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CDC WAKES UP AND SMELLS USDA BSe ... TSS

flounder

Well-known member
##################### Bovine Spongiform Encephalopathy #####################

Subject: Transmission of New Bovine Prion to Mice
Date: July 6, 2006 at 1:18 pm PST
Transmission of

New Bovine Prion

to Mice

Thierry G.M. Baron,* Anne-Gaëlle Biacabe,*

Anna Bencsik,* and Jan P.M. Langeveld†

We previously reported that cattle were affected by a

prion disorder that differed from bovine spongiform

encephalopathy (BSE) by showing distinct molecular features

of disease-associated protease-resistant prion protein

(PrPres). We show that intracerebral injection of such

isolates into C57BL/6 mice produces a disease with preservation

of PrPres molecular features distinct from BSE.

Until recently, transmissible spongiform encephalopathy

(TSE) in cattle was believed to be caused by a single

strain of infectious agent identified at the beginning of

a foodborne epidemic of bovine spongiform encephalopathy

(BSE). Characterization of the infectious agent associated

with BSE showed unique features. These include

defined incubation periods and distribution of brain lesions

after transmission to wild-type mice, not only directly

from cattle, but also after natural or experimentally

induced cross-species transmission (1,2). The uniform features

of the disease in cattle have also been shown by

analysis of the distribution of neurodegenerative brain

lesions at different places during the BSE epidemic (3,4).

Western blot analyses of protease-resistant prion protein

(PrPres) accumulating in the brains of animals and

humans with BSE have demonstrated specific molecular

features. These include a low molecular mass of unglycosylated

PrPres with high proportions of diglycosylated

PrPres (5,6). However, recent studies reported cases of

prion abnormalities in cattle with different PrPres features

(7,8). Three cattle isolates from France have been reported,

characterized by a higher apparent molecular mass of

unglycosylated PrPres (H-type isolates) and decreased levels

of diglycosylated PrPres when compared with BSE isolates

(7). In addition. only PrPres from H-type isolates were

labeled by monoclonal antibody P4 with defined PrPres N

terminus epitope specificity, in contrast with PrPres from

BSE isolates, which suggests a different cleavage by proteinase

K of the disease-associated protein (9).

Twenty years after identification of the BSE epidemic

in cattle, the origin of the BSE agent remains controversial

(10,11). Researchers have often considered the most

likely source to be a recycled infectious agent derived

from prion-associated diseases found in other species,

such as scrapie in sheep and goats. The recent description

of unusual phenotypes of bovine prion diseases distinct

from BSE is therefore puzzling (7). This situation has

been reinforced by a second bovine amyloidotic spongiform

encephalopathy found in cattle in Italy (8). However,

whether such cases of bovine prion disorders were transmissible,

and to what extent the infectious agent caused

specific features distinct from BSE, have not been

demonstrated.

The Study

Experimental groups of 20 (4- to 6-week old) C57BL/6

female mice (Charles River, L’Arbresle, France) were

injected intracerebrally with 20 µL of 10% (weight/volume)

homogenates per mouse prepared from brain stem

samples of 3 cattle TSE isolates. Two of the isolates were

characterized, as previously described (7), by a higher

molecular mass of unglycosylated PrPres (H-type isolates)

and labeling with P4 monoclonal antibody (Table). A typical

cattle BSE isolate was also analyzed. Mice were

housed and cared for in an appropriate biohazard prevention

area (A3) according to European (directive

86/609/EEC) and French ethical committee (decree

87–848) guidelines. Mice were checked at least weekly for

neurologic clinical signs and were killed when they exhibited

signs of distress or confirmed evolution of clinical

signs. The whole brain of every second mouse was frozen

and stored at –80°C before Western blot analysis. The

other brains were fixed in 4% paraformaldehyde for other

histopathologic studies.

Frozen mouse brain tissues and fixed brain tissues were

examined by Western blot analysis and immunohistochemical

tests as previously described (12,13). PrPres extracted

from half of whole brain was detected with monoclonal

antibodies Sha31 (1:10 from TeSeE sheep/goat Western

blot, Bio-Rad, Hercules, CA, USA) (14) and (340 ng/mL)

(15). These antibodies are directed against the 144-

WEDRYYRE-151 and 88-WGQGG-92 murine amino

acid PrP sequences, respectively. Antibody 12B2, which

has an N-terminal specificity similar to that of monoclonal

antibody P4, shows poor binding to BSE-derived PrPres,

but unlike P4, binds with high affinity to prion protein

from most mammalian species, including mice and cattle.

Bound antibodies were detected by using enhanced enzymatic

chemiluminescence (Amersham, Little Chalfont,

UK) or Supersignal (Pierce, Rockford, IL, USA) and visualized

either on film (Biomax, Eastman Kodak, Rochester,

NY, USA) or directly in an image analysis system

(Versadoc, Bio-Rad). Molecular masses of PrPres glycoforms

were determined as the average of the center positions

of the bands from at least 3 repeated electrophoretic

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 12, No. 7, July 2006 1125

*Agence Française de Sécurité Sanitaire des Aliments, Lyon,

France; and †Central Institute for Animal Disease Control,

Lelystad, the Netherlands

procedures, as measured by comparison with a biotinylated

marker (B2787, Sigma, Saint Louis, MO, USA)

included on each gel. Immunologic reactivities of antibodies

12B2 and Sha31 were compared in Western blots run in

parallel with the same samples with both antibodies.

After intracerebral injection of cattle brain samples into

C57BL/6 mice, disease was observed in mice with the 2 Htype

isolates, as well as with the BSE sample. Survival

periods of mice and results of PrPres detection among mice

analyzed by Western blot are shown in the Table.

Western blot analysis of PrPres from H-type–infected

mouse brains in comparison with BSE-infected mice is

shown in Figure 1. All positive mice in the same experimental

group showed the same Western blot pattern. This

pattern showed higher molecular mass PrPres glycoforms in

mice infected with H-type isolates than in mice infected

with a typical BSE agent (1.1- to 1.5-Da difference in the

unglycosylated PrPres (Figure 1A). Studies of PrPres protease

cleavage showed that only the PrPres of mice infected

with H-type isolates was recognized by antibody 12B2

(Figure 1B). This finding is in contrast to the result

obtained with monoclonal antibody Sha31 directed against

an epitope in the central region of the protein, which

showed that the 12B2 epitope was preserved in Htype–

infected mice. Thus, the molecular features of H-type

cattle isolates, which are distinct from those of the BSE

agent, were maintained after development of disease in

mice.

Histopathologic analysis showed vacuolar lesions in

the thalamus (Figure 2A) that were absent from the hypothalamus,

cochlear nucleus, and superior collicules. These

3 neuroanatomic sites were severely affected in C57BL/6

mice brain after primary passage of the BSE agent, as we

and others have reported (1). Abnormal PrP was detected

only in amyloid plaques (Figure 2B), in contrast to what

was reported after BSE transmission in C57BL/6 mice (1).

Conclusions

Our data show that the recently identified bovine Htype

isolates involve an infectious agent that can induce

development of a disease across a species barrier, while

maintaining the specific associated PrPres molecular signature.

This evidence in favor of a new bovine prion strain in

cattle suggests that BSE is not the only transmissible prion

disease in cattle. The origin of such cases has not been

determined (7). These cases suggest either the existence of

alternative origins of such diseases in cattle or phenotypic

changes of PrPres after infection with the BSE agent.

However, based on analysis of molecular features of prion

diseases in cattle, this situation is similar to that in humans

(5), in which different subtypes of sporadic Creutzfeldt-

Jakob disease agents are found.

DISPATCHES

1126 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 12, No. 7, July 2006

Figure 1. Western blot analysis of disease-associated prion protein

(PrPres) from proteinase K–treated brain homogenates of

C57BL/6 mice infected with type H (lanes 2 and 4) or bovine

spongiform encephalopathy isolates (lanes 3 and 5). PrPres of mice

infected with an experimental scrapie strain (C506M3) (6) was

used as a control (lane 1). Monoclonal antibodies used for detection

of PrPres were Sha31 in panel A and 12B2 in panel B. Lane M,

molecular mass markers: 39.8, 29, 20.1, and 14.3 kDa.

Acknowledgments

We thank Jérémy Verchère and Dominique Canal for excellent

technical assistance, Emilie Antier and Clément Lavigne for

performing animal experiments, and Karel Riepema, Esther de

Jong, and Jorg Jacobs for production and characterization of

monoclonal antibody 12B2.

This study was supported by the Agence Française de

Sécurité Sanitaire des Aliments, the Neuroprion Network of

Excellence (FOOD-CT-2004-506579) (EUROSTRAINS project),

the Dutch Ministry of Agriculture, Environmental

Management and Food (8041869000), and NeuroPrion (FOODCT-

2004-506579)(STOPPrions project).

Dr Baron is head of the Unité Agents Transmissibles Non

Conventionnels, Agence Française de Sécurité Sanitaire des

Aliments, in Lyon. His research focuses on diagnosis of prion

diseases of ruminants and characterization of the disease-associated

prion protein and infectious agents, with particular emphasis

on atypical forms of these diseases.

References

1. Fraser H, Bruce ME, Chree A, McConnell I, Wells GA. Transmission

of bovine spongiform encephalopathy and scrapie to mice. J Gen

Virol. 1992;73:1891–7.

2. Green R, Horrocks C, Wilkinson A, Hawkins SA, Ryder SJ. Primary

isolation of the bovine spongiform encephalopathy agent in mice:

agent definition based on a review of 150 transmissions. J Comp

Pathol. 2005;132:117–31.

3. Simmons MM, Harris P, Jeffrey M, Meek SC, Blamire IW, Wells GA.

BSE in Great Britain: consistency of the neurohistopathological findings

in two random annual samples of clinically suspect cases. Vet

Rec. 1996;138:175–7.

4. Orge L, Simas JP, Fernandes AC, Ramos M, Galo A. Similarity of the

lesion profile of BSE in Portuguese cattle to that described in British

cattle. Vet Rec. 2000;147:486–8.

5. Collinge J, Sidle KC, Meads J, Ironside J, Hill AF. Molecular analysis

of prion strain variation and the aetiology of ‘new variant’ CJD.

Nature. 1996;383:685–90.

6. Baron TG, Biacabe A-G. Molecular analysis of the abnormal prion

protein during coinfection of mice by bovine spongiform

encephalopathy and a scrapie agent. J Virol. 2001;75:107–14.

7. Biacabe A-G, Laplanche J-L, Baron L, Ryder SJ. Distinct molecular

phenotypes in bovine prion diseases. EMBO Rep. 2004;5:110–4.

8. Casalone C, Zanusso G, Acutis P, Ferrari S, Capucci L, Tagliavini F,

et al. Identification of a second bovine amyloidotic spongiform

encephalopathy: molecular similarities with sporadic Creutzfeldt-

Jakob disease. Proc Natl Acad Sci U S A. 2004;101:3065–70.

9. Thuring CM, Erkens JH, Jacobs JG, Bossers JG, van Keulen LJ,

Garssen GJ, et al. Discrimination between scrapie and bovine spongiform

encephalopathy in sheep by molecular size immunoreactivity

and glycoprofile of prion protein. J Clin Microbiol. 2004;42:972–80.

10. Marsh RF. Bovine spongiform encephalopathy: a new disease of cattle?

Arch Virol Suppl. 1993;7:255–9.

11. European Commission. Opinion on: hypotheses on the origin and

transmission of BSE. Brussels: EC Health and Consumer Protection

Directorate General; 2001. p. 1–67.

Transmission of New Bovine Prion to Mice

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 12, No. 7, July 2006 1127

Figure 2. Histopathologic analysis of brain of a C57BL/6 mouse

infected with a type H isolate. A) Characteristic vacuolar lesions in

the thalamus (hematoxylin and eosin stained, scale bar = 60 µm).

B) Immunohistochemical analysis of prion protein with monoclonal

antibody 12B2 (diluted 1:200) shows the absence of granular

deposition, but the presence of plaques in the thalamus. The inset

shows that plaques are amyloids since they bind Congo red and

show birefringence in polarized light (scale bar = 60 µm, scale bar

in inset = 16 µm).

12. Baron T, Crozet C, Biacabe A-G, Philippe S, Verchère J, Bencsik A,

et al. Molecular analysis of the protease-resistant prion protein in

scrapie and bovine spongiform encephalopathy transmitted to ovine

transgenic and wild-type mice. J Virol. 2004;78:6243–51.

13. Bencsik AA, Debeer S, Baron T. An alternative pretreatment procedure

in animal transmissible spongiform encephalopathies diagnosis

using PrPsc immunohistochemistry. J Histochem Cytochem.

2005;53:1199–202.

14. Feraudet C, Morel N, Simon S, Volland H, Frobert Y, Créminon C, et

al. Screening of 145 anti-PrP monoclonal antibodies for their capacity

to inhibit PrPsc replication in infected cells. J Biol Chem.

2005;280:11247–58.

15. Yull HM, Ritchie DL, Langeveld JP, van Zijderveld FG, Bruce ME,

Ironside JW, et al. Detection of type 1 prion protein in variant

Creutzfeldt-Jakob disease. Am J Pathol. 2006;168:151–7.

Address for correspondence: Thierry G.M. Baron, Unité Agents

Transmissibles Non Conventionnels, Agence Française de Sécurité

Sanitaire des Aliments, 31 Ave Tony Garnier, 69364 Lyon CEDEX 07,

France; email: [email protected]


http://www.cdc.gov/ncidod/EID/vol12no07/pdfs/vol12no07.pdf


Medical Sciences
Identification of a second bovine amyloidotic spongiform encephalopathy: Molecular similarities with sporadic Creutzfeldt-Jakob disease

Cristina Casalone *, Gianluigi Zanusso , Pierluigi Acutis *, Sergio Ferrari , Lorenzo Capucci , Fabrizio Tagliavini ¶, Salvatore Monaco ||, and Maria Caramelli *
*Centro di Referenza Nazionale per le Encefalopatie Animali, Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, Via Bologna, 148, 10195 Turin, Italy; Department of Neurological and Visual Science, Section of Clinical Neurology, Policlinico G.B. Rossi, Piazzale L.A. Scuro, 10, 37134 Verona, Italy; Istituto Zooprofilattico Sperimentale della Lombardia ed Emilia Romagna, Via Bianchi, 9, 25124 Brescia, Italy; and ¶Istituto Nazionale Neurologico "Carlo Besta," Via Celoria 11, 20133 Milan, Italy


Edited by Stanley B. Prusiner, University of California, San Francisco, CA, and approved December 23, 2003 (received for review September 9, 2003)

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are mammalian neurodegenerative disorders characterized by a posttranslational conversion and brain accumulation of an insoluble, protease-resistant isoform (PrPSc) of the host-encoded cellular prion protein (PrPC). Human and animal TSE agents exist as different phenotypes that can be biochemically differentiated on the basis of the molecular mass of the protease-resistant PrPSc fragments and the degree of glycosylation. Epidemiological, molecular, and transmission studies strongly suggest that the single strain of agent responsible for bovine spongiform encephalopathy (BSE) has infected humans, causing variant Creutzfeldt-Jakob disease. The unprecedented biological properties of the BSE agent, which circumvents the so-called "species barrier" between cattle and humans and adapts to different mammalian species, has raised considerable concern for human health. To date, it is unknown whether more than one strain might be responsible for cattle TSE or whether the BSE agent undergoes phenotypic variation after natural transmission. Here we provide evidence of a second cattle TSE. The disorder was pathologically characterized by the presence of PrP-immunopositive amyloid plaques, as opposed to the lack of amyloid deposition in typical BSE cases, and by a different pattern of regional distribution and topology of brain PrPSc accumulation. In addition, Western blot analysis showed a PrPSc type with predominance of the low molecular mass glycoform and a protease-resistant fragment of lower molecular mass than BSE-PrPSc. Strikingly, the molecular signature of this previously undescribed bovine PrPSc was similar to that encountered in a distinct subtype of sporadic Creutzfeldt-Jakob disease.


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

C.C. and G.Z. contributed equally to this work.

||To whom correspondence should be addressed.

E-mail: [email protected]
www.pnas.org/cgi/doi/10.1073/pnas.0305777101


http://www.pnas.org/cgi/content/abstract/0305777101v1




TSS

#################### https://lists.aegee.org/bse-l.html ####################
 

flounder

Well-known member
##################### Bovine Spongiform Encephalopathy #####################

USDA 2004 ENHANCED BSE SURVEILLANCE PROGRAM AND HOW NOT TO FIND BSE CASES
(OFFICIAL DRAFT OIG REPORT)

snip...

CATTLE With CNS Symptoms Were NOT Always Tested

snip...

Between FYs 2002 and 2004, FSIS condemned 680 cattle of all ages due to CNS
symptoms. About 357 of these could be classified as adult. We could validate
that ONLY 162 were tested for BSE (per APHIS records. ...

snip...

WE interviewed officials at five laboratories that test for rabies. Those
officials CONFIRMED THEY ARE NOT REQUIRED TO SUBMIT RABIES-NEGATIVE SAMPLES
TO APHIS FOR BSE TESTING. A South Dakota laboratory official said they were
not aware they could submit rabies-negative samples to APHIS for BSE
testing. A laboratory official in another State said all rabies-negative
cases were not submitted to APHIS because BSE was ''NOT ON THEIR RADAR
SCREEN." Officials from New York, Wisconsin, TEXAS, and Iowa advised they
would NOT submit samples from animals they consider too young. Four of the
five States contacted defined this age as 24 months; Wisconsin defined it as
30 months. TEXAS officials also advised that they do not always have
sufficient tissue remaining to submit a BSE sample. ...

snip...

FULL TEXT 54 PAGES OF HOW NOT TO FIND BSE IN USA ;

http://www.house.gov/reform/min/pdfs_108_2/pdfs_inves/pdf_food_usda_mad_cow_july_13_ig_rep.pdf

HUMAN TSE USA 2005

Animal Prion Diseases Relevant to Humans (unknown types?)
Thu Oct 27, 2005 12:05
71.248.128.109

About Human Prion Diseases /
Animal Prion Diseases Relevant to Humans

Bovine Spongiform Encephalopathy (BSE) is a prion
disease of cattle. Since 1986, when BSE was recognized,
over 180,000 cattle in the UK have developed the
disease, and approximately one to three million are
likely to have been infected with the BSE agent, most
of which were slaughtered for human consumption before
developing signs of the disease. The origin of the
first case of BSE is unknown, but the epidemic was
caused by the recycling of processed waste parts of
cattle, some of which were infected with the BSE agent
and given to other cattle in feed. Control measures
have resulted in the consistent decline of the epidemic
in the UK since 1992. Infected cattle and feed exported
from the UK have resulted in smaller epidemics in other
European countries, where control measures were applied
later.

Compelling evidence indicates that BSE can be
transmitted to humans through the consumption of prion
contaminated meat. BSE-infected individuals eventually
develop vCJD with an incubation time believed to be on
average 10 years. As of November 2004, three cases of
BSE have been reported in North America. One had been
imported to Canada from the UK, one was grown in
Canada, and one discovered in the USA but of Canadian
origin. There has been only one case of vCJD reported
in the USA, but the patient most likely acquired the
disease in the United Kingdom. If current control
measures intended to protect public and animal health
are well enforced, the cattle epidemic should be
largely under control and any remaining risk to humans
through beef consumption should be very small. (For
more details see Smith et al. British Medical Bulletin,
66: 185. 2003.)

Chronic Wasting Disease (CWD) is a prion disease of elk
and deer, both free range and in captivity. CWD is
endemic in areas of Colorado, Wyoming, and Nebraska,
but new foci of this disease have been detected in
Nebraska, South Dakota, New Mexico, Wisconsin,
Mississippi Kansas, Oklahoma, Minnesota, Montana, and
Canada. Since there are an estimated 22 million elk and
deer in the USA and a large number of hunters who
consume elk and deer meat, there is the possibility
that CWD can be transmitted from elk and deer to
humans. As of November 2004, the NPDPSC has examined 26
hunters with a suspected prion disease. However, all of
them appeared to have either typical sporadic or
familial forms of the disease. The NPDPSC coordinates
with the Centers for Disease Control and state health
departments to monitor cases from CWD-endemic areas.
Furthermore, it is doing experimental research on CWD
transmissibility using animal models. (For details see
Sigurdson et al. British Medical Bulletin. 66: 199.
2003 and Belay et al. Emerging Infectious Diseases.
10(6): 977. 2004.)

http://www.cjdsurveillance.com/abouthpd-animal.html

SEE STEADY INCREASE IN SPORADIC CJD IN THE USA FROM
1997 TO 2004. SPORADIC CJD CASES TRIPLED, and that is
with a human TSE surveillance system that is terrible
flawed. in 1997 cases of the _reported_ cases of cjd
were at 54, to 163 _reported_ cases in 2004. see stats
here;

p.s. please note the 47 PENDING CASES to Sept. 2005

p.s. please note the 2005 Prion D. total 120(8)
8=includes 51 type pending, 1 TYPE UNKNOWN ???

p.s. please note sporadic CJD 2002(1) 1=3 TYPE UNKNOWN???

p.s. please note 2004 prion disease (6) 6=7 TYPE
UNKNOWN???

http://www.cjdsurveillance.com/resources-casereport.html

CWD TO HUMANS = sCJD ???

AS implied in the Inset 25 we must not _ASSUME_ that
transmission of BSE to other species will invariably
present pathology typical of a scrapie-like disease.

snip...

http://www.bseinquiry.gov.uk/files/yb/1991/01/04004001.pdf

snip...end
full text ;

http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf

VERY VERY IMPORTANT THING TO REMEMBER

>> Differences in tissue distribution could require new regulations
>> regarding specific risk material (SRM) removal.

Research Project: Study of Atypical Bse

Location: Virus and Prion Diseases of Livestock

Project Number: 3625-32000-073-07
Project Type: Specific C/A

Start Date: Sep 15, 2004
End Date: Sep 14, 2007

Objective:
The objective of this cooperative research project with Dr. Maria Caramelli
from the Italian BSE Reference Laboratory in Turin, Italy, is to conduct
comparative studies with the U.S. bovine spongiform encephalopathy (BSE)
isolate and the atypical BSE isolates identified in Italy. The studies will
cover the following areas: 1. Evaluation of present diagnostics tools used
in the U.S. for the detection of atypical BSE cases. 2. Molecular comparison
of the U.S. BSE isolate and other typical BSE isolates with atypical BSE
cases. 3. Studies on transmissibility and tissue distribution of atypical
BSE isolates in cattle and other species.

Approach:
This project will be done as a Specific Cooperative Agreement with the
Italian BSE Reference Laboratory, Istituto Zooprofilattico Sperimentale del
Piemonte, in Turin, Italy. It is essential for the U.S. BSE surveillance
program to analyze the effectiveness of the U.S diagnostic tools for
detection of atypical cases of BSE. Molecular comparisons of the U.S. BSE
isolate with atypical BSE isolates will provide further characterization of
the U.S. BSE isolate. Transmission studies are already underway using brain
homogenates from atypical BSE cases into mice, cattle and sheep. It will be
critical to see whether the atypical BSE isolates behave similarly to
typical BSE isolates in terms of transmissibility and disease pathogenesis.
If transmission occurs, tissue distribution comparisons will be made between
cattle infected with the atypical BSE isolate and the U.S. BSE isolate.
Differences in tissue distribution could require new regulations regarding
specific risk material (SRM) removal.

http://www.ars.usda.gov/research/projects/projects.htm?ACCN_NO=408490

3.57 The experiment which might have determined whether BSE and scrapie were
caused by the same agent (ie, the feeding of natural scrapie to cattle) was
never undertaken in the UK. It was, however, performed in the USA in 1979,
when it was shown that cattle inoculated with the scrapie agent endemic in
the flock of Suffolk sheep at the United States Department of Agriculture in
Mission, Texas, developed a TSE quite unlike BSE. 32 The findings of the
initial transmission, though not of the clinical or neurohistological
examination, were communicated in October 1988 to Dr Watson, Director of the
CVL, following a visit by Dr Wrathall, one of the project leaders in the
Pathology Department of the CVL, to the United States Department of
Agriculture. 33 The results were not published at this point, since the
attempted transmission to mice from the experimental cow brain had been
inconclusive. The results of the clinical and histological differences
between scrapie-affected sheep and cattle were published in 1995. Similar
studies in which cattle were inoculated intracerebrally with scrapie inocula
derived from a number of scrapie-affected sheep of different breeds and from
different States, were carried out at the US National Animal Disease Centre.
34 The results, published in 1994, showed that this source of scrapie agent,
though pathogenic for cattle, did not produce the same clinical signs of
brain lesions characteristic of BSE.

http://www.bseinquiry.gov.uk/report/volume2/chaptea3.htm#820543

The findings of the initial transmission, though not of the clinical or
neurohistological examination, were communicated in October 1988 to Dr
Watson, Director of the CVL, following a visit by Dr Wrathall, one of the
project leaders in the Pathology Department of the CVL, to the United States
Department of Agriculture. 33

http://www.bseinquiry.gov.uk/files/yb/1988/10/00001001.pdf

http://www.bseinquiry.gov.uk/report/volume2/chaptea3.htm#820546

The results were not published at this point, since the attempted
transmission to mice from the experimental cow brain had been inconclusive.
The results of the clinical and histological differences between
scrapie-affected sheep and cattle were published in 1995. Similar studies in
which cattle were inoculated intracerebrally with scrapie inocula derived
from a number of scrapie-affected sheep of different breeds and from
different States, were carried out at the US National Animal Disease Centre.
34 The
results, published in 1994, showed that this source of scrapie agent, though
pathogenic for cattle, did not produce the same clinical signs of brain
lesions characteristic of BSE.

3.58 There are several possible reasons why the experiment was not performed
in the UK. It had been recommended by Sir Richard Southwood (Chairman of the
Working Party on Bovine Spongiform Encephalopathy) in his letter to the
Permanent Secretary of MAFF, Mr (now Sir) Derek Andrews, on 21 June 1988, 35
though it was not specifically recommended in the Working Party Report or
indeed in the Tyrrell Committee Report (details of the Southwood Working
Party and the Tyrell Committee can be found in vol. 4: The Southwood Working
Party, 1988-89 and vol. 11: Scientists after Southwood respectively). The
direct inoculation of scrapie into calves was given low priority, because of
its high cost and because it was known that it had already taken place in
the USA. 36 It was also felt that the results of such an experiment would be
hard to interpret. While a negative result would be informative, a positive
result would need to demonstrate that when scrapie was transmitted to
cattle, the disease which developed in cattle was the same as BSE. 37 Given
the large number of strains of scrapie and the possibility that BSE was one
of them, it would be necessary to transmit every scrapie strain to cattle
separately, to test the hypothesis properly. Such an experiment would be
expensive. Secondly, as measures to control the epidemic took hold, the need
for the experiment from the policy viewpoint was not considered so urgent.
It was felt that the results would be mainly of academic interest. 38

http://www.bseinquiry.gov.uk/report/volume2/chaptea3.htm#820550

http://www.bseinquiry.gov.uk/report/volume2/chaptea3.htm

REPORT OF THE COMMITTEE ON SCRAPIE

Chair: Dr. Jim Logan, Cheyenne, WY

Vice Chair: Dr. Joe D. Ross, Sonora, TX

Dr. Deborah L. Brennan, MS; Dr. Beth Carlson, ND; Dr. John R. Clifford, DC;
Dr. Thomas F. Conner, OH; Dr. Walter E. Cook, WY; Dr. Wayne E. Cunningham,
CO; Dr. Jerry W. Diemer, TX; Dr. Anita J. Edmondson, CA; Dr. Dee Ellis, TX;
Dr. Lisa A. Ferguson, MD; Dr. Keith R. Forbes, NY; Dr. R. David Glauer, OH;
Dr. James R. Grady, CO; Dr. William L. Hartmann, MN; Dr. Carolyn Inch, CAN;
Dr. Susan J. Keller, ND; Dr. Allen M. Knowles, TN; Dr. Thomas F. Linfield,
MT; Dr. Michael R. Marshall, UT; Dr. Cheryl A. Miller, In; Dr. Brian V.
Noland, CO; Dr. Charles Palmer, CA; Dr. Kristine R. Petrini, MN; Mr. Stan
Potratz, IA; Mr. Paul E. Rodgers, CO; Dr. Joan D. Rowe, CA; Dr. Pamela L.
Smith, IA; Dr. Diane L. Sutton, MD; Dr. Lynn Anne Tesar, SD; Dr. Delwin D.
Wilmot, NE; Dr. Nora E. Wineland, CO; Dr. Cindy B. Wolf, MN.

The Committee met on November 9, 2005, from 8:00am until 11:55am, Hershey
Lodge and Convention Center, Hershey, Pennsylvania. The meeting was called
to order by Dr. Jim Logan, chair, with vice chairman Dr. Joe D. Ross
attending. There were 74 people in attendance.

The Scrapie Program Update was provided by Dr. Diane Sutton, National
Scrapie Program Coordinator, United States Department of Agriculture (USDA),
Animal and Plant Health Inspection Services (APHIS), Veterinary Services
(VS). The complete text of the Status Report is included in these
Proceedings.

Dr. Patricia Meinhardt, USDA-APHIS-VS-National Veterinary Services
Laboratory (NVSL) gave the Update on Genotyping Labs and Discrepancies in
Results. NVSL conducts investigations into discrepancies on genotype testing
results associated with the Scrapie Eradication Program. It is the policy of
the Program to conduct a second genotype test at a second laboratory on
certain individual animals. Occasionally, there are discrepancies in those
results. The NVSL conducts follow-up on these situations through additional
testing on additional samples from the field and archive samples from the
testing laboratories.

For the period of time from January 1, 2005, until October 15, 2005, there
were 23 instances of discrepancies in results from 35 flocks. Of those 23
instances, 14 were caused by laboratory error (paperwork or sample mix-up),
3 results from field error, 5 were not completely resolved, and 1 originated
from the use of a non-approved laboratory for the first test. As a result of
inconsistencies, one laboratory’s certification was revoked by APHIS-VS.

snip...

Infected and Source Flocks

As of September 30, 2005, there were 105 scrapie infected and source flocks.
There were a total of 165** new infected and source flocks reported for FY
2005. The total infected and source flocks that have been released in FY
2005 was 128. The ratio of infected and source flocks cleaned up or placed
on clean up plans vs. new infected and source flocks discovered in FY 2005
was 1.03 : 1*. In addition 622 scrapie cases were confirmed and reported by
the National Veterinary Services Laboratories (NVSL) in FY 2005, of which
130 were RSSS cases. Fifteen cases of scrapie in goats have been reported
since 1990. The last goat case was reported in May 2005. Approximately 5,626
animals were indemnified comprised of 49% non-registered sheep, 45%
registered sheep, 1.4% non-registered goats and 4.6% registered goats.

Regulatory Scrapie Slaughter Surveillance (RSSS)

RSSS was designed to utilize the findings of the Center for Epidemiology and
Animal Health (CEAH) Scrapie: Ovine Slaughter Surveillance (SOSS) study. The
results of SOSS can be found at
http://www.aphis.usda.gov/vs/ceah/cahm/Sheep/sheep.htm . RSSS started April
1,

2003. It is a targeted slaughter surveillance program which is designed to
identify infected flocks for clean-up. During FY 2005 collections increased
by 32% overall and by 90% for black and mottled faced sheep improving
overall program effectiveness and efficiency as demonstrated by the 26%
decrease in percent positive black faced sheep compared to FY 2004. Samples
have been collected from 62,864 sheep since April 1, 2003, of which results
have been reported for 59,105 of which 209 were confirmed positive. During
FY 2005, 33,137 samples were collected from 81 plants. There have been 130
NVSL confirmed positive cases (30 collected in FY 2004 and confirmed in FY
2005 and 100 collected and confirmed in FY 2005) in FY 2005. Face colors of
these positives were 114 black, 14 mottled, 1 white and 1 unknown. The
percent positive by face color is shown in the chart below.

Scrapie Testing

In FY 2005, 35,845 animals have been tested for scrapie: 30,192 RSSS; 4,742
regulatory field cases; 772 regulatory third eyelid biopsies; 10 third
eyelid validations; and 129 necropsy validations (chart 9).

Animal ID

As of October 04, 2005, 103,580 sheep and goat premises have been assigned
identification numbers in the Scrapie National Generic Database. Official
eartags have been issued to 73,807 of these premises.

*This number based on an adjusted 12 month interval to accommodate the 60
day period for setting up flock plans.

http://www.usaha.org/committees/reports/2005/report-scr-2005.pdf

Date: April 30, 2006 at 4:49 pm PST
SCRAPIE USA UPDATE AS of March 31, 2006

2 NEW CASES IN GOAT, 82 INFECTED SOURCE FLOCKS, WITH 4 NEW INFECTED SOURCE
FLOCKS IN MARCH, WITH 19 SCRAPIE INFECTED RSSS REPORTED BY NVSL

http://www.aphis.usda.gov/vs/nahps/scrapie/monthly_report/monthly-report.html

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
 
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