Subject: Opinion of the Scientific Panel BIOHAZ: Protocol for the evaluation
of rapid post mortem tests to detect TSE in small ruminants [1]
Date: June 25, 2007 at 11:21 am PST
Opinion of the Scientific Panel BIOHAZ: Protocol for the evaluation of rapid
post mortem tests to detect TSE in small ruminants [1]
Last updated: 22 June 2007 Publication Date: 22 June 2007
Adopted on 7 June 2007. (Question N° EFSA-Q-2007-055)
Summary
Annex X to Regulation (EC) No 999/2001 lays down rules for the prevention,
control and eradication of certain transmissible spongiform encephalopathies
and lists the approved rapid tests which may be used within the framework of
the EU monitoring programmes. The approval of these tests was based on SSC
and EFSA evaluation protocols and its recommendations on the suitability or
otherwise of the evaluated tests for inclusion in the EU programme for TSE
monitoring.
The EC will now launch a new open call for expressions of interest, for
rapid tests for use in the framework of TSE monitoring. This call is
intended to cover tests for TSE detection ante- and post-mortem in cattle
and sheep and goats. Evaluation of these tests is based on a protocol
developed by TSE testing experts and covers different steps including a
pre-assessment, an assessment of the application dossier, a laboratory
evaluation, approval of the package insert and a field trial. EFSA was asked
by the EC to revise and update the three current protocols for the
evaluation of TSE tests in ruminants taking into account the experience
gained in past evaluation rounds.
This opinion reports on the revised protocol for the evaluation of post
mortem TSE tests in small ruminants.
In 2003 the European Commission (EC) (DG SANCO and DG JRC and its IRMM) and
EFSA, started evaluation of rapid tests for TSE epidemio-surveillance in
small ruminants. During the previous evaluation process, differences were
observed between tests in terms of analytical sensitivity. However, the
significance of such differences both in term of field diagnostic
sensitivity and biological relevance could not be scientifically assessed at
the time of evaluation. Moreover, following the implementation of active
surveillance programs in the EU using tests that were validated, a new type
of TSE (atypical scrapie cases/NOR98) not previously recognized in the EU,
was detected in small ruminants. Currently atypical/Nor98 has been detected
in a large number of European countries and approximately constitutes 80% of
test positive cases identified in EU. Data collected in this EU active
surveillance program clearly indicate that all the validated tests do not
perform equally toward atypical cases and that difference in performance
result in under- or non recognition of various types of scrapie.
The EFSA Scientific Panel on Biological Hazards (BIOHAZ) has agreed on a
revised evaluation protocol which takes into account the experience gained
in past evaluation rounds and knowledge accumulated from the active
surveillance program. New tests have to successfully pass all stages of the
evaluation process. Progress to the next stage requires successful
completion of the previous stage and therefore the process can be suspended
at any stage of the evaluation.
This protocol ensures that newly approved tests will not be inferior to
previously approved BSE post mortem screening tests. In addition to previous
evaluation criteria, the revised protocol considers each test's performance
with respect to (i) detection of classical scrapie, atypical scrapie and BSE
in sheep and (ii) detection of preclinical cases and (iii) limitations posed
by analytical sensitivity in comparison with bioassay. The criteria in this
revised protocol introduce more comprehensive and higher standards than have
previously been approved for validation of small ruminant post mortem TSE
tests for classical scrapie and BSE as well as for atypical scrapie.
Considering data available about abnormal PrP distribution in the three
recognized small ruminants TSE forms (BSE, classical scrapie and atypical
scrapie) the use of brainstem appears to be the best compromise for
detection of all TSE agents in small ruminants. In consequence, officially
confirmed (by CRL and NRL) positive/negative brainstem will be used for the
evaluation of tests.
The BIOHAZ panel recommends that tests already approved for the detection of
TSE in small ruminants should be required to participate in the new
evaluation in order to confirm their robustness and their ability to fulfil
the additional performance requirements (e.g. atypical cases and analytical
sensitivity). This re-iterates a recommendation of their recent Opinion on
the EU TSE Community Reference Laboratory report on batch testing of TSE
rapid tests: sample selection and test sensitivity issues[2] . It is further
recommended that tests that are not able to meet requirements for detection
of all types of TSE (classical scrapie, BSE and atypical scrapie) not be
considered for testing small ruminants in the field. Tests that fail to meet
a requirement in respect of a particular tissue type (lymphoid/CNS) should
not be recommended for application on that tissue. Finally, taking into
account the experience gained in the TSE test batch testing protocol and
because knowledge in the TSE field is rapidly evolving, the BIOHAZ panel
recommends that a system of periodic re-assessment of test approval based on
both test field performance and evolving EU policy objectives should be
considered by the Risk Managers.
____________________________
[1] For citation purposes: Scientific Opinion of the Panel on Biological
Hazards on a request from the European Commission on a protocol for the
evaluation of rapid post mortem tests to detect TSE in small ruminants. The
EFSA Journal (2007) 509, 1-31
[2] For citation purposes: Opinion of the Scientific Panel on Biological
Hazards on a request from the European Commission on the CRL report on batch
testing of TSE rapid tests: sample selection and test sensitivity issues,
The EFSA Journal (2007), 443, 1-18.
http://www.efsa.europa.eu/en/science/bi ... _smru.html
Opinion
http://www.efsa.europa.eu/etc/medialib/ ... mru_en.pdf
Summary
http://www.efsa.europa.eu/etc/medialib/ ... ary_en.pdf
Subject: NOR98-LIKE STRAIN OF SCRAPIE FOUND IN WYOMING
Date: April 11, 2007 at 12:47 pm PST
PRESS RELEASE
March 16, 2007
Wyoming Livestock Board
2020 Carey Avenue 4th Floor
Cheyenne, Wyoming 82002
For more information contact: Dr. Walter Cook at (307) 631-2974 [weekend] or
(307) 777-6443 [weekday]
*****FOR IMMEDIATE RELEASE*****
NOR98-LIKE STRAIN OF SCRAPIE FOUND IN WYOMING
CHEYENNE, Wyo. - On Friday, March 16, 2007, the Wyoming Livestock Board
(WLSB) was notified by officials of the USDA Animal Plant Health Inspection
Service (APHIS) that an adult female sheep had tested positive for a form of
scrapie consistent with the Nor98 strain. The ewe was slaughtered in
Michigan, where it was tested as part of USDA's regulatory scrapie slaughter
surveillance program and traced back to a flock in Wyoming. The results of
this case are distinctly different from those seen for bovine spongiform
encephalopathy (BSE) or classical scrapie.
Scrapie is a transmissible spongiform encephalopathy and falls into the same
category of diseases as chronic wasting disease, found in deer and elk, and
bovine spongiform encephalopathy, found in cattle. The disease is limited to
sheep and goats and takes years to affect an animal after it has been
infected. Scrapie causes sheep to itch and scratch (scrape) wool off, change
their behavior and lose body condition; it ultimately ends in death.
Nor98-like scrapie differs from classical scrapie in the distribution of
brain lesions and in the course of disease progression and epidemiology.
Some sheep that are genetically resistant to the classic form of the disease
may be susceptible to the Nor98-like strain. Oddly, Nor98-like scrapie is
usually diagnosed during surveillance in animals without clinical signs.
There are no known human health risks associated with either form of
scrapie.
This is the first time a Nor98-like strain of scrapie has been documented in
the United States. It gets the "Nor98-like" name because it is similar to a
case first diagnosed in Norway in 1998. This strain of scrapie is a rare
disease even in Europe. Since 1998, fewer than 300 cases have been diagnosed
in all of Europe. It is usually seen in single animals and does not tend to
become widespread in a flock. In contrast, in flocks infected by classical
scrapie typically more than 10 percent of the genetically susceptible
animals test positive.
"This provides evidence that the surveillance program is working," said
Bryce Reece, executive director of the Wyoming Wool Growers Association. "It
also indicates that the program is on the cutting-edge of science to detect
such a rare disease during standard surveillance."
The Wyoming Livestock Board does not expect the Nor98-like strain of scrapie
to become a major disease problem for the sheep industry in Wyoming. Risk is
limited because diagnosis of Nor98-like scrapie is usually an incidental
event, with even highly-exposed flock mates of the positive animal normally
unaffected.
The infected ewe lambed in it in what is considered a low-risk,
range-lambing environment. Nonetheless, the WLSB, APHIS and the Wyoming Wool
Growers Association plan to assertively pursue this case to make sure that
this strain of scrapie is extinguished and does not establish itself in the
U.S.
The agencies continue to encourage producers to monitor their sheep for
signs of scrapie and other diseases, and to notify their veterinarian if
they discover anything unusual.
The positive ewe was purchased as an adult within the last several years and
moved to a Wyoming flock near the Black Hills. The producer was notified and
his flock quarantined as a precautionary measure. An epidemiologic
investigation is ongoing and the producer has been cooperative. The case
fits the pattern found in Europe - a single, older sheep that was not
exhibiting clinical signs of scrapie.
The regulatory scrapie slaughter surveillance program is a targeted
slaughter surveillance program for sheep and goats designed to identify
infected animals and flocks. USDA is conducting this surveillance as part of
a program to eradicate scrapie from the United States by the end of 2010.
Reece said that the sheep industry supports this program and is committed to
eliminating scrapie from the United States.
###
http://wlsb.state.wy.us/NewReleases/07M ... ESSRLS.pdf
SCRAPIE UPDATE USA AS OF MARCH 2007 NOR98 INCLUDED
http://www.aphis.usda.gov/animal_health ... ie_rpt.pps
NOR98-LIKE STRAIN OF SCRAPIE FOUND IN WYOMING (1791 lines)
From: Terry S. Singeltary Sr. <[log in to unmask]>
Date: Wed, 11 Apr 2007 15:08:15 -0500
http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... T=0&P=8315
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]
http://www.pnas.org/cgi/doi/10.1073/pnas.0502296102
http://www.pnas.org/cgi/content/abstract/0502296102v1
TSS
of rapid post mortem tests to detect TSE in small ruminants [1]
Date: June 25, 2007 at 11:21 am PST
Opinion of the Scientific Panel BIOHAZ: Protocol for the evaluation of rapid
post mortem tests to detect TSE in small ruminants [1]
Last updated: 22 June 2007 Publication Date: 22 June 2007
Adopted on 7 June 2007. (Question N° EFSA-Q-2007-055)
Summary
Annex X to Regulation (EC) No 999/2001 lays down rules for the prevention,
control and eradication of certain transmissible spongiform encephalopathies
and lists the approved rapid tests which may be used within the framework of
the EU monitoring programmes. The approval of these tests was based on SSC
and EFSA evaluation protocols and its recommendations on the suitability or
otherwise of the evaluated tests for inclusion in the EU programme for TSE
monitoring.
The EC will now launch a new open call for expressions of interest, for
rapid tests for use in the framework of TSE monitoring. This call is
intended to cover tests for TSE detection ante- and post-mortem in cattle
and sheep and goats. Evaluation of these tests is based on a protocol
developed by TSE testing experts and covers different steps including a
pre-assessment, an assessment of the application dossier, a laboratory
evaluation, approval of the package insert and a field trial. EFSA was asked
by the EC to revise and update the three current protocols for the
evaluation of TSE tests in ruminants taking into account the experience
gained in past evaluation rounds.
This opinion reports on the revised protocol for the evaluation of post
mortem TSE tests in small ruminants.
In 2003 the European Commission (EC) (DG SANCO and DG JRC and its IRMM) and
EFSA, started evaluation of rapid tests for TSE epidemio-surveillance in
small ruminants. During the previous evaluation process, differences were
observed between tests in terms of analytical sensitivity. However, the
significance of such differences both in term of field diagnostic
sensitivity and biological relevance could not be scientifically assessed at
the time of evaluation. Moreover, following the implementation of active
surveillance programs in the EU using tests that were validated, a new type
of TSE (atypical scrapie cases/NOR98) not previously recognized in the EU,
was detected in small ruminants. Currently atypical/Nor98 has been detected
in a large number of European countries and approximately constitutes 80% of
test positive cases identified in EU. Data collected in this EU active
surveillance program clearly indicate that all the validated tests do not
perform equally toward atypical cases and that difference in performance
result in under- or non recognition of various types of scrapie.
The EFSA Scientific Panel on Biological Hazards (BIOHAZ) has agreed on a
revised evaluation protocol which takes into account the experience gained
in past evaluation rounds and knowledge accumulated from the active
surveillance program. New tests have to successfully pass all stages of the
evaluation process. Progress to the next stage requires successful
completion of the previous stage and therefore the process can be suspended
at any stage of the evaluation.
This protocol ensures that newly approved tests will not be inferior to
previously approved BSE post mortem screening tests. In addition to previous
evaluation criteria, the revised protocol considers each test's performance
with respect to (i) detection of classical scrapie, atypical scrapie and BSE
in sheep and (ii) detection of preclinical cases and (iii) limitations posed
by analytical sensitivity in comparison with bioassay. The criteria in this
revised protocol introduce more comprehensive and higher standards than have
previously been approved for validation of small ruminant post mortem TSE
tests for classical scrapie and BSE as well as for atypical scrapie.
Considering data available about abnormal PrP distribution in the three
recognized small ruminants TSE forms (BSE, classical scrapie and atypical
scrapie) the use of brainstem appears to be the best compromise for
detection of all TSE agents in small ruminants. In consequence, officially
confirmed (by CRL and NRL) positive/negative brainstem will be used for the
evaluation of tests.
The BIOHAZ panel recommends that tests already approved for the detection of
TSE in small ruminants should be required to participate in the new
evaluation in order to confirm their robustness and their ability to fulfil
the additional performance requirements (e.g. atypical cases and analytical
sensitivity). This re-iterates a recommendation of their recent Opinion on
the EU TSE Community Reference Laboratory report on batch testing of TSE
rapid tests: sample selection and test sensitivity issues[2] . It is further
recommended that tests that are not able to meet requirements for detection
of all types of TSE (classical scrapie, BSE and atypical scrapie) not be
considered for testing small ruminants in the field. Tests that fail to meet
a requirement in respect of a particular tissue type (lymphoid/CNS) should
not be recommended for application on that tissue. Finally, taking into
account the experience gained in the TSE test batch testing protocol and
because knowledge in the TSE field is rapidly evolving, the BIOHAZ panel
recommends that a system of periodic re-assessment of test approval based on
both test field performance and evolving EU policy objectives should be
considered by the Risk Managers.
____________________________
[1] For citation purposes: Scientific Opinion of the Panel on Biological
Hazards on a request from the European Commission on a protocol for the
evaluation of rapid post mortem tests to detect TSE in small ruminants. The
EFSA Journal (2007) 509, 1-31
[2] For citation purposes: Opinion of the Scientific Panel on Biological
Hazards on a request from the European Commission on the CRL report on batch
testing of TSE rapid tests: sample selection and test sensitivity issues,
The EFSA Journal (2007), 443, 1-18.
http://www.efsa.europa.eu/en/science/bi ... _smru.html
Opinion
http://www.efsa.europa.eu/etc/medialib/ ... mru_en.pdf
Summary
http://www.efsa.europa.eu/etc/medialib/ ... ary_en.pdf
Subject: NOR98-LIKE STRAIN OF SCRAPIE FOUND IN WYOMING
Date: April 11, 2007 at 12:47 pm PST
PRESS RELEASE
March 16, 2007
Wyoming Livestock Board
2020 Carey Avenue 4th Floor
Cheyenne, Wyoming 82002
For more information contact: Dr. Walter Cook at (307) 631-2974 [weekend] or
(307) 777-6443 [weekday]
*****FOR IMMEDIATE RELEASE*****
NOR98-LIKE STRAIN OF SCRAPIE FOUND IN WYOMING
CHEYENNE, Wyo. - On Friday, March 16, 2007, the Wyoming Livestock Board
(WLSB) was notified by officials of the USDA Animal Plant Health Inspection
Service (APHIS) that an adult female sheep had tested positive for a form of
scrapie consistent with the Nor98 strain. The ewe was slaughtered in
Michigan, where it was tested as part of USDA's regulatory scrapie slaughter
surveillance program and traced back to a flock in Wyoming. The results of
this case are distinctly different from those seen for bovine spongiform
encephalopathy (BSE) or classical scrapie.
Scrapie is a transmissible spongiform encephalopathy and falls into the same
category of diseases as chronic wasting disease, found in deer and elk, and
bovine spongiform encephalopathy, found in cattle. The disease is limited to
sheep and goats and takes years to affect an animal after it has been
infected. Scrapie causes sheep to itch and scratch (scrape) wool off, change
their behavior and lose body condition; it ultimately ends in death.
Nor98-like scrapie differs from classical scrapie in the distribution of
brain lesions and in the course of disease progression and epidemiology.
Some sheep that are genetically resistant to the classic form of the disease
may be susceptible to the Nor98-like strain. Oddly, Nor98-like scrapie is
usually diagnosed during surveillance in animals without clinical signs.
There are no known human health risks associated with either form of
scrapie.
This is the first time a Nor98-like strain of scrapie has been documented in
the United States. It gets the "Nor98-like" name because it is similar to a
case first diagnosed in Norway in 1998. This strain of scrapie is a rare
disease even in Europe. Since 1998, fewer than 300 cases have been diagnosed
in all of Europe. It is usually seen in single animals and does not tend to
become widespread in a flock. In contrast, in flocks infected by classical
scrapie typically more than 10 percent of the genetically susceptible
animals test positive.
"This provides evidence that the surveillance program is working," said
Bryce Reece, executive director of the Wyoming Wool Growers Association. "It
also indicates that the program is on the cutting-edge of science to detect
such a rare disease during standard surveillance."
The Wyoming Livestock Board does not expect the Nor98-like strain of scrapie
to become a major disease problem for the sheep industry in Wyoming. Risk is
limited because diagnosis of Nor98-like scrapie is usually an incidental
event, with even highly-exposed flock mates of the positive animal normally
unaffected.
The infected ewe lambed in it in what is considered a low-risk,
range-lambing environment. Nonetheless, the WLSB, APHIS and the Wyoming Wool
Growers Association plan to assertively pursue this case to make sure that
this strain of scrapie is extinguished and does not establish itself in the
U.S.
The agencies continue to encourage producers to monitor their sheep for
signs of scrapie and other diseases, and to notify their veterinarian if
they discover anything unusual.
The positive ewe was purchased as an adult within the last several years and
moved to a Wyoming flock near the Black Hills. The producer was notified and
his flock quarantined as a precautionary measure. An epidemiologic
investigation is ongoing and the producer has been cooperative. The case
fits the pattern found in Europe - a single, older sheep that was not
exhibiting clinical signs of scrapie.
The regulatory scrapie slaughter surveillance program is a targeted
slaughter surveillance program for sheep and goats designed to identify
infected animals and flocks. USDA is conducting this surveillance as part of
a program to eradicate scrapie from the United States by the end of 2010.
Reece said that the sheep industry supports this program and is committed to
eliminating scrapie from the United States.
###
http://wlsb.state.wy.us/NewReleases/07M ... ESSRLS.pdf
SCRAPIE UPDATE USA AS OF MARCH 2007 NOR98 INCLUDED
http://www.aphis.usda.gov/animal_health ... ie_rpt.pps
NOR98-LIKE STRAIN OF SCRAPIE FOUND IN WYOMING (1791 lines)
From: Terry S. Singeltary Sr. <[log in to unmask]>
Date: Wed, 11 Apr 2007 15:08:15 -0500
http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... T=0&P=8315
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]
http://www.pnas.org/cgi/doi/10.1073/pnas.0502296102
http://www.pnas.org/cgi/content/abstract/0502296102v1
TSS
