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From: TSS ()
Subject: SEAC Draft minutes of the open session of the 93rd meeting held on 6th July 2006 (atypical BSE USA)
Date: August 22, 2006 at 3:03 pm PST


Draft minutes of the open session of the 93rd meeting held on 6th July 2006


The Chair noted that recent reports described two cases of BSE in cattle in the United States of America (USA) as being similar to atypical cases of BSE found in a number of European countries. The Chair suggested that the term "atypical BSE", used in the USA report, is potentially confusing and that this would be discussed under any other business. Dr Danny Matthews (Veterinary Laboratories Agency [VLA]) explained that data from western blots of the USA cases resembled that of a small number of atypical cases of BSE in France. A study of the French cases had shown the condition to be transmissible to mice by intracerebral (ic) inoculation with the neuropathological phenotype maintained on transmission3. Claims have been made about the existence of atypical cases of BSE in other countries but these have yet to be confirmed. No study has yet examined the tissue distribution of abnormal prion protein (PrPSc) or infectivity in such atypical cases of BSE.

3 Baron et al. (2006) Transmission of new bovine prion to mice. Emerging. Infect. Diseases. 12, 1125-1128.


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.


1126 Emerging Infectious Diseases • • Vol. 12, No. 7, July 2006

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.


PLEASE NOTE, if spontaneous scrapie or CWD does not occur, then why is it that only BSE and sproadic CJD are capable of spontaneous mutation $$$

Science 24 September 2004:
Vol. 305. no. 5692, pp. 1918 - 1921
DOI: 10.1126/science.1103581

A Fresh Look at BSE
Bruce Chesebro*
Mad cow disease, or bovine spongiform encephalopathy (BSE), is the cattle form of a family of progressive brain diseases. These diseases include scrapie in sheep, Creutzfeldt-Jakob disease (CJD) in humans, and chronic wasting disease (CWD) in deer and elk. They are also known as either "prion diseases" because of the association of a misfolded cellular prion protein in pathogenesis or "transmissible spongiform encephalopathies" (TSEs) because of the spongelike nature of the damaged brain tissue (1).

The recent discovery of two BSE-infected cows, one in Canada and one in the United States, has dramatically increased concern in North America among meat producers and consumers alike over the extent to which BSE poses a threat to humans as well as to domestic and wild animals. The European BSE epidemic of the late-1980s seems to have been initiated a decade earlier in the United Kingdom by changes in the production of meat and bone meal (MBM) from rendered livestock, which led to contamination of MBM with the BSE infectious agent. Furthermore, the fact that UK farmers fed this rendered MBM to younger animals and that this MBM was distributed to many countries may have contributed to the ensuing BSE epidemic in the United Kingdom and internationally (2).

Despite extensive knowledge about the spread of BSE through contaminated MBM, the source of BSE in Europe remains an unsolved mystery (2). It has been proposed that BSE could be derived from a cross-species infection, perhaps through contamination of MBM by scrapie-infected sheep tissues (see the figure). Alternatively, BSE may have been an endemic disease in cattle that went unnoticed because of its low level of horizontal transmission. Lastly, BSE might have originated by "spontaneous" misfolding of the normal cellular prion protein into the disease-associated abnormal isoform (3), which is postulated to be the infectious agent or "prion."

Five possible sources of BSE in North American cattle. Sheep, deer, and elk could spread prion diseases (TSEs) to cattle through direct animal contact or contamination of pastures. Endemic BSE has not been proven to exist anywhere in the world, but it is difficult to exclude this possibility because of the inefficient spread of BSE infectivity between individual animals (2). BSE caused by spontaneous misfolding of the prion protein has not been proven.

Spontaneous protein misfolding is not a new phenomenon as proteins are known to sometimes misfold after synthesis. Cells in turn have devised ingenious ways to deal with this problem. These include molecular chaperone proteins that bind to misfolded proteins and help them to unfold, and organelles called proteosomes that degrade misfolded or unwanted proteins. However, although misfolded prion proteins have been generated in test tubes as well as in cultured cells, it has been difficult to demonstrate that such misfolded abnormal prion proteins are infectious (4, 5). Even the most recent data do not prove conclusively that infectivity has been generated in vitro because misfolded synthetic prion proteins were not able to transfer disease directly to wild-type mice (6). To obtain infectivity and subsequent prion disease, the misfolded proteins had to be inoculated and incubated for 1 to 2 years in transgenic mice that overexpressed a mutant version of the prion protein. Previous data from this group showed that transgenic mice expressing high amounts of prion protein developed neurological disease without inoculation of misfolded prion protein (7). Thus, at the biochemical level, the critical attributes of the misfolded prion protein required for infectivity are not known, and misfolding of prion protein alone may not be sufficient to generate an infectious agent (8).
Nevertheless, the idea that BSE might originate due to the spontaneous misfolding of prion proteins has received renewed interest in the wake of reports suggesting the occurrence of atypical BSE (9-11). These results imply that new strains of cattle BSE might have originated separately from the main UK outbreak. Where and how might such strains have originated? Although such rare events cannot be studied directly, any number of sources of the original BSE strain could also explain the discovery of additional BSE strains in cattle (see the figure). However, it would be worrisome if spontaneous BSE were really a valid etiology because such a mechanism would be impossible to prevent--unlike other possible scenarios that could be controlled by large-scale eradication of TSE-positive animals.

Another way to look at this problem is to examine evidence for possible spontaneous TSE disease in other animals besides cattle. Spontaneous BSE would be extremely difficult to detect in cattle, where horizontal spread is minimal. However, in the case of the sheep TSE disease, scrapie, which spreads from ewes to lambs at birth as well as between adults, spontaneous disease should be detectable as new foci of clinical infection. In the early 1950s scrapie was eradicated in both Australia and New Zealand, and the mainland of both these countries has remained scrapie-free ever since. This scrapie-free status is not the result of selection of sheep resistant to scrapie because sheep from New Zealand are as susceptible as their UK counterparts to experimental scrapie infection (12). These experiments of man and nature appear to indicate that spontaneous clinical scrapie does not occur in sheep. Similarly, because CWD is known to spread horizontally, the lack of CWD in the deer or elk of eastern North America but its presence in western regions would also argue against a spontaneous disease mechanism. This is particularly noteworthy in New Zealand, where there are large numbers of deer and elk farms and yet no evidence of spontaneous CWD. If spontaneous scrapie does not occur in sheep or deer, this would suggest that spontaneous forms of BSE and sporadic Creutzfeldt-Jakob disease (sCJD) are unlikely to be found in cattle or humans. The main caveat to this notion is that spontaneous disease may arise in some animal species but not others. In humans, sCJD--which is considered by some researchers to begin by spontaneous misfolding of the prion protein--usually takes more than 50 years to appear. Thus, in animals with a shorter life-span, such as sheep, deer, and cattle, an analogous disease mechanism might not have time to develop.

What can we conclude so far about BSE in North America? Is the BSE detected in two North American cows sporadic or spontaneous or both? "Sporadic" pertains to the rarity of disease occurrence. "Spontaneous" pertains to a possible mechanism of origin of the disease. These are not equivalent terms. The rarity of BSE in North America qualifies it as a sporadic disease, but this low incidence does not provide information about cause. For the two reported North American BSE cases, exposure to contaminated MBM remains the most likely culprit. However, other mechanisms are still possible, including cross-infection by sheep with scrapie or cervids with CWD, horizontal transmission from cattle with endemic BSE, and spontaneous disease in individual cattle. Based on our understanding of other TSEs, the spontaneous mechanism is probably the least likely. Thus, "idiopathic" BSE--that is, BSE of unknown etiology--might be a better term to describe the origin of this malady.

What does all this imply about testing cattle for BSE in North America? Current testing in the United States indicates that BSE is rare (one positive result in 40,000 cattle tested). However, additional testing of 200,000 head of slaughtered cattle over the next 1 to 2 years, as recently proposed by the U.S. Department of Agriculture (USDA), should tell us the incidence more precisely. Nevertheless, if any rare cases are detected, we may still not know their origin. If evidence arises of a focal occurrence of BSE, we might gain important insight into unexpected sources of contamination. However, because current tests do not seem to be able to detect BSE in infected animals less than 30 months of age, even more extensive testing will not completely guarantee the negative status of younger animals in the food chain. Therefore, the alternative option of testing all slaughtered cattle, as implemented in some countries such as Japan, would appear to provide little additional benefit. This fact has been acknowledged as the basis for a new agreement between the United States and Japan aimed at reestablishing the beef trade between the two countries.

One problem with the current U.S. testing program was the announcement a few months ago of unconfirmed positive BSE tests in two additional North American animals that were subsequently found to be negative when tested with the more accurate method of Western blotting. The public release of information about unconfirmed positive tests detected by the rapid test used for mass screening may be a good idea in the interest of openness, but it has the potential to create unwarranted anxiety. If unconfirmed positives are a frequent occurrence, it would seem reasonable to follow a more cautious approach and wait until confirmatory testing is complete before publicly announcing the details.

Based on the experience of many European countries, the mainstays of controlling BSE in cattle and avoiding spread to humans are threefold: first, eliminate feeding of ruminant tissues to ruminants; second, remove high-risk cattle tissues from human food; and third, continue to test for BSE in cattle in order to monitor progress with the elimination of the disease on a local and national basis. In the next 12 months, after extensive USDA test results are available, the extent of any possible BSE spread in the United States will be better documented. But, in fact, the United States and Canada have already instituted the most important steps to prevent the spread of cattle BSE in advance of the results--that is, a ban on feeding ruminant MBM to other ruminants and removal of high-risk tissues from meat for human consumption. It is hoped that the new data will not deviate enough from previous predictions to require further measures for management of this problem. The most important line of defense against any possible spread of BSE will be to maintain strict vigilance in the implementation of the current regulations.


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P. G. Smith, R. Bradley, Br. Med. Bull. 66, 185 (2003) [Medline].
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A. G. Biacabe et al., EMBO Rep. 5, 110 (2004) [Medline].
Y. Yamakawa et al., Jpn. J. Infect. Dis. 56, 221 (2003) [Medline].
C. Casalone et al., Proc. Natl. Acad. Sci. U.S.A. 101, 3065 (2004) [Medline].
E. F. Houston et al., J. Gen. Virol. 83, 1247 (2002) [Medline].

US atypical BSE – further details

As reported in the last BSE Report (Which? BSE May 2006) French research findings

concerning the two most recent cases of BSE in the USA suggest that these cases were

not typical of BSE in cattle and may reflect a sporadic form of the disease.


n the two US cases, discovered in herds in Texas and Alabama, threre was an absence

of telltale spongy lesions caused by prions. In addition, the prions in brain tissue

samples from these cows seemed to be distributed differently from the classic form.

Laboratory studies on mice in France showed that both the classic and atypical strains

could be spread from one animal to another, but the atypical strain might happen

spontaneously in cattle. The Texas and Alabama cows were older animals, as were

some of the other animals in Europe with seemingly atypical forms of BSE.31

Linda Detwiler, a former Agriculture Department veterinarian who consults for major

food companies, cautioned against making that assumption. "I think it's kind of early to

say that would be the case," Detwiler said. Other theories, she said, suggest the

atypical strain might come from a mutation of BSE or even from a related disease in


The US Agriculture Department has stated that whatever the cause there is no reason

to change federal testing or control measures. "It's most important right now, till the

science tells us otherwise, that we treat this as BSE regardless," the department's chief

veterinarian, John Clifford, said in an interview. ...

A ProMED-mail post

ProMED-mail is a program of the
International Society for Infectious Diseases

Date: Tue 6 Jun 2006
From: Terry Singeltary
Source: [edited]

USDA Confirms BSE Tests On U.S. Cows Found Identical To Atypical Cases In
A USDA official confirmed that the positive BSE tests in 2 U.S.-born cattle
were indeed an "atypical" type of the disease.

A USDA spokesman acknowledged Friday [2 Jun 2006] that positive BSE tests
from 2 domestic-born cattle were from a rare strain of the disease found in
a small number of European cases.

BSE, scientifically known as bovine spongiform encephalopathy and commonly
known as mad cow disease, is a degenerative, fatal disease affecting the
central nervous system of adult cattle.

USDA officials have declined in the past to provide such details, but
released information Friday [2 Jun 2006] after a French researcher revealed
earlier this week that the cases in Texas last year 2005 and Alabama last
spring 2006 were identical to "atypical" cases of BSE found in France.

Scientists from around the world are trying to quantify the significance of
these rare cases. They also want to know whether these cases may be sporadic.

In an e-mail, a USDA spokesman said the cases raise "many unanswered
questions about these unusual findings, and additional research is needed
to help characterize the significance -- or lack of significance -- of any
of these findings."

The USDA spokesperson said nothing in the test results of the 2 cattle
justifies any changes in surveillance, disease control or public-health
measures already being taken in the U.S.

Terry Singeltary

Date: Tue 6 Jun 2006
From: Terry Singeltary
Source: Farmers Weekly [edited]

Cattle disease might be unknown strain of BSE
Scientists across Europe and the United States are following the emergence
of a new Transmissible Spongiform Encephalopathy (TSE) in cattle that could
be a new strain of BSE.

Speaking last weekend at an international conference on prion diseases in
domestic livestock (such as BSE in cows and scrapie in sheep and goats),
scientists from France and Italy described how the disease had been
detected in a small number of cattle ranging from 5 to 15 years old.

The strain differs from BSE in that it has a longer incubation time and is
consequently being found in older cattle.

The new strain also demonstrates different characteristics from BSE in
laboratory tests and was originally detected through active surveillance of
live animals rather than during inspection of a suspect fallen animal.

Marion Simmons of the Veterinary Laboratory Agency at Weybridge urged
caution, saying there are not yet sufficient supporting data to suggest
that the disease is a new strain of BSE.

Terry Singeltary

[It has long been debated whether this atypical form is sporadic or whether
the sporadic appearance was an atypical form. There does not seem to be a
good explanation, which simply highlights the need for more research and
understanding of this disease. - Mod.TG]

[see also:
BSE, bovine - USA: atypical strain 20060601.1525]

ProMED-mail makes every effort to verify the reports that
are posted, but the accuracy and completeness of the
information, and of any statements or opinions based
thereon, are not guaranteed. The reader assumes all risks in
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Order Code RS22345

Updated July 18, 2006


BSE (“Mad Cow Disease”): A Brief Overview

Geoffrey S. Becker

Specialist in Agricultural Policy

Resources, Science, and Industry Division


1 This report, which replaces CRS Issue Brief IB10127, Mad Cow Disease: Agricultural Issues

for Congress, summarizes and updates information in other CRS reports, listed on page 6.

Sources for facts and citation to reports and studies can be found in these CRS reports.

Congressional Research Service ˜ The Library of Congress

CRS Report for Congress

Received through the CRS Web

Order Code RS22345

Updated July 18, 2006

BSE (“Mad Cow Disease”): A Brief Overview

Geoffrey S. Becker

Specialist in Agricultural Policy

Resources, Science, and Industry Division


The appearance of BSE (bovine spongiform encephalopathy or “mad cow disease”)

in North America in 2003 raised meat safety concerns and disrupted trade for cattle and

beef producers. A major issue for Congress has been how to rebuild foreign confidence

in the safety of U.S. beef and regain lost markets like Japan and Korea. Among other

issues are whether additional measures are needed to further protect the public and cattle

herd, and concerns over the relative costs and benefits of such measures for consumers,

taxpayers and industry. This report will be updated if significant developments ensue.1

What Is BSE?

BSE (bovine spongiform encephalopathy or “mad cow disease”) is a fatal

neurological disease of cattle, believed to be transmitted mainly by feeding infected cattle

parts back to cattle. More than 187,000 cases have been reported worldwide, 183,000 of

them in the United Kingdom (UK) where BSE was first identified in 1986. The annual

number of new cases has declined steeply since 1992. Humans who eat contaminated

beef are believed susceptible to a rare but fatal brain wasting disease, variant Creutzfeldt-

Jakob disease (vCJD). About 160 people, most in the UK, have been diagnosed with

vCJD since 1986, but none has been linked to any Canadian or U.S. meat consumption.

BSE in North America

BSE has been reported in 11 North American cattle, 10 born here and one imported

from the UK. The first native case was an Alberta, Canada, beef cow reported in May

2003. Canada has since reported six more cases, most recently in July 2006 in a 50-

month-old dairy cow in Manitoba. The first U.S. case was in a Canadian-born dairy cow

found in Washington state in December 2003. The other two U.S. cases were a 12-yearold

Texas-born and -raised beef cow, found in November 2004 but not confirmed until

June 2005, and a 10-year-old Alabama beef cow found in late February 2006.


In epidemiological investigations of the three U.S. cases, the U.S. Department of

Agriculture (USDA) was unable to track down all related animals of interest, but those

that were located tested negative for the disease. Despite a beef recall, some meat from

the first U.S. BSE cow may have been consumed, USDA said, adding, however, that the

highest-risk tissues never entered the food supply. No materials from the other two U.S.

cows entered the food supply, USDA also said. In the recent Alabama case, authorities

were unable to determine the cow’s herd of origin. Animal health officials initially

indicated that all of the North American cases were caused by the consumption of BSEcontaminated

feed. However, USDA reportedly now believes that the two native-born

U.S. cattle had “atypical” BSE, which differs from other cases. If these cases are

determined to be “spontaneous,” that may affect future control strategies.


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

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.

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.

Research Project: Study of Atypical Bse

Location: Virus and Prion Diseases of Livestock

2005 Annual Report

This report serves to document research conducted under a specific
cooperative agreement between ARS and the Italian Reference Centre for
Animal TSE (CEA) at the Istituto Zooprofilattico Sperimentale, Turin, Italy.
Additional details of research can be found in then report for the parent
project 3625-32000-073-00D, Transmission, Differentiation, and Pathobiology
of Transmissible Spongiform Encephalopathies. The aim of the cooperative
research project conducted by the CEA and ARS is to compare the U.S. bovine
spongiform encephalopathy (BSE) isolate and the bovine amyloidotic
spongiform encephalopathy isolates (BASE) identified in Italy. The first
objective was to determine whether diagnostic methods routinely used by USDA
are able to identify the Italian BASE cases. For this purpose, CEA received
the immunohistochemistry (IHC) protocol developed by APHIS-USDA. The IHC
protocol was reproduced and standardized in the CEA laboratory and will be
applied to the Italian BSE and BASE cases. Furthermore, fixed brainstem
sections and frozen brainstem material from Italian BSE and BASE cases will
be sent to ARS for analysis using USDA IHC and Western blot (WB) methods.
These studies will enable us to determine whether the present diagnostic
tools (IHC and WB) employed at the USDA will be able to detect the Italian
BASE cases and also enable us to compare Italian BSE and BASE with the U.S.
BSE cases.

Research Project: Transmission, Differentiation, and Pathobiology of
Transmissible Spongiform Encephalopathies

Location: Virus and Prion Diseases of Livestock

Title: Where We've Been and Where We're Going with Bse Testing in the United

item Hall, Mark - NVSL-APHIS-USDA
item Richt, Juergen
item Davis, Arthur - NVSL-APHIS-USDA
item Levings, Randall - NVSL-APHIS-USDA

Submitted to: American Association of Veterinary Laboratory Diagnosticians
Publication Type: Abstract
Publication Acceptance Date: September 1, 2005
Publication Date: November 3, 2005
Citation: Hall, M.S., Richt, J.A., Davis, A.J., Levings, R.L. 2005. Where
We've Been and Where We're Going with Bse Testing in the United States
[abstract]. 48th Annual Meeting of the American Association of Veterinary
Laboratory Diagnosticians. P. 20.

Technical Abstract: A review of the laboratory aspects of the United States
Department of Agriculture's (USDA) Bovine Spongiform Encephalopathy (BSE)
Surveillance Program from its beginning to the present day will be provided.
Validated diagnostic tests for BSE require brain tissue. There are no ante
mortem (blood/serum) tests for BSE available at present. From a historical
perspective, diagnostic tests for BSE continue to evolve. The original
diagnostic test method was histopathology in which sections of brain were
examined under a microscope, and the classical vacuoles and spongiform
change in specific areas of the brain would allow a diagnosis to be made.
This method was accurate but only allowed a diagnosis to be made relatively
late in the course of the disease. In the mid-1990s, immunohistochemistry
(IHC) and Western blotting were developed which allow the detection of the
abnormal form of the prion protein (PrPSc) and a diagnosis could be made
prior to the development of spongiform changes and clinical signs. In the
past decade, so-called "rapid tests" have been introduced commercially for
BSE. Five commercial tests are currently licensed/permitted in the United
States for BSE. These licensed tests include the Prionics Western blot,
Prionics ELISA, Enfer/Abbott ELISA, IDEXX ELISA, and the BioRad ELISA. This
presentation will discuss various attributes of the validated test methods
available today. Both IHC and Western blot are considered confirmatory tests
for BSE by the World Organisation of Animal Health (OIE). IHC provides for a
specific immunological detection of PrPSc and enables the specific
anatomical location to be determined. Western blot provides both
immunological detection of PrPSc as well as specific molecular weight
characterizations; certain Western blot procedures can be extremely
sensitive due to various concentration procedures before analysis of the
sample. The OIE recommended Western blot and IHC methods for confirmatory
diagnosis of BSE used by USDA and the Veterinary Laboratories Agency in
Weybridge, England, will be discussed. The overall enhanced testing plan
that has been used for the past 18 months will be described including
changes that have occurred during this time. The USDA's BSE enhanced
surveillance plan has been a very successful national surveillance testing
program that has been a shared effort between state veterinary diagnostic
laboratories as part of the National Animal Health Laboratory Network and
the National Veterinary Services Laboratories.

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.

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.

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


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.


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 . 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.

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:

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



Subject: SCRAPIE and CWD USA UPDATE July 19, 2006
Date: July 19, 2006 at 12:06 pm PST

Infected and Source Flocks

As of May 31, 2006, there were 93 scrapie infected and source flocks (Figure 3). There were 12 new infected and source flocks reported in May (Figure 4) with a total of 67 flocks reported for FY 2006 (Figure 5). The total infected and source flocks that have been released in FY 2006 are 53 (Figure 6), with 7 flocks released in May. The ratio of infected and source flocks released to newly infected and source flocks for FY 2006 = 0.79 : 1. In addition, as of May 31, 2006, 216 scrapie cases have been confirmed and reported by the National Veterinary Services Laboratories (NVSL), of which 33 were RSSS cases (Figure 7). This includes 33 newly confirmed cases in May 2006 (Figure 8). Eighteen cases of scrapie in goats have been reported since 1990 (Figure 9). The last goat case was reported in March 2006. New infected flocks, source flocks, and flocks released for FY 2006 are depicted in Chart 3. New infected and source statuses from 1997 to 2006 are depicted in Chart 4.


Scrapie Testing

In FY 2006, 26,185 animals have been tested for scrapie : 22,634 RSSS*; 2063 regulatory field cases; 61 necropsy validations, 5 rectal biopsy and 1427 regulatory third eyelid biopsies (Chart 9). ...



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