Release No. 0046.08
Contact:
USDA Press Office (202) 720-4623
Statement by Secretary of Agriculture Ed Schafer Regarding Hallmark/Westland
Meat Packing Company Two Year Product Recall
February 17, 2008
"Today, USDA is announcing additional actions as a result of the ongoing
investigation at Hallmark/Westland Meat Packing Company. USDA's Food Safety
and Inspection Service (FSIS) has evidence that Hallmark/Westland did not
consistently contact the FSIS public health veterinarian in situations in
which cattle became non-ambulatory after passing ante-mortem inspection,
which is not compliant with FSIS regulations. Because the cattle did not
receive complete and proper inspection FSIS has determined them to be unfit
for human food and the company is conducting a recall.
The United States enjoys one of the safest food supplies in the world. To
help ensure the safety of the food supply, we implement a series of
safeguards to protect against foodborne disease. These safeguards include
in-plant procedures to reduce dangerous foodborne pathogens such as E. coli
O157:H7 and Salmonella. It also includes the removal of specified risk
materials-those tissues demonstrated to contain the bovine spongiform
encephalopathy agent in infected cattle-from the human food chain, along
with the U.S. Food and Drug Administration's 1997 ruminant to ruminant feed
ban. The prohibition of non-ambulatory cattle from the food supply is an
additional safeguard against bovine spongiform encephalopathy.
Upon notification of possible violations of USDA regulations, we immediately
began an investigation and placed products from this plant destined for the
National School Lunch Program, the Emergency Food Assistance Program and the
Food Distribution Program on Indian Reservations on hold. Since then, we
also suspended all Federal food and nutrition program contracts with
Hallmark/Westland Meat Packing Company. To date, Hallmark/Westland Meat
Packing Company remains suspended by the Food Safety and Inspection Service.
The products destined for the Federal food assistance programs, including
the National School Lunch Program, will now be removed from schools and
other holding facilities and destroyed.
I am dismayed at the in-humane handling of cattle that has resulted in the
violation of food safety regulations at the Hallmark/Westland Meat Packing
Company. It is extremely unlikely that these animals were at risk for BSE
because of the multiple safeguards; however, this action is necessary
because plant procedures violated USDA regulations.
In addition, our Office of the Inspector General and the Food Safety and
Inspection Service continue the investigation. We will respond immediately
if further findings warrant. Details about this recall and USDA actions are
available at www.usda.gov/actions . "
#
http://www.usda.gov/wps/portal/usdahome?contentidonly=true&contentid=2008/02/0046.xml
>>>It also includes the removal of specified risk materials-those tissues
demonstrated to contain the bovine spongiform encephalopathy agent in
infected cattle-from the human food chain, along with the U.S. Food and Drug
Administration's 1997 ruminant to ruminant feed ban. The prohibition of
non-ambulatory cattle from the food supply is an additional safeguard
against bovine spongiform encephalopathy. <<<
in my opinion, this is a food safety issue.
SOME FACTS BELOW, this 8/4/97 feed ban usda et al are so proud of was/is nothing but ink on paper. it was never enforced. thousands and thousands of tons of mad cow protein in commerce in 2006 and 2007. usda et al forgets to add this to their phony statements ;
SRM SPECIFIED RISK MATERIALS RUMINANT TO RUMINANT ANIMAL PROTEIN IN COMMERCE 2006-2007
http://madcowspontaneousnot.blogspot.com/2008/02/specified-risk-materials-srm.html
Geographical BSE Risk (GBR) assessments covering 2000-2006
Date : 01.08.2006
http://www.efsa.europa.eu/EFSA/Scientific_Document/GBR_assessments_table_Overview_assessed_countries_2002-2006.pdf
USDA CERTIFIED H-BASE MAD COW SCHOOL LUNCH PROGRAM
http://cjdmadcowbaseoct2007.blogspot.com/2008/02/usda-certified-h-base-mad-cow-school.html
http://tinyurl.com/yul2lw
[Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirement for the Disposition of Non-Ambulatory Disabled Cattle 03-025IFA 03-025IFA-2 Terry S. Singeltary Page 1 of 17 9/13/2005
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf
Audit Report Animal and Plant Health Inspection Service Bovine Spongiform Encephalopathy (BSE) Surveillance Program – Phase II and Food Safety and Inspection Service Controls Over BSE Sampling, Specified Risk Materials, and Advanced Meat Recovery Products - Phase III
Report No. 50601-10-KC January 2006
Finding 2 Inherent Challenges in Identifying and Testing High-Risk Cattle Still Remain Our prior report identified a number of inherent problems in identifying and testing high-risk cattle. We reported that the challenges in identifying the universe of high-risk cattle, as well as the need to design procedures to obtain an appropriate representation of samples, was critical to the success of the BSE surveillance program. The surveillance program was designed to target nonambulatory cattle, cattle showing signs of CNS disease (including cattle testing negative for rabies), cattle showing signs not inconsistent with BSE, and dead cattle. Although APHIS designed procedures to ensure FSIS condemned cattle were sampled and made a concerted effort for outreach to obtain targeted samples, industry practices not considered in the design of the surveillance program reduced assurance that targeted animals were tested for BSE. In our prior report, we recommended that APHIS work with public health and State diagnostic laboratories to develop and test rabies-negative samples for BSE. This target group is important for determining the prevalence of BSE in the United States because rabies cases exhibit clinical signs not inconsistent with BSE; a negative rabies test means the cause of the clinical signs has not been diagnosed. APHIS agreed with our recommendation and initiated an outreach program with the American Association of Veterinary Laboratory Diagnosticians, as well as State laboratories. APHIS also agreed to do ongoing monitoring to ensure samples were obtained from this target population. Although APHIS increased the samples tested from this target group as compared to prior years, we found that conflicting APHIS instructions on the ages of cattle to test resulted in inconsistencies in what samples were submitted for BSE testing. Therefore, some laboratories did not refer their rabies negative samples to APHIS in order to maximize the number tested for this critical target population. In addition, APHIS did not monitor the number of submissions of rabies negative samples for BSE testing from specific laboratories.
snip...
An NVSL official stated that APHIS is not concerned with rabies negatives samples from cattle less than 30 months of age. This position, however, is contrary to APHIS’ published target population. Our prior audit recognized the significant challenge for APHIS to obtain samples from some high-risk populations because of the inherent problems with obtaining voluntary compliance and transporting the carcasses for testing. USDA issued rules to prohibit nonambulatory animals (downers) from entering the food supply at inspected slaughterhouses. OIG recommended, and the International Review Subcommittee33 emphasized, that USDA should take additional steps to assure that facilitated pathways exist for dead and nonambulatory cattle to allow for the collection of samples and proper disposal of carcasses. Between June 1, 2004, and May 31, 2005, the APHIS database documents 27,617 samples were collected showing a reason for submission of nonambulatory and 325,225 samples were collected with reason of submission showing "dead." APHIS made extensive outreach efforts to notify producers and private veterinarians of the need to submit and have tested animals from these target groups. They also entered into financial arrangements with 123 renderers and other collection sites to reimburse them for costs associated with storing, transporting, and collecting samples. However, as shown in exhibit F, APHIS was not always successful in establishing agreements with non-slaughter collection sites in some States. APHIS stated that agreements do not necessarily reflect the entire universe of collection sites and that the presentation in exhibit F was incomplete because there were many collection sites without a payment involved or without a formal agreement. We note that over 90 percent of the samples collected were obtained from the 123 collection sites with agreements and; therefore, we believe agreements offer the best source to increase targeted samples in underrepresented areas. We found that APHIS did not consider industry practices in the design of its surveillance effort to provide reasonable assurance that cattle exhibiting possible clinical signs consistent with BSE were tested. Slaughter facilities do not always accept all cattle arriving for slaughter because of their business requirements. We found that, in one State visited, slaughter facilities pre-screened and rejected cattle (sick/down/dead/others not meeting business Downers and Cattle that Died on the Farm standards) before presentation for slaughter in areas immediately adjacent or contiguous to the official slaughter establishment. These animals were not inspected and/or observed by either FSIS or APHIS officials located at the slaughter facilities. FSIS procedures state that they have no authority to inspect cattle not presented for slaughter. Further, APHIS officials stated they did not believe that they had the authority to go into these sorting and/or screening areas and require that the rejected animals be provided to APHIS for BSE sampling. Neither APHIS nor FSIS had any process to assure that animals left on transport vehicles and/or rejected for slaughter arrived at a collection site for BSE testing. FSIS allows slaughter facilities to designate the area of their establishment where federal inspection is performed; this is designated as the official slaughter establishment.34 We observed animals that were down or dead in pens outside the official premises that were to be picked up by renderers. Animals that were rejected by plant personnel were transported off the premises on the same vehicles that brought them to the plant.35 A policy statement36 regarding BSE sampling of condemned cattle at slaughter plants provided that effective June 1, 2004, FSIS would collect BSE samples for testing: 1) from all cattle regardless of age condemned by FSIS upon ante mortem inspection for CNS impairment, and 2) from all cattle, with the exception of veal calves, condemned by FSIS upon ante mortem inspection for any other reason. FSIS Notice 28-04, dated May 20, 2004, informed FSIS personnel that, "FSIS will be collecting brain samples from cattle at federally-inspected establishments for the purpose of BSE testing." The notice further states that, "Cattle off-loaded from the transport vehicle onto the premises of the federally-inspected establishment (emphasis added), whether dead or alive, will be sampled by the FSIS Public Health Veterinarian (PHV) for BSE after the cattle have been condemned during ante mortem inspection. In addition, cattle passing ante mortem inspection but later found dead prior to slaughter will be condemned and be sampled by the FSIS PHV." APHIS has the responsibility for sampling dead cattle off-loaded onto plant-owned property that is adjoining to, but not considered part of, the "official premises.37 FSIS procedures38 provide that "Dead cattle that are off-loaded to facilitate the off-loading of live animals, but that will be re-loaded onto the transport vehicle, are not subject to sampling by FSIS. While performing our review in one State, we reviewed the circumstances at two slaughter facilities in the State that inspected and rejected unsuitable cattle before the animals entered the official receiving areas of the plants. This pre-screening activity was conducted in areas not designated by the facility as official premises of the establishment and not under the review or supervision of FSIS inspectors. The plant rejected all nonambulatory and dead/dying/sick animals delivered to the establishment. Plant personnel refused to offload any dead or downer animals to facilitate the offloading of ambulatory animals. Plant personnel said that the driver was responsible for ensuring nonambulatory animals were humanely euthanized and disposing of the carcasses of the dead animals. Plant personnel informed us that they did not want to jeopardize contracts with business partners by allowing unsuitable animals on their slaughter premises. In the second case, one family member owned a slaughter facility while another operated a livestock sale barn adjacent to the slaughter facility. The slaughter facility was under FSIS’ supervision while the sale barn was not. Cattle sometimes arrived at the sale barn that were sick/down/dead or would die or go down while at the sale barn. According to personnel at the sale barn, these animals were left for the renderer to collect. The healthy ambulatory animals that remained were marketed to many buyers including the adjacent slaughter facility. When the slaughter facility was ready to accept the ambulatory animals for processing, the cattle would be moved from the sale barn to the slaughter facility where they were subject to FSIS’ inspection. We requested the slaughter facilities to estimate the number of cattle rejected on a daily basis (there were no records to confirm the estimates). We visited a renderer in the area and found that the renderer had a contract with APHIS to collect samples for BSE testing. In this case, although we could not obtain assurance that all rejected cattle were sampled, the renderer processed a significant number of animals, as compared to the slaughter plants’ estimates of those rejected. Due to the close proximity (less than 5 miles) of the renderer to the slaughter facilities, and the premium it paid for dead cattle that were in good condition, there was a financial incentive for transport drivers to dispose of their dead animals at this renderer.
USDA/OIG-A/50601-10-KC Page 25
In our discussions with APHIS officials in Wisconsin and Iowa, they confirmed that there were plants in their States that also used pre-screening practices. On May 27, 2005, we requested APHIS and FSIS to provide a list of all slaughter facilities that pre-screened cattle for slaughter in locations away from the area designated as the official slaughter facility. Along with this request, we asked for information to demonstrate that either APHIS or FSIS confirmed there was a high likelihood that high-risk animals were sampled at other collection sites. In response to our request, the APHIS BSE Program Manager stated that APHIS did not have information on slaughter plants that pre-screen or screen their animals for slaughter suitability off their official plant premises. To their knowledge, every company or producer that submits animals for slaughter pre-sorts or screens them for suitability at various locations away from the slaughter facility. For this reason, USDA focused its BSE sample collection efforts at other types of facilities such as renderers, pet food companies, landfills, and dead stock haulers. Further, in a letter to OIG on June 14, 2005, the administrators of APHIS and FSIS noted the following: "…we believe that no specific actions are necessary or appropriate to obtain reasonable assurance that animals not presented for slaughter are being tested for BSE. There are several reasons for our position. First, we do not believe that the practice is in fact causing us to not test a significant enough number of animals in our enhanced surveillance program to invalidate the overall results. Second, OIG has concluded that because of the geographical proximity and business relationships of the various entities involved in the case investigated, there is reasonable assurance that a majority of the rejected cattle had been sampled. Third, it is also important to remember that the goal of the enhanced surveillance program is to test a sufficient number of animals to allow us to draw conclusions about the level of BSE (if any) in the American herd…We believe that the number we may be not testing because of the "pre-sorting" practice does not rise to a significant level. The number of animals tested to date has far exceeded expectations, so it is reasonable to infer that there are few of the animals in question, or that we are testing them at some other point in the process…APHIS estimated…there were approximately 446,000 high risk cattle…[and APHIS has]…tested over 375,000 animals in less than 1 year. This indicated that we are missing few animals in the high-risk population, including those that might be pre-sorted before entering a slaughter facility’s property." snip... APHIS notes that for the current surveillance program, it had established regional goals and APHIS was not trying to meet particular sampling levels in particular States. However, we believe that it would be advantageous for APHIS to monitor collection data and increase outreach when large geographical areas such as the above States do not provide samples in proportion to the numbers and types of cattle in the population. We also disagree with APHIS/FSIS’ contention that because they have tested over 375,000 of their 446,000 estimate of high risk cattle, few in the high-risk population are being missed, including those that might be pre-screened before entering a slaughter facility’s property. In our prior audit, we reported that APHIS underestimated the high-risk population; we found that this estimate should have been closer to 1 million animals (see Finding 1). We recognize that BSE samples are provided on a voluntary basis; however, APHIS should consider industry practice in any further maintenance surveillance effort. Animals unsuitable for slaughter exhibiting symptoms not inconsistent with BSE should be sampled and their clinical signs recorded. However, this cited industry practice results in rejected animals not being made available to either APHIS or FSIS veterinarians for their observation and identification of clinical signs exhibited ante mortem. Although these animals may be sampled later at other collection sites, the animals are provided post mortem without information as to relevant clinical signs exhibited ante mortem. For these reasons, we believe APHIS needs to
USDA/OIG-A/50601-10-KC Page 27
observe these animals ante mortem when possible to assure the animals from the target population are ultimately sampled and the clinical signs evaluated.
snip... http://www.usda.gov/oig/webdocs/50601-10-KC.pdf
[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)
http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf
APHIS-2006-0041-0006 TSE advisory committee for the meeting December 15, 2006
http://www.regulations.gov/fdmspublic/ContentViewer?objectId=09000064801f3413&disposition=attachment&contentType=msw8
Attachment to Singeltary comment January 28, 2007
Greetings APHIS, I would kindly like to submit the following to ;
BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01 [Federal Register: January 9, 2007 (Volume 72, Number 5)] [Proposed Rules] [Page 1101-1129] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr09ja07-21]
http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=09000064801f8152
BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01 Date: January 9, 2007 at 9:08 am PST
http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=09000064801f3412
In this context, a word is in order about the US testing program. After the discovery of the first (imported) cow in 2003, the magnitude of testing was much increased, reaching a level of >400,000 tests in 2005 (Figure 4).
Neither of the 2 more recently indigenously infected older animals with
nonspecific clinical features would have been detected without such testing,
and neither would have been identified as atypical without confirmatory
Western blots. Despite these facts, surveillance has now been decimated to
40,000 annual tests (USDA news release no. 0255.06, July 20, 2006) and
invites the accusation that the United States will never know the true
status of its involvement with BSE.
snip...
http://www.cdc.gov/ncidod/EID/vol12no12/06-0965.htm
CDC DR. PAUL BROWN TSE EXPERT COMMENTS 2006
The U.S. Department of Agriculture was quick to assure the public earlier
this week that the third case of mad cow disease did not pose a risk to
them, but what federal officials have not acknowledged is that this latest
case indicates the deadly disease has been circulating in U.S. herds for at
least a decade.
The second case, which was detected last year in a Texas cow and which USDA
officials were reluctant to verify, was approximately 12 years old.
These two cases (the latest was detected in an Alabama cow) present a
picture of the disease having been here for 10 years or so, since it is
thought that cows usually contract the disease from contaminated feed they
consume as calves. The concern is that humans can contract a fatal,
incurable, brain-wasting illness from consuming beef products contaminated
with the mad cow pathogen.
"The fact the Texas cow showed up fairly clearly implied the existence of
other undetected cases," Dr. Paul Brown, former medical director of the
National Institutes of Health's Laboratory for Central Nervous System
Studies and an expert on mad cow-like diseases, told United Press
International. "The question was, 'How many?' and we still can't answer
that."
Brown, who is preparing a scientific paper based on the latest two mad cow
cases to estimate the maximum number of infected cows that occurred in the
United States, said he has "absolutely no confidence in USDA tests before
one year ago" because of the agency's reluctance to retest the Texas cow
that initially tested positive.
USDA officials finally retested the cow and confirmed it was infected seven
months later, but only at the insistence of the agency's inspector general.
"Everything they did on the Texas cow makes everything USDA did before 2005
suspect," Brown said. ...snip...end
http://www.upi.com/ConsumerHealthDaily/view.php?StoryID=20060315-055557-1284r
CDC - Bovine Spongiform Encephalopathy and Variant Creutzfeldt ...
Dr. Paul Brown is Senior Research Scientist in the Laboratory of Central
Nervous System ... Address for correspondence: Paul Brown, Building 36, Room
4A-05, ...
http://www.cdc.gov/ncidod/eid/vol7no1/brown.htm
PAUL BROWN COMMENT TO ME ON THIS ISSUE
Tuesday, September 12, 2006 11:10 AM
"Actually, Terry, I have been critical of the USDA handling of the mad cow
issue for some years, and with Linda Detwiler and others sent lengthy detailed critiques and
recommendations to both the USDA and the Canadian Food Agency."
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0703&L=sanet-mg&T=0&P=8125
Volume 12, Number 12–December 2006
PERSPECTIVE
On the Question of Sporadic
or Atypical Bovine SpongiformEncephalopathy and
Creutzfeldt-Jakob Disease
Paul Brown,* Lisa M. McShane,† Gianluigi Zanusso,‡ and Linda Detwiler§
A link between BSE and
sporadic CJD has been suggested on the basis of laboratory
studies but is unsupported by epidemiologic observation.
Such a link might yet be established by the discovery
of a specific molecular marker or of particular combinations
of trends over time of typical and atypical BSE and various
subtypes of sporadic CJD, as their numbers are influenced
by a continuation of current public health measures that
exclude high-risk bovine tissues from the animal and
human food chains.
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.
SNIP...
PLEASE READ FULL TEXT ;
http://www.cdc.gov/ncidod/EID/vol12no12/06-0965.htm?s_cid=eid06_0965_e
THE SEVEN SCIENTIST REPORT ***
http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-EC244-Attach-1.pdf
full text ;
http://bse-atypical.blogspot.com/2006/08/bse-atypical-texas-and-alabama-update.html
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
Sunday, February 17, 2008
Monday, February 11, 2008
Evaluation of the Human Transmission Risk of an Atypical Bovine Spongiform Encephalopathy Prion Strain
Thursday, January 31, 2008
Evaluation of the Human Transmission Risk of an Atypical Bovine Spongiform Encephalopathy Prion Strain
J. Virol. doi:10.1128/JVI.02561-07Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.
Thursday, January 31, 2008Evaluation of the Human Transmission Risk of an Atypical Bovine Spongiform Encephalopathy Prion Strain J. Virol. doi:10.1128/JVI.02561-07Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.
Evaluation of the Human Transmission Risk of an Atypical Bovine Spongiform Encephalopathy Prion Strain
Qingzhong Kong*, Mengjie Zheng, Cristina Casalone, Liuting Qing, Shenghai Huang, Bikram Chakraborty, Ping Wang, Fusong Chen, Ignazio Cali, Cristiano Corona, Francesca Martucci, Barbara Iulini, Pierluigi Acutis, Lan Wang, Jingjing Liang, Meiling Wang, Xinyi Li, Salvatore Monaco, Gianluigi Zanusso, Wen-Quan Zou, Maria Caramelli, and Pierluigi Gambetti*Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA; CEA, Istituto Zooprofilattico Sperimentale, 10154 Torino, Italy; Department of Neurological and Visual Sciences, University of Verona, 37134 Verona, Italy
* To whom correspondence should be addressed. Email: qxk2@case.edu. pxg13@case.edu.
Abstract
Bovine spongiform encephalopathy (BSE), the prion disease in cattle, was widely believed to have only one strain (BSE-C). BSE-C causes the fatal prion disease named new variant Creutzfeldt-Jacob disease in humans. Two atypical BSE strains, BASE (or BSE-L) and BSE-H, have been discovered in several countries since 2004; their transmissibility and phenotypes in humans are unknown. We investigated the infectivity and human phenotype of BASE by inoculating transgenic (Tg) mice expressing the human prion protein with brain homogenates from two BASE-affected cattle. Sixty percent of the inoculated Tg mice became infected after 20-22 months incubation, a transmission rate higher than those reported for BSE-C. A quarter of BASE-infected Tg mice, but none of the Tg mice infected with a sporadic human prion disease, showed presence of pathogenic prion protein isoforms in the spleen, indicating that the BASE prion is intrinsically lymphotropic. The pathological prion protein isoforms in BASE-infected humanized Tg mouse brains are different from those of the original cattle BASE or sporadic human prion disease. Minimal brain spongiosis and long incubation time are observed in the BASE-infected Tg mice. These results suggest that, in humans, BASE is a more virulent BSE strain and likely lymphotropic.
http://jvi.asm.org/cgi/content/abstract/JVI.02561-07v1?papetoc
for those interested, further into this study ;
INTRODUCTION
Overwhelming evidence indicates that BSE, a prion disease that has been detected in several hundred thousand cattle in the UK and many other countries since the 1980s, has been transmitted to humans through the consumption of prion contaminated beef, causing a prion disease named variant Creutzfeldt-Jakob disease (vCJD) (5, 20). Over 200 cases of vCJD have been reported around the world (19). In 2004 two types of bovine prion disease that differ from the original BSE, now named classical BSE (BSE-C), were reported (4, 8). The two atypical BSE were associated with prion protein (PrP) scrapie isoforms (PrPSc) that, after protease digestion, displayed distinct electrophoretic mobility or ratios of the PrPSc glycoforms different from those of BSE-C (4, 8). Currently, a total of at least 36 cases of these two atypical BSE have been reported in cattle older than eight years (5; Caramelli, M., unpublished data). The two atypical BSE are identified as BASE (bovine amyloidotic spongiform encephalopathy) or L-type and H- type, respectively; the “L” and “H” identify the higher and lower electrophoretic positions of their protease-resistant PrPSc isoforms (7). The bovine phenotype and the PrPSc molecular features of BASE have been described in detail (8). The histopathology and PrP immunostaining pattern of BASE are characterized by the presence of prion amyloid plaques, and a more rostral distribution of the PrPSc, which, at variance with BSE-C, is present in the cerebral cortex including the hippocampus but is underrepresented in the brain stem (8). These phenotypic features and PrPSc characteristics resemble a subtype of sporadic Creutzfeldt-Jakob disease (sCJD) named sCJDMV2, which affects subjects who are methionine (M)/valine (V) heterozygous at codon 129 of the PrP gene, and it is associated with PrPSc identified as type 2 (15). This similarity has raised the question as of whether sCJDMV2 is not sporadic but acquired from the consumption of BASE-contaminated meat (5, 8). To begin to investigate the transmissibility to humans and the “human” disease phenotype of BASE, including the involvement of the lymphoreticular system, we have inoculated brain homogenates from BASE- affected cattle to Tg mice expressing normal human PrP with Met at codon 129 (HuPrP-129M) in a mouse PrP ablated background [Tg(HuPrP)] (13). The inoculated Tg mice were examined for attack rate and the disease phenotype, including the presence and characteristics of protease- resistant PrPSc in the brain and spleen, the histopathology, along with the PrPSc topography and pattern of deposition in the brain.
RESULTS
To assess the transmissibility of BASE in humans, two BASE isolates (8) were used to intracerebrally inoculate 30 Tg40 mice that express normal level of human PrP-129M. More than half of the inoculated mice (18/30) became infected, as determined by the presence of protease-resistant PrPSc, with an average incubation time of 649±34 days for BASE isolate 1 and 595±28 days for BASE isolate 2, respectively (Table 1). Ten of the 18 infected mice that could be examined showed clear clinical signs of disease (Table 1), including hunched back, ruffled fur, lethargy, occasional wobbling and rigid tail. These signs were best detected in the younger mice because in mice older than 24 months they became difficult to distinguish from aging- related changes.
All the Tg40 mice were examined for the presence of proteinase K (PK)-resistant PrPSc in the brain by immunoblot analysis both directly and after enrichment with sodium phosphotungstate (NaPTA) precipitation. Such immunoblot analysis with three monoclonal antibodies (3F4, 6H4, 8H4) to various PrP regions (12, 14, 25) showed that all 18 BASE-infected Tg40 mice accumulated comparable amounts of proteinase K (PK)-resistant PrPSc in the brain (Figure 1A, Table 1, and data not shown). The electrophoretic mobility of PK-resistant PrPSc fragments from all the BASE-infected Tg40 mice was indistinguishable from that of the PK- resistant PrPSc present in either the BASE inoculum or sCJDMM2 that contains PrPSc type 2 (Figure 1A). The PK-resistant PrPSc fragments associated with both the BASE-infected Tg40 mice and the BASE isolates migrated slightly faster than those of BSE-C as originally reported (8). Measurements with software that automatically calculates the mid-point of the bands revealed a difference of 0.29±0.12 kDa in gel mobility between the unglycosylated PK-resistant PrPSc bands of BASE (native as well as from the Tg40 mice) and BSE-C.
The glycoform ratio of PrPSc in the BASE-infected Tg40 mice was slightly different from that of the BASE isolates (Figure 1B), and both were quite different from that of BSE-C (Figure 1B). The monoglycosylated form (the middle band) was the most prominent species in the BASE inocula where the glycoform ratio (diglycosylated : monoglycosylated : unglycosylated) is 32:41:27, whereas the diglycosylated form (the top band) was slightly more intense than the monoglycosylated form in BASE-infected Tg40 mice where the glycoform ratio is 44:39:17 (Figure 1B). In contrast, the diglycosylated form accounted for over 70% of the total PrPSc in BSE-C (glycoform ratio 72:20:8).
PrPSc in the spleen was also examined after NaPTA enrichment for all 30 BASE- inoculated Tg40 mice. PK-resistant PrPSc was readily detected in the spleen of 4 mice (Figure 1C), all of which also contained PK-resistant PrPSc in the brain. The electrophoretic mobility of the spleen PrPSc was similar to that of the brain PrPSc. The glycoform ratio of the spleen PrPSc was different from that of the brain and was characterized by the prominence of the monoglycosylated and unglycosylated forms (Figure 1C), but the glycoform ratio may have been affected by the NaPTA enrichment. In contrast, none of the 9 Tg40 mice inoculated with sCJDMM1 had detectable PK-resistant PrPSc in the spleen after NaPTA enrichment (data not shown).
None of the 12 BASE-infected Tg40 mice examined showed prominent and consistent histopathological changes related to prion diseases (Figure 2A). Focal, ambiguous spongiform degeneration was observed in 2 mice. No PrP amyloid plaques were observed in BASE-infected Tg40 mice. Histoblot analysis with mAb 3F4 showed a very distinct and selective distribution of PrPSc (Figure 3A-D). Particular nuclei or group of adjacent peri-ventricular nuclei in the thalamus, hypothalamus and brain stem were intensely immunostained for PrPSc (Figure 3B-D). In contrast, PrPSc appeared to be overall less intense in the cerebral and cerebellar cortices (Figure 3A-D). Immunohistochemical staining of paraffin-embedded brain tissue with 3F4 revealed PrP deposits in five of the 11 BASE-infected Tg40 mice examined. PrPSc deposits that stained intensely in the histoblots consisted of relatively large and well circumscribed granules (Figure 3E and G). Fine granular or small plaque-like aggregate patterns were occasionally seen in inferior regions of the cerebral cortex and in the thalamus (Figure 3I and data not shown). In contrast, widespread mostly fine granular staining was detected in the cerebral cortex of symptomatic Tg40 mice inoculated with sCJDMM1 brain homogenate (Figure 3J).
The histopathological features of the BASE-inoculated Tg40 mice were quite different from those observed following inoculation with brain homogenates from the two forms of sporadic CJD, sCJDMM1 and sCJDMM2. The sCJDMM1-inoculated Tg40 mice had widespread spongiform degeneration in the cerebrum (Figure 2B) and moderate apoptosis of neuronal cells without spongiform degeneration in the cerebellum (13). Widespread spongiform degeneration was also seen in Tg40 mice inoculated with sCJDMM2 brain homogenate (Data not shown).
DISCUSSION
We have shown that 60% of our Tg40 mice (in inbred FVB background) that express normal level of human PrP-129M became infected 20-22 months after intracerebral (i.c.) inoculation with 0.3mg of brain tissue from the two BASE isolates, suggesting a titer of approximately 3 ID50 units per mg of brain tissue in the Tg40 line. A ~20% attack rate has been reported in the Tg650 line (in a mixed 129/Sv x C57BL/6 background) after i.c. inoculation with 2mg brain tissues from BSE-C affected cattle (2). It is noteworthy that the Tg650 mice express human PrP-129M at 5-8x normal level, and high PrP levels are known to increase prion transmissibility (9, 17, 22). Inefficient BSE-C transmissions (0-30%) in Tg mouse lines of other genetic backgrounds expressing human PrP-129M at 1x or 2x normal levels have also been reported by different groups (1, 3). Although it is difficult to compare results from different mouse lines, these findings suggest that BASE has higher transmissibility than that of BSE-C to humanized transgenic mice with PrP-129M and possibly to humans with PrP-129MM. BASE also appears to be more virulent than BSE-C in bovinized Tg mice since the incubation time for BASE is 185±12 days whereas that for BSE-C is 230±7 days (7). Nevertheless, when compared with the 100% attack rate and incubation times of ~9 months for sCJDMM1 and sCJDMM2 in the Tg40 line (Table 1), the 60% attack rate and unusually long incubation times (20-22 months) for BASE in the same Tg line suggest that the transmission barrier from BASE to humans with PrP-129MM is still quite significant.
PK-resistant PrPSc was also detected in the spleen in 4 out of 18 BASE-infected Tg40 mice. In contrast, no spleen involvement could be demonstrated in the Tg40 mice following i.c. inoculation with human PrPSc from sCJDMM1. This is the first report of the presence of PrPSc in the spleen of humanized Tg mice after i.c. inoculation with a BSE strain, suggesting that the BASE strain, like BSE-C where at least in vCJD affected subjects PrPSc and prion infectivity have been detected in spleen and tonsil (6, 11), is intrinsically lymphotropic. Therefore, lymphoid tissues of BASE-infected individuals might also carry prion infectivity.
The gel mobility of the PK-resistant PrPSc recovered from the BASE-inoculated Tg40 mice was consistently slightly faster than that of BSE-C as originally reported for BASE (8). The computed difference in gel mobility between BASE and BSE-C PrPSc is 0.29 ± 0.12 kDa, corresponding to 2-4 amino acid residues. In contrast, the gel mobility of the PK-resistant PrPSc species from BASE, BASE-infected Tg40 mice, and sCJDMM2 that was used as representative of human PrPSc type 2, was indistinguishable. This finding suggests that the PK-resistant PrPSc electrophoretic heterogeneity between BASE and BSE-C falls well within the seven amino acid variability of the N-terminus (92-99) that is consistently found in PK-resistant PrPSc type 2 (16). Therefore, despite their minor but distinct variability in gel mobility, both BASE and BSE-C PrPSc species appear to belong to the PrPSc type 2. However, the PrPSc glycoform ratios of BASE-infected Tg40 mice and the BASE inocula display a small but statistically significant difference (Figure 1). Therefore, PrPSc in BASE-infected human subjects may be expected to display a different glycoform ratio from that of BASE. It is worth noting that the electrophoretic characteristics of the PK-resistant PrPSc of some human prion strains has been faithfully reproduced by our Tg40 line as well as by other humanized mouse lines (10, 13, 21).
Two distinct histopathological and PrP immunohistochemical phenotypes have been reported following BSE-C inoculation: one reproduced the distinctive features of vCJD with the “florid” plaques which intensely immunostained for PrP, and the other was reminiscent of sCJDMM1 with prominent spongiform degeneration and no plaque PrP immunostaining (1, 23).
The brain histopathology, the PrPSc distribution and the PrP immunostaining pattern of BASE- inoculated Tg40 mice were definitely distinct from such features described above (1, 23), further supporting the notion that BASE and BSE-C are associated with two distinct prion strains (8).
The relatively easy transmission of BASE to humanized Tg mice indicates that effective cattle prion surveillance should be maintained until the extent and origin of this and other atypical forms of BSE are fully understood.
MATERIALS AND METHODS
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http://jvi.asm.org/cgi/reprint/JVI.02561-07v1
PLEASE SEE !
P02.35 Molecular Features of the Protease-resistant Prion Protein (PrPres) in H- type BSE
Biacabe, A-G1; Jacobs, JG2; Gavier-Widén, D3; Vulin, J1; Langeveld, JPM2; Baron, TGM1 1AFSSA, France; 2CIDC-Lelystad, Netherlands; 3SVA, Sweden
Western blot analyses of PrPres accumulating in the brain of BSE- infected cattle have demonstrated 3 different molecular phenotypes regarding to the apparent molecular masses and glycoform ratios of PrPres bands. We initially described isolates (H-type BSE) essentially characterized by higher PrPres molecular mass and decreased levels of the diglycosylated PrPres band, in contrast to the classical type of BSE. This type is also distinct from another BSE phenotype named L-type BSE, or also BASE (for Bovine Amyloid Spongiform Encephalopathy), mainly characterized by a low representation of the diglycosylated PrPres band as well as a lower PrPres molecular mass. Retrospective molecular studies in France of all available BSE cases older than 8 years old and of part of the other cases identified since the beginning of the exhaustive surveillance of the disease in 20001 allowed to identify 7 H- type BSE cases, among 594 BSE cases that could be classified as classical, L- or H-type BSE. By Western blot analysis of H-type PrPres, we described a remarkable specific feature with antibodies raised against the C-terminal region of PrP that demonstrated the existence of a more C-terminal cleaved form of PrPres (named PrPres#2 ), in addition to the usual PrPres form (PrPres #1). In the unglycosylated form, PrPres #2 migrates at about 14 kDa, compared to 20 kDa for PrPres #1. The proportion of the PrPres#2 in cattle seems to by higher compared to the PrPres#1. Furthermore another PK–resistant fragment at about 7 kDa was detected by some more N-terminal antibodies and presumed to be the result of cleavages of both N- and C- terminal parts of PrP. These singular features were maintained after transmission of the disease to C57Bl/6 mice. The identification of these two additional PrPres fragments (PrPres #2 and 7kDa band)
*** reminds features reported respectively in sporadic Creutzfeldt-Jakob disease and in Gerstmann-Sträussler-Scheinker (GSS) syndrome in humans.
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 twodimensional 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)
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USA MAD COW CASES IN ALABAMA AND TEXAS
***PLEASE NOTE***
USA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling it today), please note that both the ALABAMA COW, AND THE TEXAS COW,both were ''H-TYPE'', personal communication Detwiler et al Wednesday, August 22, 2007 11:52 PM. ...TSS
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=19779
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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.
Oral Abstracts 14
snip...
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 v CJD 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
Subject: Aspects of the Cerebellar Neuropathology in Nor98
Date: September 26, 2007 at 4:06 pm PST
P03.141
Aspects of the Cerebellar Neuropathology in Nor98
Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute, Norway
Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter.
*** The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
SEE FULL TEXT ;
Creutzfeldt Jakob Disease Delaware UPDATE
http://cjdmadcowbaseoct2007.blogspot.com/2008/02/creutzfeldt-jakob-disease-delaware.html
Creutzfeldt Jakob Disease Texas
http://cjdtexas.blogspot.com/
NOR-98 ATYPICAL SCRAPIE USA UPDATE AS AT OCT 2007
http://nor-98.blogspot.com/
USA MAD COW CASES IN ALABAMA AND TEXAS
***PLEASE NOTE***
USA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling it today), please note that both the ALABAMA COW, AND THE TEXAS COW,both were ''H-TYPE'', personal communication Detwiler et al Wednesday, August 22, 2007 11:52 PM. ...TSS
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=19779
NO WRITTEN CJD QUESTIONNAIRE ???
http://cjdquestionnaire.blogspot.com/
[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of BovineSpongiform Encephalopathy (BSE)
http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf
APHIS-2006-0041-0006 TSE advisory committee for the meeting December 15,2006
http://www.regulations.gov/fdmspublic/ContentViewer?objectId=09000064801f3413&disposition=attachment&contentType=msw8
Attachment to Singletary
comment
January 28, 2007
Greetings APHIS,
I would kindly like to submit the following to ;
BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES[Docket No. APHIS-2006-0041] RIN 0579-AC01[Federal Register: January 9, 2007 (Volume 72, Number 5)][Proposed Rules][Page 1101-1129]From the Federal Register Online via GPO Access [wais.access.gpo.gov][DOCID:fr09ja07-21]
http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=09000064801f8152
BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTSDERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01Date: January 9, 2007 at 9:08 am PST
http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=09000064801f3412
HIGHLY SUSPECT BSE, H-BASE, MAD COW BEEF DISTRIBUTED NATIONALLY (35 states to date), to CHILDREN AND THE ELDERLY
USDA CERTIFIED H-BASE MAD COW SCHOOL LUNCH PROGRAM
http://cjdmadcowbaseoct2007.blogspot.com/2008/02/usda-certified-h-base-mad-cow-school.html
[Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirement for the Disposition of Non-Ambulatory Disabled Cattle
03-025IFA03-025IFA-2
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
Evaluation of the Human Transmission Risk of an Atypical Bovine Spongiform Encephalopathy Prion Strain
J. Virol. doi:10.1128/JVI.02561-07Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.
Thursday, January 31, 2008Evaluation of the Human Transmission Risk of an Atypical Bovine Spongiform Encephalopathy Prion Strain J. Virol. doi:10.1128/JVI.02561-07Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.
Evaluation of the Human Transmission Risk of an Atypical Bovine Spongiform Encephalopathy Prion Strain
Qingzhong Kong*, Mengjie Zheng, Cristina Casalone, Liuting Qing, Shenghai Huang, Bikram Chakraborty, Ping Wang, Fusong Chen, Ignazio Cali, Cristiano Corona, Francesca Martucci, Barbara Iulini, Pierluigi Acutis, Lan Wang, Jingjing Liang, Meiling Wang, Xinyi Li, Salvatore Monaco, Gianluigi Zanusso, Wen-Quan Zou, Maria Caramelli, and Pierluigi Gambetti*Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA; CEA, Istituto Zooprofilattico Sperimentale, 10154 Torino, Italy; Department of Neurological and Visual Sciences, University of Verona, 37134 Verona, Italy
* To whom correspondence should be addressed. Email: qxk2@case.edu. pxg13@case.edu.
Abstract
Bovine spongiform encephalopathy (BSE), the prion disease in cattle, was widely believed to have only one strain (BSE-C). BSE-C causes the fatal prion disease named new variant Creutzfeldt-Jacob disease in humans. Two atypical BSE strains, BASE (or BSE-L) and BSE-H, have been discovered in several countries since 2004; their transmissibility and phenotypes in humans are unknown. We investigated the infectivity and human phenotype of BASE by inoculating transgenic (Tg) mice expressing the human prion protein with brain homogenates from two BASE-affected cattle. Sixty percent of the inoculated Tg mice became infected after 20-22 months incubation, a transmission rate higher than those reported for BSE-C. A quarter of BASE-infected Tg mice, but none of the Tg mice infected with a sporadic human prion disease, showed presence of pathogenic prion protein isoforms in the spleen, indicating that the BASE prion is intrinsically lymphotropic. The pathological prion protein isoforms in BASE-infected humanized Tg mouse brains are different from those of the original cattle BASE or sporadic human prion disease. Minimal brain spongiosis and long incubation time are observed in the BASE-infected Tg mice. These results suggest that, in humans, BASE is a more virulent BSE strain and likely lymphotropic.
http://jvi.asm.org/cgi/content/abstract/JVI.02561-07v1?papetoc
for those interested, further into this study ;
INTRODUCTION
Overwhelming evidence indicates that BSE, a prion disease that has been detected in several hundred thousand cattle in the UK and many other countries since the 1980s, has been transmitted to humans through the consumption of prion contaminated beef, causing a prion disease named variant Creutzfeldt-Jakob disease (vCJD) (5, 20). Over 200 cases of vCJD have been reported around the world (19). In 2004 two types of bovine prion disease that differ from the original BSE, now named classical BSE (BSE-C), were reported (4, 8). The two atypical BSE were associated with prion protein (PrP) scrapie isoforms (PrPSc) that, after protease digestion, displayed distinct electrophoretic mobility or ratios of the PrPSc glycoforms different from those of BSE-C (4, 8). Currently, a total of at least 36 cases of these two atypical BSE have been reported in cattle older than eight years (5; Caramelli, M., unpublished data). The two atypical BSE are identified as BASE (bovine amyloidotic spongiform encephalopathy) or L-type and H- type, respectively; the “L” and “H” identify the higher and lower electrophoretic positions of their protease-resistant PrPSc isoforms (7). The bovine phenotype and the PrPSc molecular features of BASE have been described in detail (8). The histopathology and PrP immunostaining pattern of BASE are characterized by the presence of prion amyloid plaques, and a more rostral distribution of the PrPSc, which, at variance with BSE-C, is present in the cerebral cortex including the hippocampus but is underrepresented in the brain stem (8). These phenotypic features and PrPSc characteristics resemble a subtype of sporadic Creutzfeldt-Jakob disease (sCJD) named sCJDMV2, which affects subjects who are methionine (M)/valine (V) heterozygous at codon 129 of the PrP gene, and it is associated with PrPSc identified as type 2 (15). This similarity has raised the question as of whether sCJDMV2 is not sporadic but acquired from the consumption of BASE-contaminated meat (5, 8). To begin to investigate the transmissibility to humans and the “human” disease phenotype of BASE, including the involvement of the lymphoreticular system, we have inoculated brain homogenates from BASE- affected cattle to Tg mice expressing normal human PrP with Met at codon 129 (HuPrP-129M) in a mouse PrP ablated background [Tg(HuPrP)] (13). The inoculated Tg mice were examined for attack rate and the disease phenotype, including the presence and characteristics of protease- resistant PrPSc in the brain and spleen, the histopathology, along with the PrPSc topography and pattern of deposition in the brain.
RESULTS
To assess the transmissibility of BASE in humans, two BASE isolates (8) were used to intracerebrally inoculate 30 Tg40 mice that express normal level of human PrP-129M. More than half of the inoculated mice (18/30) became infected, as determined by the presence of protease-resistant PrPSc, with an average incubation time of 649±34 days for BASE isolate 1 and 595±28 days for BASE isolate 2, respectively (Table 1). Ten of the 18 infected mice that could be examined showed clear clinical signs of disease (Table 1), including hunched back, ruffled fur, lethargy, occasional wobbling and rigid tail. These signs were best detected in the younger mice because in mice older than 24 months they became difficult to distinguish from aging- related changes.
All the Tg40 mice were examined for the presence of proteinase K (PK)-resistant PrPSc in the brain by immunoblot analysis both directly and after enrichment with sodium phosphotungstate (NaPTA) precipitation. Such immunoblot analysis with three monoclonal antibodies (3F4, 6H4, 8H4) to various PrP regions (12, 14, 25) showed that all 18 BASE-infected Tg40 mice accumulated comparable amounts of proteinase K (PK)-resistant PrPSc in the brain (Figure 1A, Table 1, and data not shown). The electrophoretic mobility of PK-resistant PrPSc fragments from all the BASE-infected Tg40 mice was indistinguishable from that of the PK- resistant PrPSc present in either the BASE inoculum or sCJDMM2 that contains PrPSc type 2 (Figure 1A). The PK-resistant PrPSc fragments associated with both the BASE-infected Tg40 mice and the BASE isolates migrated slightly faster than those of BSE-C as originally reported (8). Measurements with software that automatically calculates the mid-point of the bands revealed a difference of 0.29±0.12 kDa in gel mobility between the unglycosylated PK-resistant PrPSc bands of BASE (native as well as from the Tg40 mice) and BSE-C.
The glycoform ratio of PrPSc in the BASE-infected Tg40 mice was slightly different from that of the BASE isolates (Figure 1B), and both were quite different from that of BSE-C (Figure 1B). The monoglycosylated form (the middle band) was the most prominent species in the BASE inocula where the glycoform ratio (diglycosylated : monoglycosylated : unglycosylated) is 32:41:27, whereas the diglycosylated form (the top band) was slightly more intense than the monoglycosylated form in BASE-infected Tg40 mice where the glycoform ratio is 44:39:17 (Figure 1B). In contrast, the diglycosylated form accounted for over 70% of the total PrPSc in BSE-C (glycoform ratio 72:20:8).
PrPSc in the spleen was also examined after NaPTA enrichment for all 30 BASE- inoculated Tg40 mice. PK-resistant PrPSc was readily detected in the spleen of 4 mice (Figure 1C), all of which also contained PK-resistant PrPSc in the brain. The electrophoretic mobility of the spleen PrPSc was similar to that of the brain PrPSc. The glycoform ratio of the spleen PrPSc was different from that of the brain and was characterized by the prominence of the monoglycosylated and unglycosylated forms (Figure 1C), but the glycoform ratio may have been affected by the NaPTA enrichment. In contrast, none of the 9 Tg40 mice inoculated with sCJDMM1 had detectable PK-resistant PrPSc in the spleen after NaPTA enrichment (data not shown).
None of the 12 BASE-infected Tg40 mice examined showed prominent and consistent histopathological changes related to prion diseases (Figure 2A). Focal, ambiguous spongiform degeneration was observed in 2 mice. No PrP amyloid plaques were observed in BASE-infected Tg40 mice. Histoblot analysis with mAb 3F4 showed a very distinct and selective distribution of PrPSc (Figure 3A-D). Particular nuclei or group of adjacent peri-ventricular nuclei in the thalamus, hypothalamus and brain stem were intensely immunostained for PrPSc (Figure 3B-D). In contrast, PrPSc appeared to be overall less intense in the cerebral and cerebellar cortices (Figure 3A-D). Immunohistochemical staining of paraffin-embedded brain tissue with 3F4 revealed PrP deposits in five of the 11 BASE-infected Tg40 mice examined. PrPSc deposits that stained intensely in the histoblots consisted of relatively large and well circumscribed granules (Figure 3E and G). Fine granular or small plaque-like aggregate patterns were occasionally seen in inferior regions of the cerebral cortex and in the thalamus (Figure 3I and data not shown). In contrast, widespread mostly fine granular staining was detected in the cerebral cortex of symptomatic Tg40 mice inoculated with sCJDMM1 brain homogenate (Figure 3J).
The histopathological features of the BASE-inoculated Tg40 mice were quite different from those observed following inoculation with brain homogenates from the two forms of sporadic CJD, sCJDMM1 and sCJDMM2. The sCJDMM1-inoculated Tg40 mice had widespread spongiform degeneration in the cerebrum (Figure 2B) and moderate apoptosis of neuronal cells without spongiform degeneration in the cerebellum (13). Widespread spongiform degeneration was also seen in Tg40 mice inoculated with sCJDMM2 brain homogenate (Data not shown).
DISCUSSION
We have shown that 60% of our Tg40 mice (in inbred FVB background) that express normal level of human PrP-129M became infected 20-22 months after intracerebral (i.c.) inoculation with 0.3mg of brain tissue from the two BASE isolates, suggesting a titer of approximately 3 ID50 units per mg of brain tissue in the Tg40 line. A ~20% attack rate has been reported in the Tg650 line (in a mixed 129/Sv x C57BL/6 background) after i.c. inoculation with 2mg brain tissues from BSE-C affected cattle (2). It is noteworthy that the Tg650 mice express human PrP-129M at 5-8x normal level, and high PrP levels are known to increase prion transmissibility (9, 17, 22). Inefficient BSE-C transmissions (0-30%) in Tg mouse lines of other genetic backgrounds expressing human PrP-129M at 1x or 2x normal levels have also been reported by different groups (1, 3). Although it is difficult to compare results from different mouse lines, these findings suggest that BASE has higher transmissibility than that of BSE-C to humanized transgenic mice with PrP-129M and possibly to humans with PrP-129MM. BASE also appears to be more virulent than BSE-C in bovinized Tg mice since the incubation time for BASE is 185±12 days whereas that for BSE-C is 230±7 days (7). Nevertheless, when compared with the 100% attack rate and incubation times of ~9 months for sCJDMM1 and sCJDMM2 in the Tg40 line (Table 1), the 60% attack rate and unusually long incubation times (20-22 months) for BASE in the same Tg line suggest that the transmission barrier from BASE to humans with PrP-129MM is still quite significant.
PK-resistant PrPSc was also detected in the spleen in 4 out of 18 BASE-infected Tg40 mice. In contrast, no spleen involvement could be demonstrated in the Tg40 mice following i.c. inoculation with human PrPSc from sCJDMM1. This is the first report of the presence of PrPSc in the spleen of humanized Tg mice after i.c. inoculation with a BSE strain, suggesting that the BASE strain, like BSE-C where at least in vCJD affected subjects PrPSc and prion infectivity have been detected in spleen and tonsil (6, 11), is intrinsically lymphotropic. Therefore, lymphoid tissues of BASE-infected individuals might also carry prion infectivity.
The gel mobility of the PK-resistant PrPSc recovered from the BASE-inoculated Tg40 mice was consistently slightly faster than that of BSE-C as originally reported for BASE (8). The computed difference in gel mobility between BASE and BSE-C PrPSc is 0.29 ± 0.12 kDa, corresponding to 2-4 amino acid residues. In contrast, the gel mobility of the PK-resistant PrPSc species from BASE, BASE-infected Tg40 mice, and sCJDMM2 that was used as representative of human PrPSc type 2, was indistinguishable. This finding suggests that the PK-resistant PrPSc electrophoretic heterogeneity between BASE and BSE-C falls well within the seven amino acid variability of the N-terminus (92-99) that is consistently found in PK-resistant PrPSc type 2 (16). Therefore, despite their minor but distinct variability in gel mobility, both BASE and BSE-C PrPSc species appear to belong to the PrPSc type 2. However, the PrPSc glycoform ratios of BASE-infected Tg40 mice and the BASE inocula display a small but statistically significant difference (Figure 1). Therefore, PrPSc in BASE-infected human subjects may be expected to display a different glycoform ratio from that of BASE. It is worth noting that the electrophoretic characteristics of the PK-resistant PrPSc of some human prion strains has been faithfully reproduced by our Tg40 line as well as by other humanized mouse lines (10, 13, 21).
Two distinct histopathological and PrP immunohistochemical phenotypes have been reported following BSE-C inoculation: one reproduced the distinctive features of vCJD with the “florid” plaques which intensely immunostained for PrP, and the other was reminiscent of sCJDMM1 with prominent spongiform degeneration and no plaque PrP immunostaining (1, 23).
The brain histopathology, the PrPSc distribution and the PrP immunostaining pattern of BASE- inoculated Tg40 mice were definitely distinct from such features described above (1, 23), further supporting the notion that BASE and BSE-C are associated with two distinct prion strains (8).
The relatively easy transmission of BASE to humanized Tg mice indicates that effective cattle prion surveillance should be maintained until the extent and origin of this and other atypical forms of BSE are fully understood.
MATERIALS AND METHODS
snip...end...tss
http://jvi.asm.org/cgi/reprint/JVI.02561-07v1
PLEASE SEE !
P02.35 Molecular Features of the Protease-resistant Prion Protein (PrPres) in H- type BSE
Biacabe, A-G1; Jacobs, JG2; Gavier-Widén, D3; Vulin, J1; Langeveld, JPM2; Baron, TGM1 1AFSSA, France; 2CIDC-Lelystad, Netherlands; 3SVA, Sweden
Western blot analyses of PrPres accumulating in the brain of BSE- infected cattle have demonstrated 3 different molecular phenotypes regarding to the apparent molecular masses and glycoform ratios of PrPres bands. We initially described isolates (H-type BSE) essentially characterized by higher PrPres molecular mass and decreased levels of the diglycosylated PrPres band, in contrast to the classical type of BSE. This type is also distinct from another BSE phenotype named L-type BSE, or also BASE (for Bovine Amyloid Spongiform Encephalopathy), mainly characterized by a low representation of the diglycosylated PrPres band as well as a lower PrPres molecular mass. Retrospective molecular studies in France of all available BSE cases older than 8 years old and of part of the other cases identified since the beginning of the exhaustive surveillance of the disease in 20001 allowed to identify 7 H- type BSE cases, among 594 BSE cases that could be classified as classical, L- or H-type BSE. By Western blot analysis of H-type PrPres, we described a remarkable specific feature with antibodies raised against the C-terminal region of PrP that demonstrated the existence of a more C-terminal cleaved form of PrPres (named PrPres#2 ), in addition to the usual PrPres form (PrPres #1). In the unglycosylated form, PrPres #2 migrates at about 14 kDa, compared to 20 kDa for PrPres #1. The proportion of the PrPres#2 in cattle seems to by higher compared to the PrPres#1. Furthermore another PK–resistant fragment at about 7 kDa was detected by some more N-terminal antibodies and presumed to be the result of cleavages of both N- and C- terminal parts of PrP. These singular features were maintained after transmission of the disease to C57Bl/6 mice. The identification of these two additional PrPres fragments (PrPres #2 and 7kDa band)
*** reminds features reported respectively in sporadic Creutzfeldt-Jakob disease and in Gerstmann-Sträussler-Scheinker (GSS) syndrome in humans.
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 twodimensional 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)
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USA MAD COW CASES IN ALABAMA AND TEXAS
***PLEASE NOTE***
USA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling it today), please note that both the ALABAMA COW, AND THE TEXAS COW,both were ''H-TYPE'', personal communication Detwiler et al Wednesday, August 22, 2007 11:52 PM. ...TSS
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=19779
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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.
Oral Abstracts 14
snip...
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 v CJD 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
Subject: Aspects of the Cerebellar Neuropathology in Nor98
Date: September 26, 2007 at 4:06 pm PST
P03.141
Aspects of the Cerebellar Neuropathology in Nor98
Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute, Norway
Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter.
*** The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
SEE FULL TEXT ;
Creutzfeldt Jakob Disease Delaware UPDATE
http://cjdmadcowbaseoct2007.blogspot.com/2008/02/creutzfeldt-jakob-disease-delaware.html
Creutzfeldt Jakob Disease Texas
http://cjdtexas.blogspot.com/
NOR-98 ATYPICAL SCRAPIE USA UPDATE AS AT OCT 2007
http://nor-98.blogspot.com/
USA MAD COW CASES IN ALABAMA AND TEXAS
***PLEASE NOTE***
USA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling it today), please note that both the ALABAMA COW, AND THE TEXAS COW,both were ''H-TYPE'', personal communication Detwiler et al Wednesday, August 22, 2007 11:52 PM. ...TSS
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=19779
NO WRITTEN CJD QUESTIONNAIRE ???
http://cjdquestionnaire.blogspot.com/
[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of BovineSpongiform Encephalopathy (BSE)
http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf
APHIS-2006-0041-0006 TSE advisory committee for the meeting December 15,2006
http://www.regulations.gov/fdmspublic/ContentViewer?objectId=09000064801f3413&disposition=attachment&contentType=msw8
Attachment to Singletary
comment
January 28, 2007
Greetings APHIS,
I would kindly like to submit the following to ;
BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES[Docket No. APHIS-2006-0041] RIN 0579-AC01[Federal Register: January 9, 2007 (Volume 72, Number 5)][Proposed Rules][Page 1101-1129]From the Federal Register Online via GPO Access [wais.access.gpo.gov][DOCID:fr09ja07-21]
http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=09000064801f8152
BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTSDERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01Date: January 9, 2007 at 9:08 am PST
http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=09000064801f3412
HIGHLY SUSPECT BSE, H-BASE, MAD COW BEEF DISTRIBUTED NATIONALLY (35 states to date), to CHILDREN AND THE ELDERLY
USDA CERTIFIED H-BASE MAD COW SCHOOL LUNCH PROGRAM
http://cjdmadcowbaseoct2007.blogspot.com/2008/02/usda-certified-h-base-mad-cow-school.html
[Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirement for the Disposition of Non-Ambulatory Disabled Cattle
03-025IFA03-025IFA-2
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
Friday, February 8, 2008
Creutzfeldt Jakob Disease Delaware UPDATE
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