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From: TSS ()
Subject: SEAC Food standards agency atypical scrapie contingency plan
Date: July 18, 2007 at 12:39 pm PST

Position Statement


Food standards agency atypical scrapie contingency plan
1. In June 2006 the Food Standards Agency (FSA) Board considered current precautionary risk management measures for small ruminants. The Board agreed that current precautionary measures were sufficient. However, they wished to develop a contingency plan in case SEAC’s understanding of the risk of atypical scrapie for human health changed. To inform this contingency plan the FSA requested SEAC advice on potential outcomes of research on atypical scrapie, or surveillance results, that may lead to a change in SEAC’s estimate of the risk to human health.

2. In February 2006 the SEAC sheep subgroup published a position statement on atypical scrapie1 which concluded that atypical scrapie should be considered a distinct transmissible spongiform encephalopathy (TSE) of small ruminants and not simply a variant of classical scrapie. While there was no evidence that atypical scrapie could infect humans, a theoretical risk could not be excluded. SEAC concluded, however, that there were insufficient data available to adequately assess the potential risks to human health. The subgroup recommended that an adequate assessment of the potential risk to human health of atypical scrapie might come from studies on the prevalence, transmission in animal models, tissue distribution and human health surveillance.

3. SEAC considered the potential significance of the outcomes of these areas of research for the human health risk from atypical scrapie, based on scenarios put forward by the FSA2.

4. The SEAC sheep subgroup statement concludes that there could be around 82,000 sheep in the UK infected with atypical scrapie. Future surveillance and epidemiological studies along with the analysis of sheep brain tissue samples dating back to 1964 may confirm the historical presence of the disease, changes in prevalence over time, and whether or not atypical scrapie may occur in countries previously thought to be free from classical and atypical scrapie. SEAC considered that the identification of historical cases, new cases in scrapie-free countries, and changes in prevalence of atypical scrapie would be significant from a public health perspective. If such data indicate that atypical scrapie has been present for many years, and is not increasing in prevalence then, by analogy with classical scrapie the human health risk would be considered low. However, if atypical scrapie were found to be spreading rapidly, this would imply it is a new disease and any human health risk would be more uncertain. It is therefore important to continue to assess the historic prevalence of atypical scrapie, and for archived sheep samples be analysed for the presence of the disease.

5. A human health risk would only be confirmed by concomitant changes in the prevalence of new types of Creutzfeldt-Jakob Disease (CJD). Because of the long incubation periods of prion diseases, such data may not become apparent for many years, although atypical scrapie has been identified in a UK sheep from 1989, implying that humans may have been exposed to atypical scrapie via the dietary route for a number of years. In the absence of data suggesting a link to a new type of CJD SEAC would be unlikely to change its current assessment of the human health risk.

Transmission studies
6. Results from transmission studies using non-human primates, particularly via the oral route, would strongly inform the understanding of human health risk. The immune and lymphoreticular systems of non-human primates are closely related to those of humans and the peripheral pathogenesis of TSEs in non-human primates mimics that in humans. However, non-human primates only provide data relating to one genotype, MM, which comprises about 37% of the UK population3. Assessment of the level of risk would require comparison with transmissions of other TSEs in the same models, in particular BSE, some of which are already available.

7. Humanised mice can provide data on all three human prion protein genotypes. It is important to be aware of the possibility that such mice may not show any clinical sign of infection after primary transmission of atypical scrapie, yet a secondary transmission from these animals to others may result in clinical disease due to loss of the interspecies transmission barrier. Although humanised mice are a good model for human disease, it will be critical to compare the behaviour of atypical scrapie with other TSEs, especially classical scrapie and BSE, in several mouse models after secondary transmission in order to obtain the most reliable risk assessments.

8. The barrier to transmission of atypical scrapie between animal and human can be tested in vitro by cell free conversion assays. However, care is needed in interpreting the significance of such experiments as ex vivo data do not always correlate well with in vivo studies. Nevertheless, they could provide data on whether conversion of the normal prion protein in humans to the abnormal form by the atypical scrapie prion is or is not possible.

Tissue Distribution
9. Little is known about the tissue distribution of abnormal prion protein (PrPsc) and infectivity in sheep with atypical scrapie. If atypical scrapie is found to be a health risk to humans, data from studies to assess the tissue distribution of PrPsc and infectivity are essential to allow an assessment of the risk under specific control measures.

Human Health
10. Establishing a definitive link between an animal and a human TSE is extremely difficult. Animal model data will only be indicative, and not definitive, although if carried out appropriately could be strongly indicative of a human health risk. The emergence of a new type of CJD which shows the same transmission characteristics as atypical scrapie in non-human primates and humanised mice would provide a strong indication that transmission had occurred through the consumption of infected material. Thus, ongoing human surveillance is critical.

11. It is difficult to conclude that atypical scrapie is not a human health risk from negative experimental or surveillance results. However, negative results from current and retrospective surveillance and transmission studies, over a significant period of time to allow for possibly long incubation periods, would imply a negligible human health risk.

12. It is not possible to assess the human health risk from atypical scrapie, or changes in risk, in the absence of hard scientific data. No single data set is likely to be definitive and it would be essential to consider all the information available, rather than data from single studies in isolation. Studies comparing the properties of atypical scrapie and other TSE agents using the same animal model, especially humanised mice or non-human primates, would be most informative in the short term. Surveillance data to assess any association between forms of CJD and atypical scrapie prevalence would be most persuasive but are unlikely to become available in the short term. SEAC would have to review experimental methods and results, should they emerge, before any conclusion of a change to the risk to human health from atypical scrapie could be made.

1 (97 KB)
2 (110 KB)
3 Palmer and Collinge (1993) Mutations and polymorphisms in the prion protein gene. Hum. Mutat. 2, 168-173.

Page updated: 16 July, 2007

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:

Published online before print March 20, 2001
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.041490898

Adaptation of the bovine spongiform encephalopathy agent to primates and
comparison with Creutzfeldt- Jakob disease: Implications for human health
Corinne Ida Lasmézas*, [dagger] , Jean-Guy Fournier*, Virginie Nouvel*,
Hermann Boe*, Domíníque Marcé*, François Lamoury*, Nicolas Kopp [Dagger
] , Jean-Jacques Hauw§, James Ironside¶, Moira Bruce [||] , Dominique
Dormont*, and Jean-Philippe Deslys*

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)


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.


The recognition of a variant of the human transmissible spongiform
encephalopathy (TSE) Creutzfeldt-Jakob Disease (vCJD) in the U.K. in
1996 raised the major concern that it would correspond to human
infection with the agent responsible for bovine spongiform
encephalopathy (BSE; ref. 1). Transmission of BSE to macaques provided
the first experimental evidence as it produced a disease close to vCJD
in humans (2). Strain typing in inbred mice (consisting of measuring the
incubation period and establishing lesion profiles corresponding to the
strain-specific distribution of brain vacuolation) allows reliable
identification of TSE strains (3). This method, together with
biochemical methods, has revealed a single phenotype for the agents of
BSE and the British cases of vCJD (4-6). Mice expressing only the bovine
prion protein (PrP) were highly susceptible to vCJD and BSE, which
induced the same disease (7). Thus, it is now well established that BSE
has caused vCJD, probably by alimentary contamination. In this respect,
the finding of abnormal PrP labeling in the gastrointestinal tract and
lymphatic tissues of orally BSE-contaminated lemurs shows that the BSE
agent can infect primates by the oral route (8). About 1 million
contaminated cattle may have entered the human food chain, and the
future number of vCJD cases could range from 63 to 136,000 depending on
the incubation period of BSE in humans (9). Unlike sporadic CJD (sCJD)
and iatrogenic CJD (iCJD) linked to the administration of contaminated
growth hormone extracted from human hypophyses, in vCJD, the infectious
agent seems to be widely distributed in lymphoid organs, as pathological
PrP (PrPres) can be detected in tonsils, lymph nodes, spleen, and
appendix even in the preclinical phase of the disease (10, 11). This
raises a public health issue with regard to the risk of iatrogenic
transmission of vCJD through surgical instruments, grafts, blood
transfusion, or parenteral administration of biological products of
human origin. However, this risk is difficult to assess, because it
largely depends on factors such as the virulence of the BSE agent
adapted to primates and the efficiency of secondary transmission to
humans by a peripheral route such as the i.v. one. A further issue is
whether vCJD accidentally acquired from humans would be recognized. The
latter poses the question of a phenotypic variation of the BSE agent
after successive transmissions in humans: does it retain its strain
characteristics, and does it induce a pathology similar to that observed
in the previous host? A 9-year history of transmission of BSE to
primates and mice enables us today to clarify a number of these
important points.

Although BSE has mainly affected the U.K., two definite cases and one
probable case of vCJD have now been reported in France in people who
have never resided in the U.K. (12, 13). We strain-typed the first of
these cases to establish its origin. Strain typing in C57BL/6 mice of
BSE, French, and British vCJD was compared with that of BSE passaged in
nonhuman primates, thus allowing us to study the effect of serial
passages in primates. Comparisons were also made with French cases of
sCJD and iCJD and two strains of scrapie (one of French and one of U.S.
origin). Our findings provide experimental demonstration that the same
agent, namely that responsible for the cattle disease BSE, has caused
vCJD both in France and in the U.K., in line with biochemical data and
with the fact that, until 1996, about 10% of the beef consumed in France
was imported from the U.K. We found that the BSE agent in nonhuman
primates is similar to that causing vCJD in humans and tends to evolve
rapidly toward a primate-adapted variant. Furthermore, we showed that
the strain responsible for iCJD is closely related to that of one
patient with sCJD, and, more unexpectedly, that these agents were
similar to the French scrapie strain studied (but different from the
U.S. scrapie strain). This finding requires a cautious interpretation
for several reasons, not least because of the inevitably limited number
of TSE strains that can be studied by such a cumbersome method as strain
typing. Nonetheless, it also prompts reconsideration of the possibility
that, in some instances, sheep and human TSEs can share a common origin.


ISSUED 13/05/1999


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.
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: Received June 7, 2000;
revised July 3, 2000; accepted July 5, 2000.


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.


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.


Scrapie to Humans?

Neuroepidemiology. 1985;4(4):240-9. Related Articles, Links

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.

Date: May 9, 2007 at 6:43 pm PST

SCRAPIE UPDATE USA AS OF MARCH 2007 Atypical NOR98 now documented

Draft open minutes of the 97th meeting held on 10th May 2007


24. Question one related to changes in the prevalence of atypical
scrapie. Members considered that changes in prevalence would
be most significant if concomitant changes occurred in the
prevalence of new types of CJD cases. However, it was
acknowledged that, because of the long incubation periods of prion
diseases, such changes may take years or even decades to
emerge. Surveillance should continue so that any changes in
prevalence of CJD types can be detected.
25. Question two related to the implications of finding atypical scrapie
in countries previously thought to be free from classical and
atypical scrapie. Members noted that in the absence of any data
which suggests a link between types of CJD and atypical scrapie
such a scenario would not change the assessment of risk.
26. Question three related to the perception of risk should atypical
scrapie be found to have a similar epidemiology to classical
scrapie. Members responded that if historic data show the disease
had been around for many years this may suggest the risk was
low, however the long incubation period of human prion diseases
© SEAC 2006
made it impossible to draw firm conclusions at this time. It was
noted that the earliest atypical scrapie case identified was from
1989 highlighting that this is not a very new disease. Members
considered it important to continue to assess the prevalence of
atypical scrapie and that historic sheep samples be analysed for
the presence of atypical scrapie.

Dr Matthews noted that atypical
scrapie had now been found in the United States of America.

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.


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. ...end
(from full text study pdf...TSS)

PMID: 6997404


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.

Office Note


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

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

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



1997 TO 2006. SPORADIC CJD CASES TRIPLED, with phenotype
of 'UNKNOWN' strain growing. ...

There is a growing number of human CJD cases, and they were presented last
week in San Francisco by Luigi Gambatti(?) from his CJD surveillance

He estimates that it may be up to 14 or 15 persons which display selectively
SPRPSC and practically no detected RPRPSC proteins.

From: Terry S. Singeltary Sr. <[log in to unmask]>
Date: Tue, 10 Jul 2007 15:56:51 -0500

From: Terry S. Singeltary Sr. <[log in to unmask]>
Date: Wed, 11 Jul 2007 16:36:17 -0500


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