QUESTION said:
What the H*LL is wrong with the USDA. The evidence clearly shows animals exhibiting high risk behavior for BSE or BASE, downers going into the human food chain that is a feedban violation. Recall it all and dump it. Yeah the animals were treated badly but the more pressing issue is that school kids could be eating BSE or BASE contaminated meat. Well i guess it will take a few years for it to incubate by then the company owners will shut the doors and take the profits and laugh about how many US people are showing signs of vCJD. :roll:
PLEASE note, the Texas confirmed mad cow was atypical h-base bse.
WHAT THIS Texas cow was, we will never know if it was BSE or BASE a-z. ...tss
FOR IMMEDIATE RELEASE
Statement
May 4, 2004
Media Inquiries: 301-827-6242
Consumer Inquiries: 888-INFO-FDA
Statement on Texas Cow With Central Nervous System Symptoms
On Friday, April 30 th , the Food and Drug Administration learned that a cow with central nervous system symptoms had been killed and shipped to a processor for rendering into animal protein for use in animal feed.
FDA, which is responsible for the safety of animal feed, immediately began an investigation. On Friday and throughout the weekend, FDA investigators inspected the slaughterhouse, the rendering facility, the farm where the animal came from, and the processor that initially received the cow from the slaughterhouse.
FDA's investigation showed that the animal in question had already been rendered into "meat and bone meal" (a type of protein animal feed). Over the weekend FDA was able to track down all the implicated material. That material is being held by the firm, which is cooperating fully with FDA.
Cattle with central nervous system symptoms are of particular interest because cattle with bovine spongiform encephalopathy or BSE, also known as "mad cow disease," can exhibit such symptoms. In this case, there is no way now to test for BSE. But even if the cow had BSE, FDA's animal feed rule would prohibit the feeding of its rendered protein to other ruminant animals (e.g., cows, goats, sheep, bison).
FDA is sending a letter to the firm summarizing its findings and informing the firm that FDA will not object to use of this material in swine feed only. If it is not used in swine feed, this material will be destroyed. Pigs have been shown not to be susceptible to BSE. If the firm agrees to use the material for swine feed only, FDA will track the material all the way through the supply chain from the processor to the farm to ensure that the feed is properly monitored and used only as feed for pigs.
To protect the U.S. against BSE, FDA works to keep certain mammalian protein out of animal feed for cattle and other ruminant animals. FDA established its animal feed rule in 1997 after the BSE epidemic in the U.K. showed that the disease spreads by feeding infected ruminant protein to cattle.
Under the current regulation, the material from this Texas cow is not allowed in feed for cattle or other ruminant animals. FDA's action specifying that the material go only into swine feed means also that it will not be fed to poultry.
FDA is committed to protecting the U.S. from BSE and collaborates closely with the U.S. Department of Agriculture on all BSE issues. The animal feed rule provides crucial protection against the spread of BSE, but it is only one of several such firewalls. FDA will soon be improving the animal feed rule, to make this strong system even stronger.
####
http://www.fda.gov/bbs/topics/news/2004/NEW01061.html
Communicated by:
ProMED-mail <
[email protected]>
******
[2] USA: National Prion Disease Pathology Surveillance Center
Date: June 2007
Source: National Prion Disease Pathology Surveillance Center (USA) [edited]
<http://www.cjdsurveillance.com/pdf/case-table.pdf>
CJD Cases examined
----------------------
Year / Referrals / Prion disease / Sporadic / Familial / Iatrogenic / vCJD
1996 / 42 / 32 / 26 / 4 / 0 / 0
1997 / 115 / 68 / 57 / 9 / 0 / 0
1998 / 93 / 53 / 45 / 7 / 1 / 0
1999 / 114 / 69 / 61 / 8 / 0 / 0
2000 / 151 / 103 / 89 / 14 / 0 / 0
2001 / 208 / 116 / 106 / 9 / 0 / 0
2002 / 255 / 143 / 118 / 23 / 2 / 0
2003 / 272 / 174 / 132 / 41 / 0 / 0
2004 / 334 / 183 / 157 / 21 / 0 / 1*
2005 / 352 / 195 / 152 / 37 / 1 / 0
2006 / 372 / 186 / 143 / 30 / 0 / 1**
2007 / 120 / 68 / 35 / 7 / 0 / 0
TOTAL / 2428*** / 1390**** / 1121 / 210 / 4 / 2
*Acquired in UK
** Acquired in Saudi Arabia
*** Includes 17 inconclusive and 9 pending (1 from 2006, 8 from 2007.
**** Includes 17 non-vCJD type unknown (2 from 1996, 2 from 1997, 1
from 2001, 1 from 2003, 4 from 2004, 3 from 2005, 4 from 2006) and 36
type pending (2 from 2005, 8 from 2006, 26 from 2007).
Notes:
-- Cases are listed based on the year of death when available. If the
year of death is not available, the year of sample receipt is used.
-- Referrals: Cases with possible or probable prion disease from
which brain tissue or blood in the case of familial disease were submitted.
-- Inconclusive: Cases in which the samples were not sufficient to
make a diagnosis.
-- Non-vCJD type unknown are cases in which the tissue submitted was
adequate to establish the presence but not the type; in all cases,
vCJD could be excluded.
--
Communicated by:
Terry S. Singeltary Sr. <
[email protected]>
[In submitting these data, Terry S. Singeltary Sr. draws attention to
the steady increase in the "type unknown" category, which, according
to their definition, comprises cases in which vCJD could be excluded.
The total of 26 cases for the current year (2007) is disturbing,
possibly symptomatic of the circulation of novel agents.
Characterization of these agents should be given a high priority. - Mod.CP]
[see also:
snip...
************************************************************
Become a ProMED-mail Premium Subscriber at
<http://www.isid.org/ProMEDMail_Premium.shtml>
************************************************************
Visit ProMED-mail's web site at <http://www.promedmail.org>.
http://pro-med.blogspot.com/2007/11/proahedr-prion-disease-update-2007-07.html
SEE STEADY INCREASE IN SPORADIC CJD IN THE USA FROM
1997 TO 2006. SPORADIC CJD CASES TRIPLED, with phenotype
of 'UNKNOWN' strain growing. ...
http://www.cjdsurveillance.com/resources-casereport.html
There is a growing number of human CJD cases, and they were presented last
week in San Francisco by Luigi Gambatti(?) from his CJD surveillance
collection.
He estimates that it may be up to 14 or 15 persons which display selectively
SPRPSC and practically no detected RPRPSC proteins.
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf
PLEASE NOTE IN USA CJD UPDATE AS AT JUNE 2007, please note steady increase
in ''TYPE UNKNOWN''. ...TSS
1 Acquired in the United Kingdom; 2 Acquired in Saudi Arabia; 3 Includes 17
inconclusive and 9 pending (1 from 2006, 8
from 2007); 4 Includes 17 non-vCJD type unknown (2 from 1996, 2 from 1997, 1
from 2001, 1 from 2003, 4 from 2004, 3
from 2005, 4 from 2006) and 36 type pending (2 from 2005, 8 from 2006,
*** 26 from 2007)
http://www.cjdsurveillance.com/pdf/case-table.pdf
Volume 12, Number 12–December 2006
Perspective
On the Question of Sporadic or Atypical Bovine Spongiform Encephalopathy and
Creutzfeldt-Jakob Disease
Paul Brown,* Lisa M. McShane,† Gianluigi Zanusso,‡ and Linda Detwiler§
*Bethesda, Maryland, USA; †National Institutes of Health, Bethesda,
Maryland, USA; ‡University of Verona, Verona, Italy; and §Virginia-Maryland
Regional College of Veterinary Medicine, College Park, Maryland, USA
snip...
Sporadic CJD
The possibility that at least some cases of apparently sporadic CJD might be
due to infection by sporadic cases of BSE cannot be dismissed outright.
Screening programs needed to identify sporadic BSE have yet to be
implemented, and we know from already extant testing programs that at least
a proportion of infected animals have no symptoms and thus would never be
identified in the absence of systematic testing. Thus, sporadic BSE (or for
that matter, sporadic disease in any mammalian species) might be occurring
on a regular basis at perhaps the same annual frequency as sporadic CJD in
humans, that is, in the range of 1 case per million animals.
Whether humans might be more susceptible to atypical forms of BSE cannot be
answered at this time. Experimentally transmitted BASE shows shorter
incubation periods than BSE in at least 1 breed of cattle, bovinized
transgenic mice, and Cynomolgus monkeys (12,13). In humanized transgenic
mice, BASE transmitted, whereas typical BSE did not transmit (13).
Paradoxically, the other major phenotype (H) showed an unusually long
incubation period in bovinized transgenic mice (12).
The limited experimental evidence bearing on a possible relationship between
BSE and sporadic CJD is difficult to interpret. The original atypical BASE
strain of BSE had a molecular protein signature very similar to that of 1
subtype (type 2 M/V) of sporadic CJD in humans (5). In another study, a
strain of typical BSE injected into humanized mice encoding valine at codon
129 showed a glycopattern indistinguishable from the same subtype of
sporadic CJD (15). In a third study, the glycopatterns of both the H and L
strains of atypical BSE evidently did not resemble any of the known sporadic
CJD subtypes (12).
To these molecular biology observations can be added the epidemiologic data
accumulated during the past 30 years. The hypothesis that at least some
cases of apparently sporadic CJD are due to unrecognized BSE infections
cannot be formally refuted, but if correct, we might expect by now to have
some epidemiologic evidence linking BSE to at least 1 cluster of apparently
sporadic cases of CJD. Although only a few clusters have been found (and
still fewer published), every proposed cluster that has been investigated
has failed to show any common exposure to bovines. For that matter, no
common exposure has been shown to any environmental vehicles of infection,
including the consumption of foodstuffs from bovine, ovine, and porcine
sources, the 3 livestock species known to be susceptible to transmissible
spongiform encephalopathies. Additional negative evidence comes from several
large case-control studies in which no statistically significant dietary
differences were observed between patients with sporadic CJD and controls
(16,17).
On the other hand, the difficulty of establishing a link between BSE and CJD
may be compounded by our ignorance of the infectious parameters of a
sporadic form of BSE (e.g., host range, tissue distribution of infectivity,
route of transmission, minimum infectious dose for humans, whether single or
multiple). Presumably, these parameters would resemble those of variant CJD;
that is, high infectivity central nervous system and lymphoreticular tissues
of an infected cow find their way into products consumed by humans.
Transmissions that might have occurred in the past would be difficult to
detect because meat products are generally not distributed in a way that
results in detectable geographic clusters.
Barring the discovery of a specific molecular signature (as in variant CJD),
the most convincing clue to an association will come from the observation of
trends over time of the incidence of typical and atypical BSE and of
sporadic and variant CJD. With 4 diseases, each of which could have
increasing, unchanging, or decreasing trends, there could be 81 (34)
possible different combinations. However, it is highly likely that the
trends for typical BSE and variant CJD will both decrease in parallel as
feed bans continue to interrupt recycled contamination. The remaining
combinations are thus reduced to 9 (32), and some of them could be highly
informative.
For example, if the incidence of atypical BSE declines in parallel with that
of typical BSE, its candidacy as a sporadic form of disease would be
eliminated (because sporadic disease would not be influenced by current
measures to prevent oral infection). If, on the other hand, atypical BSE
continues to occur as typical BSE disappears, this would be a strong
indication that it is indeed sporadic, and if in addition at least 1 form of
what is presently considered as sporadic CJD (such as the type 2 M/V subtype
shown to have a Western blot signature like BASE) were to increase, this
would suggest (although not prove) a causal relationship (Figure 5).
Recognition of the different forms of BSE and CJD depends upon continuing
systematic testing for both bovines and humans, but bovine testing will be
vulnerable to heavy pressure from industry to dismantle the program as the
commercial impact of declining BSE cases ceases to be an issue. Industry
should be aware, however, of the implications of sporadic BSE. Its
occurrence would necessitate the indefinite retention of all of the public
health measures that exclude high-risk bovine tissues from the animal and
human food chains, whereas its nonoccurrence would permit tissues that are
now destroyed to be used as before, once orally acquired BSE has
disappeared.
http://www.cdc.gov/ncidod/EID/vol12no12/06-0965.htm
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734.
http://jama.ama-assn.org/http://www.neurology.org/cgi/eletters/60/2/176#535
please notice Texas 2006 ;
† Confirmed in United Kingdom and reported to Texas Department of State
Health Services
through Centers for Disease Control and Prevention.
Only 1 case of variant
CJD has ever been diagnosed in Texas.
The patient was a former resident of the
United Kingdom, where the exposure
was likely to have occurred. Texas has a
population of 23 million, and since the
national rate of sporadic CJD is about 1
per million, it is expected that
approximately 23 cases of CJD would
occur each year in the state. Therefore,
it is believed that CJD is currently underreported
in Texas. ...END...TSS
also see ;
http://www.dshs.state.tx.us/idcu/disease/creutzfeldt-jakob/data/
Creutzfeldt-Jakob Disease in Northeast Texas,
J.A. Rawlings,*1 K.A.
Hendricks1, O.M. Nuno1, D.A. Brown1, D.A. Evans2, Texas Department of
Health, 1Austin and 2Tyler, Texas
Creutzfeldt-Jacob Disease (CJD), a transmissible spongiform
encephalopathy, is caused by prions composed of proteinaceous material
devoid of nucleic acid. CJD occurs sporadically (generally 1
case/1,000,000 population per year) in older patients (average age of
65) and is characterized by rapidly progressive dementia, accompanied by
severe muscle spasms and incoordination. Death usually occurs within 3
to 12 months (average 7 months). CJD activity in Texas, which has a
population of nearly 19 million, appeared to be typical. The statewide
death rate for 1995 and 1996 was just under 1/1,000,000. In April of
1997, the Texas Department of Health became aware of an increased number
of possible CJD cases in a 23-county area of NE Texas with a population
of just over one million. After review of medical and pathology records,
four patients were identified with definite classic CJD and three were
identified with probable CJD. Dates of death for the eight patients were
from April, 1996 through mid-July 1997. The patients were from 46
through 65 years of age; four were male and three were female. A
case-control study to identify risks for CJD in NE Texas has been initiated.
http://www.jifsan.umd.edu/tse/Rawlings.htm
Division of Neuropathology
Pierluigi Gambetti, M.D.,
Director
-----------------------------------
CASE WESTERN RESERVE UNIVERSITY
March 30, 1998
Dr. Gerald A, Campbell
The University of Texas
Medical Branch at Galveston
Division of Neuropathology
Department of Pathology
Galveston, Texas
Dear Dr Campbell,
We performed Western immunoblot analysis on the frozen tissue from your case
#AU97-435 (our #098-28). The Immunoblot reveals the presence of
protease-resistant prion protein (PrPres) confirming the diagnosis of prion
disease. The immunoblot pattern of PrPres is consistent with the diagnosis
of Creutzfeldt-Jakob disease.
Thank you for referring to us this interesting case.
Sincerely,
Piero Parchi, M.D.
Pierluigi Gambetti, M.D.
PP:sbDivision of Neuropathology
Pierluigi Gambetti, M.D.,
Director
Case Western Reserve University
snip...end
-------- Original Message --------
Subject: re-BSE prions propagate as either variant CJD-like or sporadic CJD
Date: Thu, 28 Nov 2002 10:23:43-0000
From: "Asante, Emmanuel A" <
[email protected]>
To: "'mailto:
[email protected]"<
[email protected]>
Dear Terry,
I have been asked by Professor Collinge to respond to your request. I am a
Senior Scientist in the MRC Prion Unit and the lead author on the paper. I
have attached a pdf copy of the paper for your attention. Thank you for your
interest in the paper. In respect of your first question, the simple answer
is, yes. As you will find in the paper, we have managed to associate the
alternate phenotype to type 2 PrPSc, the commonest sporadic CJD. It is too
early to be able to claim any further sub-classification in respect of
Heidenhain variant CJD or Vicky Rimmer's version. It will take further
studies, which are on-going, to establish if there are sub-types to our
initial finding which we are now reporting. The main point of the paper is
that, as well as leading to the expected new variant CJD phenotype, BSE
transmission to the 129-methionine genotype can lead to an alternate
phenotype which is indistinguishable from type 2 PrPSc. I hope reading the
paper will enlighten you more on the subject. If I can be of any further
assistance please to not hesitate to ask.
Best wishes.
Emmanuel Asante
<>
____________________________________
Dr. Emmanuel A Asante MRC Prion Unit & Neurogenetics Dept. Imperial College
School of Medicine (St. Mary's) Norfolk Place, LONDON W2 1PG Tel: +44 (0)20
7594 3794 Fax: +44 (0)20 7706 3272 email:
[email protected]. (until
9/12/02)New e-mail:
[email protected].
(active from now)
____________________________________END...TSS
CJD, PrP Codon 129VV, Novel PrPSc in a Young British Woman
Wed Jan 2, 2008 16:5071.248.140.49
Creutzfeldt-Jakob Disease, Prion Protein Gene Codon 129VV, and a Novel PrPSc
Type in a Young British Woman
Simon Mead, PhD, MRCP; Susan Joiner, MSc; Melanie Desbruslais, BSc;
JonathanA. Beck, BSc; Michael O'Donoghue, PhD; Peter Lantos, FRCP; Jonathan
D. F.Wadsworth, PhD; John Collinge, FRSArch Neurol. 2007;64(12):1780-1784.
Background
Variant Creutzfeldt-Jakob disease (vCJD) is an acquired prion disease
causally related to bovine spongiform encephalopathy that has occurred
predominantly in young adults. All clinical cases studied have been
methionine homozygotes at codon 129 of the prion protein gene (PRNP) with
distinctive neuropathological findings and molecular strain type (PrPSc
type4). Modeling studies in transgenic mice suggest that other PRNP
genotypes will also be susceptible to infection with bovine spongiform
encephalopathy prions but may develop distinctive phenotypes.
Objective
To describe the histopathologic and molecular investigation in ayoung
British woman with atypical sporadic CJD and valine homozygosity at PRNP
codon 129.
Design Case report, autopsy, and molecular analysis.
Setting Specialist neurology referral center, together with the laboratory
services of the MRC [Medical Research Council] Prion Unit.
Subject Single hospitalized patient.
Main Outcome Measures Autopsy findings and molecular investigation results.
Results Autopsy findings were atypical of sporadic CJD, with marked gray and
white matter degeneration and widespread prion protein (PrP) deposition.
Lymphoreticular tissue was not available for analysis. Molecular analysis of
PrPSc (the scrapie isoform of PrP) from cerebellar tissue demonstrated a
novel PrPSc type similar to that seen in vCJD (PrPSc type 4). However, this
could be distinguished from the typical vCJD pattern by an altered protease
cleavage site in the presence of the metal ion chelator EDTA.
Conclusions Further studies will be required to characterize the prion
strain seen in this patient and to investigate its etiologic relationship
with bovine spongiform encephalopathy. This case illustrates the importance
of molecular analysis of prion disease, including the use of EDTA to
investigate the metal dependence of protease cleavage patterns of PrPSc.
Author Affiliations: MRC [Medical Research Council] Prion Unit and
Department of Neurodegenerative Disease, Institute of Neurology, University
College London, National Hospital for Neurology and Neurosurgery, London,
England (Drs Mead, Wadsworth, and Collinge; Mss Joiner and Desbruslais; and
Mr Beck); and Institute of Psychiatry, King's College London (Dr Lantos).
DrO'Donoghue is now with the Department of Clinical Neurology, Nottingham
University Hospitals NHS [National Health Service] Trust, Nottingham,
England.
http://archneur.ama-assn.org/cgi/content/short/64/12/1780
North American Equity Research
New York
13 January 2004
BSE (Mad Cow) Update:
Do Reports of sCJD Clusters Matter?
· There have been seven cases of human sCJD clusters identified in the
US in the last 15 years, in which people in a specific location were
diagnosed with sCJD, resulting in rates between 2.1 and 8.4 deaths per
million people for that specific location compared with the national
average of one in 1 million. · There is no proven link between sCJD and
BSE, and hence it is considered a different disease from vCJD (which has
been linked to BSE). However, the existence of clusters raises the
question of "contamination" or "infection", and also raises the
hypothesis that rather than cases of sCJD these might have been cases of
vCJD. · Clusters are not spontaneous, they normally have a source.
Moreover, some cases of sCJD may have been improperly diagnosed as
Alzheimer's.· We continue to believe that as long as no further cases of
BSE-positive cows are found in North America and the industry has
respected the 1997 ban on animal feed for live cattle, beef consumption
in the US will not suffer. · Moreover, due to political pressure we
expect key overseas markets (Japan, South Korea, and Mexico) to open up
to US beef in the next six months – the recent 20% drop in cattle prices
can be attributed mainly to these import bans. · However, two concerns
linger and should be kept in mind by investors, 1) Has the 1997 ban on
animal feed for live cattle been honored by the beef industry? 2) Can
clusters of cases of sporadic CJD (or sCJD) really be a variant of CJD
and indeed be linked to BSE? In this note we focus on the issue of sCJD
clusters, and the potential impact that the growing debate on clusters
could have on beef consumption in the US. United States Foods
Pablo E. Zuanic(1-212)
[email protected]. M.
Bledsoe(1-212)
[email protected].
Ogbonna(212)
[email protected].
State of Our Views Regarding BSE in the US
snip...
Existence of Clusters of sCJD May Imply They Are Really Cases of vCJD
There have been seven sCJD clusters identified in the US in the last 15
years, in which people in a specific location were diagnosed with sCJD,
resulting in rates between 1.2 and 8.4 deaths per million people for
that specific location compared with the national average of one in 1
million. The existence of clusters raises the question of
"contamination" or "infection", and also raises the hypothesis that
rather than cases of sCJD these might have been cases of vCJD. Clusters
are not spontaneous, they normally have a source.
A cluster consists of two statistical improbabilities: 1) multiple cases
occurring in a relatively limited geographic area, and 2) multiple cases
occurring within the same time period. The most recent cluster was found
in Cherry Hill, New Jersey. The others have been found in Lehigh,
Pennsylvania (1986-90), Allentown, Pennsylvania (1989-92), Tampa,
Florida (1996-97), Oregon (2001-02), and Nassau County, New York
(1999-2000). Given that sCJD occurs randomly in one out of one million
cases, it is a statistical rarity to find an sCJD cluster – let alone
six. The following tables highlight known clusters in the US.
Table 1:
Clustered sCJD Deaths
Local sCJD Deaths
Time Span State Local Area Pop. (MM) Period (mo.) Total Ann'lized
1986-1990 PA Lehigh Valley 0.5 48 18 4.5
1989-1992 PA Allentown 2.5 36 15 5.0
1996-1997 FL Tampa 2.2 18 13 8.7
1996-1999 TX Denton .01 38 4 1.3
1999-2000 NY Nassau County 1.3 12 7 7.0
2001-2002 OR Entire State 3.4 24 14 7.0
2000-2003* NJ Cherry Hill Area 1.7 36 12 4.0
Source: JPMorgan.
The second table, below, shows what portion of the state's total
expected sCJD cases (as based on a one per million occurrence) were
found in the local cluster, comparing the local cluster's portion of
cases with the local area's portion of the state's total population. The
greater the factor between the former and the latter suggests a higher
statistical improbability that the cluster is spontaneous (sCJD).
Table 2: Clustered sCJD Deaths vs. Expected State Cases
Annual Statewide Local Area (% of Time Span State Local Area sCJD Deaths*
exp. state cases state pop.
1986-1990 PA Lehigh Valley 11.9 37.8% 4.5%
1989-1992 PA Allentown 12.0 41.7% 20.8%
1996-1997 FL Tampa 14.1 61.5% 15.7%
1996-1999 TX Denton 20.9 6.1% .02%
1999-2000 NY Nassau County 18.1 38.7% 7.4%
2001-2002 OR Entire State 3.4 205.9% 100.0%
2000-2003* NJ Cherry Hill Area 8.0 50.0% 21.6%
* *State cases are extrapolated based on state population and the 1 per
million national average. Source: JPMorgan.
snip...
Copyright 2003 J.P. Morgan Chase & Co.—All rights reserved.
THIS MATERIAL IS ISSUED AND DISTRIBUTED IN MALAYSIA BY J.P. MORGAN
MALAYSIA SDN. BHD. (18146-X).
########### http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############
https://lists.aegee.org/cgi-bin/wa?A2=ind0401&L=BSE-L&T=0&F=&S=&P=25337
see full text ;
http://cjdtexas.blogspot.com/
http://bse-atypical.blogspot.com/2008/01/atypical-bovine-spongiform.html
FC5.5.1
BASE Transmitted to Primates and MV2 sCJD Subtype Share PrP27-30 and PrPSc
C-terminal Truncated Fragments Zanusso, G1; Commoy, E2; Fasoli, E3; Fiorini, M3; Lescoutra, N4; Ruchoux,
MM4; Casalone, C5; Caramelli, M5; Ferrari, S3; Lasmezas, C6; Deslys, J-P4; Monaco, S3
1University of Verona, of Neurological and Visual Sciences, Italy; 2CEA, IMETI/SEPIA,
France; 3University of Verona, Neurological and Visual Sciences, Italy; 4IMETI/SEPIA,
France; 5IZSPLVA, Italy; 6The Scripps Research Insitute, USA
The etiology of sporadic Creutzfeldt-Jakob disease (sCJD), the most frequent human
prion disease, remains still unknown. The marked disease phenotype heterogeneity
observed in sCJD is thought to be influenced by the type of proteinase K-resistant
prion protein, or PrPSc (type 1 or type 2 according to the electrophoretic mobility of
the unglycosylated backbone), and by the host polymorphic Methionine/Valine (M/V)
codon 129 of the PRNP. By using a two-dimensional gel electrophoresis (2D-PAGE)
and imunoblotting we previously showed that in sCJD, in addition to the PrPSc type,
distinct PrPSc C-terminal truncated fragments (CTFs) correlated with different sCJD
subtypes. Based on the combination of CTFs and PrPSc type, we distinguished three
PrPSc patterns: (i) the first was observed in sCJD with PrPSc type 1 of all genotypes,;
(ii) the second was found in M/M-2 (cortical form); (iii) the third in amyloidogenic M/V-
2 and V/V-2 subtypes (Zanusso et al., JBC 2004) . Recently, we showed that sCJD
subtype M/V-2 shared molecular and pathological features with an atypical form of
BSE, named BASE, thus suggesting a potential link between the two conditions. This
connection was further confirmed after 2D-PAGE analysis, which showed an identical
PrPSc signature, including the biochemical pattern of CTFs. To pursue this issue, we
obtained brain homogenates from Cynomolgus macaques intracerebrally inoculated
with brain homogenates from BASE. Samples were separated by using a two
dimensional electrophoresis (2D-PAGE) followed by immunoblotting. We here show
that the PrPSc pattern obtained in infected primates is identical to BASE and sCJD
MV-2 subtype. These data strongly support the link, or at least a common ancestry,
between a sCJD subtype and BASE.
This work was supported by Neuroprion (FOOD-CT-2004-506579)
FC5.5.2
Transmission of Italian BSE and BASE Isolates in Cattle Results into a Typical
BSE Phenotype and a Muscle Wasting Disease
Zanusso, G1; Lombardi, G2; Casalone, C3; D'Angelo, A4; Gelmetti, D2;
Torcoli, G2; Barbieri, I2; Corona, C3; Fasoli, E1; Farinazzo, A1; Fiorini, M1; Gelati,
M1; Iulini, B3; Tagliavini, F5; Ferrari, S1; Monaco, S1; Caramelli, M3; Capucci, L2
1University of Verona, Neurological and Visual Sciences, Italy; 2IZSLER, Italy; 3IZSPLVA,
Italy; 4University of Turin, Animal Pathology, Italy; 5Isituto Carlo Besta, Italy
The clinical phenotype of bovine spongiform encephalopathy has been extensively
reported in early accounts of the disorder. Following the introduction of statutory active
surveillance, almost all BSE cases have been diagnosed on a pathological/molecular
basis, in a pre-symptomatic clinical stage. In recent years, the active surveillance
system has uncovered atypical BSE cases, which are characterized by distinct
conformers of the PrPSc, named high-type (BSE-H) and low-type (BSE-L), whose
clinicopathological phenotypes remain unknown. We recently reported two
Italian atypical cases with a PrPSc type similar to BSE-L, pathologically characterized
by PrP amyloid plaques. Experimental transmission to TgBov mice has recently
disclosed that BASE is caused by a distinct prion strain which is extremely virulent. A
major limitation of transmission studies to mice is the lack of reliable information on
clinical phenotype of BASE in its natural host. In the present study, we experimentally
infected Fresian/Holstein and Alpine/Brown cattle with Italian BSE and BASE isolates
by i.c. route. BASE infected cattle showed survival times significantly shorter than
BSE, a finding more readily evident in Fresian/Holstein, and in keeping with previous
observations in TgBov mice. Clinically, BSE-infected cattle developed a disease
phenotype highly comparable with that described in field BSE cases and in
experimentally challenged cattle. On the contrary, BASE-inoculated cattle
developed an amyotrophic disorder accompanied by mental dullness.
The molecular and neuropathological profiles, including PrP deposition pattern, closely
matched those observed in the original cases. This study further confirms that BASE
is caused by a distinct prion isolate and discloses a novel disease phenotype in cattle,
closely resembling the phenotype previous reported in scrapie-inoculated cattle and in
some subtypes of inherited and sporadic Creutzfeldt-Jakob disease.
P04.27
Experimental BSE Infection of Non-human Primates: Efficacy of the Oral Route
Holznagel, E1; Yutzy, B1; Deslys, J-P2; Lasmézas, C2; Pocchiari, M3; Ingrosso, L3;
Bierke, P4; Schulz-Schaeffer, W5; Motzkus, D6; Hunsmann, G6; Löwer, J1
1Paul-Ehrlich-Institut, Germany; 2Commissariat à l´Energie Atomique, France;
3Instituto Superiore di Sanità, Italy; 4Swedish Institute for Infectious Disease
control, Sweden; 5Georg August University, Germany; 6German Primate Center,
Germany
Background:
In 2001, a study was initiated in primates to assess the risk for humans
to contract BSE through contaminated food. For this purpose, BSE brain was
titrated in cynomolgus monkeys.
Aims:
The primary objective is the determination of the minimal infectious dose (MID50)
for oral exposure to BSE in a simian model, and, by in doing this, to assess the risk for
humans. Secondly, we aimed at examining the course of the disease to identify
possible biomarkers.
Methods:
Groups with six monkeys each were orally dosed with lowering amounts of
BSE brain: 16g, 5g, 0.5g, 0.05g, and 0.005g. In a second titration study,
animals were intracerebrally (i.c.) dosed (50, 5, 0.5, 0.05, and 0.005 mg).
Results:
In an ongoing study, a considerable number of high-dosed macaques already
developed simian vCJD upon oral or intracerebral exposure or are at the
onset of the clinical phase. However, there are differences in the clinical course
between orally and intracerebrally infected animals that may influence the detection
of biomarkers.
Conclusions:
Simian vCJD can be easily triggered in cynomolgus monkeys on the oral
route using less than 5 g BSE brain homogenate. The difference in the
incubation period between 5 g oral and 5 mg i.c. is only 1 year (5 years versus 4
years). However, there are rapid progressors among orally dosed monkeys that
develop simian vCJD as fast as intracerebrally inoculated animals.
The work referenced was performed in partial fulfilment of the study "BSE in
primates" supported by the EU (QLK1-2002-01096).
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
Thursday, January 3, 2008
ANIMAL HEALTH REPORT 2006 (BSE h-BASE EVENT IN ALABAMA, Scrapie, and CWD)
http://animalhealthreport2006.blogspot.com/
TSS