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/