-associated PrP and effect of PRNP genotype and age

Titre du document / Document title

High prevalence of scrapie in a dairy goat herd: tissue distribution of disease-associated PrP and effect of PRNP genotype and age

Auteur(s) / Author(s) GONZALEZ Lorenzo (1) ; MARTIN Stuart (1) ; SISO Silvia (1) ; KONOLD Timm (2) ; ORTIZ-PELKEZ Angel (2) ; PHELAN Laura (2) ; GOLDMANN Wilfred (3) ; STEWART Paula (3) ; SAUNDERS Ginny (2) ; WINDL Otto (2) ; JEFFREY Martin (1) ; HAWKINS Stephen A. C. (2) ; DAWSON Michael (2) ; HOPE James (1) ; Affiliation(s) du ou des auteurs / Author(s) Affiliation(s) (1) Veterinary Laboratories Agency (VLA-Lasswade), Pentlands Science Park, Penicuik, Midlothian EH26 OPZ, ROYAUME-UNI (2) VLA-Weybridge, Addlestone, Surrey KT15 3NB, ROYAUME-UNI (3) Roslin Institute Neuropathogenesis Division, Roslin, Midlothian EH25 9PS, ROYAUME-UNI

Résumé / Abstract

Following a severe outbreak of clinical scrapie in 2006-2007, a large dairy goat herd was culled and 200 animals were selected for post-mortem examinations in order to ascertain the prevalence of infection, the effect of age, breed and PRNP genotype on the susceptibility to scrapie, the tissue distribution of disease-associated PrP (PrPd), and the comparative efficiency of different diagnostic methods. As determined by immunohistochemical (IHC) examinations with Bar224 PrP antibody, the prevalence of preclinical infection was very high (72/200; 36.0%), with most infected animals being positive for Prpd in lymphoreticular system (LRS) tissues (68/72; 94.4%) compared to those that were positive in brain samples (38/72; 52.8%). The retropharyngeal lymph node and the palatine tonsil showed the highest frequency of PrPd accumulation (87.3% and 84.5%, respectively), while the recto-anal mucosa-associated lymphoid tissue (RAMALT) was positive in only 30 (41.7%) of the infected goats. However, the efficiency of rectal and palatine tonsil biopsies taken shortly before necropsy was similar. The probability of brain and RAMALT being positive directly correlated with the spread of PrPd within the LRS. The prevalence of infection was influenced by PRNP genetics at codon 142 and by the age of the goats: methionine carriers older than 60 months showed a much lower prevalence of infection (12/78; 15.4%) than those younger than 60 months (20/42; 47.6%); these last showed prevalence values similar to isoleucine homozygotes of any age (40/80; 50.0%). Two of seven goats with definite signs of scrapie were negative for PrPd in brain but positive in LRS tissues, and one goat showed biochemical and IHC features of PrPd different from all other infected goats. The results of this study have implications for surveillance and control policies for scrapie in goats. Revue / Journal Title Veterinary research ISSN 0928-4249 Source / Source 2009, vol. 40, no6, [Note(s): 40:65.1-40:65.13] (34 ref.) Langue / Language Anglais

Editeur / Publisher EDP Sciences, Les Ulis, FRANCE (1993) (Revue)

Mots-clés anglais / English Keywords Farming animal ; Nervous system diseases ; Central nervous system disease ; Degenerative disease ; Cerebral disorder ; Infection ; Prion disease ; Vertebrata ; Mammalia ; Ungulata ; Artiodactyla ; Prion ; Sheep ; Scrapie ; Veterinary ; Microbiology ; Spongiform encephalopathy ; Age ; Genotype ; Epidemiology ; Prevalence ; Goat ; Mots-clés français / French Keywords Animal élevage ; Pathologie du système nerveux ; Pathologie du système nerveux central ; Maladie dégénérative ; Pathologie de l'encéphale ; Infection ; Maladie à prions ; Vertebrata ; Mammalia ; Ungulata ; Artiodactyla ; Association genetique ; Prion ; Mouton ; Tremblante ; Vétérinaire ; Microbiologie ; Encéphalopathie spongiforme ; Age ; Génotype ; Epidémiologie ; Prévalence ; Chèvre ; Mots-clés espagnols / Spanish Keywords Animal cría ; Sistema nervioso patología ; Sistema nervosio central patología ; Enfermedad degenerativa ; Encéfalo patología ; Infección ; Prion enfermedad ; Vertebrata ; Mammalia ; Ungulata ; Artiodactyla ; Prion ; Carnero ; Scrapie ; Veterinario ; Microbiología ; Encefalopatía espongiforme ; Edad ; Genotipo ; Epidemiología ; Prevalencia ; Cabra ; Mots-clés d'auteur / Author Keywords scrapie ; goat ; prion disease ; transmissible spongiform encephalopathy ; Localisation / Location INIST-CNRS, Cote INIST : 14119, 35400017127359.0140

Nº notice refdoc (ud4) : 22076139


http://cat.inist.fr/?aModele=afficheN&cpsidt=22076139



Monday, November 30, 2009

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

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


Monday, November 23, 2009

BSE GBR RISK ASSESSMENTS UPDATE NOVEMBER 23, 2009 COMMISSION OF THE EUROPEAN COMMUNITIES AND O.I.E.

http://docket-aphis-2006-0041.blogspot.com/2009/11/bse-gbr-risk-assessments-update.html



Atypical Scrapie Nor-98

http://nor-98.blogspot.com/




Scrapie USA

http://scrapie-usa.blogspot.com/



TSS

SCRAPIE UPDATE CANADA 2009 (typical and atypical cases)

Flocks infected with scrapie in Canada in 2009 The CFIA, in co-operation with provincial governments and industry, launched a national scrapie surveillance program in 2005. Under the program, producers are encouraged to report animals that die on the farm or exhibit symptoms of the disease.

In addition, scrapie is a reportable disease under the Health of Animals Regulations. This means that all suspected cases must be reported to the CFIA.

The following table lists sheep flocks and/or goat herds confirmed to be infected with scrapie in Canada in 2009.

Updated: 2009-09-30

Date confirmed Location Animal type infected

April 29 Quebec Sheep

May 21* Saskatchewan Sheep

June 12 Quebec Sheep

July 23* Alberta Sheep

September 14* Ontario Sheep


*Atypical scrapie



http://www.inspection.gc.ca/english/anima/disemala/rep/2009scrtree.shtml





Wednesday, July 1, 2009

Nor98 scrapie identified in the United States J Vet Diagn Invest 21:454-463 (2009)


http://nor-98.blogspot.com/2009/07/nor98-scrapie-identified-in-united.html



Thursday, October 15, 2009

Transmissibility studies of vacuolar changes in the rostral colliculus of pigs

Research article Open Access




http://madporcinedisease.blogspot.com/2009/10/transmissibility-studies-of-vacuolar.html








TSS

Prions Are Secreted in Milk from Clinically Normal Scrapie-Exposed Sheep

Journal of Virology, August 2009, p. 8293-8296, Vol. 83, No. 16 0022-538X/09/$08.00+0 doi:10.1128/JVI.00051-09 Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Prions Are Secreted in Milk from Clinically Normal Scrapie-Exposed Sheep

B. C. Maddison,1 C. A. Baker,1 H. C. Rees,2 L. A. Terry,3 L. Thorne,3 S. J. Bellworthy,3 G. C. Whitelam,2 and K. C. Gough4* ADAS UK, Department of Biology, University of Leicester, University Road, Leicester LE1 7RH, United Kingdom,1 Department of Biology, University of Leicester, University Road, Leicester LE1 7RH, United Kingdom,2 Veterinary Laboratories Agency, Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, United Kingdom,3 School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, College Road, Sutton Bonington, Leicestershire LE12 5RD, United Kingdom4

Received 9 January 2009/ Accepted 27 May 2009

The potential spread of prion infectivity in secreta is a crucial concern for prion disease transmission. Here, serial protein misfolding cyclic amplification (sPMCA) allowed the detection of prions in milk from clinically affected animals as well as scrapie-exposed sheep at least 20 months before clinical onset of disease, irrespective of the immunohistochemical detection of protease-resistant PrPSc within lymphoreticular and central nervous system tissues. These data indicate the secretion of prions within milk during the early stages of disease progression and a role for milk in prion transmission. Furthermore, the application of sPMCA to milk samples offers a noninvasive methodology to detect scrapie during preclinical/subclinical disease.

--------------------------------------------------------------------------------

* Corresponding author. Mailing address: School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, College Road, Sutton Bonington, Leicestershire LE12 5RD, United Kingdom. Phone: 44-115-9516272. Fax: 44-115-9516440. E-mail: kevin.gough@nottingham.ac.uk

Published ahead of print on 3 June 2009.

--------------------------------------------------------------------------------

Journal of Virology, August 2009, p. 8293-8296, Vol. 83, No. 16 0022-538X/09/$08.00+0 doi:10.1128/JVI.00051-09 Copyright © 2009, American Society for Microbiology. All Rights Reserved.





http://jvi.asm.org/cgi/content/abstract/83/16/8293





TAFS INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation (January, 2009) TAFS1 STATEMENT ON TRANSMISSION OF SCRAPIE VIA MILK





http://www.tafsforum.org/position_papers/TAFS_POSITION_PAPER_TRANSMISSION_SCRAPIE_MILK_2009.pdf





Friday, December 12, 2008 Prions in Milk from Ewes Incubating Natural Scrapie





http://scrapie-usa.blogspot.com/2008/12/prions-in-milk-from-ewes-incubating.html





Sheep consumption: a possible source of spongiform encephalopathy in humans.

Davanipour Z, Alter M, ***el E, Callahan M.

A fatal spongiform encephalopathy of sheep and goats (scrapie) shares many characteristics with Creutzfeldt-Jakob disease (CJD), a similar dementing illness of humans. To investigate the possibility that CJD is acquired by ingestion of contaminated sheep products, we collected information on production, slaughtering practices, and marketing of sheep in Pennsylvania. The study revealed that sheep were usually marketed before central nervous system signs of scrapie are expected to appear; breeds known to be susceptible to the disease were the most common breeds raised in the area; sheep were imported from other states including those with a high frequency of scrapie; use of veterinary services on the sheep farms investigated and, hence, opportunities to detect the disease were limited; sheep producers in the area knew little about scrapie despite the fact that the disease has been reported in the area, and animal organs including sheep organs were sometimes included in processed food. Therefore, it was concluded that in Pennsylvania there are some 'weak links' through which scrapie-infected animals could contaminate human food, and that consumption of these foods could perhaps account for spongiform encephalopathy in humans. The weak links observed are probably not unique to Pennsylvania.





http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3915057&dopt=Abstract





Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.

PMID: 6997404





http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract





Full Scientific Reports

Experimental oral transmission of United States origin scrapie to neonatal sheep

Amir N. Hamir1, Robert A. Kunkle, Justin J. Greenlee and Juergen A. Richt Correspondence: 1Corresponding Author: Amir N. Hamir, National Animal Disease Center, ARS, USDA, 2300 Dayton Avenue, PO Box 70, Ames, IA 50010. amir.hamir@ars.usda.gov

Scrapie, a transmissible spongiform encephalopathy (TSE), is a naturally occurring fatal neurodegenerative disease of sheep and goats. The current study documents incubation periods, pathologic findings, and distribution of abnormal prion proteins (PrPSc) by immunohistochemistry and Western blot in tissues of genetically susceptible and resistant neonatal lambs inoculated with pooled brain homogenates from 13 U.S. origin scrapie-affected ewes. Nine Suffolk lambs with genotypes AA/RR/QQ (n = 5) and AA/RR/QR (n = 4) at codons 136, 154, and 171, respectively) were orally inoculated, within 12 hr of birth, with 1 ml of a 10% (w/v) brain homogenate prepared from scrapie-affected sheep brains. Inoculated animals were euthanized when advanced clinical signs of scrapie were observed. All QQ sheep developed clinical signs of scrapie, with a mean survival time of 24 months. Spongiform lesions in the brains and PrPSc deposits in the central nervous system and lymphoid tissues were present in these sheep. None of the QR sheep succumbed to the disease. A previous study that used a larger volume (30 ml of 10% brain suspension) of the same inoculum in 4-month-old Suffolk lambs of susceptible genotype documented longer survival periods (average 32 months), and only 5 of 9 inoculated sheep developed scrapie. Findings of this study suggest that orally exposed neonatal lambs of a susceptible (QQ) genotype exhibit a higher attack rate and shorter incubation period than older (4-month-old) lambs exposed to a larger dose (30x) of the same inoculum.

Key Words: Immunohistochemistry . neonatal sheep . scrapie . spongiform encephalopathy . Western blot





http://jvdi.org/cgi/content/abstract/21/1/64?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=prion&searchid=1&FIRSTINDEX=0&volume=21&issue=1&resourcetype=HWCIT





EVIDENCE OF SCRAPIE IN SHEEP AS A RESULT OF FOOD BORNE EXPOSURE

This is provided by the statistically significant increase in the incidence of sheep scrape from 1985, as determined from analyses of the submissions made to VI Centres, and from individual case and flock incident studies. ........





http://www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf





Title: Characterization of a U.S. Sheep Scrapie Isolate with Short Incubation Time

Authors

Hamir, Amirali Richt, Juergen Kunkle, Robert Greenlee, Justin Bulgin, M - UNIVERSITY OF IDAHO Gregori, L - VA MEDICAL CENTER, MD Rohwer, R - VA MEDICAL CENTER, MD

Submitted to: Veterinary Pathology Publication Type: Peer Reviewed Journal Publication Acceptance Date: April 16, 2009 Publication Date: N/A

Interpretive Summary: Scrapie is a naturally occurring fatal disease of sheep and goats. In a previous study it was shown that sheep inoculated with US scrapie inoculum (No. 13-7) induced terminal disease within an average of 19 months. We have since produced an inoculum, No. X124 from pooled brains of US origin sheep scrapie, that results in incubations nearly 3 fold shorter. The present study documents laboratory findings in tissues of sheep inoculated with No. X124. All inoculated sheep developed clinical disease and were euthanized within an average of 7.7 months post inoculation (MPI). Sheep that were genetically susceptible developed the disease faster (within 6 months). Also, the inoculum was able to induce disease in a short time (7 MPI) in a sheep that was supposed to be highly resistant to scrapie. This indicates that inoculum No. X124 appears to be more virulent than inoculum No. 13-7. Importantly this strain of scrapie represents a significant development in that it provides a natural model that requires less than 25 percent of the time for the disease to develop, thus enabling a faster pace for research investigating prion disease pathogenesis and inactivation. Technical Abstract: Scrapie is a naturally occurring fatal neurodegenerative disease of sheep and goats. Susceptibility to the disease is partly dependent upon the genetic makeup of the host. In a previous study it was shown that sheep intracerebrally inoculated with US scrapie inoculum (No. 13-7) developed terminal disease within an average of 19 months. We have since produced an inoculum, No. x124 from pooled brains of US origin sheep scrapie, that results in incubations nearly 3 fold shorter. The present study documents clinicopathological findings and the distribution of abnormal prion proteins (PrP**Sc) by immunohistochemical (IHC) and Western blot (WB) techniques, in tissues of sheep inoculated with No. x124. All inoculated sheep developed clinical disease and were euthanized within an average of 7.7 months post-inoculation (MPI). Sheep that had VV or AV at codon 136 of prion protein (PRNP) gene developed the disease faster and were euthanized at an average of 4.3 and 5.6 MPI, respectively. Also, the inoculum was able to induce disease in a short time (7 MPI) in a sheep that was relatively resistant (QR at codon 171) to scrapie. This indicates that inoculum No. x124 appears to induce scrapie in shorter time than inoculum No. 13-7, especially in sheep homozygous or heterozygous for valine at codon 136.





http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=230885





12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY

snip...

A The Present Position with respect to Scrapie

A1 The Problem

Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries.

The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep.

It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible.

Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"

Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.

snip...

76/10.12/4.6





http://www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf





Epidemiology of Scrapie in the United States 1977





http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf





http://scrapie-usa.blogspot.com/





Like lambs to the slaughter 31 March 2001 by Debora MacKenzie Magazine issue 2284

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

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

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





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







http://nor-98.blogspot.com/





http://scrapie-usa.blogspot.com/





Saturday, June 13, 2009

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009





http://cjdusa.blogspot.com/2009/06/monitoring-occurrence-of-emerging-forms.html





SEE THIS DAMNING VIDEO NOW AT THE BOTTOM OF THE BLOG BELOW ;





http://creutzfeldt-jakob-disease.blogspot.com/2009/07/usa-hiding-mad-cow-disease-victims-as.html





Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518

Prions in Milk from Ewes Incubating Natural Scrapie

Prions in Milk from Ewes Incubating Natural Scrapie

Caroline Lacroux1, Stéphanie Simon2, Sylvie L. Benestad3, Séverine Maillet2, Jacinthe Mathey1, Séverine Lugan1, Fabien Corbière1, Hervé Cassard1, Pierrette Costes1, Dominique Bergonier1, Jean-Louis Weisbecker4, Torffin Moldal3, Hugh Simmons5, Frederic Lantier6, Cécile Feraudet-Tarisse1,2, Nathalie Morel2, François Schelcher1, Jacques Grassi2, Olivier Andréoletti1*

1 UMR INRA ENVT 1225, Interactions Hôte Agent Pathogène, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France, 2 CEA, Service de Pharmacologie et d'Immunoanalyse, IBiTec-S, DSV, CEA/Saclay, Gif sur Yvette, France, 3 National Veterinary Institute, Sentrum, Oslo, Norway, 4 INRA Domaine de Langlade, Pompertuzat, France, 5 VLA Weybridge, New Haw, Addlestone, Surrey, United Kingdom, 6 INRA IASP, Centre INRA de Tours, Nouzilly, France

Abstract Since prion infectivity had never been reported in milk, dairy products originating from transmissible spongiform encephalopathy (TSE)-affected ruminant flocks currently enter unrestricted into the animal and human food chain. However, a recently published study brought the first evidence of the presence of prions in mammary secretions from scrapie-affected ewes. Here we report the detection of consistent levels of infectivity in colostrum and milk from sheep incubating natural scrapie, several months prior to clinical onset. Additionally, abnormal PrP was detected, by immunohistochemistry and PET blot, in lacteal ducts and mammary acini. This PrPSc accumulation was detected only in ewes harbouring mammary ectopic lymphoid follicles that developed consequent to Maedi lentivirus infection. However, bioassay revealed that prion infectivity was present in milk and colostrum, not only from ewes with such lympho-proliferative chronic mastitis, but also from those displaying lesion-free mammary glands. In milk and colostrum, infectivity could be recovered in the cellular, cream, and casein-whey fractions. In our samples, using a Tg 338 mouse model, the highest per ml infectious titre measured was found to be equivalent to that contained in 6 µg of a posterior brain stem from a terminally scrapie-affected ewe. These findings indicate that both colostrum and milk from small ruminants incubating TSE could contribute to the animal TSE transmission process, either directly or through the presence of milk-derived material in animal feedstuffs. It also raises some concern with regard to the risk to humans of TSE exposure associated with milk products from ovine and other TSE-susceptible dairy species.

Author Summary A decade ago, a new variant form of Creutzfeldt-Jakob disease was identified. The emergence of this prion disease in humans was the consequence of the zoonotic transmission of bovine spongiform encephalopathy through dietary exposure. Since then, the control of human exposure to prions has become a priority, and a policy based on the exclusion of known infectious materials from the food chain has been implemented. Because all investigations carried out failed to reveal evidence of infectivity in milk from affected ruminants, this product has continuously been considered as safe. In this study, we demonstrate the presence of prions in colostrum and milk from sheep incubating natural scrapie and displaying apparently healthy mammary glands. This finding indicates that milk from small ruminants could contribute to the transmission of prion disease between animals. It also raises some concern with regard to the risk to humans associated with milk products from ovine and other dairy species.

Citation: Lacroux C, Simon S, Benestad SL, Maillet S, Mathey J, et al. (2008) Prions in Milk from Ewes Incubating Natural Scrapie. PLoS Pathog 4(12): e1000238. doi:10.1371/journal.ppat.1000238

Editor: Umberto Agrimi, Istituto Superiore di Sanità, Italy

Received: July 1, 2008; Accepted: November 12, 2008; Published: December 12, 2008

Copyright: © 2008 Lacroux et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This study was financially supported by GIS infections à prion (French Research Ministry), EU FAIR (QLK-CT 2001-390), and DEFRA (SE2004, contract: CSA 6914).

Competing interests: The authors have declared that no competing interests exist.

* E-mail: o.andreoletti@envt.fr

Introduction.........


SNIP...


full text ;


http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000238



TSS


Human and animal exposure risk related to TSEs from milk

Sun Nov 9, 2008 08:46 71.248.131.35

-------------------- BSE-L@LISTS.AEGEE.ORG --------------------

Opinions

Human and animal exposure risk related to Transmissible Spongiform Encephalopathies (TSEs) from milk and milk products derived from small ruminants Scientific opinion of the Panel on Biological Hazards Question number: EFSA-Q-2008-310

Adopted date: 22 October 2008 Summary (0.1Mb)

Opinion (0.2Mb)

Summary

Following a request from the European Commission (EC), the Panel on Biological Hazards (BIOHAZ) was asked to deliver a scientific opinion on the Human and animal exposure risk related to Transmissible Spongiform Encephalopathies (TSEs) from milk and milk products derived from small ruminants.

In a recent scientific article from Konold et al., published on 8 April 2008 in BMC Veterinary Research, on "Evidence of scrapie transmission via milk" it is concluded that: ".there is a risk of the transmission of scrapie from ewe to lamb via milk or colostrum. Infection of lambs via milk may result in shedding of the infectious agent into the environment.".

The BIOHAZ Panel was invited to provide an opinion on the conclusions from the article of Konold et al. (2008), and if considered necessary, based on any additional available scientific data, to update the current risk assessments on the human and animal exposure related to Transmissible Spongiform Encephalopathies (TSEs) from milk and milk products derived from small ruminants.

When approaching the mandate the BIOHAZ Panel did not consider the zoonotic potential of small ruminant TSE agents. This aspect is considered in detail in previous EFSA documents[1],[2]. The TSE agents considered in the assessment were Classical scrapie, Atypical scrapie and BSE. Moreover, the assessment was performed employing mainly data from TSE in sheep, which were considered valid also for TSE in goats due to the lack of more specific data in that species.

The Panel considered valid the conclusion of the article of Konold et al. (2008). Expanding the article of Konold et al. (2008), another study from Lacroux et al. (2008) independently demonstrated that Classical scrapie can be transmitted from susceptible ewe to transgenic mice via colostrum and milk. It was emphasized that both studies were designed to achieve the highest possibility of transmission success and that this could differ from the field situation. The Panel noted that in both studies, milk from asymptomatic donor ewes transmitted disease, indicating that clinically healthy, Classical scrapie-incubating sheep may shed the causal agents of these TSEs in milk. Moreover, the level of prion infectivity in small ruminant milk could become higher during the course of mastitis but the somatic cell count was considered as an unreliable indicator for presence or absence of TSE infectivity in small ruminant milk.

The Panel concluded that the use of milk and milk products from a flock with Classical scrapie may carry a TSE exposure risk for humans and animals. Furthermore, the use of milk and milk products from the general small ruminant population may carry a TSE exposure risk for humans and animals due to the presence of undetected affected flocks in that population. However, because of the difference in scrapie prevalence between affected flocks and the general small ruminant population, the risk of exposure for humans and animals associated with milk and milk products from the general small ruminant population will be lower than the risk from detected scrapie affected flocks.

The Panel also concluded that the exposure to a Classical scrapie agent via milk of an infected animal can be estimated to be 4 to 5 logs10 lower than the infectivity found in the same weight of brainstem from a terminally affected animal, and 2 to 3 logs10 lower the than infectivity found in the same weight of lymphoid tissues from an animal incubating scrapie or from a clinically affected animal.

The BIOHAZ Panel further noted that no information is available concerning the presence of infectivity or PrPSc in colostrum or milk from small ruminants affected by Atypical scrapie or BSE. However, the Panel emphasized that due to the early and progressive peripheral tissue dissemination of the BSE agent in experimentally infected susceptible sheep, the occurrence of infectivity in colostrum and milk of BSE infected susceptible small ruminants would be likely. On the other hand, the apparent restricted dissemination of the agent of Atypical scrapie in affected individuals could limit its transmissibility through milk.

As there is large variation between MS in prevalence of scrapie and production of small ruminant milk, the human and animal exposure associated with small ruminant dairy products varies greatly between MS.

The Panel further concluded that breeding of sheep for relative resistance to Classical scrapie according to the previous EFSA opinion[3] can be expected to reduce human and animal exposure associated with small ruminant dairy products.

The Panel recommended to perform research in order to characterise the exposure risk via milk especially in Atypical scrapie and BSE in small ruminants, to investigate on the stability of prion infectivity in milk during further processing, and to obtain more data to confirm and expand the preliminary information available on the quantitation of infectivity levels in small ruminant milk fractions. ___________________________________ [1]Opinion of the Scientific Panel on Biological Hazards on certain aspects related to the risk of Transmissible Spongiform Encephalopathies (TSEs) in ovine and caprine animals. The EFSA Journal (2007) 466, 1-10 [2] Scientific and technical clarification in the interpretation and consideration of some facets of the conclusions of its Opinion of 8 March 2007 on certain aspects related to the risk of Transmissible Spongiform Encephalopathies (TSEs) in ovine and caprine animals. The EFSA Journal (2008) 626, 1-11 [3] Opinion of the Scientific Panel on Biological Hazards on "the breeding programme for TSE resistance in sheep", The EFSA Journal (2006), 382, 1-46

Publication date: 6 November 2008

http://www.efsa.europa.eu/EFSA/Scientific_Opinion/biohaz_op_ej849_tse_infectivity_summary_en,0.pdf?ssbinary=true


http://www.efsa.europa.eu/EFSA/Scientific_Opinion/biohaz_op_ej849_tse_infectivity_en,0.pdf?ssbinary=true



Prion Protein in Milk

Nicola Franscini1, Ahmed El Gedaily1, Ulrich Matthey1, Susanne Franitza1, Man-Sun Sy2, Alexander Bürkle3, Martin Groschup4, Ueli Braun5, Ralph Zahn1*

1 Alicon AG, Schlieren, Switzerland, 2 Institute of Pathology, Biomedical Research Building, Case Western University School of Medicine, Cleveland, Ohio, United States of America, 3 Lehrstuhl Molekulare Toxikologie, University of Konstanz, Konstanz, Germany, 4 Friedrich-Loeffler-Institut, Bundesforschungsinstitut für Tiergesundheit, Greifswald, Gemany, 5 Departement für Nutztiere, University of Zurich, Zurich, Switzerland

Abstract Background Prions are known to cause transmissible spongiform encephalopathies (TSE) after accumulation in the central nervous system. There is increasing evidence that prions are also present in body fluids and that prion infection by blood transmission is possible. The low concentration of the proteinaceous agent in body fluids and its long incubation time complicate epidemiologic analysis and estimation of spreading and thus the risk of human infection. This situation is particularly unsatisfactory for food and pharmaceutical industries, given the lack of sensitive tools for monitoring the infectious agent.

Methodology/Principal Findings We have developed an adsorption matrix, Alicon PrioTrap®, which binds with high affinity and specificity to prion proteins. Thus we were able to identify prion protein (PrPC)-the precursor of prions (PrPSc)-in milk from humans, cows, sheep, and goats. The absolute amount of PrPC differs between the species (from µg/l range in sheep to ng/l range in human milk). PrPC is also found in homogenised and pasteurised off-the-shelf milk, and even ultrahigh temperature treatment only partially diminishes endogenous PrPC concentration.

Conclusions/Significance In view of a recent study showing evidence of prion replication occurring in the mammary gland of scrapie infected sheep suffering from mastitis, the appearance of PrPC in milk implies the possibility that milk of TSE-infected animals serves as source for PrPSc.

Citation: Franscini N, Gedaily AE, Matthey U, Franitza S, Sy M-S, et al. (2006) Prion Protein in Milk. PLoS ONE 1(1): e71. doi:10.1371/journal.pone.0000071

Academic Editor: Matthew Baylis, University of Liverpool, United Kingdom

Received: October 19, 2006; Accepted: November 6, 2006; Published: December 20, 2006

Copyright: © 2006 Franscini et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: The authors have no support or funding to report.

Competing interests: The authors have declared that no competing interests exist.

* To whom correspondence should be addressed. E-mail: info@alicon.ch

http://www.plosone.org/article/fetchObjectAttachment.action;jsessionid=4BBFF07E478CCD52A627126F9BCC995A?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0000071&representation=PDF



Saturday, April 12, 2008 Evidence of scrapie transmission via milk

http://scrapie-usa.blogspot.com/2008/04/evidence-of-scrapie-transmission-via.html


HAVE ANOTHER GLASS OF CWD PRIONS COURTESY Dane County Wisconsin Mike DiMaggio, solid waste manager

http://chronic-wasting-disease.blogspot.com/2008/08/have-another-glass-of-cwd-prions.html


Friday, October 24, 2008

CBER 2007 Annual Report Assessing the Potential Risk of variant Creutzfeldt-Jakob Disease from Blood Products

http://creutzfeldt-jakob-disease.blogspot.com/2008/10/cber-2007-annual-report-assessing.html


Friday, November 07, 2008 Human and animal exposure risk related to Transmissible Spongiform Encephalopathies (TSEs) from milk and milk products derived from small ruminants

Opinions

http://scrapie-usa.blogspot.com/2008/11/human-and-animal-exposure-risk-related.html




1: J Infect Dis 1980 Aug;142(2):205-8

Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.

PMID: 6997404

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract


12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY

snip...

A The Present Position with respect to Scrapie A] The Problem

Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries.

The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep.

It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible.

Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"

Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.

snip...

76/10.12/4.6

http://www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf


Epidemiology of Scrapie in the United States 1977

http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf



http://scrapie-usa.blogspot.com/



CHAPTER 3 Animal Disease Eradication Programs and Control and Certification Programs

snip...

In FY 2007, two field cases, one validation study case, and two RSSS cases were consistent with a variant of the disease known as Nor98 scrapie.1 These five cases originated from flocks in California, Minnesota, Colorado, Wyoming, and Indiana, respectively.

snip...

http://www.aphis.usda.gov/publications/animal_health/content/printable_version/AHR_Web_PDF_07/D_Chapter_3.pdf



NOR-98 Scrapie FY 2008 to date 1

http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_rpt.pps



NOR-98 ATYPICAL SCRAPIE USA UPDATE AS AT OCT 2007

http://nor-98.blogspot.com/



TSS

Human and animal exposure risk related to Transmissible Spongiform Encephalopathies (TSEs) from milk and milk products derived from small ruminants

Opinions

Human and animal exposure risk related to Transmissible Spongiform Encephalopathies (TSEs) from milk and milk products derived from small ruminants Scientific opinion of the Panel on Biological Hazards Question number: EFSA-Q-2008-310

Adopted date: 22 October 2008 Summary (0.1Mb)

Opinion (0.2Mb)

Summary

Following a request from the European Commission (EC), the Panel on Biological Hazards (BIOHAZ) was asked to deliver a scientific opinion on the Human and animal exposure risk related to Transmissible Spongiform Encephalopathies (TSEs) from milk and milk products derived from small ruminants.

In a recent scientific article from Konold et al., published on 8 April 2008 in BMC Veterinary Research, on "Evidence of scrapie transmission via milk" it is concluded that: “…there is a risk of the transmission of scrapie from ewe to lamb via milk or colostrum. Infection of lambs via milk may result in shedding of the infectious agent into the environment…”.

The BIOHAZ Panel was invited to provide an opinion on the conclusions from the article of Konold et al. (2008), and if considered necessary, based on any additional available scientific data, to update the current risk assessments on the human and animal exposure related to Transmissible Spongiform Encephalopathies (TSEs) from milk and milk products derived from small ruminants.

When approaching the mandate the BIOHAZ Panel did not consider the zoonotic potential of small ruminant TSE agents. This aspect is considered in detail in previous EFSA documents[1],[2]. The TSE agents considered in the assessment were Classical scrapie, Atypical scrapie and BSE. Moreover, the assessment was performed employing mainly data from TSE in sheep, which were considered valid also for TSE in goats due to the lack of more specific data in that species.

The Panel considered valid the conclusion of the article of Konold et al. (2008). Expanding the article of Konold et al. (2008), another study from Lacroux et al. (2008) independently demonstrated that Classical scrapie can be transmitted from susceptible ewe to transgenic mice via colostrum and milk. It was emphasized that both studies were designed to achieve the highest possibility of transmission success and that this could differ from the field situation. The Panel noted that in both studies, milk from asymptomatic donor ewes transmitted disease, indicating that clinically healthy, Classical scrapie-incubating sheep may shed the causal agents of these TSEs in milk. Moreover, the level of prion infectivity in small ruminant milk could become higher during the course of mastitis but the somatic cell count was considered as an unreliable indicator for presence or absence of TSE infectivity in small ruminant milk.

The Panel concluded that the use of milk and milk products from a flock with Classical scrapie may carry a TSE exposure risk for humans and animals. Furthermore, the use of milk and milk products from the general small ruminant population may carry a TSE exposure risk for humans and animals due to the presence of undetected affected flocks in that population. However, because of the difference in scrapie prevalence between affected flocks and the general small ruminant population, the risk of exposure for humans and animals associated with milk and milk products from the general small ruminant population will be lower than the risk from detected scrapie affected flocks.

The Panel also concluded that the exposure to a Classical scrapie agent via milk of an infected animal can be estimated to be 4 to 5 logs10 lower than the infectivity found in the same weight of brainstem from a terminally affected animal, and 2 to 3 logs10 lower the than infectivity found in the same weight of lymphoid tissues from an animal incubating scrapie or from a clinically affected animal.

The BIOHAZ Panel further noted that no information is available concerning the presence of infectivity or PrPSc in colostrum or milk from small ruminants affected by Atypical scrapie or BSE. However, the Panel emphasized that due to the early and progressive peripheral tissue dissemination of the BSE agent in experimentally infected susceptible sheep, the occurrence of infectivity in colostrum and milk of BSE infected susceptible small ruminants would be likely. On the other hand, the apparent restricted dissemination of the agent of Atypical scrapie in affected individuals could limit its transmissibility through milk.

As there is large variation between MS in prevalence of scrapie and production of small ruminant milk, the human and animal exposure associated with small ruminant dairy products varies greatly between MS.

The Panel further concluded that breeding of sheep for relative resistance to Classical scrapie according to the previous EFSA opinion[3] can be expected to reduce human and animal exposure associated with small ruminant dairy products.

The Panel recommended to perform research in order to characterise the exposure risk via milk especially in Atypical scrapie and BSE in small ruminants, to investigate on the stability of prion infectivity in milk during further processing, and to obtain more data to confirm and expand the preliminary information available on the quantitation of infectivity levels in small ruminant milk fractions. ___________________________________ [1]Opinion of the Scientific Panel on Biological Hazards on certain aspects related to the risk of Transmissible Spongiform Encephalopathies (TSEs) in ovine and caprine animals. The EFSA Journal (2007) 466, 1-10 [2] Scientific and technical clarification in the interpretation and consideration of some facets of the conclusions of its Opinion of 8 March 2007 on certain aspects related to the risk of Transmissible Spongiform Encephalopathies (TSEs) in ovine and caprine animals. The EFSA Journal (2008) 626, 1-11 [3] Opinion of the Scientific Panel on Biological Hazards on “the breeding programme for TSE resistance in sheep”, The EFSA Journal (2006), 382, 1-46

Publication date: 6 November 2008


http://www.efsa.europa.eu/EFSA/Scientific_Opinion/biohaz_op_ej849_tse_infectivity_summary_en,0.pdf?ssbinary=true



http://www.efsa.europa.eu/EFSA/Scientific_Opinion/biohaz_op_ej849_tse_infectivity_en,0.pdf?ssbinary=true




Prion Protein in Milk Nicola Franscini1, Ahmed El Gedaily1, Ulrich Matthey1, Susanne Franitza1, Man-Sun Sy2, Alexander Bürkle3, Martin Groschup4, Ueli Braun5, Ralph Zahn1*

1 Alicon AG, Schlieren, Switzerland, 2 Institute of Pathology, Biomedical Research Building, Case Western University School of Medicine, Cleveland, Ohio, United States of America, 3 Lehrstuhl Molekulare Toxikologie, University of Konstanz, Konstanz, Germany, 4 Friedrich-Loeffler-Institut, Bundesforschungsinstitut für Tiergesundheit, Greifswald, Gemany, 5 Departement für Nutztiere, University of Zurich, Zurich, Switzerland

Abstract Background Prions are known to cause transmissible spongiform encephalopathies (TSE) after accumulation in the central nervous system. There is increasing evidence that prions are also present in body fluids and that prion infection by blood transmission is possible. The low concentration of the proteinaceous agent in body fluids and its long incubation time complicate epidemiologic analysis and estimation of spreading and thus the risk of human infection. This situation is particularly unsatisfactory for food and pharmaceutical industries, given the lack of sensitive tools for monitoring the infectious agent.

Methodology/Principal Findings We have developed an adsorption matrix, Alicon PrioTrap®, which binds with high affinity and specificity to prion proteins. Thus we were able to identify prion protein (PrPC)–the precursor of prions (PrPSc)–in milk from humans, cows, sheep, and goats. The absolute amount of PrPC differs between the species (from µg/l range in sheep to ng/l range in human milk). PrPC is also found in homogenised and pasteurised off-the-shelf milk, and even ultrahigh temperature treatment only partially diminishes endogenous PrPC concentration.

Conclusions/Significance In view of a recent study showing evidence of prion replication occurring in the mammary gland of scrapie infected sheep suffering from mastitis, the appearance of PrPC in milk implies the possibility that milk of TSE-infected animals serves as source for PrPSc.

Citation: Franscini N, Gedaily AE, Matthey U, Franitza S, Sy M-S, et al. (2006) Prion Protein in Milk. PLoS ONE 1(1): e71. doi:10.1371/journal.pone.0000071

Academic Editor: Matthew Baylis, University of Liverpool, United Kingdom

Received: October 19, 2006; Accepted: November 6, 2006; Published: December 20, 2006

Copyright: © 2006 Franscini et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: The authors have no support or funding to report.

Competing interests: The authors have declared that no competing interests exist.

* To whom correspondence should be addressed. E-mail: info@alicon.ch


http://www.plosone.org/article/fetchObjectAttachment.action;jsessionid=4BBFF07E478CCD52A627126F9BCC995A?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0000071&representation=PDF




Saturday, April 12, 2008
Evidence of scrapie transmission via milk

Saturday, April 12, 2008 Evidence of scrapie transmission via milk



http://scrapie-usa.blogspot.com/2008/04/evidence-of-scrapie-transmission-via.html




HAVE ANOTHER GLASS OF CWD PRIONS COURTESY Dane County Wisconsin Mike DiMaggio, solid waste manager


http://chronic-wasting-disease.blogspot.com/2008/08/have-another-glass-of-cwd-prions.html




Friday, October 24, 2008

CBER 2007 Annual Report Assessing the Potential Risk of variant Creutzfeldt-Jakob Disease from Blood Products


http://creutzfeldt-jakob-disease.blogspot.com/2008/10/cber-2007-annual-report-assessing.html





TSS