Expression of genes involved in the T cell signalling pathway in circulating immune cells of cattle 24 months following oral challenge with Bovine Amyloidotic Spongiform Encephalopathy (BASE)
Research article
Abstract
Background Bovine Amyloidotic Spongiform Encephalopathy (BASE) is a variant of classical BSE that affects cows and can be transmitted to primates and mice. BASE is biochemically different from BSE and shares some molecular and histo-pathological features with the MV2 sub-type of human sporadic Creutzfeld Jakob Disease (sCJD).
Identification of a second bovine amyloidotic spongiform encephalopathy: Molecular similarities with sporadic Creutzfeldt–Jakob disease
SUMMARY REPORT CALIFORNIA BOVINE SPONGIFORM ENCEPHALOPATHY CASE INVESTIGATION JULY 2012 (ATYPICAL L-TYPE BASE)
*** Final Feed Investigation Summary - California BSE Case - July 2012 ***
Update from APHIS Regarding Release of the Final Report on the BSE
Epidemiological Investigation
TEXAS ATYPICAL H-BSE MAD COW CASE
On June 24, 2005, the USDA announced receipt of final results from The
Veterinary Laboratories Agency in Weybridge, England, confirming BSE in a cow
that had conflicting test results in 2004. This cow was from Texas, died at
approximately 12 years of age, and represented the first endemic case of BSE in
the United States. (see Texas BSE Investigation, Final Epidemiology Report,
August 2005 External Web Site Policy PDF Document Icon (PDF – 83 KB))
ALABAMA ATYPICAL H-TYPE GENETIC BSE
On March 15, 2006, the USDA announced the confirmation of BSE in a cow in
Alabama. The case was identified in a non-ambulatory (downer) cow on a farm in
Alabama. The animal was euthanized by a local veterinarian and buried on the
farm. The age of the cow was estimated by examination of the dentition as
10-years-old. It had no ear tags or distinctive marks; the herd of origin could
not be identified despite an intense investigation (see second featured item
above and Alabama BSE Investigation, Final Epidemiology Report, May 2006
External Web Site PolicyPDF Document Icon (PDF – 104 KB)).
In August 2008, several ARS investigators reported that a rare, genetic
abnormality that may persist within the cattle population "is considered to have
caused" BSE in this atypical (H-type) BSE animal from Alabama. (See
Identification of a Heritable Polymorphism in Bovine PRNP Associated with
Genetic Transmissible Spongiform Encephalopathy: Evidence of Heritable BSE
External Web Site Policy. Also see BSE Case Associated with Prion Protein Gene
Mutation External Web Site Policy.)
On December 23, 2003, the U.S. Department of Agriculture (USDA) announced
a presumptive diagnosis of the first known case of BSE in the United States. It
was in an adult Holstein cow from Washington State. This diagnosis was confirmed
by an international reference laboratory in Weybridge, England, on December 25.
Trace-back based on an ear-tag identification number and subsequent genetic
testing confirmed that the BSE-infected cow was imported into the United States
from Canada in August 2001. Because the animal was non-ambulatory (a "downer
cow") at slaughter, brain tissue samples were taken by USDA's Animal and Plant
Health Inspection Service as part of its targeted surveillance for BSE. However
the animal's condition was attributed to complications from calving. After the
animal was examined by a USDA Food Safety and Inspection Service (FSIS)
veterinary medical officer both before and after slaughter, the carcass was
released for use as food for human consumption. During slaughter, the tissues
considered to be at high risk for the transmission of the BSE agent were
removed. On December 24, 2003, FSIS recalled beef from cattle slaughtered in the
same plant on the same day as the BSE positive cow. (see Bovine Spongiform
Encephalopathy in a Dairy Cow - Washington State, 2003.)
Tuesday, August 22, 2006
BSE ATYPICAL TEXAS AND ALABAMA UPDATE JANUARY 20, 2007
LAST MAD COW IN USA, IN CALIFORNIA, WAS ATYPICAL L-TYPE BASE BSE TSE PRION
DISEASE Thursday, February 20, 2014
Unnecessary precautions BSE MAD COW DISEASE Dr. William James FSIS VS Dr.
Linda Detwiler 2014
IF, spontaneous BSE was ever to be proven, it would be the industry, and
consumer’s worst nightmare. you could never ever eradicate mad cow disease, no
matter how hard you try...terry
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics
of BSE in Canada Singeltary reply ;
LET'S take a closer look at this new prionpathy or prionopathy, and then
let's look at the g-h-BSEalabama mad cow. This new prionopathy in humans? the
genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_
mad cow in the world to date like this, ......wait, it get's better. this new
prionpathy is killing young and old humans, with LONG DURATION from onset of
symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and
the plaques are very similar in some cases too, bbbut, it's not related to the
g-h-BSEalabama cow, WAIT NOW, it gets even better, the new human prionpathy that
they claim is a genetic TSE, has no relation to any gene mutation in that
family. daaa, ya think it could be related to that mad cow with the same genetic
make-up ??? there were literally tons and tons of banned mad cow protein in
Alabama in commerce, and none of it transmitted to cows, and the cows to humans
there from ??? r i g h t $$$ ALABAMA MAD COW g-h-BSEalabama In this study, we
identified a novel mutation in the bovine prion protein gene (Prnp), called
E211K, of a confirmed BSE positive cow from Alabama, United States of America.
This mutation is identical to the E200K pathogenic mutation found in humans with
a genetic form of CJD. This finding represents the first report of a confirmed
case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We
hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in
"the approximately 10-year-old cow" carrying the E221K mutation.
Saturday, August 14, 2010
BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and
VPSPr PRIONPATHY (see mad cow feed in COMMERCE IN ALABAMA...TSS)
her healthy calf also carried the mutation
(J. A. Richt and S. M. Hall PLoS Pathog. 4, e1000156; 2008).
This raises the possibility that the disease could occasionally be genetic
in origin. Indeed, the report of the UK BSE Inquiry in 2000 suggested that the
UK epidemic had most likely originated from such a mutation and argued against
the scrapierelated assumption. Such rare potential pathogenic PRNP mutations
could occur in countries at present considered to be free of BSE, such as
Australia and New Zealand. So it is important to maintain strict surveillance
for BSE in cattle, with rigorous enforcement of the ruminant feed ban (many
countries still feed ruminant proteins to pigs). Removal of specified risk
material, such as brain and spinal cord, from cattle at slaughter prevents
infected material from entering the human food chain. Routine genetic screening
of cattle for PRNP mutations, which is now available, could provide additional
data on the risk to the public. Because the point mutation identified in the
Alabama animals is identical to that responsible for the commonest type of
familial (genetic) CJD in humans, it is possible that the resulting infective
prion protein might cross the bovine-human species barrier more easily. Patients
with vCJD continue to be identified. The fact that this is happening less often
should not lead to relaxation of the controls necessary to prevent future
outbreaks.
Malcolm A. Ferguson-Smith Cambridge University Department of Veterinary
Medicine, Madingley Road, Cambridge CB3 0ES, UK e-mail: maf12@cam.ac.uk Jürgen
A. Richt College of Veterinary Medicine, Kansas State University, K224B Mosier
Hall, Manhattan, Kansas 66506-5601, USA NATURE|Vol 457|26 February 2009
BANNED MAD COW FEED IN COMMERCE IN ALABAMA
______________________________
PRODUCT
a) EVSRC Custom dairy feed, Recall # V-130-6;
b) Performance Chick Starter, Recall # V-131-6;
c) Performance Quail Grower, Recall # V-132-6;
d) Performance Pheasant Finisher, Recall # V-133-6.
CODE
None
RECALLING FIRM/MANUFACTURER
Donaldson & Hasenbein/dba J&R Feed Service, Inc., Cullman,
AL, by telephone on June 23, 2006 and by letter dated July 19, 2006. Firm
initiated recall is complete.
REASON
Dairy and poultry feeds were possibly contaminated with ruminant based
protein.
VOLUME OF PRODUCT IN COMMERCE
477.72 tons
DISTRIBUTION
AL
______________________________
PRODUCT
a) Dairy feed, custom, Recall # V-134-6;
b) Custom Dairy Feed with Monensin, Recall # V-135-6.
CODE
None. Bulk product
RECALLING FIRM/MANUFACTURER
Recalling Firm: Burkmann Feed, Greeneville, TN, by Telephone beginning on
June 28, 2006.
Manufacturer: H. J. Baker & Bro., Inc., Albertville, AL. Firm
initiated recall is complete.
REASON
Possible contamination of dairy feeds with ruminant derived meat and bone
meal.
VOLUME OF PRODUCT IN COMMERCE
1,484 tons
DISTRIBUTION
TN and WV
END OF ENFORCEMENT REPORT FOR SEPTEMBER 6, 2006
###
RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINE - CLASS II
______________________________
PRODUCT
Bulk custom made dairy feed, Recall # V-115-6
CODE
None
RECALLING FIRM/MANUFACTURER
Hiseville Feed & Seed Co., Hiseville, KY, by telephone and letter
on or about July 14, 2006. FDA initiated recall is ongoing.
REASON
Custom made feeds contain ingredient called Pro-Lak which may contain
ruminant derived meat and bone meal.
VOLUME OF PRODUCT IN COMMERCE
Approximately 2,223 tons
DISTRIBUTION
KY
______________________________
PRODUCT
Bulk custom made dairy feed, Recall # V-116-6
CODE
None
RECALLING FIRM/MANUFACTURER
Rips Farm Center, Tollesboro, KY, by telephone and letter on July 14,
2006. FDA initiated recall is ongoing.
REASON
Custom made feeds contain ingredient called Pro-Lak which may contain
ruminant derived meat and bone meal.
VOLUME OF PRODUCT IN COMMERCE
1,220 tons
DISTRIBUTION
KY
______________________________
PRODUCT
Bulk custom made dairy feed, Recall # V-117-6
CODE
None
RECALLING FIRM/MANUFACTURER
Kentwood Co-op, Kentwood, LA, by telephone on June 27, 2006. FDA initiated
recall is completed.
REASON
Possible contamination of animal feed ingredients, including ingredients
that are used in feed for dairy animals, with ruminant derived meat and bone
meal.
VOLUME OF PRODUCT IN COMMERCE
40 tons
DISTRIBUTION
LA and MS
______________________________
PRODUCT
Bulk Dairy Feed, Recall V-118-6
CODE
None
RECALLING FIRM/MANUFACTURER
Cal Maine Foods, Inc., Edwards, MS, by telephone on June 26, 2006. FDA
initiated recall is complete.
REASON
Possible contamination of animal feed ingredients, including ingredients
that are used in feed for dairy animals, with ruminant derived meat and bone
meal.
VOLUME OF PRODUCT IN COMMERCE
7,150 tons
DISTRIBUTION
MS
______________________________
PRODUCT
Bulk custom dairy pre-mixes, Recall # V-119-6
CODE
None
RECALLING FIRM/MANUFACTURER
Walthall County Co-op, Tylertown, MS, by telephone on June 26, 2006. Firm
initiated recall is complete.
REASON
Possible contamination of dairy animal feeds with ruminant derived meat
and bone meal.
VOLUME OF PRODUCT IN COMMERCE
87 tons
DISTRIBUTION
MS
______________________________
PRODUCT
Bulk custom dairy pre-mixes, Recall # V-120-6
CODE
None
RECALLING FIRM/MANUFACTURER
Ware Milling Inc., Houston, MS, by telephone on June 23, 2006. Firm
initiated recall is complete.
REASON
Possible contamination of dairy animal feeds with ruminant derived meat
and bone meal.
VOLUME OF PRODUCT IN COMMERCE
350 tons
DISTRIBUTION
AL and MS
______________________________
PRODUCT
a) Tucker Milling, LLC Tm 32% Sinking Fish Grower, #2680-Pellet,
50 lb. bags, Recall # V-121-6;
b) Tucker Milling, LLC #31120, Game Bird Breeder Pellet,
50 lb. bags, Recall # V-122-6;
c) Tucker Milling, LLC #31232 Game Bird Grower,
50 lb. bags, Recall # V-123-6;
d) Tucker Milling, LLC 31227-Crumble, Game Bird Starter, BMD Medicated, 50
lb bags, Recall # V-124-6;
e) Tucker Milling, LLC #31120, Game Bird Breeder, 50 lb bags, Recall #
V-125-6;
f) Tucker Milling, LLC #30230, 30 % Turkey Starter, 50 lb bags, Recall #
V-126-6;
g) Tucker Milling, LLC #30116, TM Broiler Finisher, 50 lb bags, Recall #
V-127-6
CODE
All products manufactured from 02/01/2005 until 06/20/2006
RECALLING FIRM/MANUFACTURER
Recalling Firm: Tucker Milling LLC, Guntersville, AL, by telephone and
visit on June 20, 2006, and by letter on June 23, 2006.
Manufacturer: H. J. Baker and Brothers Inc., Stamford, CT. Firm initiated
recall is ongoing.
REASON
Poultry and fish feeds which were possibly contaminated with ruminant
based protein were not labeled as "Do not feed to ruminants".
VOLUME OF PRODUCT IN COMMERCE
7,541-50 lb bags
DISTRIBUTION
AL, GA, MS, and TN
END OF ENFORCEMENT REPORT FOR AUGUST 9, 2006
###
Subject: MAD COW FEED RECALL AL AND FL VOLUME OF PRODUCT IN COMMERCE 125
TONS Products manufactured from 02/01/2005 until 06/06/2006
Date: August 6, 2006 at 6:16 pm PST PRODUCT
a) CO-OP 32% Sinking Catfish, Recall # V-100-6;
b) Performance Sheep Pell W/Decox/A/N, medicated, net wt. 50 lbs, Recall #
V-101-6;
c) Pro 40% Swine Conc Meal -- 50 lb, Recall # V-102-6;
d) CO-OP 32% Sinking Catfish Food Medicated, Recall # V-103-6;
*** e) "Big Jim's" BBB Deer Ration, Big Buck Blend, Recall # V-104-6;
f) CO-OP 40% Hog Supplement Medicated Pelleted, Tylosin 100 grams/ton, 50
lb. bag, Recall # V-105-6;
g) Pig Starter Pell II, 18% W/MCDX Medicated 282020, Carbadox -- 0.0055%,
Recall # V-106-6;
h) CO-OP STARTER-GROWER CRUMBLES, Complete Feed for Chickens from Hatch to
20 Weeks, Medicated, Bacitracin Methylene Disalicylate, 25 and 50 Lbs, Recall #
V-107-6;
i) CO-OP LAYING PELLETS, Complete Feed for Laying Chickens, Recall #
108-6;
j) CO-OP LAYING CRUMBLES, Recall # V-109-6;
k) CO-OP QUAIL FLIGHT CONDITIONER MEDICATED, net wt 50 Lbs, Recall #
V-110-6;
l) CO-OP QUAIL STARTER MEDICATED, Net Wt. 50 Lbs, Recall # V-111-6;
m) CO-OP QUAIL GROWER MEDICATED, 50 Lbs, Recall # V-112-6 CODE
Product manufactured from 02/01/2005 until 06/06/2006
RECALLING FIRM/MANUFACTURER Alabama Farmers Cooperative, Inc., Decatur,
AL, by telephone, fax, email and visit on June 9, 2006. FDA initiated recall is
complete.
REASON Animal and fish feeds which were possibly contaminated with
ruminant based protein not labeled as "Do not feed to ruminants".
VOLUME OF PRODUCT IN COMMERCE 125 tons
DISTRIBUTION AL and FL
END OF ENFORCEMENT REPORT FOR AUGUST 2, 2006
###
MAD COW FEED RECALL USA EQUALS 10,878.06 TONS NATIONWIDE Sun Jul 16, 2006
09:22 71.248.128.67
RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINE -- CLASS II
______________________________
PRODUCT
a) PRO-LAK, bulk weight, Protein Concentrate for Lactating Dairy Animals,
Recall # V-079-6;
b) ProAmino II, FOR PREFRESH AND LACTATING COWS, net weight 50lb (22.6
kg), Recall # V-080-6;
c) PRO-PAK, MARINE & ANIMAL PROTEIN CONCENTRATE FOR USE IN ANIMAL
FEED, Recall # V-081-6;
d) Feather Meal, Recall # V-082-6 CODE
a) Bulk
b) None
c) Bulk
d) Bulk
RECALLING FIRM/MANUFACTURER H. J. Baker & Bro., Inc., Albertville,
AL, by telephone on June 15, 2006 and by press release on June 16, 2006. Firm
initiated recall is ongoing.
REASON
Possible contamination of animal feeds with ruminent derived meat and bone
meal.
VOLUME OF PRODUCT IN COMMERCE 10,878.06 tons
DISTRIBUTION Nationwide
END OF ENFORCEMENT REPORT FOR July 12, 2006
###
what about that ALABAMA MAD COW, AND MAD COW FEED THERE FROM IN THAT STATE
???
Saturday, August 14, 2010
BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and
VPSPr PRIONPATHY
*** (see mad cow feed in COMMERCE IN ALABAMA...TSS)
BANNED MAD COW FEED IN COMMERCE IN ALABAMA
Date: September 6, 2006 at 7:58 am PST PRODUCT
a) EVSRC Custom dairy feed, Recall # V-130-6;
b) Performance Chick Starter, Recall # V-131-6;
c) Performance Quail Grower, Recall # V-132-6;
d) Performance Pheasant Finisher, Recall # V-133-6.
CODE None RECALLING FIRM/MANUFACTURER Donaldson & Hasenbein/dba
J&R Feed Service, Inc., Cullman, AL, by telephone on June 23, 2006 and
by letter dated July 19, 2006. Firm initiated recall is complete.
REASON
Dairy and poultry feeds were possibly contaminated with ruminant based
protein.
VOLUME OF PRODUCT IN COMMERCE 477.72 tons
DISTRIBUTION AL
______________________________
Saturday, August 14, 2010
BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and
VPSPr PRIONPATHY (see mad cow feed in COMMERCE IN ALABAMA...TSS)
PLOS Singeltary Comment ;
*** ruminant feed ban for cervids in the United States ? ***
31 Jan 2015 at 20:14 GMT
Saturday, January 24, 2015
Bovine Spongiform Encephalopathy: Atypical Pros and Cons
Saturday, January 31, 2015
RAPID ADVICE 17-2014 : Evaluation of the risk for public health of casings
in countries with a “negligible risk status for BSE” and on the risk of
modification of the list of specified risk materials (SRM) with regard to BSE
Conclusion/Significance: Our results point to a possibly higher degree of
pathogenicity of BASE than classical BSE in primates and also raise a question
about a possible link to one uncommon subset of cases of apparently sporadic
CJD. Thus, despite the waning epidemic of classical BSE, the occurrence of
atypical strains should temper the urge to relax measures currently in place to
protect public health from accidental contamination by BSE-contaminated
products.
SPONTANEOUS TSE
Perspectives BIOMEDICINE: A Fresh Look at BSE Bruce Chesebro*
Mad cow disease, or bovine spongiform encephalopathy (BSE), is the cattle
form of a family of progressive brain diseases. These diseases include scrapie
in sheep, Creutzfeldt-Jakob disease (CJD) in humans, and chronic wasting disease
(CWD) in deer and elk. They are also known as either "prion diseases" because of
the association of a misfolded cellular prion protein in pathogenesis or
"transmissible spongiform encephalopathies" (TSEs) because of the spongelike
nature of the damaged brain tissue (1).
The recent discovery of two BSE-infected cows, one in Canada and one in
the United States, has dramatically increased concern in North America among
meat producers and consumers alike over the extent to which BSE poses a threat
to humans as well as to domestic and wild animals. The European BSE epidemic of
the late-1980s seems to have been initiated a decade earlier in the United
Kingdom by changes in the production of meat and bone meal (MBM) from rendered
livestock, which led to contamination of MBM with the BSE infectious agent.
Furthermore, the fact that UK farmers fed this rendered MBM to younger animals
and that this MBM was distributed to many countries may have contributed to the
ensuing BSE epidemic in the United Kingdom and internationally (2).
Despite extensive knowledge about the spread of BSE through contaminated
MBM, the source of BSE in Europe remains an unsolved mystery (2). It has been
proposed that BSE could be derived from a cross-species infection, perhaps
through contamination of MBM by scrapie-infected sheep tissues (see the figure).
Alternatively, BSE may have been an endemic disease in cattle that went
unnoticed because of its low level of horizontal transmission. Lastly, BSE might
have originated by "spontaneous" misfolding of the normal cellular prion protein
into the disease-associated abnormal isoform (3), which is postulated to be the
infectious agent or "prion."
Five possible sources of BSE in North American cattle. Sheep, deer, and
elk could spread prion diseases (TSEs) to cattle through direct animal contact
or contamination of pastures. Endemic BSE has not been proven to exist anywhere
in the world, but it is difficult to exclude this possibility because of the
inefficient spread of BSE infectivity between individual animals (2). BSE caused
by spontaneous misfolding of the prion protein has not been proven. CREDIT:
KATHARINE SUTLIFF/SCIENCE
snip...
Nevertheless, the idea that BSE might originate due to the spontaneous
misfolding of prion proteins has received renewed interest in the wake of
reports suggesting the occurrence of atypical BSE (9-11). These results imply
that new strains of cattle BSE might have originated separately from the main UK
outbreak. Where and how might such strains have originated? Although such rare
events cannot be studied directly, any number of sources of the original BSE
strain could also explain the discovery of additional BSE strains in cattle (see
the figure). However, it would be worrisome if spontaneous BSE were really a
valid etiology because such a mechanism would be impossible to prevent--unlike
other possible scenarios that could be controlled by large-scale eradication of
TSE-positive animals.
Another way to look at this problem is to examine evidence for possible
spontaneous TSE disease in other animals besides cattle. Spontaneous BSE would
be extremely difficult to detect in cattle, where horizontal spread is minimal.
However, in the case of the sheep TSE disease, scrapie, which spreads from ewes
to lambs at birth as well as between adults, spontaneous disease should be
detectable as new foci of clinical infection. In the early 1950s scrapie was
eradicated in both Australia and New Zealand, and the mainland of both these
countries has remained scrapie-free ever since. This scrapie-free status is not
the result of selection of sheep resistant to scrapie because sheep from New
Zealand are as susceptible as their UK counterparts to experimental scrapie
infection (12). These experiments of man and nature appear to indicate that
spontaneous clinical scrapie does not occur in sheep. Similarly, because CWD is
known to spread horizontally, the lack of CWD in the deer or elk of eastern
North America but its presence in western regions would also argue against a
spontaneous disease mechanism. This is particularly noteworthy in New Zealand,
where there are large numbers of deer and elk farms and yet no evidence of
spontaneous CWD. If spontaneous scrapie does not occur in sheep or deer, this
would suggest that spontaneous forms of BSE and sporadic Creutzfeldt-Jakob
disease (sCJD) are unlikely to be found in cattle or humans. The main caveat to
this notion is that spontaneous disease may arise in some animal species but not
others. In humans, sCJD--which is considered by some researchers to begin by
spontaneous misfolding of the prion protein--usually takes more than 50 years to
appear. Thus, in animals with a shorter life-span, such as sheep, deer, and
cattle, an analogous disease mechanism might not have time to develop.
What can we conclude so far about BSE in North America? Is the BSE
detected in two North American cows sporadic or spontaneous or both? "Sporadic"
pertains to the rarity of disease occurrence. "Spontaneous" pertains to a
possible mechanism of origin of the disease. These are not equivalent terms. The
rarity of BSE in North America qualifies it as a sporadic disease, but this low
incidence does not provide information about cause. For the two reported North
American BSE cases, exposure to contaminated MBM remains the most likely
culprit. However, other mechanisms are still possible, including cross-infection
by sheep with scrapie or cervids with CWD, horizontal transmission from cattle
with endemic BSE, and spontaneous disease in individual cattle. Based on our
understanding of other TSEs, the spontaneous mechanism is probably the least
likely. Thus, "idiopathic" BSE--that is, BSE of unknown etiology--might be a
better term to describe the origin of this malady. ...
snip...full text ;
DR. DEHAVEN: “All right. I think we've got three different questions in
there, and I'll try to touch on each one of them.
“First of all, let me correct just a technical issue, and that is you
mentioned 1 in 10,000. And actually our surveillance system currently is
designed, the one that we have in place now is designed to detect 1 positive in
1 million cattle, and I gave some numbers between 200,000 and 268,000 that would
allow us to detect 1 in 10 million as opposed to 1 in 10,000.
“So we would, if we were able to collect in the ballpark of those numbers
of samples then we with increasing numbers of samples have an increasingly
statistically valid sample from which to determine, one, whether or not the
disease exists and, if so, at what prevalence level.
“So our real emphasis is to test as many of those animals as we can,
ensure that we get an appropriate geographical distribution, but not setting a
specific number as far as a target. Again, consistent with the recommendation
from the International Review Team, their recommendation was to test all of
them.
“So that's consistent with where we're going is to test as many as we
possibly can.
*** “As far as spontaneous cases, that is a very difficult issue. There is
no evidence to prove that spontaneous BSE occurs in cattle; but here again it's
an issue of proving a negative. We do know that CJD, the human version of the
disease, does occur spontaneously in humans at the rate of about 1 in 1 million.
We don't have enough data to definitively say that spontaneous cases of BSE in
cattle occur or do not occur.
“Again, it's a very difficult situation to prove a negative.
“So a lot of research is ongoing. Certainly if we do come up with any
positive samples in the course of this surveillance we will be looking at that
question in evaluating those samples but no scientifically hard evidence to
confirm or refute whether or not spontaneous cases of BSE occur.
snip...
http://www.usda.gov/wps/portal/!ut/p/_s.7_0_A/7_0_1OB?contentidonly=true&contentid=2004/03/0106.html
1. The BSE epidemic
1.1. The origin of the BSE epidemic will probably never be determined with
certainty.
1.2. We do not know whether or not some of the BARB cases represent truly
sporadic classical BSE. If there are spontaneous cases then BSE will never be
eradicated although reducing surveillance could make it appear that BSE has been
eradicated.
snip...
5.3. It was stated that the number of sporadic CJD cases was rising.
Participants were invited to discuss the reason for this. It was suggested that
this was likely to be due to improved surveillance with more cases of sporadic
CJD being detected (i.e. through MRI scans). There had been a similar increase
in sporadic CJD in countries which did not have a BSE epidemic but improved
their surveillance. This supported this theory and suggested that the increase
in sporadic CJD was not related to the BSE outbreak.
Atypical BSE: Transmissibility
Linda Detwiller, 5/10/2011
BASE (L) transmitted to: cattle (IC) - inc < 20 mos and oral?)
Cynomolgus macaques (IC)
Mouse lemurs (IC and oral)
wild-type mice (IC)
bovinized transgenic mice (IC and IP)
humanized transgenic mice (IC)
H cases transmitted to:
cattle – IC incubations < 20 months
bovinized transgenic mice (IC)
ovinized transgenic mice (IC)
C57BL mice (IC)
One study did not transmit to humanized PrP Met 129 mice
Evaluation of Possibility of Atypical
BSE Transmitting to Humans
Possble interpretation:
L type seems to transmit to nonhuman primates with greater ease than
classical BSE
L type also transmitted to humanized transgenic mice with higher attack
rate and shorter incubation period than classical?
H type did not transmit to Tg Hu transgenic mice
Linda Detwiller, 5/10/2011
I ask Professor Kong ;
Thursday, December 04, 2008 3:37 PM
Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform
Encephalopathies (BSE): Public Health Risk Assessment
IS the h-BSE more virulent than typical BSE as well, or the same as cBSE,
or less virulent than cBSE? just curious.....
Professor Kong reply ;
.....snip
As to the H-BSE, we do not have sufficient data to say one way or another,
but we have found that H-BSE can infect humans. I hope we could publish these
data once the study is complete. Thanks for your interest.
Best regards, Qingzhong Kong, PhD Associate Professor Department of
Pathology Case Western Reserve University Cleveland, OH 44106 USA
BSE-H is also transmissible in our humanized Tg mice. The possibility of
more than two atypical BSE strains will be discussed.
Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.
P.4.23 Transmission of atypical BSE in humanized mouse models
Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3,
Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5,
Qingzhong Kong1 1Case Western Reserve University, USA; 2Instituto
Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany;
4National Veterinary Research Institute, Poland; 5Kansas State University
(Previously at USDA National Animal Disease Center), USA
Background: Classical BSE is a world-wide prion disease in cattle, and the
classical BSE strain (BSE-C) has led to over 200 cases of clinical human
infection (variant CJD). Atypical BSE cases have been discovered in three
continents since 2004; they include the L-type (also named BASE), the H-type,
and the first reported case of naturally occurring BSE with mutated bovine PRNP
(termed BSE-M). The public health risks posed by atypical BSE were argely
undefined.
Objectives: To investigate these atypical BSE types in terms of their
transmissibility and phenotypes in humanized mice.
Methods: Transgenic mice expressing human PrP were inoculated with several
classical (C-type) and atypical (L-, H-, or Mtype) BSE isolates, and the
transmission rate, incubation time, characteristics and distribution of PrPSc,
symptoms, and histopathology were or will be examined and compared.
Results: Sixty percent of BASE-inoculated humanized mice became infected
with minimal spongiosis and an average incubation time of 20-22 months, whereas
only one of the C-type BSE-inoculated mice developed prion disease after more
than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse
brains was biochemically different from bovine BASE or sCJD. PrPSc was also
detected in the spleen of 22% of BASE-infected humanized mice, but not in those
infected with sCJD. Secondary transmission of BASE in the humanized mice led to
a small reduction in incubation time. The atypical BSE-H strain is also
transmissible with distinct phenotypes in the humanized mice, but no BSE-M
transmission has been observed so far.
Discussion: Our results demonstrate that BASE is more virulent than
classical BSE, has a lymphotropic phenotype, and displays a modest transmission
barrier in our humanized mice. BSE-H is also transmissible in our humanized Tg
mice. The possibility of more than two atypical BSE strains will be discussed.
Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.
14th International Congress on Infectious Diseases H-type and L-type
Atypical BSE January 2010 (special pre-congress edition)
18.173 page 189
Experimental Challenge of Cattle with H-type and L-type Atypical BSE
A. Buschmann1, U. Ziegler1, M. Keller1, R. Rogers2, B. Hills3, M.H.
Groschup1. 1Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany,
2Health Canada, Bureau of Microbial Hazards, Health Products & Food
Branch, Ottawa, Canada, 3Health Canada, Transmissible Spongiform Encephalopathy
Secretariat, Ottawa, Canada
Background: After the detection of two novel BSE forms designated H-type
and L-type atypical BSE the question of the pathogenesis and the agent
distribution of these two types in cattle was fully open. From initial studies
of the brain pathology, it was already known that the anatomical distribution of
L-type BSE differs from that of the classical type where the obex region in the
brainstem always displays the highest PrPSc concentrations. In contrast in
L-type BSE cases, the thalamus and frontal cortex regions showed the highest
levels of the pathological prion protein, while the obex region was only weakly
involved.
Methods:We performed intracranial inoculations of cattle (five and six per
group) using 10%brainstemhomogenates of the two German H- and L-type atypical
BSE isolates. The animals were inoculated under narcosis and then kept in a
free-ranging stable under appropriate biosafety conditions. At least one animal
per group was killed and sectioned in the preclinical stage and the remaining
animals were kept until they developed clinical symptoms. The animals were
examined for behavioural changes every four weeks throughout the experiment
following a protocol that had been established during earlier BSE pathogenesis
studies with classical BSE.
Results and Discussion: All animals of both groups developed clinical
symptoms and had to be euthanized within 16 months. The clinical picture
differed from that of classical BSE, as the earliest signs of illness were loss
of body weight and depression. However, the animals later developed hind limb
ataxia and hyperesthesia predominantly and the head. Analysis of brain samples
from these animals confirmed the BSE infection and the atypical Western blot
profile was maintained in all animals. Samples from these animals are now being
examined in order to be able to describe the pathoge esis and agent distribution
for these novel BSE types.
Conclusions: A pilot study using a commercially avaialble BSE rapid test
ELISA revealed an essential restriction of PrPSc to the central nervous system
for both atypical BSE forms. A much more detailed analysis for PrPSc and
infectivity is still ongoing.
14th ICID International Scientific Exchange Brochure - Final Abstract
Number: ISE.114
Session: International Scientific Exchange
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in
North America update October 2009
T. Singeltary Bacliff, TX, USA
Background: An update on atypical BSE and other TSE in North America.
Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE
have all been documented in North America, along with the typical scrapie's, and
atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME.
All these TSE in different species have been rendered and fed to food producing
animals for humans and animals in North America (TSE in cats and dogs ?), and
that the trading of these TSEs via animals and products via the USA and Canada
has been immense over the years, decades.
Methods: 12 years independent research of available data
Results: I propose that the current diagnostic criteria for human TSEs
only enhances and helps the spreading of human TSE from the continued belief of
the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to
continue to validate this old myth, will only spread this TSE agent through a
multitude of potential routes and sources i.e. consumption, medical i.e.,
surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics
etc.
Conclusion: I would like to submit a review of past CJD surveillance in
the USA, and the urgent need to make all human TSE in the USA a reportable
disease, in every state, of every age group, and to make this mandatory
immediately without further delay. The ramifications of not doing so will only
allow this agent to spread further in the medical, dental, surgical arena's.
Restricting the reporting of CJD and or any human TSE is NOT scientific.
Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with
Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside,
Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible
Spongiform Encephalopathy is far from an exact science, but there is enough
proven science to date that this myth should be put to rest once and for all,
and that we move forward with a new classification for human and animal TSE that
would properly identify the infected species, the source species, and then the
route.
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February
14, 2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor: In their Research Letter, Dr Gibbons and colleagues1
reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD)
has been stable since 1985. These estimates, however, are based only on reported
cases, and do not include misdiagnosed or preclinical cases. It seems to me that
misdiagnosis alone would drastically change these figures. An unknown number of
persons with a diagnosis of Alzheimer disease in fact may have CJD, although
only a small number of these patients receive the postmortem examination
necessary to make this diagnosis. Furthermore, only a few states have made CJD
reportable. Human and animal transmissible spongiform encephalopathies should be
reportable nationwide and internationally.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob
disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.
26 March 2003
Terry S. Singeltary, retired (medically) CJD WATCH
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to
comment on the CDC's attempts to monitor the occurrence of emerging forms of
CJD. Asante, Collinge et al [1] have reported that BSE transmission to the
129-methionine genotype can lead to an alternate phenotype that is
indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD
and all human TSEs are not reportable nationally. CJD and all human TSEs must be
made reportable in every state and internationally. I hope that the CDC does not
continue to expect us to still believe that the 85%+ of all CJD cases which are
sporadic are all spontaneous, without route/source. We have many TSEs in the USA
in both animal and man. CWD in deer/elk is spreading rapidly and CWD does
transmit to mink, ferret, cattle, and squirrel monkey by intracerebral
inoculation. With the known incubation periods in other TSEs, oral transmission
studies of CWD may take much longer. Every victim/family of CJD/TSEs should be
asked about route and source of this agent. To prolong this will only spread the
agent and needlessly expose others. In light of the findings of Asante and
Collinge et al, there should be drastic measures to safeguard the medical and
surgical arena from sporadic CJDs and all human TSEs. I only ponder how many
sporadic CJDs in the USA are type 2 PrPSc?
2 January 2000
British Medical Journal
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as
well
15 November 1999
British Medical Journal
vCJD in the USA * BSE in U.S.
The Lancet Infectious Diseases, Volume 3, Issue 8, Page 463, August 2003
doi:10.1016/S1473-3099(03)00715-1Cite or Link Using DOI
Tracking spongiform encephalopathies in North America
Original
Xavier Bosch
“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my
mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever
since. What I have found is that we have not been told the truth. CWD in deer
and elk is a small portion of a much bigger problem.” 49-year—old Singeltary is
one of a number of people who have remained largely unsatisfied after being told
that a close relative died from a rapidly progressive dementia compatible with
spontaneous Creutzfeldt—Jakob ...
Suspect symptoms
What if you can catch old-fashioned CJD by eating meat from a sheep
infected with scrapie?
28 Mar 01 Most doctors believe that sCJD is caused by a prion protein
deforming by chance into a killer. But Singeltary thinks otherwise. He is one of
a number of campaigners who say that some sCJD, like the variant CJD related to
BSE, is caused by eating meat from infected animals. Their suspicions have
focused on sheep carrying scrapie, a BSE-like disease that is widespread in
flocks across Europe and North America.
Now scientists in France have stumbled across new evidence that adds
weight to the campaigners' fears. To their complete surprise, the researchers
found that one strain of scrapie causes the same brain damage in mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by
some strains of scrapie," says team member Jean-Philippe Deslys of the French
Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses,
south-west of Paris. Hans Kretschmar of the University of Göttingen, who
coordinates CJD surveillance in Germany, is so concerned by the findings that he
now wants to trawl back through past sCJD cases to see if any might have been
caused by eating infected mutton or lamb...
Self-Propagative Replication of Ab Oligomers Suggests Potential
Transmissibility in Alzheimer Disease
Received July 24, 2014; Accepted September 16, 2014; Published November 3,
2014
Singeltary comment ;
Saturday, August 14, 2010
***BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama)
and VPSPr PRIONPATHY
*** (see mad cow feed in COMMERCE IN ALABAMA...TSS)
*** What irks many scientists is the USDA’s April 25 statement that the
rare disease is “not generally associated with an animal consuming infected
feed.”
The USDA’s conclusion is a “gross oversimplification,” said Dr. Paul
Brown, one of the world’s experts on this type of disease who retired recently
from the National Institutes of Health. "(The agency) has no foundation on which
to base that statement.”
Owens, Julie
From: Terry S. Singeltary Sr. [flounder9@verizon.net]
Sent: Monday, July 24, 2006 1:09 PM
To: FSIS RegulationsComments
Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of
Bovine Spongiform Encephalopathy (BSE) Page 1 of 98
FSIS, USDA, REPLY TO SINGELTARY
FDA et al thinks as much as 5.5 grams of SRM is just fine for a heifer
weighing about 600 lbs ;
''FDA has determined that each animal could have consumed, at most and in
total, five-and-one-half grams - approximately a quarter ounce -- of prohibited
material. These animals weigh approximately 600 pounds.''
Saturday, December 21, 2013
**** Complementary studies detecting classical bovine spongiform
encephalopathy infectivity in jejunum, ileum and ileocaecal junction in
incubating cattle ****
Wednesday, May 2, 2012
ARS FLIP FLOPS ON SRM REMOVAL FOR ATYPICAL L-TYPE BASE BSE RISK HUMAN AND
ANIMAL HEALTH
Saturday, June 12, 2010
PUBLICATION REQUEST AND FOIA REQUEST Project Number: 3625-32000-086-05
Study of Atypical Bse
Wednesday, July 28, 2010
re-Freedom of Information Act Project Number 3625-32000-086-05, Study of
Atypical BSE UPDATE July 28, 2010
PRION 2009 CONGRESS BOOK OF ABSTRACTS
O.4.3
Spread of BSE prions in cynomolgus monkeys (Macaca fascicularis) after
oral transmission
Edgar Holznagel1, Walter Schulz-Schaeffer2, Barbara Yutzy1, Gerhard
Hunsmann3, Johannes Loewer1 1Paul-Ehrlich-Institut, Federal Institute for Sera
and Vaccines, Germany; 2Department of Neuropathology, Georg-August University,
Göttingen, Germany, 3Department of Virology and Immunology, German Primate
Centre, Göttingen, Germany
Background: BSE-infected cynomolgus monkeys represent a relevant animal
model to study the pathogenesis of variant Creutzfeldt-Jacob disease (vCJD).
Objectives: To study the spread of BSE prions during the asymptomatic
phase of infection in a simian animal model.
Methods: Orally BSE-dosed macaques (n=10) were sacrificed at defined time
points during the incubation period and 7 orally BSE-dosed macaques were
sacrificed after the onset of clinical signs. Neuronal and non-neuronal tissues
were tested for the presence of proteinase-K-resistant prion protein (PrPres) by
western immunoblot and by paraffin-embedded tissue (PET) blot technique.
Results: In clinically diseased macaques (5 years p.i. + 6 mo.), PrPres
deposits were widely spread in neuronal tissues (including the peripheral
sympathetic and parasympathetic nervous system) and in lymphoid tissues
including tonsils. In asymptomatic disease carriers, PrPres deposits could be
detected in intestinal lymph nodes as early as 1 year p.i., but CNS tissues were
negative until 3 – 4 years p.i. Lumbal/sacral segments of the spinal cord and
medulla oblongata were PrPres positive as early as 4.1 years p.i., whereas
sympathetic trunk and all thoracic/cervical segments of the spinal cord were
still negative for PrPres. However, tonsil samples were negative in all
asymptomatic cases.
Discussion: There is evidence for an early spread of BSE to the CNS via
autonomic fibres of the splanchnic and vagus nerves indicating that
trans-synaptical spread may be a time-limiting factor for neuroinvasion. Tonsils
were predominantly negative during the main part of the incubation period
indicating that epidemiological vCJD screening results based on the detection of
PrPres in tonsil biopsies may mostly tend to underestimate the prevalence of
vCJD among humans.
Simian vCJD can be easily triggered in cynomolgus monkeys on the oral
route using less than 5 g BSE brain homogenate.
Atypical L-Type Bovine Spongiform Encephalopathy (L-BSE) Transmission to
Cynomolgus Macaques, a Non-Human Primate
Jpn. J. Infect. Dis., 64 (1), 81-84, 2011
To see a printable version of the article in the Adobe file format, click
this [PDF] link.
Short Communication
Atypical L-Type Bovine Spongiform Encephalopathy (L-BSE) Transmission to
Cynomolgus Macaques, a Non-Human Primate
Fumiko Ono, Naomi Tase1, Asuka Kurosawa3, Akio Hiyaoka, Atsushi Ohyama,
Yukio Tezuka, Naomi Wada2, Yuko Sato3, Minoru Tobiume3, Ken'ichi Hagiwara4,
Yoshio Yamakawa4*, Keiji Terao1, and Tetsutaro Sata3
The Corporation for Production and Research of Laboratory Primates,
Tsukuba 305-0843; 1Tsukuba Primate Research Center, National Institute of
Biomedical Innovation, Tsukuba 305-0843; 2Department of Veterinary Medicine,
Yamaguchi University, Yamaguchi 753-8515; and 3Department of Pathology and
4Department of Biochemistry and Cell Biology, National Institute of Infectious
Diseases, Tokyo 162-8640, Japan
(Received December 9, 2010. Accepted December 22, 2010)
--------------------------------------------------------------------------------
*Corresponding author: Mailing address: Department of Biochemistry and
Cell Biology, National Institute of Infectious Diseases, Toyama 1-23-1,
Shinjuku-ku, Tokyo 162-8640, Japan. Tel: +81-3-5285-1111 ext. 2127, Fax:
+81-3-5285-1157, E-mail: yamakawa@nih.go.jp
--------------------------------------------------------------------------------
SUMMARY: A low molecular weight type of atypical bovine spongiform
encephalopathy (L-BSE) was transmitted to two cynomolgus macaques by
intracerebral inoculation of a brain homogenate of cattle with atypical BSE
detected in Japan. They developed neurological signs and symptoms at 19 or 20
months post-inoculation and were euthanized 6 months after the onset of total
paralysis. Both the incubation period and duration of the disease were shorter
than those for experimental transmission of classical BSE (C-BSE) into macaques.
Although the clinical manifestations, such as tremor, myoclonic jerking, and
paralysis, were similar to those induced upon C-BSE transmission, no premonitory
symptoms, such as hyperekplexia and depression, were evident. Most of the
abnormal prion protein (PrPSc) was confined to the tissues of the central
nervous system, as determined by immunohistochemistry and Western blotting. The
PrPSc glycoform that accumulated in the monkey brain showed a similar profile to
that of L-BSE and consistent with that in the cattle brain used as the
inoculant. PrPSc staining in the cerebral cortex showed a diffuse synaptic
pattern by immunohistochemistry, whereas it accumulated as fine and coarse
granules and/or small plaques in the cerebellar cortex and brain stem. Severe
spongiosis spread widely in the cerebral cortex, whereas florid plaques, a
hallmark of variant Creutzfeldt-Jakob disease in humans, were observed in
macaques inoculated with C-BSE but not in those inoculated with L-BSE.
snip...
To date, 27 cases of L-BSE and 24 cases of H-BSE have been reported
worldwide (16), thus meaning that the prevalence of atypical BSE is considerably
lower than that of C-BSE. However, recent studies showed that L-BSE is easily
transmissible to transgenic mice expressing human (17,18) or bovine (19,20)
prion protein, as well as to non-human primates (21), with shorter incubation
periods than for the transmission of C-BSE to these animals. The virulent nature
of L-BSE has stimulated new concern for human public health since the
transmission of C-BSE to humans resulted in variant Creutzfeldt-Jakob disease
(vCJD) (4-7), a new emergent prion disease.
snip...
Two macaques simultaneously developed neurological signs and symptoms
19-20 months post-inoculation (mpi) with the brain homogenate of BSEI JP24. The
monkeys entered the terminal stage of the disease (total paralysis) at 24-25
mpi, Both the onset and duration of the disease were shorter than those reported
for the transmission of C-BSE to macaques by us and other groups (27,28). The
clinical manifestations such as tremor, myoclonic jerking, and paralysis were
similar to those observed during the transmission of C-BSE to ma- caques,
whereas the premonitory abnormal behaviors, such as hyperekplexia and
depression, seen upon transmission of C-BSE to macaques were not evident (27).
Histopathological analysis and IHC, performed as described previously
(29), showed that severe spongiform changes and the accumulation of Prpsc with
various patterns were detectable in the brains of both monkeys (Fig. 1).
Vacuolization was profound throughout the cerebral cortex, from the frontal to
the occipital lobes (Fig. la). Likewise, synaptic-type Prpsc precipitation (30)
was observed in the whole cerebral cortex and basal ganglia by IHC (Figs. Ib and
c). Dense precipitates and plaques of Prpsc, which had been observed in cattle
(JP24) brain (13), were not detected in the cerebrum of the monkeys. Prpsc, in
the form of small plaques or coarse granules, was, however, detected in the
molecular layer of the cerebellum (Fig. Ie). Despite the severe spongiosis in
the cerebral cortex, florid plaques, which are large Prpsc plaques surrounded
by vacuoles, a hallmark ofvCJD (4-7,30) and C-BSE transmission to macaques
(27,28), were not observed. The histopathology of the brain was therefore
similar to that reported for the brain of L-BSE (BASE)-transmitted macaques
(21).
snip...
see full text ;
Monday, September 13, 2010
atypical BSE strains and sporadic CJD strains, is there a connection and
why shouldn't there be $
Monday, September 13, 2010
atypical BSE strains and sporadic CJD strains, is there a connection and
why shouldn't there be $ A Surprisingly High Number of the Plaque-Like VV sCJD
Subtype Among the Polish sCJD-is There a Connection with BASE?
PPo4-15:
A Surprisingly High Number of the Plaque-Like VV sCJD Subtype Among the
Polish sCJD—is There a Connection with BASE?
Beata Sikorska and Pawel P. Liberski Department of Molecular Pathology and
Neuropathology; Medical University of Lodz; Lodz, Poland
Recently described bovine amyloidotic spongiform encephalopathy (BASE) or
L type BSE—was is overrepresented in Poland (15% of all cases of BSE). Moreover,
the number of BASE cases in Poland per million bovines is the highest in Europe.
A potential human risk from BASE is evident from experimental transmission to
“humanized” transgenic animals and primates. Taking into consideration that
non-human primate inoculated with BASE had a shorter incubation period than
monkeys infected with classical BSE, and that humanized Tg mice have been found
to be highly susceptible to infection with atypical form of BSE, it seems
probable that BASE may be more pathogenic for humans than BSE, but the
transmitted disease may differ from BSE-derived vCJD. Among 47 cases which have
been diagnosed as definite in our laboratory, in 19 cases complete
histopathological examination and codon 129 status were available. On the basis
of the histological pattern and codon 129 status the cases of sCJD were divided
into subtypes according to the Parchi&Gambetti classification. The
results are as follows: type 1 (MMorMV)- 42%, type 2 (VV)-32%, type 3
(MV)-10.5%, type 4c (MM)- 10.5% and type 5 (VV)-5 %. Although the number of
cases is too low to conclude a significantly different distribution of sCJD
subtypes in Polish population those data show surprisingly high number of the
plaque-like VV sCJD subtype. Interestingly, it was shown before that Tg mice
inoculated with BASE showed granular and plaque-like aggregates or PrPSc in
brains resembling those observed in VV2 subtype of sCJD.
PPo2-26:
Transmission of Classical and Atypical (L-type) Bovine Spongiform
Encephalopathy (BSE) Prions to Cynomolgus macaques
Fumiko Ono,1 Yoshio Yamakawa,2 Minoru Tobiume,3 Yuko Sato,3 Harutaka
Katano,3 Kenichi Hagiwara,2 Iori Itagaki,1 Akio Hiyaoka,1 Katuhiko Komatuzaki,1
Yasunori Emoto,1 Hiroaki Shibata,4 Yuichi Murayama,5 Keiji Terao,4 Yasuhiro
Yasutomi4 and Tetsutaro Sata3
1The Corporation for Production and Research of Laboratory Primates;
Tsukuba City, Japan; 2Departments of Cell Biology and Biochemistry; and
3Pathology; National Institute of Infectious Diseases; Tokyo, Japan; 4Tsukuba
Primate Research Center; National Institute of Biomedical Innovation; Tsukuba
City, Japan; 5Prion Disease Research Team; National Institute of Animal Health;
Tsukuba City, Japan
Key words: L-type BSE, cBSE, cynomolgus macaques, transmission
BSE prion derived from classical BSE (cBSE) or L-type BSE was
characterized by inoculation into the brain of cynomolgus macaques. The
neurologic manifestation was developed in all cynomolgus macaques at 27–43
months after intracerebral inoculation of brain homogenate from cBSE-affected
cattle (BSE JP/6). Second transmission of cBSE from macaque to macaque shortened
incubation period to 13–18 months. cBSE-affected macaques showed the similar
clinical signs including hyperekplexia, tremor and paralysis in both primary and
second transmission.
Two macaques were intracerebrally inoculated brain homogenate from the
L-type BSE-affected cattle (BSE JP/24). The incubation periods were 19–20 months
in primary transmission.
The clinical course of the L-type BSE-affected macaques differed from that
in cBSE-affected macaques in the points of severe myoclonus without
hyperekplexia. The glycoform profile of PrPSc detected in macaque CNS was
consistent with original pattern of either cBSE or L-typeBSE PrPSc,
respectively. Although severe spongiform change in the brain was remarkable in
all BSE-affected macaques, severe spongiform spread widely in cerebral cortex in
L-type BSE-affected macaques. Heavy accumulation of PrPSc surrounded by vacuola
formed florid plaques in cerebral cortex of cBSE-affected macaques. Deposit of
PrPSc in L-type BSE-affected macaque was weak and diffuse synaptic pattern in
cerebrum, but large PrPSc plaques were evident at cerebellum. MRI analysis, T2,
T1, DW and flair sequences, at the time of autopsy revealed that brain atrophy
and dilatation of cerebral ventricles were significantly severe in L-type
BSE-affected macaques. These results suggest that L-type BSE is more virulent
strain to primates comparing to cBSE.
SP1-4:
Evidence from Molecular Strain Typing
Gianluigi Zanusso Department of Neurological and Visual Sciences; Section
of Clinical Neurology; University of Verona; Verona, Italy
Key words: molecular analysis, strain typing, atypical BSE, CJD
In 2001, active surveillance for bovine spongiform encephalopathy (BSE)
led to the discovery of atypical BSE phenotypes in aged cattle distinct from
classical BSE (C-type). These atypical BSE cases had been classified as low
L-type (BASE) or high H-type BSE based on the molecular mass and the degree of
glycosylation of of the pathological prion protein (PrPSc). Transmission studies
in TgBov mice showed that H-type BSE, C-type BSE and BASE behave as distinct
prion strains with different incubation periods, PrPSc molecular patterns and
pathological phenotypes. A still unclear issue concerns the potential
transmissibility and phenotypes of atypical BSEs in humans. We previously
indicated that BASE was similar to a distinct subgroup of sporadic form of
Creutzfeldt-Jakob disease (sCJD) MV2, based on molecular similarities and on
neuropathological pattern of PrP deposition. To investigate a possible link
between BASE and sCJD, Kong et al. and Comoy et al. experimentally inoculated
TgHu mice (129MM) and a non-human primate respectively, showing in both models
that BASE was more virulent compare to BSE. Further, non-human primate
reproduced a clinical phenotype resembling to that of sCJD subtype MM2. Here, we
presented a comparative analysis of the biochemical fingerprints of PrPSc
between the different sCJD subtypes and animal TSEs and after experimental
transmission to animals.
Opinion of the Scientific Steering Committee on the GEOGRAPHICAL RISK OF
BOVINE SPONGIFORM ENCEPHALOPATHY (GBR) in POLAND Adopted on 30/03/2001
It is concluded that it is likely but not confirmed that one or several
cattle that are (pre-clinically or clinically) infected with the BSE agent are
currently present in the domestic herd of Poland (GBR III).
Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a
Primate
Emmanuel E. Comoy1*, Cristina Casalone2, Nathalie Lescoutra-Etchegaray1,
Gianluigi Zanusso3, Sophie Freire1, Dominique Marcé1, Frédéric Auvré1,
Marie-Magdeleine Ruchoux1, Sergio Ferrari3, Salvatore Monaco3, Nicole Salès4,
Maria Caramelli2, Philippe Leboulch1,5, Paul Brown1, Corinne I. Lasmézas4,
Jean-Philippe Deslys1
1 Institute of Emerging Diseases and Innovative Therapies, CEA,
Fontenay-aux-Roses, France, 2 Istituto Zooprofilattico Sperimentale del
Piemonte, Turin, Italy, 3 Policlinico G.B. Rossi, Verona, Italy, 4 Scripps
Florida, Jupiter, Florida, United States of America, 5 Genetics Division,
Brigham & Women's Hospital, Harvard Medical School, Boston,
Massachusetts, United States of America
Abstract Top Background Human variant Creutzfeldt-Jakob Disease (vCJD)
results from foodborne transmission of prions from slaughtered cattle with
classical Bovine Spongiform Encephalopathy (cBSE). Atypical forms of BSE, which
remain mostly asymptomatic in aging cattle, were recently identified at
slaughterhouses throughout Europe and North America, raising a question about
human susceptibility to these new prion strains.
Methodology/Principal Findings Brain homogenates from cattle with
classical BSE and atypical (BASE) infections were inoculated intracerebrally
into cynomolgus monkeys (Macacca fascicularis), a non-human primate model
previously demonstrated to be susceptible to the original strain of cBSE. The
resulting diseases were compared in terms of clinical signs, histology and
biochemistry of the abnormal prion protein (PrPres). The single monkey infected
with BASE had a shorter survival, and a different clinical evolution,
histopathology, and prion protein (PrPres) pattern than was observed for either
classical BSE or vCJD-inoculated animals. Also, the biochemical signature of
PrPres in the BASE-inoculated animal was found to have a higher proteinase K
sensitivity of the octa-repeat region. We found the same biochemical signature
in three of four human patients with sporadic CJD and an MM type 2 PrP genotype
who lived in the same country as the infected bovine.
Conclusion/Significance Our results point to a possibly higher degree of
pathogenicity of BASE than classical BSE in primates and also raise a question
about a possible link to one uncommon subset of cases of apparently sporadic
CJD. Thus, despite the waning epidemic of classical BSE, the occurrence of
atypical strains should temper the urge to relax measures currently in place to
protect public health from accidental contamination by BSE-contaminated
products.
Citation: Comoy EE, Casalone C, Lescoutra-Etchegaray N, Zanusso G, Freire
S, et al. (2008) Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle
to a Primate. PLoS ONE 3(8): e3017. doi:10.1371/journal.pone.0003017
Editor: Neil Mabbott, University of Edinburgh, United Kingdom
Received: April 24, 2008; Accepted: August 1, 2008; Published: August 20,
2008
Copyright: © 2008 Comoy et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the
original author and source are credited.
Funding: This work has been supported by the Network of Excellence
NeuroPrion.
Competing interests: CEA owns a patent covering the BSE diagnostic tests
commercialized by the company Bio-Rad.
* E-mail: emmanuel.comoy@cea.fr
Session I - Prions: Structure, Strain and Detection (II)
Searching for BASE Strain Signature in Sporadic Creutzfedlt-Jakob Disease
Gianluigi Zanusso
Department of Neurological and Visual Sciences, Section of Clinical
Neurology University of Verona, Verona, Italy.
Bovine amyloidotic spongiform encephalopathy (BASE) is a newly recognized
form of bovine prion disease, which was originally detected in Italy in 2004 as
an effect of active surveillance. BASE or BSE L-type (L is referred to the lower
electrophoretic PrPSc migration than classical BSE) has now been reported in
several countries, including Japan. All field cases of BASE were older than 8
years and neurologically normal at the time of slaughtered. By experimental
transmission, we defined the disease phenotype of cattle BASE, which is quite
distinct from that seen in typical BSE and characterized by mental dullness and
amyotrophy. Surprisingly, following intraspecies and interspecies transmission
the incubation period of BASE was shorter than BSE. The relatively easy
transmission of BASE isolate as well as the molecular similarity with sporadic
Creutzfeldt-Jakob disease (sCJD) have raised concern regarding its potential
passage to humans. Tg humanized mice Met/Met at codon 129 challenged with both
BSE and BASE isolates, showed a resistance to BSE but a susceptibility to BASE
at a 60% rate; in addition, BASE-inoculated Cynomolgus (129 Met/Met) had shorter
incubation periods than BSE-inoculated primates. In this study we compared the
biochemical properties of PrPSc in Cynomolgus and in TgHu Met/Met mice
challenged with BSE and BASE strains, by conventional SDS-PAGE analysis and 2D
separation. The results obtained disclose distinct conformational changes in
PrPSc, which are dependent on the inoculated host but not on the codon 129
genotype.
This work was supported by Neuroprion contract n. FOOD CT 2004 -506579
(NOE)
WE know now, and we knew decades ago, that 5.5 grams of suspect feed in
TEXAS was enough to kill 100 cows.
look at the table and you'll see that as little as 1 mg (or 0.001 gm)
caused 7% (1 of 14) of the cows to come down with BSE;
Risk of oral infection with bovine spongiform encephalopathy agent in
primates
Corinne Ida Lasmézas, Emmanuel Comoy, Stephen Hawkins, Christian Herzog,
Franck Mouthon, Timm Konold, Frédéric Auvré, Evelyne Correia, Nathalie
Lescoutra-Etchegaray, Nicole Salès, Gerald Wells, Paul Brown, Jean-Philippe
Deslys Summary The uncertain extent of human exposure to bovine spongiform
encephalopathy (BSE)--which can lead to variant Creutzfeldt-Jakob disease
(vCJD)--is compounded by incomplete knowledge about the efficiency of oral
infection and the magnitude of any bovine-to-human biological barrier to
transmission. We therefore investigated oral transmission of BSE to non-human
primates. We gave two macaques a 5 g oral dose of brain homogenate from a
BSE-infected cow. One macaque developed vCJD-like neurological disease 60 months
after exposure, whereas the other remained free of disease at 76 months. On the
basis of these findings and data from other studies, we made a preliminary
estimate of the food exposure risk for man, which provides additional assurance
that existing public health measures can prevent transmission of BSE to man.
snip...
BSE bovine brain inoculum
100 g 10 g 5 g 1 g 100 mg 10 mg 1 mg 0·1 mg 0·01 mg
Primate (oral route)* 1/2 (50%)
Cattle (oral route)* 10/10 (100%) 7/9 (78%) 7/10 (70%) 3/15 (20%) 1/15
(7%) 1/15 (7%)
RIII mice (ic ip route)* 17/18 (94%) 15/17 (88%) 1/14 (7%)
PrPres biochemical detection
The comparison is made on the basis of calibration of the bovine inoculum
used in our study with primates against a bovine brain inoculum with a similar
PrPres concentration that was inoculated into mice and cattle.8 *Data are number
of animals positive/number of animals surviving at the time of clinical onset of
disease in the first positive animal (%). The accuracy of bioassays is generally
judged to be about plus or minus 1 log. ic ip=intracerebral and intraperitoneal.
Table 1: Comparison of transmission rates in primates and cattle infected
orally with similar BSE brain inocula
Published online January 27, 2005
It is clear that the designing scientists must also have shared Mr
Bradley’s surprise at the results because all the dose levels right down to 1
gram triggered infection.
it is clear that the designing scientists must have also shared Mr
Bradleyâs surprise at the results because all the dose levels right down to 1
gram triggered infection.
Comment from Terry Singeltary This is a Comment on the Food and Drug
Administration (FDA) Notice: Draft Guidance for Industry on Ensuring Safety of
Animal Feed Maintained and Fed On-Farm; Availability
For related information, Open Docket Folder Docket folder icon
--------------------------------------------------------------------------------
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Comment View document:
Guidance for Industry Ensuring Safety of Animal Feed Maintained and Fed
On-Farm Draft Guidance FDA-2014-D-1180 Singeltary Comment
Greetings FDA et al,
I wish to comment on Guidance for Industry Ensuring Safety of Animal Feed
Maintained and Fed On-Farm Draft Guidance FDA-2014-D-1180.
Once again, I wish to kindly bring up the failed attempt of the FDA and
the ruminant to ruminant mad cow feed ban of August 4, 1997. This feed ban is
still failing today, as we speak. Even more worrisome, is the fact it is still
legal to feed cervids to cervids in the USA, in fact, the FDA only _recommends_
that deer and elk considered to be of _high_ risk for CWD do not enter the
animal food chain, but there is NO law, its only voluntary, a recipe for a TSE
prion disaster, as we have seen with the ruminant to ruminant feed ban for
cattle, where in 2007, one decade post August 1997 mad cow feed ban, where in
2007 10,000,000 POUNDS OF BANNED BLOOD LACED MEAT AND BONE MEAL WHEN OUT INTO
COMMERCE, TO BE FED OUT. Since 2007, these BSE feed ban rules have been breached
time and time again. tons and tons of mad cow feed went out in Alabama as well,
where one of the mad cows were documented, just the year before in 2006, and in
2013 and 2014, breaches so bad (OAI) Official Action Indicated were issued.
those are like the one issued where 10 million pounds of banned blood laced meat
and bone meal were fed out.
What is the use of having a Guidance for Industry Ensuring Safety of
Animal Feed Maintained and Fed On-Farm Draft Guidance FDA-2014-D-1180, if it
cannot be enforced, as we have seen with a mandatory ruminant to ruminant feed
ban?
I strenuously once again urge the FDA and its industry constituents, to
make it MANDATORY that all ruminant feed be banned to all ruminants, and this
should include all cervids as soon as possible for the following reasons...
======
In the USA, under the Food and Drug Administrations BSE Feed Regulation
(21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin)
from deer and elk is prohibited for use in feed for ruminant animals. With
regards to feed for non-ruminant animals, under FDA law, CWD positive deer may
not be used for any animal feed or feed ingredients. For elk and deer considered
at high risk for CWD, the FDA recommends that these animals do not enter the
animal feed system.
***However, this recommendation is guidance and not a requirement by law.
======
31 Jan 2015 at 20:14 GMT
*** Ruminant feed ban for cervids in the United States? ***
31 Jan 2015 at 20:14 GMT
19 May 2010 at 21:21 GMT
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics
of BSE in Canada Singeltary reply ;
Tuesday, December 23, 2014
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED
VIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE DECEMBER 2014 BSE TSE PRION
2013
Sunday, December 15, 2013
FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED
VIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE DECEMBER 2013 UPDATE
DOCKET-- 03D-0186 -- FDA Issues Draft Guidance on Use of Material From
Deer and Elk in Animal Feed; Availability
Date: Fri, 16 May 2003 11:47:37 0500
EMC 1 Terry S. Singeltary Sr. Vol #: 1
PLEASE SEE FULL TEXT SUBMISSION ;
10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN
COMMERCE USA 2007
Date: March 21, 2007 at 2:27 pm PST
REASON
Blood meal used to make cattle feed was recalled because it was cross-
contaminated with prohibited bovine meat and bone meal that had been
manufactured on common equipment and labeling did not bear cautionary BSE
statement.
VOLUME OF PRODUCT IN COMMERCE
42,090 lbs.
DISTRIBUTION
WI
REASON
Products manufactured from bulk feed containing blood meal that was cross
contaminated with prohibited meat and bone meal and the labeling did not bear
cautionary BSE statement.
VOLUME OF PRODUCT IN COMMERCE
9,997,976 lbs.
DISTRIBUTION
ID and NV
END OF ENFORCEMENT REPORT FOR MARCH 21, 2007
Terry S. Singeltary Sr.
*** See attached file(s)
No documents available.
Attachments View All (1)
Guidance for Industry Ensuring Safety of Animal Feed Maintained and Fed
On-Farm Terry Singeltary Comment View Attachment:
Sunday, April 5, 2015
*** Guidance for Industry Ensuring Safety of Animal Feed Maintained and
Fed On-Farm Draft Guidance FDA-2014-D-1180 ***
‘’AS i said before, OIE should hang up there jock strap now, since it
appears they will buckle every time a country makes some political hay about
trade protocol, commodities and futures. IF they are not going to be science
based, they should do everyone a favor and dissolve there organization.’’
Wednesday, March 11, 2015
OIE and Centers for Disease Control and Prevention Reinforce Collaboration
Saturday, April 18, 2015
vCJD TEXAS CDC Emerging Infectious Diseases May 2015 Baylor College of
Medicine Neuroscience 2014 case of human form of “mad cow disease” highlights
need for continued surveillance
Saturday, May 09, 2015
*** Psychiatric Symptoms in Patients With Sporadic Creutzfeldt-Jakob
Disease in Germany ***
Sunday, May 3, 2015
PRION2015 FORT COLLINS
Saturday, December 13, 2014
Terry S. Singeltary Sr. Publications TSE prion disease
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February
14, 2001 JAMA
snip...
lost my mom to the Heidenhain Variant of Creutzfeldt Jakob Disease hvCJD
12/14/97 confirmed. I just made a promise to mom, never forget (I could never
ever forget what I saw), and never let them forget...
layperson
Terry S. Singeltary Sr., Bacliff, Texas USA 77518 flounder9@verizon.net
posted by Terry S. Singeltary Sr. at
11:50 PM
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