----- Original Message -----
From: Terry S. Singeltary Sr.
To: Bovine Spongiform Encephalopathy
Cc: [email protected] ; [email protected] ; [email protected]
Sent: Saturday, August 19, 2006 10:27 AM
Subject: 'Atypical' strain of BSE found in U.S. cattle
Subject: 'Atypical' strain of BSE found in U.S. cattle
Date: August 19, 2006 at 7:28 am PST
RapidCityJournal.com
Friday, August 18, 2006
'Atypical' strain of BSE found in U.S. cattle
By Chris Clayton, DTN Staff Reporter, and Journal staff
The two cases of bovine spongiform encephalopathy found in U.S. cattle over the past year came from a rare strain of BSE found largely in Europe that scientists are only beginning to identify, according to research by a French scientist.
Researchers in France and Italy who presented their work at an international conference in London reported two rare strains of bovine spongiform encephalopathy that are harder to detect and affect mainly older cattle.
Thierry Baron of the French Food Safety Agency presented research indicating that a 12-year-old Texas cow testing positive for BSE last June, and the 10-year-old Alabama cow that tested positive in March, showed identical testing patterns to a small number of BSE cases in France, Sweden and Poland.
Animal scientists are calling such strains "atypical" BSE, which is different from the "typical" BSE caused by cattle eating feed with ruminant offal contaminated with a BSE protein.
They don't know whether the atypical strains are caused by something else or simply appear spontaneously in older, susceptible cattle.
Art Davis, a U.S. Department of Agriculture scientist for the Animal and Plant Health Inspection Service at the National Veterinary Services Laboratory in Ames, Iowa, said in his presentation Sunday at the London conference that the Texas and Alabama test results showed completely different prion patterns than the Washington state case discovered in December 2003.
"The classical lesions were not there," Davis said of the cases. The Washington state cow originated in Alberta, Canada, near where several other BSE cases have been found.
The "typical" BSE strain caused a mad cow disease epidemic in Great Britain beginning in the mid-1980s that killed 184,000 cattle and more than 100 people who contracted a human form of the disease caused by eating contaminated beef products.
The scientific evidence shows that in almost all cattle cases, the fatal neurological disorder was contracted through contaminated meat and bone meal fed to the cow, typically at a young age.
However, scientists finding atypical cases of BSE are beginning to question if there has been a change in the abnormal protein that causes BSE or if cattle might be susceptible to a sporadic BSE affecting older cattle.
Danny Matthews, head of transmissible spongiform encephalopathies at England's Veterinary Laboratories Agency, said recent research on atypical cases of BSE raises questions over whether older cattle can sporadically get the disease or if there are more strains of BSE than previously understood. Scientists might also be facing something new, such as "son of BSE," he said.
"We don't fully understand what atypical BSE means," Matthews said. "Is it spontaneous or another source causing it? Time will tell."
Although the test patterns in the U.S. cases and atypical cases in Europe closely matched, Baron said there were no known links among any of the positive animals. The French Food Safety Agency sent a researcher to the United States to study the positive Texas case and compare its results to known cases in France that did not match the typical BSE positive tests.
"You could place them side-by-side and not tell the difference," Baron said.
Baron also raised the prospect that the disease could be sporadic in at least a small number of older cattle. He said, however, such a conclusion would be hard to determine because of the small number of cattle with this atypical strain globally.
Dr. Sam Holland, South Dakota's state veterinarian, said there are many strains of BSE and varying degrees of infectiousness of the agent.
"What if the scenario is there is an atypical prion out there that is much less infective, has a longer incubation period and has not been recognized as part of the Great Britain BSE experience identified in 1985 and '86?" Holland said. "There could be others out there that we haven't recognized yet."
He said it is possible the atypical strains are not caused by contaminated feed.
He said it still makes sense to continue the ban on ruminant offal in cattle feed to prevent the spread of typical BSE and eventually to eliminate that disease.
"Based on what we know about BSE, it makes good sense to, number one, keep some surveillance in place; number two, watch what we import and restrict shipments and movements from places that have had those syndromes; and, number three, with what we know about BSE, it seems to be very prudent to keep our ruminant offal ban in place," Holland said. "At least for typical BSE's, it seems to be very effective. It's probably reasonable to continue the ruminant offal ban even after the last typical BSE case has been eliminated."
Editor's note: DTN, a private company based in Omaha, Neb., provides information to agriculture, energy trading markets and other weather-sensitive industries. The Rapid City Journal received a copy of DTN's story and expanded on it.
http://www.rapidcityjournal.com/articles/2006/05/31/news/local/news05.txt
Coincidently, this very important factor was left out of the above newspaper article, typical rubber stamping of the USDA et al by the media. I mean, its part of the damn title of the study. YOU would think it important enough to have added this very important factor in the newspaper article ;
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.
snip...
http://www.cdc.gov/ncidod/EID/vol12no07/pdfs/vol12no07.pdf
Published online before print February 17, 2004, 10.1073/pnas.0305777101
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.cdc.gov/ncidod/EID/vol12no07/pdfs/vol12no07.pdf
DISPATCHES
1126 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 12, No. 7, July 2006
snip...
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.
snip...
http://www.cdc.gov/ncidod/EID/vol12no07/pdfs/vol12no07.pdf
Atypical cases of TSE in cases of TSE in
cattle and sheep cattle and sheep
H. De H. De Bosschere Bosschere
CODA/CERVA CODA/CERVA
Nat. Ref. Lab. Vet. Nat. Ref. Lab. Vet. TSEs TSEs
Belgium
http://www.var.fgov.be/pdf/1100_TSEDAY.pdf
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
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/
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/
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 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
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
Subject: SCRAPIE and CWD USA UPDATE July 19, 2006
Date: July 19, 2006 at 12:06 pm PST
SCRAPIE USA UPDATE MAY 31, 2006
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.
snip...
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). ...
snip...END
http://www.aphis.usda.gov/vs/nahps/scrapie/monthly_report/monthly-report.html
DRAFT
WYOMING GAME AND FISH DEPARTMENT
CHRONIC WASTING DISEASE MANAGEMENT PLAN
February 17, 2006
snip...
5. Predicted population effects on free-ranging elk based on captive elk chronically exposed to the CWD prion.
Forty-three female elk calves were trapped at the National Elk Refuge and transported to Sybille in February 2002. Elk were housed in pens, assumed to be environmentally contaminated with the CWD prion. Elk will be held throughout their lifetimes. Elk dying will be examined and cause of death determined. From these data, it will should be possible to model free-ranging elk mortality and population dynamics under extreme circumstances of CWD prion exposure and transmission. As of December 2005 (46 months post capture), 11 of 43 elk have died due to CWD. This compares to 100% mortality in less than 25 months in elk orally inoculated with different dosages of the CWD prion.
REVISED DRAFT
http://gf.state.wy.us/downloads/pdf/CWD2005reviseddraft.pdf
Prions in Skeletal Muscles of Deer with Chronic Wasting Disease
Rachel C. Angers,1* Shawn R. Browning,1*† Tanya S. Seward,2 Christina J.
Sigurdson,4‡ Michael W. Miller,5 Edward A. Hoover,4 Glenn C. Telling1,2,3§
1Department of Microbiology, Immunology and Molecular Genetics, 2Sanders
Brown Center on Aging, 3Department of Neurology, University of Kentucky,
Lexington, KY 40536, USA. 4Department of Microbiology, Immunology and
Pathology, Colorado State University, Fort Collins, CO 80523, USA. 5Colorado
Division of Wildlife, Wildlife Research Center, Fort Collins, CO 80526, USA.
*These authors contributed equally to this work.
†Present address: Department of Infectology, Scripps Research Institute,
5353 Parkside Drive, RF-2, Jupiter, Florida, 33458, USA.
‡Present address: Institute of Neuropathology, University of Zurich,
Schmelzbergstrasse 12, 8091 Zurich, Switzerland.
§To whom correspondence should be addressed: E-mail: [email protected]
Prions are transmissible proteinaceous agents of mammals that cause fatal
neurodegenerative diseases of the central nervous system (CNS). The presence
of infectivity in skeletal muscle of experimentally infected mice raised the
possibility that dietary exposure to prions might occur through meat
consumption (1). Chronic wasting disease (CWD), an enigmatic and contagious
prion disease of North American cervids, is of particular concern. The
emergence of CWD in an increasingly wide geographic area and the
interspecies transmission of bovine spongiform encephalopathy (BSE) to
humans as variant Creutzfeldt Jakob disease (vCJD) have raised concerns
about zoonotic transmission of CWD.
To test whether skeletal muscle of diseased cervids contained prion
infectivity, Tg(CerPrP)1536 mice (2) expressing cervid prion protein
(CerPrP), were inoculated intracerebrally with extracts prepared from the
semitendinosus/semimembranosus muscle group of CWD-affected mule deer or
from CWD-negative deer. The availability of CNS materials also afforded
direct comparisons of prion infectivity in skeletal muscle and brain. All
skeletal muscle extracts from CWD-affected deer induced progressive
neurological dysfunction in Tg(CerPrP)1536 mice with mean incubation times
ranging between 360 and ~490 d, whereas the incubation times of prions from
the CNS ranged from ~230 to 280 d (Table 1). For each inoculation group, the
diagnosis of prion disease was confirmed by the presence of PrPSc in the
brains of multiple infected Tg(CerPrP)1536 mice (see supporting online
material for examples). In contrast, skeletal muscle and brain material from
CWD-negative deer failed to induce disease in Tg(CerPrP)1536 mice (Table 1)
and PrPSc was not detected in the brains of sacrificed asymptomatic mice as
late as 523 d after inoculation (supporting online material).
Our results show that skeletal muscle as well as CNS tissue of deer with CWD
contains infectious prions. Similar analyses of skeletal muscle BSE-affected
cattle did not reveal high levels of prion infectivity (3). It will be
important to assess the cellular location of PrPSc in muscle. Notably, while
PrPSc has been detected in muscles of scrapie-affected sheep (4), previous
studies failed to detect PrPSc by immunohistochemical analysis of skeletal
muscle from deer with natural or experimental CWD (5, 6). Since the time of
disease onset is inversely proportional to prion dose (7), the longer
incubation times of prions from skeletal muscle extracts compared to matched
brain samples indicated that prion titers were lower in muscle than in CNS
where infectivity titers are known to reach high levels. Although possible
effects of CWD strains or strain mixtures on these incubation times cannot
be excluded, the variable 360 to ~490 d incubation times suggested a range
of prion titers in skeletal muscles of CWD-affected deer. Muscle prion
titers at the high end of the range produced the fastest incubation times
that were ~30% longer than the incubation times of prions from the CNS of
the same animal. Since all mice in each inoculation group developed disease,
prion titers in muscle samples producing the longest incubation times were
higher than the end point of the bioassay, defined as the infectious dose at
which half the inoculated mice develop disease. Studies are in progress to
accurately assess prion titers.
While the risk of exposure to CWD infectivity following consumption of
prions in muscle is mitigated by relatively inefficient prion transmission
via the oral route (8), these
results show that semitendinosus/semimembranosus muscle, which is likely to
be consumed by humans, is a significant source of prion infectivity. Humans
consuming or handling meat from CWD-infected deer are therefore at risk to
prion exposure.
References and Notes
1. P. J. Bosque et al., Proc. Natl. Acad. Sci. U.S.A. 99, 3812 (2002).
2. S. R. Browning et al., J. Virol. 78, 13345 (2004).
3. A. Buschmann, M. H. Groschup, J. Infect. Dis. 192, 934 (2005).
4. O. Andreoletti et al., Nat. Med. 10, 591 (2004).
5. T. R. Spraker et al., Vet. Pathol. 39, 110 (2002).
6. A. N. Hamir, J. M. Miller, R. C. Cutlip, Vet. Pathol. 41, 78 (2004).
7. S. B. Prusiner et al., Biochemistry 21, 4883 (1980).
8. M. Prinz et al., Am. J. Pathol. 162, 1103 (2003).
9. This work was supported by grants from the U.S. Public Health Service
2RO1 NS040334-04 from the National Institute of Neurological Disorders and
Stroke and N01-AI-25491 from the National Institute of Allergy and
Infectious Diseases.
Supporting Online Material
www.sciencemag.org/
Materials and Methods
Fig. S1
21 November 2005; accepted 13 January 2006 Published online 26 January 2006;
10.1126/science.1122864 Include this information when citing this paper.
Table 1. Incubation times following inoculation of Tg(CerPrP)1536 mice with
prions from skeletal muscle and brain samples of CWD-affected deer.
Inocula Incubation time, mean d ± SEM (n/n0)*
Skeletal muscle Brain
CWD-affected deer
H92 360 ± 2 d (6/6) 283 ± 7 d (6/6)
33968 367 ± 9 d (8/8) 278 ± 11 d (6/6)
5941 427 ± 18 d (7/7)
D10 483 ± 8 d (8/8) 231 ± 17 d (7/7)
D08 492 ± 4 d (7/7)
Averages 426 d 264 d
Non-diseased deer
FPS 6.98 >523 d (0/6)
FPS 9.98 >454 d (0/7) >454 d (0/6)
None >490 d (0/6)
PBS >589 d (0/5)
*The number of mice developing prion disease divided by the original number
of inoculated mice is shown in parentheses. Mice dying of intercurrent
illnesses were excluded.
http://www.sciencemag.org/
www.sciencemag.org/
Supporting Online Material for
Prions in Skeletal Muscles of Deer with Chronic Wasting Disease
Rachel C. Angers, Shawn R. Browning, Tanya S. Seward, Christina J.
Sigurdson,
Michael W. Miller, Edward A. Hoover, Glenn C. Telling§
§To whom correspondence should be addressed: E-mail: [email protected]
Published 26 January 2006 on Science Express
DOI: 10.1126/science.1122864
This PDF file includes:
Materials and Methods
Fig. S1
Supporting Online Materials
Materials and Methods
Homogenates of semitendinosus/semimembranosus muscle (10% w/v in phosphate
buffered saline) were prepared from five emaciated and somnolent mule deer,
naturally
infected with CWD at the Colorado Division of Wildlife, Wildlife Research
Center.
These deer were identified as D10, D08, 33968, H92, and 5941. CWD infection
was
confirmed in all cases by the presence of histologic lesions in the brain
including
spongiform degeneration of the perikaryon, the immunohistochemical detection
of
disease-associated PrP in brain and tonsil, or by immunoblotting of
protease-resistant,
disease associated PrP (CerPrPSc). Semitendinosus/semimembranosus muscle was
also
obtained from two asymptomatic, mock inoculated deer, referred to as FPS
6.68 and 9.98,
that originated from a CWD non-endemic area and which were held indoors at
Colorado
State University from ten days of age. These control deer were confirmed
negative for
CWD by histopathological and immunohistochemical analysis of brain tissue at
autopsy.
The utmost care was taken to avoid inclusion of obvious nervous tissue when
muscle
biopsies were prepared and to ensure that contamination of skeletal muscle
samples with
CNS tissue did not occur. Fresh, single-use instruments were used to collect
each sample
biopsy and a central piece from each sample was prepared with fresh,
disposable
instruments to further isolate muscle tissue for inoculum preparation. Brain
samples for
transmission were prepared separately from muscle as additional insurance
against cross
contamination.
1
Groups of anesthetized Tg(CerPrP)1536 mice were inoculated intracerebrally
with 30 µl
of 1 % skeletal muscle or brain extracts prepared in phosphate buffered
saline (PBS).
Inoculated Tg(CerPrP) mice were diagnosed with prion disease following the
progressive
development of at least three neurologic symptoms including truncal ataxia,
‘plastic’ tail,
loss of extensor reflex, difficultly righting, and slowed movement. The time
from
inoculation to the onset of clinical signs is referred to as the incubation
time.
For PrP analysis in brain extracts of Tg(CerPrP)1536 mice, 10 % homogenates
prepared
in PBS were either untreated (-) or treated (+) with 40 µg/ml proteinase K
(PK) for one
hour at 37oC in the presence of 2% sarkosyl. Proteins were separated by
sodium dodecyl
sulfate polyacrylamide gel electrophoresis, analyzed by immunoblotting using
anti PrP
monoclonal antibody 6H4 (Prionics AG, Switzerland), incubated with
appropriate
secondary antibody, developed using ECL-plus detection (Amersham), and
analyzed
using a FLA-5000 scanner (Fuji).
2
Fig. S1
PrP in brain extracts from representative Tg(CerPrP)1536 mice receiving
muscle or CNS
tissue inocula from CWD-affected or CWD-negative deer. Extracts were either
treated
(+) or untreated (-) with proteinase K (PK) as indicated. The positions of
protein
molecular weight markers at 21.3, 28.7, 33.5 kDa (from bottom to top) are
shown to the
left of the immunoblot.
3
http://www.sciencemag.org/
Chronic Wasting Disease and Potential Transmission to Humans
Ermias D. Belay,* Ryan A. Maddox,* Elizabeth S. Williams,† Michael W. Miller,‡ Pierluigi Gambetti,§ and Lawrence B. Schonberger*
*Centers for Disease Control and Prevention, Atlanta, Georgia, USA; †University of Wyoming, Laramie, Wyoming, USA; ‡Colorado Division of Wildlife, Fort Collins, Colorado, USA; and §Case Western Reserve University, Cleveland, Ohio, USA
Suggested citation for this article: Belay ED, Maddox RA, Williams ES, Miller MW, Gambetti P, Schonberger LB. Chronic wasting disease and potential transmission to humans. Emerg Infect Dis [serial on the Internet]. 2004 Jun [date cited]. Available from: http://www.cdc.gov/ncidod/EID/vol10no6/03-1082.htm
http://www.cdc.gov/ncidod/EID/vol10no6/03-1082.htm
Research
Environmental Sources of Prion Transmission in Mule Deer
Michael W. Miller,* Elizabeth S. Williams,† N. Thompson Hobbs,‡ and Lisa L. Wolfe*
*Colorado Division of Wildlife, Fort Collins, Colorado, USA; †University of Wyoming, Laramie, Wyoming, USA; and ‡Colorado State University, Fort Collins, Colorado, USA
Suggested citation for this article: Miller MW, Williams ES, Hobbs NT, Wolfe LL. Environmental sources of prion transmission in mule deer. Emerg Infect Dis [serial on the Internet]. 2004 Jun [date cited]. Available from: http://www.cdc.gov/ncidod/EID/vol10no6/04-0010.htm
http://www.cdc.gov/ncidod/EID/vol10no6/04-0010.htm
ATYPICAL TSEs in USA CATTLE AND SHEEP ?
http://www.bseinquiry.gov.uk/files/sc/seac17/tab03.pdf
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf
CWD MAP
NOTICE CWD creeping its way to TEXAS, literally to it's border. ...
http://www.aphis.usda.gov/vs/nahps/cwd/images/counties_lg.jpg
THEN NOTICE CWD sample along that border in TEXAS, Three Year Summary of Hunter-Kill CWD sampling as of 31 August 2005 of only 191 samples, then compare to the other sample locations ;
http://www.tahc.state.tx.us/animal_health/diseases/cwd/CWD_Sampling_Aug2005.pdf
THREE NEW CASES OF CWD were announced in this same location this month ;
FOR IMMEDIATE RELEASE, JULY 7, 2006:
3 SOUTHERN NEW MEXICO DEER TEST POSITIVE FOR CHRONIC WASTING DISEASE
SANTA FE - Three deer in southern New Mexico have tested positive for chronic wasting disease, bringing the total number of confirmed CWD-infected deer in the state to 15 since the first infected deer was discovered in 2002.
The Department received test results Wednesday from the state Veterinary Diagnostic Services laboratory in Albuquerque that two wild deer captured near the White Sands Missile Range headquarters east of Las Cruces had tested positive for chronic wasting disease. A third wild deer captured in the small community of Timberon in the southern Sacramento Mountains also tested positive for the disease.
The discoveries of the infected deer were part of the Department's ongoing efforts to monitor the disease, which to date has been confined to the southern Sacramento Mountains southeast of Cloudcroft and areas surrounding the Organ Mountains near Las Cruces. Two wild elk from the southern Sacramento Mountains tested positive for the disease in December 2005.
Chronic wasting disease is a fatal neurological illness that afflicts deer, elk and moose. There is no evidence of CWD being transmitted to humans or livestock. The disease causes animals to become emaciated, display abnormal behavior and lose control of bodily functions. To date, it has been found in captive and wild deer, elk and moose in eight states and two Canadian provinces.
For more information about CWD in New Mexico and how hunters can assist in research and prevention, please visit the New Mexico Department of Game and Fish Web site, www.wildlife.state.nm.us . More information about CWD also can be found on the Chronic Wasting Disease Alliance site at www.cwd-info.org/ .
###
http://www.wildlife.state.nm.us/publications/press_releases/documents/2006/0707CWD.htm
SEE MAP NM
http://www.wildlife.state.nm.us/documents/cwdcontrolmap.pdf
STATE CWD INFORMATION
http://www.aphis.usda.gov/vs/nahps/cwd/cwd-stateinfo.html
AND of course all this mad cow feed STILL IN COMMERCE, would have nothing to do with these atypical BSE/TSE showin up in the USA ???
Subject: MAD COW FEED RECALLS ENFORCEMENT REPORT FOR AUGUST 9, 2006 KY, LA, MS, AL, GA, AND TN 11,000+ TONS
Date: August 16, 2006 at 9:19 am PST
http://www.fda.gov/bbs/topics/ENFORCE/2006/ENF00964.html
GOTTA LOVE THOSE FDA/USDA TRIPLE BSE FIREWALLS. ...TSS
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
From: Terry S. Singeltary Sr.
To: Bovine Spongiform Encephalopathy
Cc: [email protected] ; [email protected] ; [email protected]
Sent: Saturday, August 19, 2006 10:27 AM
Subject: 'Atypical' strain of BSE found in U.S. cattle
Subject: 'Atypical' strain of BSE found in U.S. cattle
Date: August 19, 2006 at 7:28 am PST
RapidCityJournal.com
Friday, August 18, 2006
'Atypical' strain of BSE found in U.S. cattle
By Chris Clayton, DTN Staff Reporter, and Journal staff
The two cases of bovine spongiform encephalopathy found in U.S. cattle over the past year came from a rare strain of BSE found largely in Europe that scientists are only beginning to identify, according to research by a French scientist.
Researchers in France and Italy who presented their work at an international conference in London reported two rare strains of bovine spongiform encephalopathy that are harder to detect and affect mainly older cattle.
Thierry Baron of the French Food Safety Agency presented research indicating that a 12-year-old Texas cow testing positive for BSE last June, and the 10-year-old Alabama cow that tested positive in March, showed identical testing patterns to a small number of BSE cases in France, Sweden and Poland.
Animal scientists are calling such strains "atypical" BSE, which is different from the "typical" BSE caused by cattle eating feed with ruminant offal contaminated with a BSE protein.
They don't know whether the atypical strains are caused by something else or simply appear spontaneously in older, susceptible cattle.
Art Davis, a U.S. Department of Agriculture scientist for the Animal and Plant Health Inspection Service at the National Veterinary Services Laboratory in Ames, Iowa, said in his presentation Sunday at the London conference that the Texas and Alabama test results showed completely different prion patterns than the Washington state case discovered in December 2003.
"The classical lesions were not there," Davis said of the cases. The Washington state cow originated in Alberta, Canada, near where several other BSE cases have been found.
The "typical" BSE strain caused a mad cow disease epidemic in Great Britain beginning in the mid-1980s that killed 184,000 cattle and more than 100 people who contracted a human form of the disease caused by eating contaminated beef products.
The scientific evidence shows that in almost all cattle cases, the fatal neurological disorder was contracted through contaminated meat and bone meal fed to the cow, typically at a young age.
However, scientists finding atypical cases of BSE are beginning to question if there has been a change in the abnormal protein that causes BSE or if cattle might be susceptible to a sporadic BSE affecting older cattle.
Danny Matthews, head of transmissible spongiform encephalopathies at England's Veterinary Laboratories Agency, said recent research on atypical cases of BSE raises questions over whether older cattle can sporadically get the disease or if there are more strains of BSE than previously understood. Scientists might also be facing something new, such as "son of BSE," he said.
"We don't fully understand what atypical BSE means," Matthews said. "Is it spontaneous or another source causing it? Time will tell."
Although the test patterns in the U.S. cases and atypical cases in Europe closely matched, Baron said there were no known links among any of the positive animals. The French Food Safety Agency sent a researcher to the United States to study the positive Texas case and compare its results to known cases in France that did not match the typical BSE positive tests.
"You could place them side-by-side and not tell the difference," Baron said.
Baron also raised the prospect that the disease could be sporadic in at least a small number of older cattle. He said, however, such a conclusion would be hard to determine because of the small number of cattle with this atypical strain globally.
Dr. Sam Holland, South Dakota's state veterinarian, said there are many strains of BSE and varying degrees of infectiousness of the agent.
"What if the scenario is there is an atypical prion out there that is much less infective, has a longer incubation period and has not been recognized as part of the Great Britain BSE experience identified in 1985 and '86?" Holland said. "There could be others out there that we haven't recognized yet."
He said it is possible the atypical strains are not caused by contaminated feed.
He said it still makes sense to continue the ban on ruminant offal in cattle feed to prevent the spread of typical BSE and eventually to eliminate that disease.
"Based on what we know about BSE, it makes good sense to, number one, keep some surveillance in place; number two, watch what we import and restrict shipments and movements from places that have had those syndromes; and, number three, with what we know about BSE, it seems to be very prudent to keep our ruminant offal ban in place," Holland said. "At least for typical BSE's, it seems to be very effective. It's probably reasonable to continue the ruminant offal ban even after the last typical BSE case has been eliminated."
Editor's note: DTN, a private company based in Omaha, Neb., provides information to agriculture, energy trading markets and other weather-sensitive industries. The Rapid City Journal received a copy of DTN's story and expanded on it.
http://www.rapidcityjournal.com/articles/2006/05/31/news/local/news05.txt
Coincidently, this very important factor was left out of the above newspaper article, typical rubber stamping of the USDA et al by the media. I mean, its part of the damn title of the study. YOU would think it important enough to have added this very important factor in the newspaper article ;
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.
snip...
http://www.cdc.gov/ncidod/EID/vol12no07/pdfs/vol12no07.pdf
Published online before print February 17, 2004, 10.1073/pnas.0305777101
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.cdc.gov/ncidod/EID/vol12no07/pdfs/vol12no07.pdf
DISPATCHES
1126 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 12, No. 7, July 2006
snip...
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.
snip...
http://www.cdc.gov/ncidod/EID/vol12no07/pdfs/vol12no07.pdf
Atypical cases of TSE in cases of TSE in
cattle and sheep cattle and sheep
H. De H. De Bosschere Bosschere
CODA/CERVA CODA/CERVA
Nat. Ref. Lab. Vet. Nat. Ref. Lab. Vet. TSEs TSEs
Belgium
http://www.var.fgov.be/pdf/1100_TSEDAY.pdf
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
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/
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/
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 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
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
Subject: SCRAPIE and CWD USA UPDATE July 19, 2006
Date: July 19, 2006 at 12:06 pm PST
SCRAPIE USA UPDATE MAY 31, 2006
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.
snip...
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). ...
snip...END
http://www.aphis.usda.gov/vs/nahps/scrapie/monthly_report/monthly-report.html
DRAFT
WYOMING GAME AND FISH DEPARTMENT
CHRONIC WASTING DISEASE MANAGEMENT PLAN
February 17, 2006
snip...
5. Predicted population effects on free-ranging elk based on captive elk chronically exposed to the CWD prion.
Forty-three female elk calves were trapped at the National Elk Refuge and transported to Sybille in February 2002. Elk were housed in pens, assumed to be environmentally contaminated with the CWD prion. Elk will be held throughout their lifetimes. Elk dying will be examined and cause of death determined. From these data, it will should be possible to model free-ranging elk mortality and population dynamics under extreme circumstances of CWD prion exposure and transmission. As of December 2005 (46 months post capture), 11 of 43 elk have died due to CWD. This compares to 100% mortality in less than 25 months in elk orally inoculated with different dosages of the CWD prion.
REVISED DRAFT
http://gf.state.wy.us/downloads/pdf/CWD2005reviseddraft.pdf
Prions in Skeletal Muscles of Deer with Chronic Wasting Disease
Rachel C. Angers,1* Shawn R. Browning,1*† Tanya S. Seward,2 Christina J.
Sigurdson,4‡ Michael W. Miller,5 Edward A. Hoover,4 Glenn C. Telling1,2,3§
1Department of Microbiology, Immunology and Molecular Genetics, 2Sanders
Brown Center on Aging, 3Department of Neurology, University of Kentucky,
Lexington, KY 40536, USA. 4Department of Microbiology, Immunology and
Pathology, Colorado State University, Fort Collins, CO 80523, USA. 5Colorado
Division of Wildlife, Wildlife Research Center, Fort Collins, CO 80526, USA.
*These authors contributed equally to this work.
†Present address: Department of Infectology, Scripps Research Institute,
5353 Parkside Drive, RF-2, Jupiter, Florida, 33458, USA.
‡Present address: Institute of Neuropathology, University of Zurich,
Schmelzbergstrasse 12, 8091 Zurich, Switzerland.
§To whom correspondence should be addressed: E-mail: [email protected]
Prions are transmissible proteinaceous agents of mammals that cause fatal
neurodegenerative diseases of the central nervous system (CNS). The presence
of infectivity in skeletal muscle of experimentally infected mice raised the
possibility that dietary exposure to prions might occur through meat
consumption (1). Chronic wasting disease (CWD), an enigmatic and contagious
prion disease of North American cervids, is of particular concern. The
emergence of CWD in an increasingly wide geographic area and the
interspecies transmission of bovine spongiform encephalopathy (BSE) to
humans as variant Creutzfeldt Jakob disease (vCJD) have raised concerns
about zoonotic transmission of CWD.
To test whether skeletal muscle of diseased cervids contained prion
infectivity, Tg(CerPrP)1536 mice (2) expressing cervid prion protein
(CerPrP), were inoculated intracerebrally with extracts prepared from the
semitendinosus/semimembranosus muscle group of CWD-affected mule deer or
from CWD-negative deer. The availability of CNS materials also afforded
direct comparisons of prion infectivity in skeletal muscle and brain. All
skeletal muscle extracts from CWD-affected deer induced progressive
neurological dysfunction in Tg(CerPrP)1536 mice with mean incubation times
ranging between 360 and ~490 d, whereas the incubation times of prions from
the CNS ranged from ~230 to 280 d (Table 1). For each inoculation group, the
diagnosis of prion disease was confirmed by the presence of PrPSc in the
brains of multiple infected Tg(CerPrP)1536 mice (see supporting online
material for examples). In contrast, skeletal muscle and brain material from
CWD-negative deer failed to induce disease in Tg(CerPrP)1536 mice (Table 1)
and PrPSc was not detected in the brains of sacrificed asymptomatic mice as
late as 523 d after inoculation (supporting online material).
Our results show that skeletal muscle as well as CNS tissue of deer with CWD
contains infectious prions. Similar analyses of skeletal muscle BSE-affected
cattle did not reveal high levels of prion infectivity (3). It will be
important to assess the cellular location of PrPSc in muscle. Notably, while
PrPSc has been detected in muscles of scrapie-affected sheep (4), previous
studies failed to detect PrPSc by immunohistochemical analysis of skeletal
muscle from deer with natural or experimental CWD (5, 6). Since the time of
disease onset is inversely proportional to prion dose (7), the longer
incubation times of prions from skeletal muscle extracts compared to matched
brain samples indicated that prion titers were lower in muscle than in CNS
where infectivity titers are known to reach high levels. Although possible
effects of CWD strains or strain mixtures on these incubation times cannot
be excluded, the variable 360 to ~490 d incubation times suggested a range
of prion titers in skeletal muscles of CWD-affected deer. Muscle prion
titers at the high end of the range produced the fastest incubation times
that were ~30% longer than the incubation times of prions from the CNS of
the same animal. Since all mice in each inoculation group developed disease,
prion titers in muscle samples producing the longest incubation times were
higher than the end point of the bioassay, defined as the infectious dose at
which half the inoculated mice develop disease. Studies are in progress to
accurately assess prion titers.
While the risk of exposure to CWD infectivity following consumption of
prions in muscle is mitigated by relatively inefficient prion transmission
via the oral route (8), these
results show that semitendinosus/semimembranosus muscle, which is likely to
be consumed by humans, is a significant source of prion infectivity. Humans
consuming or handling meat from CWD-infected deer are therefore at risk to
prion exposure.
References and Notes
1. P. J. Bosque et al., Proc. Natl. Acad. Sci. U.S.A. 99, 3812 (2002).
2. S. R. Browning et al., J. Virol. 78, 13345 (2004).
3. A. Buschmann, M. H. Groschup, J. Infect. Dis. 192, 934 (2005).
4. O. Andreoletti et al., Nat. Med. 10, 591 (2004).
5. T. R. Spraker et al., Vet. Pathol. 39, 110 (2002).
6. A. N. Hamir, J. M. Miller, R. C. Cutlip, Vet. Pathol. 41, 78 (2004).
7. S. B. Prusiner et al., Biochemistry 21, 4883 (1980).
8. M. Prinz et al., Am. J. Pathol. 162, 1103 (2003).
9. This work was supported by grants from the U.S. Public Health Service
2RO1 NS040334-04 from the National Institute of Neurological Disorders and
Stroke and N01-AI-25491 from the National Institute of Allergy and
Infectious Diseases.
Supporting Online Material
www.sciencemag.org/
Materials and Methods
Fig. S1
21 November 2005; accepted 13 January 2006 Published online 26 January 2006;
10.1126/science.1122864 Include this information when citing this paper.
Table 1. Incubation times following inoculation of Tg(CerPrP)1536 mice with
prions from skeletal muscle and brain samples of CWD-affected deer.
Inocula Incubation time, mean d ± SEM (n/n0)*
Skeletal muscle Brain
CWD-affected deer
H92 360 ± 2 d (6/6) 283 ± 7 d (6/6)
33968 367 ± 9 d (8/8) 278 ± 11 d (6/6)
5941 427 ± 18 d (7/7)
D10 483 ± 8 d (8/8) 231 ± 17 d (7/7)
D08 492 ± 4 d (7/7)
Averages 426 d 264 d
Non-diseased deer
FPS 6.98 >523 d (0/6)
FPS 9.98 >454 d (0/7) >454 d (0/6)
None >490 d (0/6)
PBS >589 d (0/5)
*The number of mice developing prion disease divided by the original number
of inoculated mice is shown in parentheses. Mice dying of intercurrent
illnesses were excluded.
http://www.sciencemag.org/
www.sciencemag.org/
Supporting Online Material for
Prions in Skeletal Muscles of Deer with Chronic Wasting Disease
Rachel C. Angers, Shawn R. Browning, Tanya S. Seward, Christina J.
Sigurdson,
Michael W. Miller, Edward A. Hoover, Glenn C. Telling§
§To whom correspondence should be addressed: E-mail: [email protected]
Published 26 January 2006 on Science Express
DOI: 10.1126/science.1122864
This PDF file includes:
Materials and Methods
Fig. S1
Supporting Online Materials
Materials and Methods
Homogenates of semitendinosus/semimembranosus muscle (10% w/v in phosphate
buffered saline) were prepared from five emaciated and somnolent mule deer,
naturally
infected with CWD at the Colorado Division of Wildlife, Wildlife Research
Center.
These deer were identified as D10, D08, 33968, H92, and 5941. CWD infection
was
confirmed in all cases by the presence of histologic lesions in the brain
including
spongiform degeneration of the perikaryon, the immunohistochemical detection
of
disease-associated PrP in brain and tonsil, or by immunoblotting of
protease-resistant,
disease associated PrP (CerPrPSc). Semitendinosus/semimembranosus muscle was
also
obtained from two asymptomatic, mock inoculated deer, referred to as FPS
6.68 and 9.98,
that originated from a CWD non-endemic area and which were held indoors at
Colorado
State University from ten days of age. These control deer were confirmed
negative for
CWD by histopathological and immunohistochemical analysis of brain tissue at
autopsy.
The utmost care was taken to avoid inclusion of obvious nervous tissue when
muscle
biopsies were prepared and to ensure that contamination of skeletal muscle
samples with
CNS tissue did not occur. Fresh, single-use instruments were used to collect
each sample
biopsy and a central piece from each sample was prepared with fresh,
disposable
instruments to further isolate muscle tissue for inoculum preparation. Brain
samples for
transmission were prepared separately from muscle as additional insurance
against cross
contamination.
1
Groups of anesthetized Tg(CerPrP)1536 mice were inoculated intracerebrally
with 30 µl
of 1 % skeletal muscle or brain extracts prepared in phosphate buffered
saline (PBS).
Inoculated Tg(CerPrP) mice were diagnosed with prion disease following the
progressive
development of at least three neurologic symptoms including truncal ataxia,
‘plastic’ tail,
loss of extensor reflex, difficultly righting, and slowed movement. The time
from
inoculation to the onset of clinical signs is referred to as the incubation
time.
For PrP analysis in brain extracts of Tg(CerPrP)1536 mice, 10 % homogenates
prepared
in PBS were either untreated (-) or treated (+) with 40 µg/ml proteinase K
(PK) for one
hour at 37oC in the presence of 2% sarkosyl. Proteins were separated by
sodium dodecyl
sulfate polyacrylamide gel electrophoresis, analyzed by immunoblotting using
anti PrP
monoclonal antibody 6H4 (Prionics AG, Switzerland), incubated with
appropriate
secondary antibody, developed using ECL-plus detection (Amersham), and
analyzed
using a FLA-5000 scanner (Fuji).
2
Fig. S1
PrP in brain extracts from representative Tg(CerPrP)1536 mice receiving
muscle or CNS
tissue inocula from CWD-affected or CWD-negative deer. Extracts were either
treated
(+) or untreated (-) with proteinase K (PK) as indicated. The positions of
protein
molecular weight markers at 21.3, 28.7, 33.5 kDa (from bottom to top) are
shown to the
left of the immunoblot.
3
http://www.sciencemag.org/
Chronic Wasting Disease and Potential Transmission to Humans
Ermias D. Belay,* Ryan A. Maddox,* Elizabeth S. Williams,† Michael W. Miller,‡ Pierluigi Gambetti,§ and Lawrence B. Schonberger*
*Centers for Disease Control and Prevention, Atlanta, Georgia, USA; †University of Wyoming, Laramie, Wyoming, USA; ‡Colorado Division of Wildlife, Fort Collins, Colorado, USA; and §Case Western Reserve University, Cleveland, Ohio, USA
Suggested citation for this article: Belay ED, Maddox RA, Williams ES, Miller MW, Gambetti P, Schonberger LB. Chronic wasting disease and potential transmission to humans. Emerg Infect Dis [serial on the Internet]. 2004 Jun [date cited]. Available from: http://www.cdc.gov/ncidod/EID/vol10no6/03-1082.htm
http://www.cdc.gov/ncidod/EID/vol10no6/03-1082.htm
Research
Environmental Sources of Prion Transmission in Mule Deer
Michael W. Miller,* Elizabeth S. Williams,† N. Thompson Hobbs,‡ and Lisa L. Wolfe*
*Colorado Division of Wildlife, Fort Collins, Colorado, USA; †University of Wyoming, Laramie, Wyoming, USA; and ‡Colorado State University, Fort Collins, Colorado, USA
Suggested citation for this article: Miller MW, Williams ES, Hobbs NT, Wolfe LL. Environmental sources of prion transmission in mule deer. Emerg Infect Dis [serial on the Internet]. 2004 Jun [date cited]. Available from: http://www.cdc.gov/ncidod/EID/vol10no6/04-0010.htm
http://www.cdc.gov/ncidod/EID/vol10no6/04-0010.htm
ATYPICAL TSEs in USA CATTLE AND SHEEP ?
http://www.bseinquiry.gov.uk/files/sc/seac17/tab03.pdf
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf
CWD MAP
NOTICE CWD creeping its way to TEXAS, literally to it's border. ...
http://www.aphis.usda.gov/vs/nahps/cwd/images/counties_lg.jpg
THEN NOTICE CWD sample along that border in TEXAS, Three Year Summary of Hunter-Kill CWD sampling as of 31 August 2005 of only 191 samples, then compare to the other sample locations ;
http://www.tahc.state.tx.us/animal_health/diseases/cwd/CWD_Sampling_Aug2005.pdf
THREE NEW CASES OF CWD were announced in this same location this month ;
FOR IMMEDIATE RELEASE, JULY 7, 2006:
3 SOUTHERN NEW MEXICO DEER TEST POSITIVE FOR CHRONIC WASTING DISEASE
SANTA FE - Three deer in southern New Mexico have tested positive for chronic wasting disease, bringing the total number of confirmed CWD-infected deer in the state to 15 since the first infected deer was discovered in 2002.
The Department received test results Wednesday from the state Veterinary Diagnostic Services laboratory in Albuquerque that two wild deer captured near the White Sands Missile Range headquarters east of Las Cruces had tested positive for chronic wasting disease. A third wild deer captured in the small community of Timberon in the southern Sacramento Mountains also tested positive for the disease.
The discoveries of the infected deer were part of the Department's ongoing efforts to monitor the disease, which to date has been confined to the southern Sacramento Mountains southeast of Cloudcroft and areas surrounding the Organ Mountains near Las Cruces. Two wild elk from the southern Sacramento Mountains tested positive for the disease in December 2005.
Chronic wasting disease is a fatal neurological illness that afflicts deer, elk and moose. There is no evidence of CWD being transmitted to humans or livestock. The disease causes animals to become emaciated, display abnormal behavior and lose control of bodily functions. To date, it has been found in captive and wild deer, elk and moose in eight states and two Canadian provinces.
For more information about CWD in New Mexico and how hunters can assist in research and prevention, please visit the New Mexico Department of Game and Fish Web site, www.wildlife.state.nm.us . More information about CWD also can be found on the Chronic Wasting Disease Alliance site at www.cwd-info.org/ .
###
http://www.wildlife.state.nm.us/publications/press_releases/documents/2006/0707CWD.htm
SEE MAP NM
http://www.wildlife.state.nm.us/documents/cwdcontrolmap.pdf
STATE CWD INFORMATION
http://www.aphis.usda.gov/vs/nahps/cwd/cwd-stateinfo.html
AND of course all this mad cow feed STILL IN COMMERCE, would have nothing to do with these atypical BSE/TSE showin up in the USA ???
Subject: MAD COW FEED RECALLS ENFORCEMENT REPORT FOR AUGUST 9, 2006 KY, LA, MS, AL, GA, AND TN 11,000+ TONS
Date: August 16, 2006 at 9:19 am PST
http://www.fda.gov/bbs/topics/ENFORCE/2006/ENF00964.html
GOTTA LOVE THOSE FDA/USDA TRIPLE BSE FIREWALLS. ...TSS
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518