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OPINION, BSE IN SHEEP, HOPING FOR BEST, PREPARING FOR WORSE

flounder

Well-known member
Opinion of the Scientific Panel BIOHAZ on the Quantitative risk assessment on the residual BSE risk in sheep meat and meat products [1]

Last updated: 15 March 2007 Publication Date: 15 March 2007

Adopted on 25 January 2007. (Question Nº EFSA-Q-2005-235)


Opinion
Summary
Summary

The European Commission (DG SANCO) requested the Scientific Panel on Biological Hazards (BIOHAZ) of the European Food Safety Authority (EFSA) for an update on the risks posed by tissues of sheep to human health in the case where Bovine Spongiform Encephalopathy (BSE) is confirmed in sheep and, more particularly, on the feasibility of carrying out a Quantitative Risk Assessment (QRA).

In replying to this mandate, the experts considered all necessary elements needed to carry out a quantitative risk assessment of BSE transmission from sheep to humans: (1) prevalence estimates of BSE infection in EU sheep (2) the amount and distribution of infectivity in sheep tissues and body fluids (3) the apparent barrier i.e. “species” barrier for transmission of BSE from sheep to humans and (4) human consumption of sheep products. The experts concluded that there are currently insufficient data for a QRA of the risks posed by tissues of sheep to human health in the case where BSE is confirmed in sheep.
However, they recognised that the prevalence of infection would have most significant impact on any QRA. Using the latest Transmissible Spongiform Encephalopathy (TSE) prevalence figures for Member States (MS) and the results of BSE/scrapie discriminatory testing, the experts were able, with certain assumptions, to estimate BSE prevalence in sheep. For example, they calculated by one method that there is a 95% confidence that in the high risk sub-group of countries there is less than 0.3-0.5 cases of BSE per 10,000 healthy-slaughtered animals.

In sheep experimentally infected with BSE, the distribution of the infectious agent (prion) in tissues is wide-spread as the prion can be found in secondary lymphoid tissue, skeletal muscle and blood. In considering more recent attempts at quantifying the risk specifically from this experimental ovine BSE, and in reviewing biochemical approaches to quantify titres in affected animals, a major stumbling block to quantification was identified to be the fact that the influence of age and genotype on the distribution of BSE infectivity in sheep is only defined qualitatively. The BIOHAZ panel agreed that absolute quantification of prions by biochemical methods was difficult. However, in the absence of comprehensive infectivity data to facilitate a QRA, it was concluded that Specified Risk Materials (SRM) removal alone was unlikely to be sufficient to eliminate the residual BSE risk to the consumer from a BSE-infected sheep carcass.

The experts further assumed that there is no intrinsic species barrier for sheep BSE transmission to humans, which is in line with past opinions of the Scientific Steering Committee. Human consumption levels of sheep meat and other sheep products (domestic produced or imported) are high within the EU. Data from two EU countries were used (Italy and GB) and gave intake estimates that were broadly in agreement with the overall trade data for sheep carcasses for these countries provided by Eurostat. This gave some confidence in using Eurostat data as basis to estimate an average daily intake of sheep meat or meat products in the EU of 8.4-9.3 g per person.
___________________________________

[1] For citation purposes: Opinion of the Scientific Panel on Biological Hazards on a request from the European Commission on the quantitative risk assessment on the residual BSE risk in sheep meat and meat products, The EFSA Journal (2007) 442, 1-44



http://www.efsa.europa.eu/en/science/biohaz/biohaz_opinions/ej442_qra_bse_sheep.html


SEE FULL OPINION 44 PAGES ;

SNIP...

4.4.4 New types of BSE in cattle and the variable pathogenicity of scrapie strains

Discriminatory testing for BSE in sheep is based on immuno-histochemistry (IHC), ELISA

and/or western blotting of brain (or lymphoid tissue) for abnormal prion protein in animals

experimentally challenged with infectious material taken from cases of cattle BSE defined as

“typical” or consistent with the original clinical and histopathological case definition of the

disease (Wells et al., 1987). The methodologies have been evaluated, and shown to be fit-forpurpose,

in an EU-wide ring trial using a variety of test materials covering oral and intracerebral

(ic) challenged sheep of a limited range of PrP genotypes, and include cases of

secondary ic transmission of sheep BSE to sheep (Stack et al., in preparation). However, the

sample-set was necessarily restricted to what was available and no meaningful estimate of the

sensitivity and specificity of these tests has been made. Nor were these tests evaluated for

their ability to discriminate types of BSE (cattle TSE) now regarded, on molecular and

histopathological criteria, to lie outside the original case definition of BSE (Buschmann et al.,

2006; Beringue et al., 2006a; Baron et al., 2006a; Casalone et al., 2004; Beringue et al.,

2006b; Baron et al., 2006b). These forms of cattle TSE have been dubbed H-type BSE and Ltype

(or BASE) BSE. The significance, origin and transmissibility of these H- and L-types of

BSE to sheep are only speculative at present and the BIOHAZ panel recommended a

The EFSA Journal (2007) 442, 1-44

Opinion on the quantitative risk assessment on the residual BSE risk in sheep

meat and meat products

www.efsa.europa.eu Page 21 of 44

watching brief on this area to monitor its relevance to the TSE risk of human consumption of

ovine products. Similarly, the potential variable pathogenicity of scrapie strains (such as

atypical scrapie) and their modification on transmission through a third species which may

affect barriers to transmission to humans remain speculative and need continual review.

4.4.5 Conclusion

The BIOHAZ panel considered that these data were not directly informative in quantifying a

sheep-to-human species barrier particularly, as referenced in section 4.4.4, since there are

many precedents for modification of TSE agents after passage through another species. For

the purposes of a QRA for sheep products, the BIOHAZ panel confirmed the use of the

previous assumption of a species barrier of 1 for putative sheep-to-human transmissions of

BSE.

4.5 Human consumption

There are few estimates of the level of consumption of sheep meat and meat products in the

European Union and most surveys focusing on nutrition and diet (e.g. the EPIC survey,

www.iarc.fr/epic ) include these foods under the cover of more general food categories.

Exceptions have included two surveys in Italy and Great Britain and these have been used to

check if Eurostat data on the production of ovine carcasses, import and export in the EU15

countries since 1995 could be used to validate EU-wide per capita annual intake data.

4.5.1 The Italian Survey

The Italian INN-CA survey covers the 1994-1996 period (Turrini et al., 2001). It randomly

sampled 1,147 households and involved 1,978 individuals of all ages. A self-compiled 7-day

food diary was used to gather data for analysis by sex and age categories. Among the food

items “sheep meat” was specified. The percentage of (sheep meat) consumers and daily food

intake by the total sample of individuals or by “consumers only” were calculated. An overall

mean daily intake was calculated of 3.2 g (median 0.0g). Understandably, consumption was

higher in the “consumers only” group (which represented 7.9% of the sample population)

with a mean and median intake of 40 and 25 g respectively.

4.5.2 The British Survey

The National Diet and Nutrition Survey of Great Britain is based on a representative

multistage random sample of 2,251 households in GB. One individual per household, 19 to 64

years of age, was requested to compile a 7-day food diary which included the category “lamb

and dishes”. As in the Italian survey the consumption figures were expressed by the total

sample of individuals or by “consumers only” (22% of total). The mean 7-day intakes were 51

g for the total sample and 226 g (median, 150 g) for “consumers only”.

The Italian and GB weekly intake were therefore comparable (22.4 g (Italy) vs. 51 g (GB) in

the whole sample population, and 280 g (Italy) vs 226 (GB) in the “consumers only” group).

(http://www.food.gov.uk/multimedia/pdfs/ndnsprintedreport.pdf, accessed on 7th March

2006)

SNIP...

6. CONCLUSIONS

6.1 General

The BIOHAZ panel retains the view that there are insufficient data for a quantitative

assessment of the risks posed by tissues of sheep to human health in the case where BSE is

confirmed in sheep. Moreover, even in the absence of quantitative information, recent data on

the preclinical distribution of PrPSc and infectivity in skeletal muscle tissues and blood

following experimental BSE challenge support their previous view that risk reduction

strategies relying on SRM removal in sheep or goats will not be fully effective.

The continuing lack of comprehensive quantitative data on species barrier and infectious load

with respect to BSE in small ruminants prevents any meaningful quantitative risk assessment

and precludes revision of the recommendations in the opinions of the Scientific Steering

Committee (EC 2002a) on safe sourcing of small ruminant materials of April 2002 and its

complement of September 2002.

snip...

The EFSA Journal (2007) 442, 1-44

Opinion on the quantitative risk assessment on the residual BSE risk in sheep

meat and meat products

www.efsa.europa.eu Page 28 of 44

7. RECOMMENDATIONS

1. More detailed evaluation of the screening and discriminatory TSE test parameters are

recommended, in tandem with continued surveillance, in order to improve the

accuracy of the BSE in sheep prevalence estimates. To facilitate this, all TSE positive

cases including secondary cases diagnosed in infected flocks should be systematically

submitted for discriminatory testing.

2. Emerging data on the early accumulation of abnormal prion protein and infectivity in

peripheral tissues of sheep exposed to natural scrapie and BSE before their detection

in the CNS re-inforce the value of maintaining current measures – especially SRM

removal, and breeding for resistance15 - previously recommended to reduce human

exposure to TSEs.

3. Further surveillance and multi-disciplinary investigation of all animal TSEs, including

atypical types of scrapie and BSE, are recommended to evaluate their implications for

human health. .......end


http://www.efsa.europa.eu/etc/medialib/efsa/science/biohaz/biohaz_opinions/ej442_bse_sheep.Par.0001.File.dat/biohaz_op_ej442_qra_sheep_en.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.

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


Published online before print October 20, 2005

Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0502296102
Medical Sciences

A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes

( sheep prion | transgenic mice )

Annick Le Dur *, Vincent Béringue *, Olivier Andréoletti , Fabienne Reine *, Thanh Lan Laï *, Thierry Baron , Bjørn Bratberg ¶, Jean-Luc Vilotte ||, Pierre Sarradin **, Sylvie L. Benestad ¶, and Hubert Laude *
*Virologie Immunologie Moléculaires and ||Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France; Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066 Toulouse, France; Agence Française de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon, France; **Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway

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

Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. 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.

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

Author contributions: H.L. designed research; A.L.D., V.B., O.A., F.R., T.L.L., J.-L.V., and H.L. performed research; T.B., B.B., P.S., and S.L.B. contributed new reagents/analytic tools; V.B., O.A., and H.L. analyzed data; and H.L. wrote the paper.

A.L.D. and V.B. contributed equally to this work.

To whom correspondence should be addressed.

Hubert Laude, E-mail: [email protected]

www.pnas.org/cgi/doi/10.1073/pnas.0502296102

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

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

Like lambs to the slaughter
31 March 2001
Debora MacKenzie
Magazine issue 2284
What if you can catch old-fashioned CJD by eating meat from a sheep infected
with scrapie?
FOUR years ago, Terry Singeltary watched his mother die horribly from a
degenerative brain disease. Doctors told him it was Alzheimer's, but
Singeltary was suspicious. The diagnosis didn't fit her violent symptoms,
and he demanded an autopsy. It showed she had died of sporadic
Creutzfeldt-Jakob disease.

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

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

The complete article is 889 words long.

full text;

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

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

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

Abstract

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

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



1: Cent Eur J Public Health 2003 Mar;11(1):19-22

Analysis of unusual accumulation of Creutzfeldt-Jakob disease cases
in Orava and Liptov regions (northern Slovak focus) 1983-2000.

Mad'ar R, Maslenova D, Ranostajova K, Straka S, Baska T.

Institute of Epidemiology, Jessenius Faculty of Medicine, Comenius
University, Sklabinska 26, Martin, 037 53 Slovakia. [email protected]

While familial cases of Creutzfeldt-Jakob disease are extremely rare
all over the world, 3 familial clusters were observed between
1983-2000 in a relatively small area situated in the North of
Slovakia. Prevalence of CJD in this area exceeded the overall
prevalence in Slovakia more than 8 times. The majority of CJD
patients admitted consuming sheep brain. Most patients lived in
small secluded villages with rather common familial intermarriage.
CJD affected both sexes equally. All patients were prior to the
disease mentally normal individuals. Shortly after the onset of CJD
their mental status deteriorated remarkably with an average survival
rate of 3.6 months.

PMID: 12690798

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ui
ds=12690798&dopt=Abstract

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

1: Eur J Epidemiol 1991 Sep;7(5):520-3
<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?db=PubMed&cmd=Display&dopt
=pubmed_pubmed&from_uid=1761109>


"Clusters" of CJD in Slovakia: the first laboratory evidence of scrapie.

Mitrova E, Huncaga S, Hocman G, Nyitrayova O, Tatara M.

Institute of Preventive and Clinical Medicine, Bratislava.

Epidemic-like occurrence of Creutzfeldt-Jakob disease was observed in
1987 in Slovakia (Orava). Search for the cause of CJD focus indicated a
coincidence of genetic and environmental risks in clustering patients.
Since Spongiform Encephalopathies might be transmitted orally, (Bovine
Spongiform Encephalopathy), the possibility of zoonotic source of CJD
cases in Orava was also considered. A deficient knowledge about the
occurrence of scrapie in Slovakia stimulated an examination of sheep
with signs of CNS disorders in two flocks of Valasky breed in Orava. In
one flock, neurohistopathological examination revealed in sheep brains
lesions characteristic for scrapie. Frozen brain tissue of these animals
were used for the detection of scrapie associated fibrils. They were
found in 2 animals from the same flock. This is the first laboratory
confirmation of scrapie in Czecho-Slovakia. The possible epidemiological
and economical implications are emphasized.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ui
ds=1761109&dopt=Abstract


STATEMENT OF DR HELEN GRANT MD FRCP
ISSUED 13/05/1999

BSE INQUIRY

http://www.bseinquiry.gov.uk/files/ws/s410.pdf
http://www.bseinquiry.gov.uk/files/ws/s410x.pdf

http://www.bseinquiry.gov.uk/evidence/ws/ws8.htm

CWD to CJD in humans (why not?), as easy as BSE/Scrapie;

The EMBO Journal, Vol. 19, No. 17 pp. 4425-4430, 2000
© European Molecular Biology Organization

Evidence of a molecular barrier limiting
susceptibility of humans, cattle and sheep to
chronic wasting disease

G.J. Raymond1, A. Bossers2, L.D. Raymond1, K.I. O?Rourke3,
L.E. McHolland4, P.K. Bryant III4, M.W. Miller5, E.S. Williams6, M.
Smits2
and B. Caughey1,7

1NIAID/NIH Rocky Mountain Laboratories, Hamilton, MT 59840,
3USDA/ARS/ADRU, Pullman, WA 99164-7030, 4USDA/ARS/ABADRL,
Laramie, WY 82071, 5Colorado Division of Wildlife, Wildlife Research
Center, Fort Collins, CO 80526-2097, 6Department of Veterinary Sciences,
University of Wyoming, Laramie, WY 82070, USA and 2ID-Lelystad,
Institute for Animal Science and Health, Lelystad, The Netherlands
7Corresponding author e-mail: [email protected] Received June 7, 2000;
revised July 3, 2000; accepted July 5, 2000.

Abstract

Chronic wasting disease (CWD) is a transmissible
spongiform encephalopathy (TSE) of deer and elk,
and little is known about its transmissibility to other
species. An important factor controlling
interspecies TSE susceptibility is prion protein (PrP)
homology between the source and recipient
species/genotypes. Furthermore, the efficiency with which
the protease-resistant PrP (PrP-res) of one
species induces the in vitro conversion of the normal PrP
(PrP-sen) of another species to the
protease-resistant state correlates with the cross-species
transmissibility of TSE agents. Here we
show that the CWD-associated PrP-res (PrPCWD) of cervids
readily induces the conversion of recombinant cervid PrP-sen
molecules to the protease-resistant state in accordance
with the known transmissibility of CWD between cervids. In contrast,
PrPCWD-induced conversions of human and bovine PrP-sen were
much less efficient, and conversion of ovine PrP-sen was
intermediate. These results demonstrate a barrier at the
molecular level that should limit the susceptibility of these non-cervid
species to CWD.

snip...

Clearly, it is premature to draw firm conclusions about CWD
passing naturally into humans, cattle and sheep, but the present
results suggest that CWD transmissions to humans would be as
limited by PrP incompatibility as transmissions of BSE or sheep
scrapie to humans. Although there is no evidence that sheep
scrapie has affected humans, it is likely that BSE has caused variant
CJD in 74 people (definite and probable variant CJD cases to
date according to the UK CJD Surveillance Unit). Given the
presumably large number of people exposed to BSE infectivity,
the susceptibility of humans may still be very low compared with
cattle, which would be consistent with the relatively inefficient
conversion of human PrP-sen by PrPBSE. Nonetheless, since
humans have apparently been infected by BSE, it would seem prudent
to take reasonable measures to limit exposure of humans
(as well as sheep and cattle) to CWD infectivity as has been
recommended for other animal TSEs.

snip...

http://www.emboj.org/current.shtml

Scrapie to Humans USA?


1: Neuroepidemiology. 1985;4(4):240-9.

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

Davanipour Z, Alter M, Sobel E, Callahan M.

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



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



Transmission of Creutzfeldt-Jakob disease by handling of dura mater.
The Lancet Volume 341(8837) January 9, 1993 pp
123-124
Weber, Thomas; Tumani, Hayrettin; Holdorff, Bernd; Collinge, John; Palmer,
Mark; Kretzschmar, Hans A.; Felgenhauer, Klaus


Sir,- Creutzfeldt-Jakob disease (CJD) can be transmitted iatrogenically by
human pituitary growth hormone, corneal transplants, and dura mater grafts
(1). Possible accidental transmission has been reported in only four
people-a neurosurgeon (2), a pathologist (3), and two laboratory technicians
(4,5) . We have encountered an unusually rapid case of CJD probably acquired
through handling of sheep and human dura mater.
In May, 1992, a 55-year-old orthopaedic surgeon developed paraesthesia of
the left arm. A few days later he had spatial disorientation, apraxia, and
gait ataxia. In June he was admitted and a neurologist suspected CJD on the
basis of the clinical signs, typical electroencephalogram (EEG) pattern, and
history. An EEG in June revealed a typical pattern of periodic biphasic and
triphasic sharp wave complexes. We saw the patient in July, 1992. He was
awake and oriented, with dyscalculia, dysgraphia, disturbed vision, apraxia
mainly of the left side, rigidity of wrists, spasticity of all muscles,
myoclonus of the left arm, increased tendon reflexes, ataxia of limbs and
trunk, and incoordination of left arm. Within 3 weeks he had impaired
consciousness and attention, mildly impaired memory, and threatening visual
hallucinations with restless turning. He had periodic states with movements
of his head and eye-bulbs resembling tonic adversive seizures. During sleep
these motor disturbances stopped. 2 1/2 months later the patient died.

This patient had worked with sheep and human dura mater from 1968 to 1972.
He handled about 150 specimens of ovine origin and at least a dozen human
preparations for research. Handling involved opening skulls with a band saw,
removing dura, and testing them either fresh (usually), preserved, or
lyophilised for mechanical qualities. These specimens were sent to a company
that has sold dura mater preparations by which CJD was transmitted in six
instances. No information was available from the company about a possible
connection with this patient's disease and the earlier cases of transmitted
CJD. Brain biopsy was consistent with diagnosis of CJD. Cerebrospinal fluid
obtained in July showed neuron-specific enolase (NSE) at 82.0 ng/mL,
compared with 16.7 ng/mL in serum of other cases (6). Proton magnetic
resonance spectroscopy of parieto-occipital and temporal grey matter,
parietal white matter, and thalamus revealed a 20-30% reduction of
N-acetylaspartate, as described (7). DNA was genotyped with allele-specific
oligonucleotides (8) and was homozygous for methionine at the polymorphic
codon 129. Subsequent direct DNA sequencing for the PrP gene open-reading
frame demonstrated normal sequence on both alleles, excluding known or novel
pathogenic PrP mutations.

It is tempting to speculate that prions were transmitted to this patient
from sheep or human dura mater through small lacerations of his skin, but
the patient and his wife did not remember any significant injury during his
four years of working with these samples. It cannot be excluded that this
was a case of sporadic CJD although this assumption is unlikely in view of
the clinical course which was similar to iatrogenic CJD transmitted by
peripheral inoculation, such as with human pituitary growth hormone or
gonadotropin or to kuru (1). Iatrogenic cases resulting from intracerebral
inoculation with the transmissible agent, for instance following dura mater
grafts (2-5), present with a dementing picture, as is usual in sporadic CJD,
rather than with ataxia as in this case.


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