Scientific Opinion on Risk of transmission of TSEs via semen and embryo transfer in small ruminants (sheep and goats)

News Story
6 January 2010

EFSA considers the risk of TSE transmission via embryo transfer and artificial insemination in small ruminants In an opinion published today, EFSA’s Panel on Biological Hazards (BIOHAZ) said that the risk of transmission of Classical scrapie through artificial insemination and embryo transfer in sheep and goats ranges from negligible to low. Experts stressed however, that data are not sufficient to conclude that the risk is negligible.

Because of similarities in the disease development process for Classical scrapie and BSE in small ruminants, experts considered the conclusions for Classical scrapie to be also valid for BSE. They could not assess the risk posed by Atypical scrapie – another Transmissible Spongiform Encephalopathy (TSE) – due to lack of knowledge about the developmental process for this particular disease and about the distribution of the infective agent in affected animals.

After reviewing all available scientific information in the field, experts stressed that there is a iatrogenic risk of TSE transmission, that is risk inherent to the artificial insemination and embryo transfer activities themselves; for instance, through the use of animal-derived hormones associated with such procedures. Moreover, in its opinion the BIOHAZ Panel pointed out that the absence of reliable figures on the annual number of artificial inseminations and embryo transfers in small ruminants in the EU hampers the quantitative assessment of the risk of TSE transmission linked to these practices. Experts made some recommendations which could reduce the risk of TSE transmission associated with these reproductive technologies and facilitate future risk assessments in this area.

Scientific Opinion on Risk of transmission of TSEs via semen and embryo transfer in small ruminants (sheep and goats) For media enquiries, please contact: Andrew Cutting, Press Officer or Steve Pagani, Head of Press Office Tel: +39 0521 036149 Email: Press@efsa.europa.eu


http://www.efsa.europa.eu/en/press/news/biohaz100106.htm




Scientific Opinion on Risk of transmission of TSEs via semen and embryo transfer in small ruminants (sheep and goats) Question number: EFSA-Q-2009-00620

Adopted: 10 October 2009 Summary (31 KB)


http://www.efsa.europa.eu/en/scdocs/doc/s1429.pdf




Opinion (440 KB)



http://www.efsa.europa.eu/en/scdocs/doc/1429.pdf




Summary

Following a request from the European Commission, the Panel on Biological Hazards (BIOHAZ) was asked to deliver a scientific opinion on the Risk of transmission of Transmissible Spongiform Encephalopathies (TSEs) via semen and embryo transfer in small ruminants (sheep and goats).

Regulation (EC) No 999/2001[1] of the European Parliament and of the Council laying down rules for the prevention, control and eradication of certain TSEs sets the specific restrictions on the placing on the market, export and import of the semen and embryos of the ovine and caprine animals.

Three articles were recently published [2,3,4] as regard to the TSE transmission risk through artificial insemination (AI) and embryo transfer (ET) techniques in small ruminants. These articles suggest that this risk would be very low or negligible.

In the light of these new data the European Commission (EC) requested EFSA to provide a scientific opinion concerning the risk of transmission of TSEs via semen and embryo transfer of small ruminants (sheep and goats).

The TSE agents considered in the assessment were: Classical scrapie, Atypical scrapie and Bovine Spongiform Encephalopathy (BSE). The risk assessment was mainly performed using data obtained in sheep. Because of the lack of specific data in goats, and because the high similarities of TSE pathogenesis between sheep and goats, this assessment was considered to be also valid in goats.

The BIOHAZ Panel considered all available scientific information related to TSE transmission via semen and embryos in small ruminants.

The Panel concluded that the risk of TSE transmission associated with semen and embryos collected from Classical Scrapie incubating sheep and goats ranges from negligible to low. However, data are insufficient to conclude that such a risk is negligible. Because of the similarities between Classical scrapie and BSE pathogenesis in small ruminants, these conclusions are also to be considered valid for BSE.

The BIOHAZ Panel considered that at this stage, the assessment of the risk of transmission by semen or embryos collected from sheep or goats affected by Atypical scrapie is not possible because of a lack of knowledge on the pathogenesis and anatomical distribution of the Atypical scrapie agent within affected animals.

Furthermore, it was highlighted that there is an inherent but unquantifiable risk of iatrogenic TSE transmission that is associated with artificial insemination and embryo transfer procedures (use of animal-derived hormones and surgical devices).

The Panel noted that absence of reliable figures on the annual number of artificial inseminations and embryo transfers performed in small ruminants in the European Union (EU) Members States hampers the quantitative assessment of the potential impact of an artificial insemination and embryo transfer transmission risk on TSE prevalence in the EU small ruminant population.

The BIOHAZ Panel recommended further assessing the Classical scrapie and BSE transmission risk associated with small ruminants semen and embryos for infectivity, using highly sensitive animal models, in semen and embryos collected from a statistically significant number of TSE infected animals bearing susceptible PrP genotypes at different stages of the disease and with different TSE agents. Moreover, specific data about pathogenesis and anatomical distribution of the Atypical scrapie agent should be generated. Investigations should include small ruminant males and females at different stages of the reproductive cycle.

The Panel further recommended the promotion of procedures to limit the risk of iatrogenic transmission of TSEs associated with ET and AI. In particular, the replacement of ruminant-derived hormones by recombinant proteins should be considered.

The BIOHAZ Panel advised that a database recording the AIs and ETs performed every year in the EU should be established.

Finally the Panel emphasised that homozygous and heterozygous ARR rams and ewes as donors and recipients would minimise the risk of Classical scrapie and BSE transmission that could be associated with reproductive technologies. Similarly, once clarified and if validated, resistant-genotype he-goats and she-goats as donors and recipients would minimise the risk of Classical scrapie and BSE transmission that could be associated with reproductive technologies.


Published: 6 January 2010 -------------------------------------------------------------


[1] Regulation (EC) No 999/2001 of the European Parliament and of the Council of 22 May 2001 laying down rules for the prevention, control and eradication of certain transmissible spongiform encephalopathies. European Community, OJ L 147, 31.5.2001, p. 1-40. [2] Sarradin P, Melo S, Barc C, Lecomte C, Andreoletti O, Lantier F, Dacheux JL and Gatti JL, 2008. Semen from scrapie-infected rams does not transmit prion infection to transgenic mice. Reproduction, 135, 415-8. [3] Wrathall AE, Holyoak GR, Parsonson IM and Simmons HA, 2008. Risks of transmitting ruminant spongiform encephalopathies (prion diseases) by semen and embryo transfer techniques. Theriogenology, 70, 725-45. [4] Low JC, Chambers J, McKelvey WA, McKendrick IJ and Jeffrey M, 2009. Failure to transmit scrapie infection by transferring preimplantation embryos from naturally infected donor sheep. Theriogenology,72, 809-16.



http://www.efsa.europa.eu/en/scdocs/scdoc/1429.htm




Monday, December 14, 2009

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease
Are Encoded by Distinct Prion Types




> Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine

> (reticular) deposits,



http://nor-98.blogspot.com/2009/12/similarities-between-forms-of-sheep.html




see also ;


> All of the Heidenhain variants were of the methionine/ methionine type 1

> molecular subtype.



http://cjdusa.blogspot.com/2009/09/co-existence-of-scrapie-prion-protein.html





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



Tuesday, June 3, 2008


SCRAPIE USA UPDATE JUNE 2008 NOR-98 REPORTED PA


http://nor-98.blogspot.com/2008/06/scrapie-usa-update-june-2008-nor-98.html




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, December 1, 2008

When Atypical Scrapie cross species barriers


http://nor-98.blogspot.com/2008/12/when-atypical-scrapie-cross-species.html



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://web.archive.org/web/20010305222246/www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf


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

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

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

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

snip...

The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie
by natural feeding to squirrel monkeys that we have reported provides
further grounds for concern that scrapie-infected meat may occasionally give
rise in humans to Creutzfeldt-Jakob disease.

PMID: 6997404

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


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://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf



Nature. 1972 Mar 10;236(5341):73-4.

Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek DC.

Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)

C. J. GIBBS jun. & D. C. GAJDUSEK

National Institute of Neurological Diseases and Stroke, National Institutes
of Health, Bethesda, Maryland

SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey
(Macaca fascicularis) with an incubation period of more than 5 yr from the
time of intracerebral inoculation of scrapie-infected mouse brain. The
animal developed a chronic central nervous system degeneration, with ataxia,
tremor and myoclonus with associated severe scrapie-like pathology of
intensive astroglial hypertrophy and proliferation, neuronal vacuolation and
status spongiosus of grey matter. The strain of scrapie virus used was the
eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained
as ninth intracerebral passage of the agent in goat brain, from Dr R. L.
Chandler (ARC, Compton, Berkshire).


http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.html



Epidemiology of Scrapie in the United States 1977


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


http://web.archive.org/web/20030513212324/http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf





Monday, September 1, 2008

RE-FOIA OF DECLARATION OF EXTRAORDINARY EMERGENCY BECAUSE OF AN ATYPICAL T.S.E. (PRION DISEASE) OF FOREIGN ORIGIN IN THE UNITED STATES [No. 00-072-1] September 1, 2008


http://foiamadsheepmadrivervalley.blogspot.com/2008/09/re-foia-of-declaration-of-extraordinary.html



Thursday, October 15, 2009

SCRAPIE UPDATE CANADA 2009 (typical and atypical cases)


http://scrapie-usa.blogspot.com/2009/10/scrapie-update-canada-2009-typical-and.html




Friday, May 29, 2009

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


http://scrapie-usa.blogspot.com/2009/05/characterization-of-us-sheep-scrapie.html




Monday, August 03, 2009

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


http://scrapie-usa.blogspot.com/2009/08/prions-are-secreted-in-milk-from.html




November 2009 Monthly Report Fiscal Year 2010


Positive Scrapie Cases

As of November 30, 2009, 16 positive cases in sheep or goats were reported by the National Veterinary Services Laboratories (NVSL); 13 were field cases and 3 were Regulatory Scrapie Slaughter Surveillance (RSSS) cases collected between October 1, 2009 and November 30, 2009 and confirmed by December 18, 2009 (Figure 7). Field cases are positive animals tested as part of a disease investigation including potentially exposed, exposed, and suspect animals. TWENTY ONE cases of scrapie in goats have been confirmed by NVSL since implementation of the regulatory changes in FY 2002 (Figure 8). The most recent positive goat case was confirmed rectal biopsy positive in November 2009 and originated in the same herd in Michigan as the positive goat cases that were found in FY 2008. The positive goat has been held in quarantine for research by USDA's Agricultural Research Service since 2008.

snip...

Does not include Nor98-like Scrapie cases found through RSSS (2 in FY 2007 and 1 in FY 2008)


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



SCRAPIE USA REPORT FISCAL YEAR 2008

Positive Scrapie Cases

As of September 30, 2008, 176 new scrapie cases were confirmed and reported by the National Veterinary Services Laboratories (NVSL) in FY 2008 (Figure 5). Of these, 134 were field cases and 42* were Regulatory Scrapie Slaughter Surveillance (RSSS) cases (collected between October 1, 2007 and September 30, 2008) (Slide 15). The field case total includes multiple cases from the same flocks. One of the positive field cases was genotyped as AAQR. THIS IS THE FIRST CONFIRMED CASE OF CLASSICAL SCRAPIE IN THE UNITED STATES IN A SHEEP OF THIS GENOTYPE. THE ONLY WHITE-FACED RSSS POSITIVE WAS COMPATIBLE WITH NOR98-LIKE SCRAPIE. Nineteen cases of scrapie in goats have been confirmed by NVSL since implementation of the regulatory changes in FY 2002 (Figure 6) including five goat cases in FY 2008 that originated from the same herd in Michigan.



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




Greetings,


> (Figure 6) including five goat cases in FY 2008 that originated from the same herd in Michigan.


This is highly unusual for goats, and I strenuously urge that there should be an independent investigation into finding the common denominator for these 5 goats in the same herd in Michigan with Scrapie. ...


Kind Regards,
Terry



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



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

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

TAFS1 Position Paper on BSE in small ruminants (January 2009)

UPDATED: TAFS POSITION PAPER ON BSE IN SMALL RUMINANTS (January 2009) TAFS Position Paper - BSE in Small Ruminants- (246 kB) ??????? BSE ???? TAFS ????????? (Japanese version not updated; status May 2007)

TAFS INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation

(January 2009)

TAFS1 Position Paper on BSE in small ruminants

The recognition in 2004 that a French goat killed in 2002(25) was infected with BSE raised the profile of prion diseases in small ruminants in Europe, especially with respect to the risk that this may represent to consumers. Research into BSE in small ruminants, using experimental infections of sheep with BSE, were expanded and will inevitably add to our understanding of how BSE behaves in sheep and goats if infected. Meanwhile surveillance for prion diseases in small ruminants in Europe has identified scrapie cases in most countries, sometimes only in small numbers, but the evolving process of data analysis and scientific investigation is challenging past assumptions about the recognition and behaviour of prion infections of small ruminants. In particular, there is an intensification of the search for BSE amongst positive cases detected by surveillance, making use of newer discriminatory tools. This paper summarises recent results, both published or soon to be published, and their implications to both consumers and authorities who are responsible for ensuring the protection of consumers.

please see full text 17 pages ;



http://www.tafsforum.org/position_papers/TAFS%20POSITION%20STATEMENT%20ON%20BSE%20IN%20SMALL%20RUMINANTS_2009.pdf



-------------------- mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000205/!x-usc:mailto:BSE-L@LISTS.AEGEE.ORG --------------------

When Atypical Scrapie cross species barriers

Authors

Andreoletti O., Herva M. H., Cassard H., Espinosa J. C., Lacroux C., Simon S., Padilla D., Benestad S. L., Lantier F., Schelcher F., Grassi J., Torres, J. M., UMR INRA ENVT 1225, Ecole Nationale Veterinaire de Toulouse.France; ICISA-INlA, Madrid, Spain; CEA, IBiTec-5, DSV, CEA/Saclay, Gif sur Yvette cedex, France; National Veterinary Institute, Postboks 750 Sentrum, 0106 Oslo, Norway, INRA IASP, Centre INRA de Tours, 3738O Nouzilly, France.

Content

Atypical scrapie is a TSE occurring in small ruminants and harbouring peculiar clinical, epidemiological and biochemical properties. Currently this form of disease is identified in a large number of countries. In this study we report the transmission of an atypical scrapie isolate through different species barriers as modeled by transgenic mice (Tg) expressing different species PRP sequence.

The donor isolate was collected in 1995 in a French commercial sheep flock. inoculation into AHQ/AHQ sheep induced a disease which had all neuro-pathological and biochemical characteristics of atypical scrapie. Transmitted into Transgenic mice expressing either ovine or PrPc, the isolate retained all the described characteristics of atypical scrapie.

Surprisingly the TSE agent characteristics were dramatically different v/hen passaged into Tg bovine mice. The recovered TSE agent had biological and biochemical characteristics similar to those of atypical BSE L in the same mouse model. Moreover, whereas no other TSE agent than BSE were shown to transmit into Tg porcine mice, atypical scrapie was able to develop into this model, albeit with low attack rate on first passage.

Furthermore, after adaptation in the porcine mouse model this prion showed similar biological and biochemical characteristics than BSE adapted to this porcine mouse model. Altogether these data indicate.

(i) the unsuspected potential abilities of atypical scrapie to cross species barriers

(ii) the possible capacity of this agent to acquire new characteristics when crossing species barrier

These findings raise some interrogation on the concept of TSE strain and on the origin of the diversity of the TSE agents and could have consequences on field TSE control measures.



http://www.neuroprion.org/resources/pdf_docs/conferences/prion2008/abstract-book-prion2008.pdf



SCRAPIE USA

INFECTED AND SOURCE FLOCKS

There were 20 scrapie infected and source flocks with open statuses (Figure 3) as of April, 30, 2008. Twenty eight new infected and source flocks have been designated in FY 2008 (Figure 4); three source flocks were reported in April. ...snip

POSITIVE SCRAPIE CASES

As of April 30, 2008, 122 new scrapie cases have been confirmed and reported by the National Veterinary Services Laboratories (NVSL) in FY 2008 (Figure 6). Of these, 103 were field cases and 19* were Regulatory Scrapie Slaughter Surveillance (RSSS) cases (collected in FY 2008 and reported by May 20, 2008). Positive cases reported for April 2008 are depicted in Figure 7. Eighteen cases of scrapie in goats have been confirmed by NVSL since implementation of the regulatory changes in FY 2002 (Figure 8). The most recent positive goat case was confirmed in February 2008 and originated from the same herd in Michigan as the other FY 2008 goat cases. ...snip

CAPRINE SCRAPIE PREVALENCE STUDY (CSPS)

snip...

However, four positive goats have been identified this fiscal year through field investigations. One was a clinical suspect submitted for testing and the other three originated from the birth herd of the clinical case.

ANIMALS SAMPLED FOR SCRAPIE TESTING

As of April 30, 2008, 26,703 animals have been sampled for scrapie testing: 23,378 RSSS, 1,517 goats for the CSPS study, 1,466 regulatory field cases, 270 regulatory third eyelid biopsies, and 72 regulatory rectal biopsies (chart 8).

TESTING OF LYMPHOID TISSUE OBTAINED BY RECTAL BIOPSY WAS APPROVED BY USDA AS AN OFFICIAL LIVE-ANIMAL TEST ON JANUARY 11, 2008. ...

PLEASE NOTE, (FIGURE 6), Scrapie Confirmed Cases in FY 2008 MAP, PA 3, 1**, Two cases-state of ID UNKNOWN, 1 case Nor98-like**



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



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



P03.141

Aspects of the Cerebellar Neuropathology in Nor98

Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute,

Norway Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.



http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf



Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.

Edited by Stanley B. Prusiner, University of California, San Francisco, CA, and approved September 12, 2005 (received for review March 21, 2005)



http://www.pnas.org/cgi/content/abstract/0502296102v1



NOR-98 ATYPICAL SCRAPIE 5 cases documented in USA in 5 different states USA 007



http://nor-98.blogspot.com/2008/04/seac-spongiform-encephalopathy-advisory.html



Tuesday, June 3, 2008 SCRAPIE USA UPDATE JUNE 2008 NOR-98 REPORTED PA



http://nor-98.blogspot.com/2008/06/scrapie-usa-update-june-2008-nor-98.html



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



Monday, December 1, 2008 When Atypical Scrapie cross species barriers



http://nor-98.blogspot.com/2008/12/when-atypical-scrapie-cross-species.html




Saturday, January 24, 2009 Research Project: Detection of TSE Agents in Livestock, Wildlife, Agricultural Products, and the Environment Location: 2008 Annual Report



http://bse-atypical.blogspot.com/2009/01/research-project-detection-of-tse.html




TSS

TAFS1 STATEMENT ON TRANSMISSION OF SCRAPIE VIA MILK (January, 2009)

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

Introduction In April 2008, TAFS published a statement on the transmission of scrapie via milk, prompted by the publication of results that provided strong evidence of transmission of scrapie to lambs by the feeding of milk from scrapie-infected ewes(4). More recently, another publication has further clarified the mechanisms of transmission(5), and together the results have enabled a review of the implications by the European Food Safety Authority(3), and prompted initial regulatory action by the European Commission. This statement represents a revision of the TAFS statement to take into account the recent data and interpretation.

TAFS welcomes publication of these findings. They contribute to the understanding of the mechanisms of transmission of scrapie as a prion disease of sheep and goats that has been known for over 200 years. Scrapie is not a highly contagious disease. It does not spread easily, but it is difficult to eradicate. It is known to spread between sheep, both from ewe to lamb and to other unrelated sheep and goats. The exact route of transmission has not been determined so far. There are several possible routes, which include contact with placenta of infected ewes, or possibly before birth while the lamb is still in the womb. Transmission via milk and/or uterine fluids after birth are additional possibilities. Ewe to lamb transmission(4) This study attempted to assess the scope for transmission, under a worst-case scenario, by collecting milk from sheep of highly susceptible genetic makeup (high risk group), at a time when they were either about to die of scrapie, or when the first clinical signs were seen. Their milk was collected and fed to lambs that were born to uninfected mothers and kept in isolation while they received the milk. These lambs were also of the most susceptible genotype (VRQ/VRQ).

The lambs have been shown to be infected by the testing of tissue samples collected either while still alive, by biopsy, or from some that had died of other diseases. None have yet reached the point of clinical disease themselves, and infectivity itself has not been demonstrated. Tests have revealed the

1 TAFS is an international platform created by a group of scientists, food industry experts, animal health regulators, epidemiologists, diagnosticians, food producers, and consumers. Its purpose is to establish and maintain lines of communication for the dissemination of reliable information to the public that can maintain confidence in the safety of food with regard to Transmissible Animal Diseases.

TAFS

2

presence of abnormal prion protein (PrPSc) that is normally recognised as a marker for the presence of infectivity. The success of the study was dependent on having scrapie-free lambs to receive the milk. Despite having fully susceptible ewes and susceptible lambs, the ease with which the lambs were infected is a surprise. The experimental design anticipated transmission to smaller numbers of lambs. For this reason lambs received both milk and colostrum (the milk produced within the first 24-48 hours after lambing) from the same ewe in order to maximise the likelihood of transmission. As a result, the authors could not conclude whether transmission occurred via colostrum, milk or both. The study will therefore now be repeated, feeding lambs with either colostrum or milk. This is important for several reasons.

* Firstly, colostrum would not be used for human consumption.

* Secondly, colostrum is rich in protein and antibodies that help to protect the lamb in the early days of life before its own immune system is fully developed. For that reason farmers sometimes collect and freeze colostrum to feed to other lambs, sometimes pooling it to feed to several lambs. This practice could increase the potential for infection of lambs at their most vulnerable time of life.

Although the study described below confirms the presence of infectivity in colostrum, it is necessary to establish the status of colostrum from sheep that are unaffected by other pathogens. In other words, the result should be dependent solely on the presence of scrapie in an otherwise healthy sheep. Ewe to mouse transmission(5) This study also made use of a naturally infected experimental flock of sheep in France, but differed from the previous study in that the flock was infected with both scrapie and Maedi-Visna (MV). MV is a viral disease, that has previously been shown to potentially predispose to the transmission of scrapie via milk(6). It causes a form of mastitis (lympho-proliferative chronic mastitis) that particularly involves the formation of discrete ectopic lymphoid follicles in the mammary tissue. These have previously been shown to stain heavily for abnormal prion protein(9) in scrapie infected sheep(6). In the French study, the researchers compensated for some of the difficulties normally presented by mouse inoculation studies, of not being able to inoculate sufficient material into a mouse to guarantee transmission, by concentrating their starting material (colostrum and milk). In addition, they used highly sensitive mice (Tg338)(7), that were genetically modified to produce sheep prion protein of the VRQ genotype(10). The study was supported by post-mortem examination of many sheep for the presence of abnormal PrP in the udder, and for the presence or absence of mastitis. Although the biological assay study has not been completed, it has reached a point where it is possible to conclude conclusively that particular fractions of milk are infectious. Preliminary findings include:

* Abnormal PrP was only detected in ewes that harboured ectopic lymphoid follicles, and correlated with the detection of abnormal PrP in other peripheral lymph nodes. This therefore limited the positivity to sheep with the most susceptible genotypes that are predisposed to peripheral infection (VRQ/VRQ; VRQ/ARQ; ARQ/ARQ).

* In addition, abnormal PrP was detected in lacteal ducts and mammary acini suggesting a high probability that it would be excreted in milk/colostrum.

* Nevertheless, infectivity studies detected scrapie infectivity in both colostrum (collected within 12 hours of lambing) and milk (collected 20 days after lambing). The infectivity was associated with cellular, cream and casein-whey fractions.

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* Most critically, infectivity was even detected in fractions derived from sheep in which there was no visible clinical or pathological evidence of mastitic lesions.

* In all samples, preliminary estimations suggest that infectivity levels are very low, but potentially higher in mastitic milk or colostrum than from healthy udders.

EFSA BioHazards Panel Opinion(3) The findings summarised above were supported by EFSA, but the BioHazards panel stressed that in both studies conditions had been maximised to facilitate detection of infectivity. In other words, they were worst-case scenarios, and may not be fully representative of natural infection in farm animals. Nevertheless, the conclusion, that both animals and humans were clearly at risk of exposure to scrapie infectivity via milk could not be ignored. Scrapie prevalence varies between countries, but is so low as to represent only a small risk to consumers from national populations of small ruminants. The risk relating to flocks/herds in which scrapie has been diagnosed was, however, greater and possibly warranted specific action to limit exposure risks. This is important as past assumptions that risk management measures could be limited to the exclusion of mastitic milk from the human food chain have been demonstrated to be untenable, given the findings in the French study of infectivity in milk from sheep with apparently healthy udders. EFSA stressed that it’s assessment of human health risk had not changed from its previous positions in 2007 and 2008(1,2). As suggested by the French researchers, a combination of low infectivity levels in milk, and low prevalence of scrapie, coupled with the historical absence of a definite link between scrapie and human disease, suggested that milk from the general population of small ruminants could be considered low risk. The BioHazards Panel could not offer specific advice with respect to risk from milk of sheep infected with BSE or atypical scrapie(8,10), but anticipated that the recognised peripheral distribution of infectivity in some small ruminants infected with BSE could lead to the presence of infectivity in milk. Atypical scrapie has not yet been identified in peripheral tissues of infected animals. Risk Management Options Further to the EFSA and AFSSA Opinions, the EU agreed to new controls on 26 November 2008 (SANCO/3660/2008), but will be applied when legislative changes are in force. These recognise the potential role of milk in spreading classical scrapie (or BSE) between small ruminants, and are primarily intended to protect animal health. Consequently:-

* While investigations into a case of suspect TSE in a sheep or goat continue, the use of milk and milk products derived from the animals in the flock/herd in question will be restricted to that holding until confirmatory results are available.

* After confirmation that the diagnosis is of classical scrapie, milk and milk products from the flock cannot be sold for feeding to ruminant species. Sale for feeding to non-ruminants will be confined to use within the borders of the Member State concerned. These measures apply until all susceptible animals have been culled.

* A derogation allowing the deferring of culling for up to 5 years in specific circumstances has been reduced to 18 months in dairy herds/flocks. ? Imports of milk and milk products into Member States, intended for feeding to ruminants, will need to be subject to additional certification relating to the scrapie status of the flock/herd of origin. These represent only a part of the raft of regulatory actions that apply to classical scrapie affected flocks or herds in Europe. The culling of genetically susceptible sheep or all sheep or goats in the flock/herd, and voluntary programmes of breeding for resistance in sheep are also involved. If BSE cannot be excluded, the flock or the herd must be culled and any milk or milk products on the holding destroyed. The new measures do highlight however that the focus of attention is on the

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protection of animal health, by reducing opportunities for the spread of infection. Realistically, it is probable that the effect of the measures will vary significantly from country to county, depending on the prevalence of scrapie, the number of small ruminant dairy herds/flocks and the extent to which milk from sheep and goats is sold for animal feed. In many countries small ruminant milk production is only a minor component of industry objectives. TAF Position Scrapie is not recognised as a risk to humans, although this cannot be ruled out with certainty .The risk to humans from scrapie, and the scientific uncertainties that underpin any statement on risk, have been discussed at length in the EFSA Opinions cited below. Since there is no established evidence to date that scrapie poses a risk to human health, the finding that infectivity is present in milk of scrapie-infected animals does not give any reason to change our view that ovine and caprine milk are safe for human consumption. These results do not at the moment have any direct implications with respect to the risk from BSE in milk from cattle. Although an equivalent study has not been conducted in cattle, other studies attempting to find infectivity in bovine milk have not succeeded. Proving the total absence of infectivity is extremely difficult. The evidence for the absence of natural spread of BSE between cattle, from cow to calf or between unrelated cattle does however suggest that even in natural equivalent of this experiment, the feeding of calves on cows’ milk, transmission has not occurred, or does so only rarely. Consequently, cows’ milk is unlikely to carry BSE infectivity that might put consumers at risk. Furthermore, the control measures that have been put in place to eradicate BSE, and protect consumers in the interim, are succeeding in reducing numbers of infected cattle year by year. In conclusion, the studies, and their interpretation by EFSA, help to better understand the epidemiology of scrapie and exposure risks faced. Despite the precautionary impetus for additional measures to further strengthen animal health protection in regard to small ruminant TSEs, the question of the safety of products derived from bovine milk destined for human consumption remains unchanged.

References.

1. EFSA (2007). 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. 8 March 2007. The EFSA Journal. 466:1-10. Available at:-


http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178620775196.htm



2. EFSA (2008). 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. 626:1-11. Available at:


http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178685986247.htm



3. EFSA (2008). Scientific opinion of the Scientific Panel on Biological Hazards on the human and animal exposure risk related to Transmissible Spongiform Encephalopathies (TSEs) from milk and milk products derived from small ruminants. The EFSA Journal. 849:2-38.Available at:-



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



4. Konold et al.: Evidence of scrapie transmission via milk, BMC Veterinary Research 2008, 4:14;


http://www.biomedcentral.com/1746-6148/4/14




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5. Lacroux, C., Simon, S., Benestad, S.L., Maillet, S., Mathey, J., Lugan, S., Corbiere, F., Cassard, H., Costes, P., Bergonier, D., WEisbecker, J-L., Moldal, T., Simmons, H., Lantier, F., Feraudet-Tarisse, C., Morel, N., Schelcher, F., Grassi, J. & Andreoletti, O. (2008) Prions in milk from ewes incubating natural scrapie. PLoS Pathogens. 4:12.


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




6. Ligios, C., Sigurdson, C.J., Santucciu, C., Carcassola, G., Manco, G., Basagni, M., Maestrale, C., Cancedda, M.G., Madau, L. & Aguzzi, A. (2005). PrPSc in mammary glands of sheep affected by scrapie and mastitis. Nat. Med. 11:1137-1138.

7. Vilotte, J.L., Soulier, S., Essalmani, R., Stinnakre, M.G., Vaiman, D., Lepourry, L., Da Silva, J.C., Besnard, N., Dawson, M., Buschmann, A., Groschup, M., Petit, S., Madelaine, M.F., Rakatobe, S., Le Dur, A., Vilette, D. & Laude, H. (2001). Markedly increased susceptibility to natural sheep scrapie of transgenic mice expressing ovine prp. J. Virol. 75:5977-84.

8. TAFS (2007) – Position paper on Atypical scrapie and Atypical BSE.



(http://www.tafsforum.org/position_papers/TAFS_POSITION_PAPER_ON_ATYPICAL_SCRAPIE_AND_%20ATYPICAL_BSE_070516.pdf)



9. TAFS (2007) – Position paper on the safety of bovine milk and bovine milk products


(http://www.tafsforum.org/position_papers/TAFS_POSITION_PAPER_ON_MILK_05-04-07.pdf)



10. TAFS (May 2007/2009) – Position paper on BSE in small ruminants.


(http://www.tafsforum.org/position_papers/TAFS%20POSITION%20STATEMENT%20ON%20BSE%20IN%20SMALL%20RUMINANTS_2009.pdf)





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





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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: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000172/!x-usc:mailto: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

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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: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000172/!x-usc:mailto: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



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

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



Attending Dr.: Date / Time Admitted : 12/14/97 1228

UTMB University of Texas Medical Branch Galveston, Texas 77555-0543 (409) 772-1238 Fax (409) 772-5683 Pathology Report

FINAL AUTOPSY DIAGNOSIS Autopsy' Office (409)772-2858

FINAL AUTOPSY DIAGNOSIS

I. Brain: Creutzfeldt-Jakob disease, Heidenhain variant.



http://creutzfeldt-jakob-disease.blogspot.com/2008/07/heidenhain-variant-creutzfeldt-jakob.html





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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





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