CREUTZFELDT JAKOB DISEASE

Assessing Prion Infectivity of Human Urine in Sporadic Creutzfeldt-Jakob Disease

2011-12-23T08:38:00.001-08:00

Volume 18, Number 1—January 2012

Research

Assessing Prion Infectivity of Human Urine in Sporadic Creutzfeldt-Jakob Disease

Silvio Notari1, Liuting Qing1, Maurizio Pocchiari, Ayuna Dagdanova, Kristin Hatcher, Arend Dogterom, Jose F. Groisman, Ib Bo Lumholtz, Maria Puopolo, Corinne Lasmezas, Shu G. Chen, Qingzhong Kong, and Pierluigi Gambetti Author affiliations: Case Western Reserve University, Cleveland, Ohio, USA (S. Notari, L. Qing, A. Dagdanova, K. Hatcher, S.G. Chen, Q. Kong, P. Gambetti); Istituto Superiore di Sanità, Rome, Italy (M. Pocchiari, M. Puopolo); Ferring Pharmaceuticals, Hvidore, Denmark (A. Dogterom); Instituto Massone, Buenos Aires, Argentina (J.F. Groisman); BL Consult ApS, Copenhagen, Denmark (I.B. Lumholtz); The Scripps Research Institute, Jupiter, Florida, USA (C. Lasmezas)

Abstract Prion diseases are neurodegenerative conditions associated with a misfolded and infectious protein, scrapie prion protein (PrPSc). PrPSc propagate prion diseases within and between species and thus pose risks to public health. Prion infectivity or PrPSc presence has been demonstrated in urine of experimentally infected animals, but there are no recent studies of urine from patients with Creutzfeldt-Jakob disease (CJD). We performed bioassays in transgenic mice expressing human PrP to assess prion infectivity in urine from patients affected by a common subtype of sporadic CJD, sCJDMM1. We tested raw urine and 100-fold concentrated and dialyzed urine and assessed the sensitivity of the bioassay along with the effect of concentration and dialysis on prion infectivity. Intracerebral inoculation of transgenic mice with urine from 3 sCJDMM1 patients failed to demonstrate prion disease transmission, indicating that prion infectivity in urine from sCJDMM1 patients is either not present or is <0.38 infectious units/mL.

snip...

Discussion The present study demonstrates that the urine from patients affected by advanced sCJDMM1, the most common sCJD subtype that alone accounts for ≈60% of all human prion diseases, contains either no prion infectivity or an infectivity titer that is below the detection limit of our bioassays. The bioassays were done in Tg mice expressing human PrP-129M (Tg40) following inoculation with urine obtained from patients with sCJDMM1 and a variety of positive and negative controls. In limit dilution experiments, Tg40 mice inoculated with MF preparations obtained from the brains of 3 urine donors with sCJDMM1 had prion disease develop at up to 105 or 104 dilutions of the brain tissue equivalent depending on whether the MF preparations were inoculated directly or after spiking into concentrated and dialyzed normal human urine.

To enhance the sensitivity of our system, urine samples were concentrated and dialyzed before inoculation. Similar procedures have been used in all the previous studies on prion infectivity of urine (13,22,23), except for the study by Gregori et al. (21). Our procedure is similar to that used by Seeger et al., who reported the detection of prion infectivity in urine from scrapie inoculated mice affected by nephritis (23). Although we demonstrated in the spiking experiment with MF from sCJDMM1 that the 100× concentration and dialysis procedure did not cause infectivity loss (Table 3), the infectivity of the prion-spiked preparation decreased 20-fold when 100× concentrated and dialyzed urine was used as carrier compared with PBS. On the basis of these findings, we estimated that if prion infectivity is present at all in sCJDMM1 urine, it is at most 0.38 IU/mL if the 20-fold infectivity loss is factored in. Because the nature of the potential PrPSc in urine from CJD patients is not known, this urine PrPSc species might show even higher loss of infectivity in the concentrated and dialyzed urine carrier than the brain PrPSc preparations used in the spiking experiments. To address this concern, we inoculated 33 Tg40 mice with raw urine from one of the 3 donors with sCJDMM1. No recipient mice showed evidence of prion disease suggesting an infectivity ranging from 0.0 and 0.11 IU/per mL (upper limit of 95% CI) as estimated by the Poisson distribution.

Although asymptomatic disease in recipient mice associated with NaPTA- undetectable minute amounts of PrPSc cannot be excluded, our inability to detect prion infectivity in human urine of patients with sCJDMM1 differs from several recent experimental studies on urine of prion-affected animals. Low prion infectivity has been demonstrated in urine from scrapie-infected hamsters (21,22), CWD-infected deer (13), and in scrapie-infected mice affected by lymphocytic nephritis. In the last study, however, no urine infectivity was found in non-nephritic mice (23). Three additional studies have demonstrated the presence of PrPSc in urine from scrapie-infected hamsters and CWD-infected deer using protein misfolding cyclic amplification (PMCA) (13,34,35). However, this highly sensitive procedure can detect prion concentrations below the level of detectability of bioassays.

The most likely explanation for the discrepancy between our negative results on human urine and the positive findings by bioassay in urine from animals resides in the different locale and mode of formation of the prion agents. In all the published animal experiments, including bioassays and PMCA, the prion disease was induced by intracerebral or oral administration of exogenous prions, whereas we examined urine infectivity in a naturally occurring sporadic human prion disease. In exogenously acquired prion diseases, PrPSc is much more likely to be widely present in nonneural peripheral organs, including blood, kidney, and bladder, which is likely the result of early exposure of peripheral organs to the inoculated prions. In sCJD, which is believed to occur spontaneously in the brain (rather than being acquired by infection from exogenous prions), only minute amounts of PrPSc have been detected in a few nonneural peripheral organs and tissues such as skeletal muscle and spleen (6–8,10). In contrast, in variant CJD (vCJD), the form of CJD acquired by consumption of BSE-infected beef, the spread of PrPSc to peripheral organs is much wider and typically involves lymph nodes, tonsil, spleen, portions of the intestinal tract, and the skeletal muscle (7,10,36,37), as well as kidney and other organs (9). These considerations indicate that vCJD (not sCJD) in principle is more similar to the exogenously acquired animal prion diseases that have been used to study prion infectivity in urine. Therefore, vCJD urine that is more likely to contain prion infectivity should be tested by PMCA or bioassay. However, the reported infectivity of animal urine might also result, at least in some instances, from contamination with feces.

Recent data have proved that feces from hamsters infected with scrapie by the oral route and to a lesser extent through intracerebral and intraperitoneal inoculation, contain a discrete amount of PrPSc and prion infectivity (38,39). Infectivity has been demonstrated also in feces from deer orally infected by CWD (40). In hamsters and mice, metabolic cages were used for urine collection, a method in which cross-contamination by feces may actually occur. However, prion infectivity was also demonstrated in urine from CWD-infected deer from which urine collection could easily be performed by catheterization (although this procedure was not mentioned by the authors) (13).

Although additional studies are still needed to determine whether minute amounts of prion infectivity or PrPSc are present in urine from patients with sCJD and to assess the presence of infectious prion in urine from patients with every other form and subtype of human prion diseases, our study shows that urine from patients with sCJDMM1, the most common subtype of sCJD, does not contain prion infectivity detectable by our bioassay and suggests that no significant prionuria occurs in this common subtype of human prion disease.

Dr Notari is an instructor at the Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA. His research interests are the prion diseases with particular focus on the characteristics of PrPSc in different CJD subtypes and their relationships with infectivity.

http://wwwnc.cdc.gov/eid/article/18/1/11-0589_article.htm

Friday, March 25, 2011

Detection of Prion Protein in Urine-Derived Injectable Fertility Products by a Targeted Proteomic Approach

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/detection-of-prion-protein-in-urine.html

Sunday, December 18, 2011

A blood test for variant Creutzfeldt‐Jakob disease: briefing note for patients, carers and health professionals

http://vcjdtransfusion.blogspot.com/2011/12/blood-test-for-variant-creutzfeldtjakob.html

Friday, December 23, 2011

Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate Model

Volume 18, Number 1—January 2012 Dispatch

http://transmissiblespongiformencephalopathy.blogspot.com/2011/12/oral-transmission-of-l-type-bovine.html

TSS

Creutzfeldt-Jacob Disease Question Asked by Lord Walton of Detchant P-Capt filter

2011-12-16T10:12:00.000-08:00

Health: Creutzfeldt-Jacob Disease Question Asked by Lord Walton of Detchant

To ask Her Majesty's Government what is their estimate of the number of individuals in the United Kingdom carrying the prion responsible for the non-variant Creutzfeldt-Jacob Disease (CJD); and whether they propose to recommend the widespread use of the P-CAPT filter on blood available for transfusion, so as to prevent the transmission of this infective agent.[HL14081]

The Parliamentary Under-Secretary of State, Department of Health (Earl Howe): Human prion diseases not classified as variant (v) Creutzfeldt-Jakob disease (CJD) include sporadic CJD, iatrogenic CJD and familial CJD (including Gerstmann-Straussler-Scheinker (GSS) syndrome). While there are no reliable data on the prevalence of these conditions, in total they affect about 1:1,000,000 of the population per

15 Dec 2011 : Column WA284

annum. Data on deaths due to all forms of CJD are published monthly by the United Kingdom Creutzfeldt-Jakob disease Research and Surveillance Unit and can be found at: www.cjd.ed.ac.uk/figures.htm.

The P-Capt filter is marketed by Macopharma for the removal of prions from leucodepleted blood to reduce the risk of transmission of vCJD. While there is evidence of presumed transmissions of vCJD via blood transfusions from donors who later went on to develop clinical vCJD, there is no evidence of other forms of CJD being transmitted by transfusion.

The potential use of the P-Capt filter, to reduce the risk of potential transmission of vCJD, is under consideration by the Advisory Committee on the Safety of Blood Tissues and Organs (SaBTO) and will be on the agenda for the SaBTO's first 2012 meeting to be held on 9 March 2012.

http://www.publications.parliament.uk/pa/ld201011/ldhansrd/text/111215w0001.htm#11121582000225

FC5.1.1

Transmission Results in Squirrel Monkeys Inoculated with Human sCJD, vCJD, and GSS Blood Specimens: the Baxter Study

Brown, P1; Gibson, S2; Williams, L3; Ironside, J4; Will, R4; Kreil, T5; Abee, C3 1Fondation Alliance BioSecure, France; 2University of South Alabama, USA; 3University of Texas MD Anderson Cancer Center, USA; 4Western General Hospital, UK; 5Baxter BioSience, Austria

Background: Rodent and sheep models of Transmissible Spongiform Encephalopathy (TSE) have documented blood infectivity in both the pre-clinical and clinical phases of disease. Results in a (presumably more appropriate) non-human primate model have not been reported.

Objective: To determine if blood components (red cells, white cells, platelets, and plasma) from various forms of human TSE are infectious.

Methods: Blood components were inoculated intra-cerebrally (0.1 ml) and intravenously (0.5 ml) into squirrel monkeys from 2 patients with sporadic Creutzfeldt- Jakob disease (sCJD) and 3 patients with variant Creutzfeldt-Jakob disease (vCJD). Additional monkeys were inoculated with buffy coat or plasma samples from chimpanzees infected with either sCJD or Gerstmann-StrÃ¤ussler-Scheinker disease (GSS). Animals were monitored for a period of 5 years, and all dying or sacrificed animals had post-mortem neuropathological examinations and Western blots to determine the presence or absence of the misfolded prion protein (PrPTSE).

Results: No transmissions occurred in any of the animals inoculated with blood components from patients with sporadic or variant CJD. All donor chimpanzees (sCJD and GSS) became symptomatic within 6 weeks of their pre-clinical phase plasmapheresis, several months earlier than the expected onset of illness. One monkey inoculated with purified leukocytes from a pre-clinical GSS chimpanzee developed disease after 36 months.

Conclusion: No infectivity was found in small volumes of blood components from 4 patients with sporadic CJD and 3 patients with variant CJD. ***However, a single transmission from a chimpanzee-passaged strain of GSS shows that infectivity may be present in leukocytes, and the shock of general anaesthesia and plasmspheresis appears to have triggered the onset of illness in pre-clinical donor chimpanzees.

Saturday, September 5, 2009

TSEAC MEETING FEBRUARY 12, 2004 THE BAXTER STUDY GSS

snip...

http://tseac.blogspot.com/2011/06/tseac-meeting-august-1-2011-donor.html

Wednesday, June 29, 2011

TSEAC Meeting August 1, 2011 donor deferral Saudi Arabia vCJD risk blood and blood products

http://tseac.blogspot.com/2011/06/tseac-meeting-august-1-2011-donor.html

Wednesday, August 24, 2011

All Clinically-Relevant Blood Components Transmit Prion Disease following a Single Blood Transfusion: A Sheep Model of vCJD

http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/all-clinically-relevant-blood.html

Wednesday, August 24, 2011

There Is No Safe Dose of Prions

http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/there-is-no-safe-dose-of-prions.html

stupid is, as stupid does, and some times, you just can’t fix stupid $$$

TSS

Second iatrogenic CJD case confirmed Korea

2011-12-12T08:23:00.000-08:00

Second iCJD case confirmed

Date 2011-12-09 Hit

25

Second iCJD case confirmed

- Investigation is planned for all CJD patients that can be traced to check whether they have received a dura mater graft, etc -

Korea Centers for Disease Control and Prevention (KCDC; Director Jun, Byung Yool) informed that an additional case of iCJD has been confirmed in a patient who was earlier reported to have been infected with sporadic CJD (sCJD) through the study of the patient’s medical history. This iCJD seems to have occurred after the transplant of the dura mater graft.

The patient in the case is a 48-year-old man who was diagnosed with sCJD in Jul. 2011 at a hospital located in the metropolitan area and his case was reported through the legal communicable disease reporting system. According to this man’s medical record, he got a surgery for intracranial hemorrhage caused by an external injury in May 1988 and received a transplant of the “Lyodura” dura mater.

Generally, it is very rare to carry out a transplant of the dura mater in the surgery for intracranial hemorrhage and the manufacturing history of the dura mater used in the transplantation in this case couldn’t be found.

KCDC has requested the Korean Neurological Association, the Korean Medical Association, and the Korean Hospital Association, etc to keep detailed records of medical histories related to iCJD including operation histories of the patients suspected of having sCJD.

KCDC also said that it would conduct a tracking investigation to check and confirm the possibility of exposure to the risk of iCJD infections by all the CJD patients that can be traced with medical records at hospitals of all levels including the CJD patients that have been reported through the legal communicable disease reporting system since 2000.

http://english.mw.go.kr/front_eng/al/sal0201vw.jsp?PAR_MENU_ID=1002&MENU_ID=100203&page=1&CONT_SEQ=261181&SEARCHKEY=&SEARCHVALUE=

Press Release

Date
8 Dec. / (2 pages)
Division
Telephone

Manager/POC
Park, Hye Kyung/Huh, Chang Ho
Division of Infectious Disease Control
043-719-7120

043-719-7116

Second iCJD case confirmed

- Investigation is planned for all CJD patients that can be traced to check whether they have received a dura mater graft, etc

-

□ Korea Centers for Disease Control and Prevention (KCDC; Director Jun, Byung Yool) informed that an additional case of iCJD has been confirmed in a patient who was earlier reported to have been infected with sporadic CJD (sCJD) through the study of the patient’s medical history. This iCJD seems to have occurred after the transplant of the dura mater graft.

□ The patient in the case is a 48-year-old man who was diagnosed with sCJD in Jul. 2011 at a hospital located in the metropolitan area and his case was reported through the legal communicable disease reporting system. According to this man’s medical record, he got a surgery for intracranial hemorrhage caused by an external injury in May 1988 and received a transplant of the “Lyodura” dura mater.

○ Generally, it is very rare to carry out a transplant of the dura mater in the surgery for intracranial hemorrhage and the manufacturing history of the dura mater used in the transplantation in this case couldn’t be found.

□ KCDC has requested the Korean Neurological Association, the Korean Medical Association, and the Korean Hospital Association, etc to keep detailed records of medical histories related to iCJD including operation histories of the patients suspected of having sCJD.

□ KCDC also said that it would conduct a tracking investigation to check and confirm the possibility of exposure to the risk of iCJD infections by all the CJD patients that can be traced with medical records at hospitals of all levels including the CJD patients that have been reported through the legal communicable disease reporting system since 2000.

iCJD-tracking investigation plan (draft)

[Attachment]

http://download.mw.go.kr/front/modules/download.jsp?BOARD_ID=1365&CONT_SEQ=261181&FILE_SEQ=78227&FILE_NAME=[ENG][12.8.FRI] second case of iCJD confirmed.docx

=============================

Thursday, December 08, 2011

A case of Iatrogenic Creutzfeldt Jakob Disease (iCJD) in a patient who had received a German-manufactured human dura mater graft 23 years ago

http://creutzfeldt-jakob-disease.blogspot.com/2011/12/case-of-iatrogenic-creutzfeldt-jakob.html

Thursday, December 8, 2011

S. Korea confirms second case of iatrogenic Creutzfeldt-Jakob disease 48-year-old man

2011/12/08 11:08 KST

http://usdavskorea.blogspot.com/2011/12/s-korea-confirms-second-case-of.html

Wednesday, November 30, 2011

First iCJD Death Confirmed in Korea

http://creutzfeldt-jakob-disease.blogspot.com/2011/11/first-icjd-death-confirmed-in-korea.html

http://usdavskorea.blogspot.com/

Saturday, June 25, 2011

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque

"BSE-L in North America may have existed for decades"

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html

http://transmissiblespongiformencephalopathy.blogspot.com/

http://creutzfeldt-jakob-disease.blogspot.com/

http://bseusa.blogspot.com/

http://bse-atypical.blogspot.com/

http://madcowusda.blogspot.com/

http://chronic-wasting-disease.blogspot.com/

http://nor-98.blogspot.com/

http://scrapie-usa.blogspot.com/

TSS

A case of Iatrogenic Creutzfeldt Jakob Disease (iCJD) in a patient who had received a German-manufactured human dura mater graft 23 years ago

2011-12-08T19:54:00.000-08:00

Date
1 Dec. / (8 pages)
Division
Telephone

Manager/POC
Park, Hye Kyung/Huh, Chang Ho
Division of Infectious Disease Control
043-719-7120

043-719-7116

A case of Iatrogenic Creutzfeldt Jakob Disease (iCJD) in a patient who had received a German-manufactured human dura mater graft 23 years ago

- First case in Korea but it has nothing to do with the variant CJD known as “human mad cow disease” -

- Currently, there is no risk of CJD transmission since new, safe dura mater alternatives are being used.

□ Korea Centers for Disease Control and Prevention (KCDC; Director Jun, Byung Yool) informed that the first case of iatrogenic Creutzfeldt-Jakob disease(iCJD) was confirmed in a patient who had received a human dura mater graft with the German-made brain tissue as results of biopsy and animal tests.

* iCJD: CJD contracted in the process of medical treatment caused by a transplanted tissue, etc

□This first victim of iCJD in Korea is a 54-year-old woman who had received a transplant of the membrane manufactured in Germany under the trade name Lyodura in 1987. She began displaying symptoms of CJD in June 2010, 23 years after she received the dura mater graft. Initially, the patient was suspected to have contracted sporadic CJD (sCJD) and she died in Nov. 2010 while the investigation was still being conducted.

○ It is presumed that the German-manufactured dura mater used had been taken from a cadaver of a patient infected with sCJD.

* Sporadic CJD(sCJD): It affects about one person in every one million people per year worldwide.

□ KCDC emphasized that iCJD has nothing to do with the variant CJD* and it was not contracted from the patient’s daily life but due to the transplantation of the German-made dura mater (Lyodura). It also added that then, the materials were not well controlled but now safe dura mater alternatives are being used.

* Variant CJD develops after one has eaten infected beef products from cows with BSE (Bovine Spongioform Encephalopathy ).

○ Also, it is said that since May 1987, the concerned manufacturer has been conducting a deactivation process against prions (an infectious agent composed of protein), known to cause CJD, to remove the possibility of CJD infection.

□ Around 400 cases of iCJD have been reported in 20 countries worldwide and approximately 200 cases of them broke out after the dura mater transplantations, over a half of which have taken place in Japan after the transplants of the concerned German-manufactured dura mater. The probability of developing iCJD after the brain tissue graft is 1/500 ~ 2,000.

□ According to the KCDC, a team of experts in cooperation with the Korean Neurological Association, and the Korean Neurosurgical Society, etc has been formed to trace people known to have received the surgery in the 1980s with their medical records and neurosurgical tests under their consents.

Attachment

1. General Info of CJD

2. Domestic CJD control status

3. Q & As

General Info of CJD

󰊱 iatrogenic CJD

○iCJD is caused by surgical transplants of the dura mater or the cornea of a person infected with an abnormal form of a protein called a “prion protein”. It can also be passed on through injection of hormones extracted from a brain of an infected person.

Causes of iCJD

① It is passed on through contaminated injections of human growth hormones or gonadotropic hormone or through surgical transplants of the dura mater.

② It is caused by transplants of the cornea extracted from a patient confirmed or suspected of having a human prion disease.

③ It is caused by exposure to contaminated surgical equipment used on people with CJD.

󰊲 Types of CJD

There are four types of CJD

○ sporadic CJD, inherited CJD, and iatrogenic CJD according to the channel of infection and clinical features

- and variant CJD

Categorization

Characteristics

CJD

Sporadic CJD

(sCJD)

Degenerative brain disorder caused by the accumulation in the brain of an abnormal form of a protein called a “prion protein.”

(It affects 0.5~2 persons in every one million per year worldwide)

Inherited CJD

It is caused by a genetic mutation.

Iatrogenic CJD (iCJD)
It is caused by surgical transplants of the dura mater or the cornea of an infected person. It can also be passed on through injection of hormones extracted from a brain of an infected person.

※ Brain, spinal cord, and eyeball are most vulnerable to this disease

Variant CJD
It can develop after one has consumed prions contained SRMs of cattle with BSE (Bovine Spongioform Encephalopathy).

※ SRM: Specified risk materials that contain considerable amounts of abnormal protein called “prion protein,” which is the cause of mad cow disease, such as cow brain, intestines, and spinal cord, etc

CJD Control Status

󰊱 Operation of the monitoring system

○ It has been subject to the sentinel surveillance as CJD including vCJD was designated as a legal communicable disease in 2001.

- As it was designated as “Communicable Disease, Class III.”, it has become mandatory to report an outbreak of CJD.

○ Confirmation is made by an investigation of individual cases reported.

- Legal ground for the authority to issue an order for autopsy for the confirmation of the disease has been prepared (‘11~)

○ (In Korea) Less than 30 cases suspected of sCJD infection are reported each year.

[[No. of patients suspected of having contracted CJD (2001~Oct. 2011)]

(Unit: person)

Category
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011

(as of 26 Oct.)

Total
5
9
19
13
15
19
18
28
30
29
25

Gender
Male
2
5
7
8
7
11
13
15
13
14
13

Female
3
4
12
5
8
8
5
13
17
15
12

* The numbers of CJD outbreak cases reported in 2009~2011 are tentative figures.

󰊲 Operation of the diagnosis system

○ Hallym University Sacred Heart Hospital has been running a CJD autopsy and diagnosis center from 2006

- 10 autopsies and 10 biopsies have been conducted so far.

Year
Total
Apr. 2006
2007
2008
2009
2010
Nov. 2011

Total (No. of cases)
*20
1
4
5
4
5
1

Autopsy
10
-
2
2
3
3
-

Biopsy
10
1
2
3
1
2
1

* Result of Autopsy/Biopsy

-No case suspected of variant CJD has been found yet.

- 7 cases of sCJD

- 2 cases of Alzheimer’s disease

- One case of genetic CJD

- One case of iCJD (the case confirmed this time)

- 7 uncategorized cases (these are the cases showing clinical features suspected of being related to a prion disease that need to be compared with results of further clinical tests and investigations.)

- Two cases displaying no clinical features of CJD

Q & As

Related to Lyodura, a German-made dura mater ;

1. What is Lyodura?

☞ Lyodura is a medical product manufactured and introduced by B. Braun, a hospital supply company based in Germany in 1969. The raw material for Lyodura is the dura mater of a human cadaver and it is used in neurosurgery.

2. How is Lyodura related to iCJD?

☞ The first case of CJD caused by Lyodura was reported in US in 1987 and FDA recalled the product. The manufacturer added the prion deactivation process using NaOH.

☞ The second case was reported in New Zealand and CDC banned the use of the materials produced before May 1987. However, a worldwide recall of the product was not issued. Therefore, it is likely that many other countries have used the contaminated materials for some years.

☞ WHO recommends not using cadaveric dura mater grafts in 1997. (MMWR, CDC, 2008)

3.Is Lyodura being used in Korea, currently?

☞ Some Lyodura products are known to have been imported and used in the past but Korea now bans human dura mater imports.

☞ The concerned product was produced before Apr. 1987 and it didn’t go through the prion deactivation process.

* KFDA(founded in 1998) does not have a record of the importation of the concerned product and it is difficult to find and check related records or data with a company which imported the product since it was imported a long time ago.

4. How many patients have received transplants of Lyodura? And has there been any similar case since?

☞ Since more than 20 years have passed after the concerned Lyodura was used. Therefore, it is difficult to find and check related data. We are trying to find a proper way to identify the status of the use of the product* and there has been no similar case found yet.

* Records of imports of the product to be checked through the importers and medical records at large medical institutions to be examined, etc

☞ The number of patients who had received the transplants of Lyodura cannot be exactly identified. However, because the patient in this case was found to have received the transplant in 1987, it is likely that there are more cases of Lyodura transplants besides this one.

☞ Since this is the first case in Korea confirmed after CJD monitoring began in 2001. A further study of possible CJD outbreaks caused by Lyodura needs to be considered.

5. What are the products that are being used as an alternative dura mater? Is there any risk of iCJD infection by them?

☞ Currently, five dura mater alternative products are being imported through four companies. No CJD case has been reported concerning those products not just in Korea but also in other countries and given the manufacturing procedure, etc, there is no risk of CJD outbreak.

※ The safety test for medical treatment materials is implemented by KFDA in accordance with the “Medical Device Act,” “Regulations for Approval, etc of Medical Device (KFDA Notification)” and “Regulations for Reviewing Technical Document, etc of Medical Device (KFDA Notification).”

6. What are the causes of iCJD besides Lyodura?

☞ 1) It is passed on through contaminated injections of human growth hormones or gonadotropic hormone or through surgical transplants of the dura mater.

2) It is caused by transplants of the cornea extracted from a patient confirmed or suspected of having a human prion disease.

3) It is caused by exposure to contaminated surgical equipment used on people with CJD.

7. Isn’t it possible that CJD in this confirmed case was due to such causes described above other than the transplant of the dura mater?

☞ iCJD is mainly caused by the transplants of the dura mater and injections of human growth hormones.

8. The case was introduced first in a thesis. Hasn’t the government been aware of this case up to now?

☞ The published thesis was written before the animal tests were completed. The government was planning to announce the case with a result verified and confirmed through the animal tests and consultations with experts.

9. Isn’t it that the CJD monitoring system and epidemiological investigation have missed out on this case?

☞ The incubation period of the disease in this case between the patient’s exposure to the risk and the outbreak was 23 years, which was such a long time. Medical records concerning the risks and interviews with patients and guardians are being carried out through the epidemiological investigation. However, in this case, the surgery was done a long ago and the transplant of the dura mater was a part of a series of the operation that the patient received then. Therefore, the patient’s surgery record then had to be look at to find out necessary facts.

10. Is it possible that there is any CJD patients that were failed to be exactly categorized as in this case?

☞ The neural tissue test has to be conducted for confirmation of CJD. However, since there is culturally negative perception toward a brain biopsy or autopsy after one’s death in Korea, it is difficult to confirm the disease through the test. Therefore, CJD is being categorized based on major symptoms, results of a brain MRI, brain wave test, and cerebral spinal fluid examination, etc.

☞ Various risks and records of one’s travel to countries where the variant CJD broke out and one’s family history, etc are examined through interviews. However, since this disease has a long incubation period, if a patient cannot exactly remember related matters or details or it is difficult to have an interview with the person, sufficient data might not be able to be acquired.

11. Should iCJD be considered a medical malpractice?

☞ When the surgery was done, the risk of the concerned product was not known and it was widely used in neurosurgery.

Therefore, it seems difficult to say that the incident was caused by a doctor’s medical judgment or mischoice.

12. How do hospitals and the government deal with CJD patients now? How is the cadaver of a CJD patient treated?

☞ Since CJD is designated as the “Communicable Disease, Class III,” when a suspected patient is found, the hospital reports it to the KCDC which then carries out an epidemiological investigation.

☞ Hospital manages the patient according to the CJD control guidance. Since CJD is not infected through general contact, the patient doesn’t need to be isolated. If no damage or autopsy is done on the cadaver of the patient, waterproofing is done on the cadaver to keep the body fluid from flowing out.

13. How is a patient diagnosed with CJD being controlled? What action should be taken for a CJD patient who hasn’t been diagnosed yet?

☞ A patient doesn’t have to be isolated but shall observe general cautions for prevention of infection. Some scholars insist that after a biopsy for diagnosis is conducted and before a scar caused by the biopsy gets healed, there is a risk of infection due to exposure of body fluids such as cerebrospinal liquid or tissues that can cause the infection, thus requiring limited isolation of the patient.

☞ There is no way of controlling a CJD patient who hasn’t been diagnosed. Therefore, in order to ensure accurate CJD diagnosis at hospitals, training should be done on medical personnel.

http://download.mw.go.kr/front/modules/download.jsp?BOARD_ID=1365&CONT_SEQ=260967&FILE_SEQ=77999&FILE_NAME=ENG-[보도참고자료]의인성CJD첫발견(최종).hwp.docx

2011/12/08 11:08 KST

S. Korea confirms second case of Creutzfeldt-Jakob disease

SEOUL, Dec. 8 (Yonhap) -- South Korea's health authorities on Thursday confirmed the country's second case of Creutzfeldt-Jakob disease (CJD), a degenerative neurological disorder.

A 48-year-old man was diagnosed with iatrogenic CJD (iCJD) on Wednesday, according to the Center for Disease Control. The person's identity was withheld for privacy reasons.

The report of the country's second-ever iCJD case comes after a 54-year-old woman was found last month to have died from the same disease that is often transmitted by the use of defective prion proteins found in surgical tissue graft products.

The woman had received brain surgery using Lyodura, a tissue graft product, some 23 years ago. The KCDC said the man in the latest case had also received Lyodura during brain surgery in 1988.

This form of CJD has an incubation period of more than 20 years but once symptoms occur, death usually takes place within a year.

CJD is the most common of so-called human prion diseases with one person in every 1 million diagnosed each year worldwide. It is an invariably fatal illness with death occurring after the onset of dementia, hallucinations, coordination dysfunction and seizures.

The animal form of the disease is called bovine spongiform encephalopathy (BSE) which is commonly called mad cow disease. BSE also leaves holes in the brain that resemble a sponge.

bdk@yna.co.kr

(END)

http://english.yonhapnews.co.kr/business/2011/12/08/51/0502000000AEN20111208002700320F.HTML

Envt.15:

Prediction for Potential Risk Factors Through the Association Study Between Epidemiological Data and SNPs of Prion Protein Gene in the Korean Population and Suspected CJD Patients

Suyeon Kim,† Sol Moe Lee, Jae Wook Hyeon, Bo-Yeong Choi, Chi-Kyeong Kim, Jun Sun Park and Young Ran Ju

National Institute of Health, Korea CDC; Cheongwongun, Chungcheongbukdo, Korea;†Presenting author; Email: tenksy@nih.go.kr

Cases of the suspected CJD patients and reports of probable CJD have been increased due to a social uneasiness for import permission of beef from western countries reported BSE outbreak since 2008 in Korea CDC. It has been hard to definite diagnosis them due to Korean funeral culture though reports of probable sporadic CJD and genetic CJD have been increased in Korea. First of all, we need to clear the characteristics of PRNP gene in Korean population and to analyze the association between the endemic environmental factors and SNPs of the gene to predict the underlying cause.

We sequenced up to 5kb of the genomic region including the promoter region, exon I and exon II to analyze the correlation between SNPs of 185 suspected patients and diagnostic factors, and between SNPs of PRNP gene of 296 normal population and 60 epidemiologic factors like medical and familial history and diet. General statistical analyses were carried out by using SPSS statistic 18 (SPSS Inc., NY). Their significance levels were determined by the chi-square test (Fisher’s exact test).

We identified 19 SNPs in normal group and 15 SNPs gene in suspected patients’ group in their promoter and exon II regions. Our statistic analyses demonstrated that between rs1799990 (+385A>G; 129MV), rs28933385 (+598A>G; 200EK) and patient factors in suspected patients’ group showed significantly. In normal population group, between rs2756271 (-14605A>G), rs73612131 (-13537A>T), -14409 (C>T), rs1800014 (+655A>G; 219EK), +695(T>G; 232MR) and +591 (C>T; 197NN) SNPs and several demographic and dietary factors like an intake frequency of beef or ham were significantly associated.

In this study, we could predict the potential risk factors through the association study between SNPs of PRNP gene and several epidemiological factors. Especially, significance level of some dietary habits might show higher than other factors. However, we cannot entirely decide them risk factors of genetic markers in prion disease without identification of environmental or other causes of definite CJD patients though we found de novo SNP and significant result of PRNP. We expect to elucidate clearly their association through the combination of our results with other clinical information including additional clues.

PRION 2011

http://www.prion2011.ca/files/PRION_2011_Timetable-ENG_(May_5-11).pdf

J Neurol Neurosurg Psychiatry 2002;72:792-793 doi:10.1136/jnnp.72.6.792

Short report

Creutzfeldt-Jakob disease 38 years after diagnostic use of human growth hormone

http://jnnp.bmj.com/content/72/6/792.full

landesbioscience.com

Wednesday, November 30, 2011

First iCJD Death Confirmed in Korea

http://creutzfeldt-jakob-disease.blogspot.com/2011/11/first-icjd-death-confirmed-in-korea.html

Thursday, December 8, 2011

S. Korea confirms second case of iatrogenic Creutzfeldt-Jakob disease 48-year-old man

2011/12/08 11:08 KST

http://usdavskorea.blogspot.com/2011/12/s-korea-confirms-second-case-of.html

Tuesday, March 29, 2011

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY EXPOSURE SPREADING VIA HOSPITALS AND SURGICAL PROCEDURES AROUND THE GLOBE

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/transmissible-spongiform-encephalopathy.html

Monday, February 01, 2010

Import Alert 57-20 and 84-03 Human Dura Mater and risk factors there from due to Creutzfeldt Jakob Disease (CJD)

http://creutzfeldt-jakob-disease.blogspot.com/2010/02/import-alert-57-20-and-84-03-human-dura.html

Wednesday, June 29, 2011

TSEAC Meeting August 1, 2011 donor deferral ...

http://tseac.blogspot.com/2011/06/tseac-meeting-august-1-2011-donor.html

U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001

http://tseac.blogspot.com/2011/02/usa-50-state-bse-mad-cow-conference.html

Saturday, June 25, 2011

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque

"BSE-L in North America may have existed for decades"

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html

Sunday, June 26, 2011

Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/risk-analysis-of-low-dose-prion.html

Wednesday, August 24, 2011

There Is No Safe Dose of Prions

http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/there-is-no-safe-dose-of-prions.html

Wednesday, August 24, 2011

All Clinically-Relevant Blood Components Transmit Prion Disease following a Single Blood Transfusion: A Sheep Model of vCJD

http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/all-clinically-relevant-blood.html

EFSA Journal 2011 The European Response to BSE: A Success Story

This is an interesting editorial about the Mad Cow Disease debacle, and it's ramifications that will continue to play out for decades to come ;

Monday, October 10, 2011

EFSA Journal 2011 The European Response to BSE: A Success Story

snip...

EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.

snip...

http://www.efsa.europa.eu/en/efsajournal/pub/e991.htm?emt=1

http://www.efsa.europa.eu/en/efsajournal/doc/e991.pdf

see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;

http://transmissiblespongiformencephalopathy.blogspot.com/2011/10/efsa-journal-2011-european-response-to.html

http://transmissiblespongiformencephalopathy.blogspot.com/

Thursday, August 4, 2011

Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011

(SEE VIDEO)

http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html

Saturday, December 3, 2011

Candidate Cell Substrates, Vaccine Production, and Transmissible Spongiform Encephalopathies

Volume 17, Number 12—December 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/12/candidate-cell-substrates-vaccine.html

Saturday, November 19, 2011

Novel Prion Protein in BSE-affected Cattle, Switzerland

http://transmissiblespongiformencephalopathy.blogspot.com/2011/11/novel-prion-protein-in-bse-affected.html

Saturday, December 3, 2011

Isolation of Prion with BSE Properties from Farmed Goat

Volume 17, Number 12—December 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/12/isolation-of-prion-with-bse-properties.html

Sunday, August 21, 2011

The British disease, or a disease gone global, The TSE Prion Disease

(SEE VIDEO)

http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/british-disease-or-disease-gone-global.html

Saturday, March 5, 2011

MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html

Monday, September 26, 2011

L-BSE BASE prion and atypical sporadic CJD

http://bse-atypical.blogspot.com/2011/09/l-bse-base-prion-and-atypical-sporadic.html

Thursday, July 08, 2010

Nosocomial transmission of sporadic Creutzfeldt–Jakob disease: results from a risk-based assessment of surgical interventions Public release date: 8-Jul-2010

http://creutzfeldt-jakob-disease.blogspot.com/2010/07/nosocomial-transmission-of-sporadic.html

Tuesday, May 04, 2010

Review of the Human Pituitary Trust Account and CJD Issue 20 January 2010

http://creutzfeldt-jakob-disease.blogspot.com/2010/05/review-of-human-pituitary-trust-account.html

Monday, August 31, 2009

HUMAN BODY PARTS FOR SALE TO THE HIGHEST BIDDER Inside a Creepy Global Body Parts Business

http://creutzfeldt-jakob-disease.blogspot.com/2009_08_01_archive.html

Thursday, October 23, 2008

Creutzfeldt-Jakob Disease Associated with Cadaveric Dura Mater Grafts – Japan, 1979-2008 : UPDATE

http://creutzfeldt-jakob-disease.blogspot.com/2008/10/creutzfeldt-jakob-disease-associated.html

Sunday, December 16, 2007

Risk factors for sporadic Creutzfeldt-Jakob disease

http://creutzfeldt-jakob-disease.blogspot.com/2007/12/risk-factors-for-sporadic-creutzfeldt.html

some old history ;

Subject:
Japan releases bad Lyodura lot numbers

From:
tom tom@cyber-dyne.com

Reply-To:
Bovine Spongiform Encephalopathy BSE-L@UNI-KARLSRUHE.DE

Date:
Wed, 20 Sep 2000 14:53:39 -0800

Content-Type:
text/plain

Parts/Attachments:
text/plain (62 lines)

######### Bovine Spongiform Encephalopathy #########

This is hot, they actually published the bad lot numbers on the Lyodura in
the newspaper. NIH has fought off US residents for years. on the growth
hormone lot numbers, to protect their crazy man in North Carolina who
insisted on injecting crude pituitary extracts. Some recipients do want to
know whether they got an injection from a bad lot; some don't -- but I
never heard from anyone who wanted Big Brother making the decision for them.

There is a staggering amount of this Lyodura implanted in people: Japan
alone imported "12,545 boxes
of the dura mater, manufactured in 1982 by B. Braun Melsungen AG." It
doesn't say how many uses per box or how many boxes comprise a serial
number, or how many individuals were pooled per serial number.

It would be so cool if some serial number 2105 or so is still around --
then we could test it to see what species it came from (I say sheep, given
that is what their contract surgeon, who died of CJD a few years
thereafter, was removing as dura mater source).

tom

CJD-linked product banned in U.S. was imported to ...

Kyodo World Service Wed, Sep 20, 2000

TOKYO, Sept. 21 (Kyodo) -- The government on Wednesday admitted to the
likelihood that Japan imported German medical products which reportedly
caused Creutzfeldt-Jakob Disease (CJD) even after the United States had
warned of the danger in 1987, contradicting its previous claims.

Kazuo Maruta, a senior official at the Health and Welfare Ministry, said
the German-made dried dura mater used for brain surgery produced in 1982
was likely to have been imported before 1997.

The U.S. Food and Drug Administration (FDA) in 1987 issued a domestic
advisory not to use such dura mater made in that year, after learning about
a report that it could cause CJD.

Symptoms of the disease include rapidly progressive dementia, loss of
cerebral functions, and paralysis of limbs, with parts of the brain
becoming sponge-like.

Maruta, chief of the ministry's Pharmaceutical and Medical Safety
Bureau, told members of the Health and Welfare Committee at the House of
Representatives that it is "likely" that the product, Lyodura with serial
numbers 2000 to 2999, was imported into Japan.

He cited a report by Tokyo importer Nihon B.S.S. which said 12,545 boxes
of the dura mater, manufactured in 1982 by B. Braun Melsungen AG, were
imported that year.

Health and Welfare Minister Yuji Tsushima also told the committee, "It
was impossible (for the government) to foresee the dangers of the product."

Previously, the ministry has denied the possibility of any imports,
insisting that Lyodura with the serial number 2105, which the U.S.
government said caused the first-discovered case of CJD, was not imported
into Japan.

The German firm recalled the 2105 Lyodura in early 1987 and the FDA
advised domestic medical facilities to abandon the product with serial
numbers from 2000 to 2999.

It was only 10 years later that the Japanese ministry prohibited use of
the product.

More than 40 people, including CJD victims and their relatives, have
filed two damages suits with the Tokyo District Court and the Otsu District
Court, Shiga Prefecture, accusing the Japanese companies involved and the
German firm of negligence, as well as the Japanese government.

############ http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############

Subject:
Re: Japan releases bad Lyodura lot numbers

From:
tom tom@cyber-dyne.com

Reply-To:
Bovine Spongiform Encephalopathy BSE-L@UNI-KARLSRUHE.DE

Date:
Thu, 21 Sep 2000 06:36:13 -0800

Content-Type:
text/plain

Parts/Attachments:
text/plain (54 lines)

######### Bovine Spongiform Encephalopathy #########

It would be so cool if some serial number 2105 or so is still around --

then we could test it to see what species it came from (I say sheep, given

that is what their contract surgeon, who died of CJD a few years

thereafter, was removing as dura mater source).

You think that Lyodura grafts were made of other origin than human? Do you

have references to that? Thought they were of human origin solely and that

only animal products were used for ie. catgut / sutures?

I was surprised to find that xenotransplants have been going on for decades
on a truly massive scale in many countries. It is not just cowgut surgical
sutures, but anything and everything that doesn't set off too bad an immune
response. One of the more insiduous aspects of the BSE epidemic is the
large number of bovinebiologicals that came onto the international comodity
markets. We saw just one British company selling 40,000 bovine pericardium
patches at year for use in human heart valve replacements.

I posted many months back all the species used previously for dura mater
transplants in human, as seen in simple Medline searches. I also posted
some ideas on how to experimentally determine the species of origin for a
given piece of dura mater, be it still in the box or removed from a
iatrogenic CJD cadaver (there are a couple of intrinsic proteins that could
be seen with IgG).

I also posted a newspaper account of the German orthopedic surgeon employed
by this dura mater company to remove dura mater from sheep brain. The
cause of his CJD was never determined (though the diagnosis was not in
doubt); it could have been anything from handling sheep scrapie dura mater
to inherited. I don't know if he also handled human dura mater for the
company. Scrapie is only uncommonly reported in German sheep.

The idea here is not to make assumptions about the species origin of
Lyodura, but rather to test the species origin experimentally. The purpose
here is not to investigate the company.

Rather, Japan may have inadvertently done the scrapie-to-human
intra-cerebral injection experiment that medical ethics prevents us from
doing directly today. This would complement the successful in vitro
conversion experiments that you and your colleagues have published.

Given the scale of dura mater use in Japan, there may still be boxes left
of dura mater in the 2000-2999 serial number range. Or there may be
material recoverable from 2105 recipients. Given the low incidence of CJD
compared to scrapie, I would say that if any of the dura mater is sheep,
the whole episode can be probably be attributed to scrapie.

tom

############ http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############

Subject:
Re: Japan releases bad Lyodura lot numbers

From:
tom tom@cyber-dyne.com

Reply-To:
Bovine Spongiform Encephalopathy BSE-L@UNI-KARLSRUHE.DE

Date:
Thu, 21 Sep 2000 08:48:32 -0800

Content-Type:
text/plain

Parts/Attachments:
text/plain (169 lines)

######### Bovine Spongiform Encephalopathy #########

Alex,

Mon, 19 Jul 1999 was when this came up. Here is the relevent Lancet article.

Transmission of Creutzfeldt-Jakob disease by handling of dura mater.

The Lancet Volume 341(8837) January 9, 1993 pp 123-124
Weber, Thomas; Tumani, Hayrettin; Holdorff, Bernd; Collinge, John; Palmer,
Mark; Kretzschmar, Hans A.; Felgenhauer, Klaus

Sir,- Creutzfeldt-Jakob disease (CJD) can be transmitted iatrogenically by human pituitary growth
hormone, corneal transplants, and dura mater grafts (1). Possible accidental transmission has been
reported in only four people-a neurosurgeon (2), a pathologist (3), and two laboratory technicians
(4,5) . We have encountered an unusually rapid case of CJD probably acquired through handling of sheep and human dura mater.

In May, 1992, a 55-year-old orthopaedic surgeon developed paraesthesia of the left arm. A few days
later he had spatial disorientation, apraxia, and gait ataxia. In June he was admitted and a neurologist
suspected CJD on the basis of the clinical signs, typical electroencephalogram (EEG) pattern, and
history. An EEG in June revealed a typical pattern of periodic biphasic and triphasic sharp wave
complexes.

We saw the patient in July, 1992. He was awake and oriented, with dyscalculia, dysgraphia, disturbed
vision, apraxia mainly of the left side, rigidity of wrists, spasticity of all muscles, myoclonus of the left
arm, increased tendon reflexes, ataxia of limbs and trunk, and incoordination of left arm. Within 3 weeks he had impaired consciousness and attention, mildly impaired memory, and threatening visual
hallucinations with restless turning. He had periodic states with movements of his head and eye-bulbs
resembling tonic adversive seizures. During sleep these motor disturbances stopped. 2 1/2 months later
the patient died.

This patient had worked with sheep and human dura mater from 1968 to 1972. He handled about 150
specimens of ovine origin and at least a dozen human preparations for research. Handling involved
opening skulls with a band saw, removing dura, and testing them either fresh (usually), preserved, or
lyophilised for mechanical qualities.

These specimens were sent to a company that has sold dura mater preparations by which CJD was
transmitted in six instances. No information was available from the company about a possible connection with this patient's disease and the earlier cases of transmitted CJD.

Brain biopsy was consistent with diagnosis of CJD. Cerebrospinal fluid obtained in July showed
neuron-specific enolase (NSE) at 82.0 ng/mL, compared with 16.7 ng/mL in serum of other cases (6).
Proton magnetic resonance spectroscopy of parieto-occipital and temporal grey matter, parietal white
matter, and thalamus revealed a 20-30% reduction of N-acetylaspartate, as described (7). DNA was
genotyped with allele-specific oligonucleotides (8) and was homozygous for methionine at the
polymorphic codon 129. Subsequent direct DNA sequencing for the PrP gene open-reading frame
demonstrated normal sequence on both alleles, excluding known or novel pathogenic PrP mutations.

It is tempting to speculate that prions were transmitted to this patient from sheep or human dura mater
through small lacerations of his skin, but the patient and his wife did not remember any significant
injury during his four years of working with these samples. It cannot be excluded that this was a case
of sporadic CJD although this assumption is unlikely in view of the clinical course which was similar to iatrogenic CJD transmitted by peripheral inoculation, such as with human pituitary growth hormone or gonadotropin or to kuru (1). Iatrogenic cases resulting from intracerebral inoculation with the
transmissible agent, for instance following dura mater grafts (2-5), present with a dementing picture,
as is usual in sporadic CJD, rather than with ataxia as in this case.

=-==-=-=-

Iatrogenic scrapie from sheep dura mater?

Mon, 19 Jul 1999 Listserve and Lancet January 9, 1993 pp 123-124

An orthopaedic surgeon employed by the Lyodura company [Braun Melsungen] extracted dura mater from sheep and human cadavers and came down with fast CJD 22 years later. The ratio of sheep to human dura mater he collected was150 sheep to 12 humans. Apparently the surgeon and the sheep were German.

Scrapie has long been present in Germany but reported levels are very low, about a flock a year has to be destroyed. I am not aware of any high sensitivity tests or random screening every being used in Germany to assess the levels of preclinical animals.

This raises the question, what did the lyodura company do with so much dura mater from sheep? The
market for specialty surgical products was overwelmingly in humans in 1968. Are there companies
today that sell sheep dura mater for research? The Lancet article only says it was for research -- but
in what species? Perhaps dura mater gives an immune response across species after processing, ruling out its use in humans. But blood type or other genetic differences do not matter within humans, ie,
there is no tissue matching with dura mater.

How CJD could show up from a handful of human dura mater donations with sporadic CJD supposedly so rare -- this would be extraordinary bad luck that any of 150 sheep + 12 humans could have carried the disease. On the other hand, there would be no surprise at all if a case of subclinical scrapie showed up in 150 sheep. [While Germany only reports one case a year of scrapie and destroys the flock, the disease nonetheless persists, indicating under-reporting.]

This raises the question, have dura mater recipients or the surgeon subsequently been strain-typed?
This might give a very different outcome than other forms of iatrogenic CJD or simply co-classify with
pituitary growth hormone if route of infection (injected, oral, hereditary, etc.) is more important than
strain source.

Otherwise, iatrogenic scrapie (like cwdCJD) is somwhat unpredictable in its gel pattern (though strains
of scrapie in other primate species might be re-examined). The original scrapie strain is not be
identifiable directly because material was not likely retained. Strain-typing was not available at the
time of the article -- but Collinge was one of the authors.

There is little doubt that scrapie could be transfered to humans by intracerebral injection (based on lack
of species barrier in primates) and that processed pooled (human?) dura mater can carry sufficient
infectivity to cause CJD. Animal experiments have not commonly used sheep dura mater as experimental dose source.

If any humans received sheep dura mater, it is doubtful that this will be disclosed or that specific
recipients will be identified to their doctors. It is probably better to trace backwards from affected
recipients -- see if they strain-type out to be sheep.

Japan has been particularly hard hit by dura mater CJD (curious in itself) and researchers there might
be motivated to find out what happened. I am not aware of agricultural agencies that would impede
research over there.

############ http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############

Subject:
Re: CJD * Lyodura-B.Braun Melsungen AG, Germany

From:
Jennifer Cooke jcooke@ACCESS.FAIRFAX.COM.AU

Reply-To:
Bovine Spongiform Encephalopathy BSE-L@UNI-KARLSRUHE.DE

Date:
Wed, 29 Sep 1999 00:24:32 +1000

Content-Type:
text/plain

Parts/Attachments:
text/plain (55 lines)

Cear Terry,

I devoted most of one chapter in my book, Cannibals Cows & the CJD
Catastrophe (Random House Australia) to CJD deaths from dura mater
including Lyodura, that have been reported in the literature since the
initial FDA warning about Lyodura in 1987.

Several cases related to 1982 - either because the Lyodura was manufactured
in that year, or the operation of the victim took place in that year.
One confidential settlement I know of was to the family of a British man
who died of CJD in 1989 following a Lyodura graft in 1985.

There have now been four deaths in Australia from CJD after Lyodura grafts
- all of which related to operations carried out in 1982. The latest death
occurred in June this year - which means that the incubation period has now
blown out to more than 17 years for this type of peripheral infection.
Quite horrifying. I believe the family intends to sue ...

Regards,

Jennifer Cooke

----------

> From: Roland Heynkes

> To: BSE-L@UNI-KARLSRUHE.DE

> Subject: Re: [BSE-L] CJD * Lyodura-B.Braun Melsungen AG, Germany

> Date: Tuesday, September 28, 1999 4:02 AM

>
> Dear Terry,

>
> > Terry S. Singeltary Sr., Bacliff, Texas USA -- Greetings, I was hoping

> > Roland or someone, could tell me if this Company (Lyodura-B.Braun

> > Melsungen AG, Germany) is still paying out settlements for the medical

> > deaths from CJD and their product?

> > How far back, has their product been found to be infected and or, was
it

> > found to be deadly in 1982?

> > Was the material in 1982 taken from cows or humans or both?

> >
> I am sorry but I don't know that and at the moment I am very busy in a

> colon cancer project. Therefore I cannot help you. But perhaps Herbert

> Schaefer in Spangenberg (Tel./Fax: 05663/1212) can help you. He works for

> the large German television transmitter ZDF and investigated the lyodura

> problem of this company some years ago.
>

> best regards
>
> Roland Heynkes
>
> Erkwiesenstr. 19
> D-52072 Aachen (Germany)
> Tel.: +49 (0)241/932070
> Fax: +49 (0)241/932071
> email: roland@heynkes.de
> http://www.heynkes.de

=================================

source

011254 2002-03-29 10:07 60 CJD--LYODURA ''DEADLY HARVEST'' BSE-L

008699 2000-09-21 14:53 67 Re: Japan releases bad Lyodura lot numbers BSE-L

008695 2000-09-21 08:48 190 Re: Japan releases bad Lyodura lot numbers BSE-L

008692 2000-09-21 08:44 52 Re: Japan releases bad Lyodura lot numbers BSE-L

008694 2000-09-21 06:36 74 Re: Japan releases bad Lyodura lot numbers BSE-L

008691 2000-09-20 14:53 81 Japan releases bad Lyodura lot numbers BSE-L

006872 1999-09-29 14:05 96 Re: CJD * Lyodura-B.Braun Melsungen AG, Germany BSE-L

006871 1999-09-29 00:24 77 Re: CJD * Lyodura-B.Braun Melsungen AG, Germany BSE-L

006862 1999-09-27 19:02 48 Re: CJD * Lyodura-B.Braun Melsungen AG, Germany BSE-L

006860 1999-09-27 10:35 32 CJD * Lyodura-B.Braun Melsungen AG, Germany BSE-L

http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html

https://lists.aegee.org/cgi-bin/wa?A0=BSE-L

TSS

First iCJD Death Confirmed in Korea

2011-11-30T08:32:00.000-08:00

First iCJD Death Confirmed in Korea

Korea's Centers for Disease Control and Prevention, announced Tuesday, that a 54-year old woman died of Creutzfeldt-Jakob disease in November last year.

The incurable and invariably fatal brain disease has a long latent period and creates holes in the brain when an outbreak occurs.

Authorities believe the woman contracted the disease during brain surgery in 1987 when she received a transplanted membrane from overseas.

[Interview : Park Hye-kyung, Head of Infectious Diseases Surveillance
Centers for Disease Control and Prevention]

"The deceased patient went through a brain tumor surgery and received a transplant of a dura mater called 'Lyodura' that was imported from Germany.

Her CJD symptoms appeared twenty-three years later, in June 2010."

Korea's health ministry, however, said that, there is NO correlation, between the woman's case, and the variant Creutzfeldt-Jakob Disease, which is often referred to as, human mad cow disease.
Currently there are four known types of CJDs.

The most common form is called sCJD, or sporadic CJD, which accounts for nearly 90 percent of all outbreaks and its cause is known to be natural mutation.

There is also the familial type of CJD, which is believed to be genetic.

The vCJD, or variant Creutzfeldt-Jakob disease is transmitted from cattle with mad cow disease.

This woman's case was Korea's first case of iCJD, or iatrogenic Creutzfeldt-Jakob disease which is caused by transplants of infected human tissues.

Some 400 iCJD cases have been reported in 20 countries throughout the world.

Doctors say that iCJD cases such as this one are very rare because the German manufacturer who supplied the membrane to the woman halted production of dura mater in 1987. and many producers have since reinforced preventive measures.

The World Health Organization also banned production of membranes from tissue extracted from corpses in 1997.

[Interview : Kim Yun-joong, Neurology professor
Hallym Medical School]

"Most providers reinforced the inactivation of infectivity by raising the level of sodium hydroxide.
That is the reason why outbreaks rarely occured after 1987."

The Centers for Disease Control said that they will follow-up with other patients who went through similar surgeries in the '80s.. to trace whether there might be other cases.
Song Ji-sun, Arirang News.

NOV 30, 2011

Reporter : song@arirang.co.kr

http://www.arirang.co.kr/News/News_View.asp?nseq=123123&code=Ne2&category=2

http://english.hani.co.kr/arti/english_edition/e_national/507847.html

http://english.chosun.com/site/data/html_dir/2011/11/30/2011113001421.html

Envt.15:

Prediction for Potential Risk Factors Through the Association Study Between Epidemiological Data and SNPs of Prion Protein Gene in the Korean Population and Suspected CJD Patients

Suyeon Kim,† Sol Moe Lee, Jae Wook Hyeon, Bo-Yeong Choi, Chi-Kyeong Kim, Jun Sun Park and Young Ran Ju

National Institute of Health, Korea CDC; Cheongwongun, Chungcheongbukdo, Korea;†Presenting author; Email: tenksy@nih.go.kr

Cases of the suspected CJD patients and reports of probable CJD have been increased due to a social uneasiness for import permission of beef from western countries reported BSE outbreak since 2008 in Korea CDC. It has been hard to definite diagnosis them due to Korean funeral culture though reports of probable sporadic CJD and genetic CJD have been increased in Korea. First of all, we need to clear the characteristics of PRNP gene in Korean population and to analyze the association between the endemic environmental factors and SNPs of the gene to predict the underlying cause.

We sequenced up to 5kb of the genomic region including the promoter region, exon I and exon II to analyze the correlation between SNPs of 185 suspected patients and diagnostic factors, and between SNPs of PRNP gene of 296 normal population and 60 epidemiologic factors like medical and familial history and diet. General statistical analyses were carried out by using SPSS statistic 18 (SPSS Inc., NY). Their significance levels were determined by the chi-square test (Fisher’s exact test).

We identified 19 SNPs in normal group and 15 SNPs gene in suspected patients’ group in their promoter and exon II regions. Our statistic analyses demonstrated that between rs1799990 (+385A>G; 129MV), rs28933385 (+598A>G; 200EK) and patient factors in suspected patients’ group showed significantly. In normal population group, between rs2756271 (-14605A>G), rs73612131 (-13537A>T), -14409 (C>T), rs1800014 (+655A>G; 219EK), +695(T>G; 232MR) and +591 (C>T; 197NN) SNPs and several demographic and dietary factors like an intake frequency of beef or ham were significantly associated.

In this study, we could predict the potential risk factors through the association study between SNPs of PRNP gene and several epidemiological factors. Especially, significance level of some dietary habits might show higher than other factors. However, we cannot entirely decide them risk factors of genetic markers in prion disease without identification of environmental or other causes of definite CJD patients though we found de novo SNP and significant result of PRNP. We expect to elucidate clearly their association through the combination of our results with other clinical information including additional clues. ...

PRION 2011

http://www.prion2011.ca/files/PRION_2011_Timetable-ENG_(May_5-11).pdf

THE SECONDARY TRANSMISSION OF CJD/VCJD BY INVASIVE DIAGNOSTIC, SURGICAL OR DENTAL PROCEDURES

The aim of this review was to examine the evidence for the secondary transmission of CJD/vCJD by invasive diagnostic, surgical or dental procedures. The relevant data derive from three sources:

• case reports

• case-control studies

• experimental studies of the transmission of prion disease to animals using surgical instruments or surrogates.

A systematic review was undertaken to identify all relevant studies. Details of the literature searches and inclusion criteria may be found in Appendix 2.

3.1 Case reports

By July 2000, only seven cases of CJD worldwide were known to have been transmitted by invasive diagnostic or surgical procedures which did not involve transplantation or grafting. Two cases were transmitted in 1974 by stereotactic EEG using probes cleaned by a method which would no longer be considered adequate. Symptomatic neurological disease developed after 20 months in one patient and after 16 months in the other.16

After sterilisation and storage in formaldehyde vapour for two years, the probes were implanted in the brain of a chimpanzee, who developed signs of encephalopathy 18 months after implantation.17 A further five cases have been attributed to neurosurgery (median incubation period 17 months, range 12-28).18 These presumably include the case infected by cranial surgery in 1965, with an incubation period of 26 months19 and three cases infected in the UK in the 1950s in which the incubation period was 18-24 months.20 No cases of CJD attributable to invasive diagnostic or surgical procedures without transplantation or grafting have been identified more recently than the 1970s.18

No cases of CJD have been securely attributed to dental procedures. However, in Japan two patients treated by the same dentist developed CJD, and it is possible that one or both were infected in this way.21

3.2 Case-control studies

Seven studies were identified which recorded histories of surgical and dental procedures in cases with definite or probable

CJD and in matched controls22,23,24,25,26,27,28 (for details, see Appendix 2). Two of these studies27,28 used substantially the same cases, but different controls. An eighth study, the EUROSURGYCJD study, is ongoing.29

Case-control studies are inevitably problematic as they depend on respondent recall of past events. Case-control studies of CJD are particularly problematic because the cases are not able to respond for themselves, and therefore past events are further filtered through the memory of another respondent (usually a close family member). Some of the included studies attempted to achieve comparability by collecting information on both cases and controls from similar respondents; others introduced a source of bias by using the controls themselves as respondents.

4

The validity of case-control studies also depends on the appropriate choice of controls. Some of the included studies used controls drawn from hospital settings. This may distort the results as such controls are likely to have higher than average exposure frequencies for surgical interventions.30,23,24,25,26,27,28

Ideally, therefore, only those studies would have been included which both drew their control group from the community and used similar respondents as a source of data for cases and controls. However, no studies were identified which met these criteria.

The best quality evidence available is therefore derived from five studies which used community controls who responded directly: these are the studies by Collins et al,22 Davanipour et al,23 Juan et al,25 Kondo and Kuroiwa,26 and Ward et al.28 The studies by Collins et al22 and Ward et al28 found that a history of any surgery was associated with a significantly increased risk of CJD (odds ratio 1.7-1.8), while Kondo and Kuroiwa found that any surgery in the five years preceding diagnosis was associated with a relative risk of developing CJD of 3.5 (p<0.01)26 (for details, see Appendix 2 Table 1).

see full report here ;

http://www.nice.org.uk/nicemedia/live/11332/31760/31760.pdf

J Neurol Neurosurg Psychiatry 2002;72:792-793 doi:10.1136/jnnp.72.6.792

Short report

Creutzfeldt-Jakob disease 38 years after diagnostic use of human growth hormone

http://jnnp.bmj.com/content/72/6/792.full

Monday, July 18, 2011

Impact of Being Placed at Risk of Creutzfeldt-Jakob Disease: A Qualitative Study of Blood Donors to Variant CJD Cases and Patients Potentially Surgically Exposed to CJD

http://creutzfeldt-jakob-disease.blogspot.com/2011/07/impact-of-being-placed-at-risk-of.html

Tuesday, March 29, 2011

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY EXPOSURE SPREADING VIA HOSPITALS AND SURGICAL PROCEDURES AROUND THE GLOBE

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/transmissible-spongiform-encephalopathy.html

Wednesday, June 29, 2011

TSEAC Meeting August 1, 2011 donor deferral ...

http://tseac.blogspot.com/2011/06/tseac-meeting-august-1-2011-donor.html

Thursday, July 08, 2010

Nosocomial transmission of sporadic Creutzfeldt–Jakob disease: results from a risk-based assessment of surgical interventions Public release date: 8-Jul-2010

http://creutzfeldt-jakob-disease.blogspot.com/2010/07/nosocomial-transmission-of-sporadic.html

Tuesday, May 04, 2010

Review of the Human Pituitary Trust Account and CJD Issue 20 January 2010

http://creutzfeldt-jakob-disease.blogspot.com/2010/05/review-of-human-pituitary-trust-account.html

Saturday, January 26, 2008

CJD HGH BODY SNATCHERS Saturday, January 26, 2008 CJD HGH BODY SNATCHERS HORMONE DRUGS LED TO CJD DEATH

09:00 - 26 January 2008

http://creutzfeldt-jakob-disease.blogspot.com/2008/01/cjd-hgh-body-snatchers.html

Sunday, November 21, 2010

Preclinical Deposition of Pathological Prion Protein in Muscle of Experimentally Infected Primates and potential Iatrogenic TSE there from

http://creutzfeldt-jakob-disease.blogspot.com/2010/11/preclinical-deposition-of-pathological.html

Monday, February 01, 2010

Import Alert 57-20 and 84-03 Human Dura Mater and risk factors there from due to Creutzfeldt Jakob Disease (CJD)

http://creutzfeldt-jakob-disease.blogspot.com/2010/02/import-alert-57-20-and-84-03-human-dura.html

http://creutzfeldt-jakob-disease.blogspot.com/2010/11/prosecutors-call-for-prison-terms-for.html

Saturday, June 25, 2011

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque

"BSE-L in North America may have existed for decades"

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html

Sunday, June 26, 2011

Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/risk-analysis-of-low-dose-prion.html

Wednesday, August 24, 2011

There Is No Safe Dose of Prions

http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/there-is-no-safe-dose-of-prions.html

Wednesday, August 24, 2011

All Clinically-Relevant Blood Components Transmit Prion Disease following a Single Blood Transfusion: A Sheep Model of vCJD

http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/all-clinically-relevant-blood.html

Friday, September 2, 2011

Supreme Court clears ‘PD Notebook’ of distortion over USA MAD COW CONTROVERSY

http://usdavskorea.blogspot.com/2011/09/supreme-court-clears-pd-notebook-of.html

http://usdavskorea.blogspot.com/

Sunday, August 21, 2011

The British disease, or a disease gone global, The TSE Prion Disease

http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/british-disease-or-disease-gone-global.html

Thursday, August 4, 2011

Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011

(see video here) ;

http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html

http://www.youtube.com/watch?v=c0tWkNvhO4g

http://www.youtube.com/watch?v=zf3lfz9NrT4

Saturday, March 5, 2011

MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html

http://creutzfeldt-jakob-disease.blogspot.com/

http://transmissiblespongiformencephalopathy.blogspot.com/

http://bseusa.blogspot.com/

http://bse-atypical.blogspot.com/

http://madcowusda.blogspot.com/

http://chronic-wasting-disease.blogspot.com/

http://nor-98.blogspot.com/

http://scrapie-usa.blogspot.com/

TSS

Case report Sporadic fatal insomnia in a young woman: A diagnostic challenge: Case Report TEXAS

2011-11-09T10:38:00.000-08:00

HOW TO TURN A POTENTIAL MAD COW VICTIM IN THE USA, INTO A HAPPENSTANCE OF BAD LUCK, A SPONTANEOUS MUTATION FROM NOTHING.

OR WAS IT $$$

Case report Sporadic fatal insomnia in a young woman: A diagnostic challenge: Case Report

Karen M Moody , Lawrence B Schonberger , Ryan A Maddox , Wen-Quan Zou , Laura Cracco and Ignazio Cali

BMC Neurology 2011, 11:136doi:10.1186/1471-2377-11-136

Published:

31 October 2011

Abstract (provisional)

Background

Sporadic fatal insomnia (sFI) and fatal familial insomnia (FFI) are rare human prion diseases.

Case presentation

We report a case of a 33-year-old female who died of a prion disease for whom the diagnosis of sFI or FFI was not considered clinically. Following death of this patient, an interview with a close family member indicated the patient's illness included a major change in her sleep pattern, corroborating the reported autopsy diagnosis of sFI. Genetic tests identified no prion protein (PrP) gene mutation, but neuropathological examination and molecular study showed protease-resistant PrP (PrPres) in several brain regions and severe atrophy of the anterior-ventral and medial-dorsal thalamic nuclei similar to that described in FFI.

Conclusions

In patients with suspected prion disease, a characteristic change in sleep pattern can be an important clinical clue for identifying sFI or FFI; polysomnography (PSG), genetic analysis, and nuclear imaging may aid in diagnosis.

snip...

Case presentation

Clinical findings In February 2007, the Centers for Disease Control and Prevention (CDC) and the National Prion Disease Pathology Surveillance Center (NPDPSC) notified the Texas Department of State Health Services (DSHS) of a 32-year-old woman with an 18-month history of progressive neurological symptoms suggestive of CJD. (Table 1) Based on the medical record and her neurologist, her illness began in August 2005 with attention deficits and progressive memory loss. In June 2006, she demonstrated anisocoria and bizarre behavior, including talking incoherently to herself, and she was then referred to psychiatry. On a mini-mental state examination, she scored abnormally low in the measure of attention and calculation and she had reduced ability to repeat the names of three unrelated objects [14]. Later in 2006 she was described as being in constant motion, having unfocused hand gestures, and continued difficulty with ambulation. She was reported as alert, but confused, sad, and having difficulty with her thought process. Physicians caring for the case patient discussed the possibility of several diagnoses such as viral encephalopathy, paranoid schizophrenia, and subacute sclerosing panencephalitis, yet the overall etiology remained unclear. By February 2007, the patient was unable to ambulate and became bed-bound. She continued to demonstrate bizarre behavior, inability to follow commands, and unintelligible speech. The patient expired in June 2007, 22 months after the onset of illness.

Over the course of her illness, she had EEGs, magnetic resonance imaging (MRI) studies, and cerebrospinal fluid (CSF) tests. The EEG study performed in July 2006 showed generalized slowing with bilateral periodic lateralized epileptiform discharges. A second EEG performed two to three weeks later was unsuccessful due to excessive movements of the patient. In April 2006, an MRI study was negative for intracranial abnormalities. Another MRI study was completed in February 2007 and it showed supratentorial parenchymal atrophy with no other acute intracranial findings. CSF studies performed in March 2007 were normal, including the amount of the 14-3-3 protein determined.

Because of the age of the patient and the potential for variant or iatrogenic CJD, in July 2007 an investigator from the DSHS (KMM) interviewed a family member to obtain additional information about the patient’s travel history, past medical history, and the symptoms of the present illness. The patient had a history of travel outside the continental United States to Puerto Rico during 1995-96 where she had lived approximately one year. Her surgical history included two back surgeries for internal disc disruption and degenerative disc disease. An anterior lumbar discectomy with interbody fusion at L4-5 was performed in November 2000 utilizing cadaver donated bone and in August 2001 another fusion was performed at L5-S1 utilizing autologous bone. The donor of cadaver bone was pre-screened minimizing the possibility of iatrogenic transmission. There was no familial history of progressive neurological disease or dementia-like illness. The family member also confirmed the clinical history including the onset in August 2005 of progressive memory loss and, in February 2006, bizarre behavior that included the patient’s sitting in a chair for hours making noises that progressively got louder.

Following preliminary autopsy results, the NPDPSC requested the DSHS re-interview the family to ask specifically about the patient’s pattern of sleep. When questioned about insomnia, the family member recalled that the patient had experienced disturbed sleep at the time of her disease onset. The family member also reported that the patient’s sleep pattern progressively deteriorated throughout her illness. Some nights, for example, the patient did not sleep. On other nights when she did appear to be sleeping, her sleep was intermittent. During nights that the patient did not sleep, she would roam the house at all hours, unable to calm down. By August of 2006, four hours was the maximum amount of sleep the patient would get in one stretch and at times she would go two to three days without sleep. Medications were prescribed to help her sleep but they were not beneficial.

Genetic analysis Sequencing of the PrP gene open reading frame revealed methionine homozygosity at codon 129, with no pathogenic mutation.

snip...

see full text ;

http://www.biomedcentral.com/content/pdf/1471-2377-11-136.pdf

===================

Clinical findings In February 2007, the Centers for Disease Control and Prevention (CDC) and the National Prion Disease Pathology Surveillance Center (NPDPSC) notified the Texas Department of State Health Services (DSHS) of a 32-year-old woman with an 18-month history of progressive neurological symptoms suggestive of CJD. (Table 1) Based on the medical record and her neurologist, her illness began in August 2005 with attention deficits and progressive memory loss. In June 2006, she demonstrated anisocoria and bizarre behavior, including talking incoherently to herself, and she was then referred to psychiatry.

=====================

AND THAT MY FRIENDS, IS HOW YOU EXPLAIN SOMETHING AWAY INTO NOTHING. IT'S THE USDA ET AL MAD COW WAY $$$

how many times have we seen this happen? time and time again.

sporadic FFI or nvCJD Texas style ???

DEEP THROAT TO TSS 2000-2001 (take these old snips of emails with how ever many grains of salt you wish. ...tss)

The most frightening thing I have read all day is the report of Gambetti's finding of a new strain of sporadic cjd in young people...Dear God, what in the name of all that is holy is that!!! If the US has different strains of scrapie.....why????than the UK...then would the same mechanisms that make different strains of scrapie here make different strains of BSE...if the patterns are different in sheep and mice for scrapie.....could not the BSE be different in the cattle, in the mink, in the humans.......I really think the slides or tissues and everything from these young people with the new strain of sporadic cjd should be put up to be analyzed by many, many experts in cjd........bse.....scrapie Scrape the damn slide and put it into mice.....wait.....chop up the mouse brain and and spinal cord........put into some more mice.....dammit amplify the thing and start the damned research.....This is NOT rocket science...we need to use what we know and get off our butts and move....the whining about how long everything takes.....well it takes a whole lot longer if you whine for a year and then start the research!!! Not sure where I read this but it was a recent press release or something like that: I thought I would fall out of my chair when I read about how there was no worry about infectivity from a histopath slide or tissues because they are preserved in formic acid, or formalin or formaldehyde.....for God's sake........ Ask any pathologist in the UK what the brain tissues in the formalin looks like after a year.......it is a big fat sponge...the agent continues to eat the brain ......you can't make slides anymore because the agent has never stopped........and the old slides that are stained with Hemolysin and Eosin......they get holier and holier and degenerate and continue...what you looked at 6 months ago is not there........Gambetti better be photographing every damned thing he is looking at.....

Okay, you need to know. You don't need to pass it on as nothing will come of it and there is not a damned thing anyone can do about it. Don't even hint at it as it will be denied and laughed at.......... USDA is gonna do as little as possible until there is actually a human case in the USA of the nvcjd........if you want to move this thing along and shake the earth....then we gotta get the victims families to make sure whoever is doing the autopsy is credible, trustworthy, and a saint with the courage of Joan of Arc........I am not kidding!!!! so, unless we get a human death from EXACTLY the same form with EXACTLY the same histopath lesions as seen in the UK nvcjd........forget any action........it is ALL gonna be sporadic!!!

And, if there is a case.......there is gonna be every effort to link it to international travel, international food, etc. etc. etc. etc. etc. They will go so far as to find out if a sex partner had ever traveled to the UK/europe, etc. etc. .... It is gonna be a long, lonely, dangerous twisted journey to the truth. They have all the cards, all the money, and are willing to threaten and carry out those threats....and this may be their biggest downfall...

Thanks as always for your help. (Recently had a very startling revelation from a rather senior person in government here..........knocked me out of my chair........you must keep pushing. If I was a power person....I would be demanding that there be a least a million bovine tested as soon as possible and agressively seeking this disease. The big players are coming out of the woodwork as there is money to be made!!! In short: "FIRE AT WILL"!!! for the very dumb....who's "will"! "Will be the burden to bare if there is any coverup!"

again it was said years ago and it should be taken seriously....BSE will NEVER be found in the US! As for the BSE conference call...I think you did a great service to freedom of information and making some people feign integrity...I find it scary to see that most of the "experts" are employed by the federal government or are supported on the "teat" of federal funds. A scary picture! I hope there is a confidential panel organized by the new government to really investigate this thing.

You need to watch your back........but keep picking at them.......like a buzzard to the bone...you just may get to the truth!!! (You probably have more support than you know. Too many people are afraid to show you or let anyone else know. I have heard a few things myself... you ask the questions that everyone else is too afraid to ask.)

END...TSS

nvCJD Clinical course

The clinical course of disease in the ten patients was distinct from that usually seen in sporadic CJD (table 2). Nine had behavioural changes as an early clinical feature and were referred to a psychiatrist. In four patients, an early symptom was dysaesthesiae and in another, pain in the feet persisted throughout the illness. Nine patients developed ataxia early in the course of the disease. While all patients developed progressive dementia, in only two was memory impairment part of initial clinical presentation. Seven of the patients developed myoclonus, often late in the course of the disease, and three had choreoathetosis. None of the cases had the electroencephalographic (EEG) features usually associated with CJD.

http://www.cjd.ed.ac.uk/lancet.htm

http://cjdmadcowbaseoct2007.blogspot.com/2008/07/new-prionopathy-update-july-10-2008.html

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.

http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000156

http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.ppat.1000156&representation=PDF

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)

http://prionpathy.blogspot.com/2010/08/bse-case-associated-with-prion-protein.html

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

http://www.nature.com/nature/journal/v457/n7233/full/4571079b.html

Thursday, June 23, 2011

Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html

Thursday, July 21, 2011

A Second Case of Gerstmann-Sträussler-Scheinker Disease Linked to the G131V Mutation in the Prion Protein Gene in a Dutch Patient Journal of Neuropathology & Experimental Neurology:

August 2011 - Volume 70 - Issue 8 - pp 698-702

http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/second-case-of-gerstmann-straussler.html

PLEASE NOTE *

Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.

snip...

The rancher was a ''dead stock'' feeder using mostly (> 95 %) downer or dead dairy cattle...

http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf

Saturday, June 25, 2011

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque

"BSE-L in North America may have existed for decades"

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html

Sunday, June 26, 2011

Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/risk-analysis-of-low-dose-prion.html

Monday, May 11, 2009

Rare BSE mutation raises concerns over risks to public health

http://bse-atypical.blogspot.com/2009/05/rare-bse-mutation-raises-concerns-over.html

Wednesday, July 28, 2010

Atypical prion proteins and IBNC in cattle DEFRA project code SE1796 FOIA Final report

http://bse-atypical.blogspot.com/2010/07/atypical-prion-proteins-and-ibnc-in.html

IBNC

"All of the 15 cattle tested showed that the brains had abnormally accumulated prion protein."

Saturday, February 28, 2009

NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS "All of the 15 cattle tested showed that the brains had abnormally accumulated PrP" 2009

SEAC 102/2

http://bse-atypical.blogspot.com/2009/02/new-results-on-idiopathic-brainstem.html

2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006

http://bse-atypical.blogspot.com/2006/08/bse-atypical-texas-and-alabama-update.html

Friday, May 13,

2011 EFSA Joint Scientific Opinion on any possible epidemiological or molecular association between TSEs in animals and humans

http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/efsa-joint-scientific-opinion-on-any.html

Sunday, May 01, 2011

STUDY OF ATYPICAL BSE 2010 Annual Report May 2011

http://bse-atypical.blogspot.com/2011/05/study-of-atypical-bse-2010-annual.html

Tuesday, November 08, 2011

Can Mortality Data Provide Reliable Indicators for Creutzfeldt-Jakob Disease Surveillance? A Study in France from 2000 to 2008 Vol. 37, No. 3-4, 2011

Original Paper

Conclusions:These findings raise doubt about the possibility of a reliable CJD surveillance only based on mortality data.

http://creutzfeldt-jakob-disease.blogspot.com/2011/11/can-mortality-data-provide-reliable.html

Friday, November 04, 2011

Diagnostic accuracy of cerebrospinal fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada: a 6-year prospective study Research article

http://creutzfeldt-jakob-disease.blogspot.com/2011/11/diagnostic-accuracy-of-cerebrospinal.html

Monday, September 26, 2011

Variably Protease-Sensitive Prionopathy, Prionpathy, Prionopathy, FFI, GSS, gCJD, hvCJD, sCJD, TSE, PRION, update 2011

http://prionopathy.blogspot.com/2011/09/variably-protease-sensitive-prionopathy.html

Monday, June 27, 2011

Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease

http://prionopathy.blogspot.com/2011/06/comparison-of-sheep-nor98-with-human.html

Thursday, July 10, 2008

A New Prionopathy update July 10, 2008

http://cjdmadcowbaseoct2007.blogspot.com/2008/07/new-prionopathy-update-july-10-2008.html

Thursday, July 10, 2008

A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease update July 10, 2008 Friday, June 20, 2008

http://cjdmadcowbaseoct2007.blogspot.com/2008/07/novel-human-disease-with-abnormal-prion.html

Sunday, August 10, 2008

A New Prionopathy OR more of the same old BSe and sporadic CJD

http://creutzfeldt-jakob-disease.blogspot.com/2008/08/new-prionopathy-or-more-of-same-old-bse.html

Sunday, August 24, 2008

Sporadic Fatal Insomnia with Unusual Biochemical and Neuropathological Findings

http://sporadicffi.blogspot.com/2008/08/sporadic-fatal-insomnia-with-unusual.html

Here we go folks. AS predicted. THIS JUST OUT ! as i predicted, more BSe. ...

Tuesday, August 03, 2010

Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein

http://creutzfeldt-jakob-disease.blogspot.com/2010/08/variably-protease-sensitive-prionopathy.html

Monday, August 9, 2010

Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein or just more PRIONBALONEY ?

snip...see full text ;

http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/variably-protease-sensitive-prionopathy.html

http://prionopathy.blogspot.com/2011/05/variably-protease-sensitive-prionopathy.html

O.K. let's compare some recent cases of this prionpathy in other countries besides Gambetti's first 10 recently, that he claims is a spontaneous event, from a genetic disorder, that is not genetic, but sporadic, that is related to no animal TSE in North America, or the world. ...

http://prionunitusaupdate2008.blogspot.com/2010/08/variably-protease-sensitive-prionopathy.html

http://prionopathy.blogspot.com/

http://prionpathy.blogspot.com/

http://sporadicffi.blogspot.com/

Sunday, August 09, 2009

CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009

http://creutzfeldt-jakob-disease.blogspot.com/2009/08/cjdstraight-talk-withjames.html

Tuesday, August 18, 2009

BSE-The Untold Story - joe gibbs and singeltary 1999 - 2009

http://madcowusda.blogspot.com/2009/08/bse-untold-story-joe-gibbs-and.html

2011

EFSA Journal 2011 The European Response to BSE: A Success Story

This is an interesting editorial about the Mad Cow Disease debacle, and it's ramifications that will continue to play out for decades to come ;

Monday, October 10, 2011

EFSA Journal 2011 The European Response to BSE: A Success Story

snip...

EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.

snip...

http://www.efsa.europa.eu/en/efsajournal/pub/e991.htm?emt=1

http://www.efsa.europa.eu/en/efsajournal/doc/e991.pdf

see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;

http://transmissiblespongiformencephalopathy.blogspot.com/2011/10/efsa-journal-2011-european-response-to.html

Monday, September 26, 2011

L-BSE BASE prion and atypical sporadic CJD

http://bse-atypical.blogspot.com/2011/09/l-bse-base-prion-and-atypical-sporadic.html

Thursday, August 4, 2011

Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html

CANADA CJD UPDATE 2011

CJD Deaths Reported by CJDSS1, 1994-20112 As of January 31, 2011

3. Final classification of 49 cases from 2009, 2010, 2011 is pending.

snip...

http://www.phac-aspc.gc.ca/hcai-iamss/cjd-mcj/cjdss-ssmcj/pdf/stats_0111-eng.pdf

USA 2011

USA

National Prion Disease Pathology Surveillance Center

Cases Examined1

(November 1, 2010)

Year Total Referrals2 Prion Disease Sporadic Familial Iatrogenic vCJD

1996 & earlier 51 33 28 5 0 0

1997 114 68 59 9 0 0

1998 87 51 43 7 1 0

1999 121 73 65 8 0 0

2000 146 103 89 14 0 0

2001 209 119 109 10 0 0

2002 248 149 125 22 2 0

2003 274 176 137 39 0 0

2004 325 186 164 21 0 13

2005 344 194 157 36 1 0

2006 383 197 166 29 0 24

2007 377 214 187 27 0 0

2008 394 231 205 25 0 0

2009 425 258 215 43 0 0

2010 333 213 158 33 0 0

TOTAL 38315 22656 1907 328 4 3

1 Listed based on the year of death or, if not available, on year of referral;

2 Cases with suspected prion disease for which brain tissue and/or blood (in familial cases) were submitted;

3 Disease acquired in the United Kingdom;

4 Disease was acquired in the United Kingdom in one case and in Saudi Arabia in the other case;

5 Includes 18 cases in which the diagnosis is pending, and 18 inconclusive cases;

6 Includes 23 (22 from 2010) cases with type determination pending in which the diagnosis of vCJD has been excluded.

http://www.cjdsurveillance.com/pdf/case-table.pdf

Please notice where sporadic CJD cases in 1996 went from 28 cases, to 215 cases in 2009, the highest recorded year to date. sporadic CJD is on a steady rise, and has been since 1996.

I also urge you to again notice these disturbing factors in lines 5 and 6 ;

5 Includes 18 cases in which the diagnosis is pending, and 18 inconclusive cases;

6 Includes 23 (22 from 2010) cases with type determination pending in which the diagnosis of vCJD has been excluded.

========end=====tss=====2011

PPS POLITICAL PRION SCIENCE $$$

Creutzfeldt-Jakob Disease Surveillance in Texas

http://cjdtexas.blogspot.com/2010/06/usa-cases-of-dpcjd-rising-with-24-cases.html

Sunday, July 11, 2010

CJD or prion disease 2 CASES McLennan County Texas population 230,213 both cases in their 40s

http://creutzfeldt-jakob-disease.blogspot.com/2010/07/cjd-2-cases-mclennan-county-texas.html

http://cjdtexas.blogspot.com/

see the continuing rise of sporadic CJD in Texas here ;

http://www.dshs.state.tx.us/idcu/disease/creutzfeldt-jakob/data/

Saturday, March 5, 2011

MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html

Sunday, August 21, 2011

The British disease, or a disease gone global, The TSE Prion Disease

(see video here)

http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/british-disease-or-disease-gone-global.html

U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ?

(see video at bottom)

http://creutzfeldt-jakob-disease.blogspot.com/2009/07/usa-hiding-mad-cow-disease-victims-as.html

Sunday, September 6, 2009

MAD COW USA 1997

(SEE SECRET VIDEO)

http://madcowusda.blogspot.com/2009/09/mad-cow-usa-1997-video.html

Tuesday, November 01, 2011

Could we face the return of CJD? Experts fear it may lie dormant in thousands

http://creutzfeldt-jakob-disease.blogspot.com/2011/11/could-we-face-return-of-cjd-experts.html

MAD COW DISEASE, TEXAS STYLE

http://www.organicconsumers.org/articles/article_23850.cfm

Wednesday, June 15, 2011

Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html

Wednesday, March 31, 2010

Atypical BSE in Cattle

To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE.

In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2

Thursday, August 12, 2010

Seven main threats for the future linked to prions

First threat

The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.

***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.

Second threat

snip...

http://www.neuroprion.org/en/np-neuroprion.html

Rural and Regional Affairs and Transport References Committee

The possible impacts and consequences for public health, trade and agriculture of the Government’s decision to relax import restrictions on beef Final report June 2010

2.66 Dr Fahey also told the committee that in the last two years a link has been established between forms of atypical CJD and atypical BSE. Dr Fahey said that: They now believe that those atypical BSEs overseas are in fact causing sporadic Creutzfeldt-Jakob disease. They were not sure if it was due to mad sheep disease or a different form. If you look in the textbooks it looks like this is just arising by itself. But in my research I have a summary of a document which states that there has never been any proof that sporadic Creutzfeldt-Jakob disease has arisen de novo—has arisen of itself. There is no proof of that. The recent research is that in fact it is due to atypical forms of mad cow disease which have been found across Europe, have been found in America and have been found in Asia. These atypical forms of mad cow disease typically have even longer incubation periods than the classical mad cow disease.50

http://www.aph.gov.au/senate/committee/rrat_ctte/mad_cows/report/report.pdf

ANOTHER ATYPICAL CJD CASE (POTENTIALLY OCCUPATIONAL TIED TO BEEF INDUSTRY) IN TEXAS THAT WAS SWEPT UNDER THE RUG

CJD TEXAS 38 YEAR OLD FEMALE WORKED SLAUGHTERING CATTLE EXPOSED TO BRAIN AND SPINAL CORD MATTER

"Up until about 6 years ago, the pt worked at Tyson foods where she worked on the assembly line, slaughtering cattle and preparing them for packaging. She was exposed to brain and spinal cord matter when she would euthanize the cattle."

Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas

Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas.She left 6 Kids and a Husband.The Purpose of this web is to give information in Spanish to the Hispanic community, and to all the community who want's information about this terrible disease.-

Physician Discharge Summary, Parkland Hospital, Dallas Texas

Admit Date: 12/29/2009 Discharge Date: 1/20/2010 Attending Provider: Greenberg, Benjamin Morris; General Neurology Team: General Neurology Team

Linda was a Hispanic female with no past medical history presents with 14 months of incresing/progressive altered mental status, generalized weakness, inability to walk, loss of appetite, inability to speak, tremor and bowel/blader incontinence.She was, in her usual state of health up until February, 2009, when her husbans notes that she began forgetting things like names and short term memories. He also noticed mild/vague personality changes such as increased aggression. In March, she was involved in a hit and run MVA,although she was not injured. The police tracked her down and ticketed her. At that time, her son deployed to Iraq with the Army and her husband assumed her mentation changes were due to stress over these two events. Also in March, she began to have weakness in her legs, making it difficult to walk. Over the next few months, her mentation and personality changes worsened, getting to a point where she could no longer recognized her children. She was eating less and less. She was losing more weight. In the last 2-3 months, she reached the point where she could not walk without an assist, then 1 month ago, she stopped talking, only making grunting/aggressive sounds when anyone came near her. She also became both bowel and bladder incontinent, having to wear diapers. Her '"tremor'" and body jerks worsened and her hands assumed a sort of permanent grip position, leading her family to put tennis balls in her hands to protect her fingers.

The husband says that they have lived in Nebraska for the past 21 years. They had seen a doctor there during the summer time who prescribed her Seroquel and Lexapro, Thinking these were sx of a mood disorder. However, the medications did not help and she continued to deteriorate clinically. Up until about 6 years ago, the pt worked at Tyson foods where she worked on the assembly line, slaughtering cattle and preparing them for packaging. She was exposed to brain and spinal cord matter when she would euthanize the cattle. The husband says that he does not know any fellow workers with a similar illness. He also says that she did not have any preceeding illness or travel.

http://www.recordandoalinda.com/index.php?option=com_content&view=article&id=19:cjd-english-info&catid=9:cjd-ingles&Itemid=8

[Terry S. Singeltary Sr. has added the following comment:

"According to the World Health Organisation, the future public health threat of vCJD in the UK and Europe and potentially the rest of the world is of concern and currently unquantifiable. However, the possibility of a significant and geographically diverse vCJD epidemic occurring over the next few decades cannot be dismissed.

http://whqlibdoc.who.int/publications/2003/9241545887.pdf

Terry S. Singeltary Sr. has added the following comment:

"According to the World Health Organisation, the future public health threat of vCJD in the UK and Europe and potentially the rest of the world is of concern and currently unquantifiable. However, the possibility of a significant and geographically diverse vCJD epidemic occurring over the next few decades cannot be dismissed.

The key word here is diverse. What does diverse mean? If USA scrapie transmitted to USA bovine does not produce pathology as the UK c-BSE, then why would CJD from there look like UK vCJD?"

http://www.promedmail.org/direct.php?id=20100405.1091

When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2

The conclusions state that, at present, the only TSE agent demonstrated to be zoonotic is the classical BSE agent. Active screening has allowed the identification of 3 new forms of animal TSEs (H-type atypical BSE, L-type atypical BSE, and atypical scrapie), but the information obtained has major limitations due to the unknown sensitivity of the current monitoring system for these TSEs. There is no epidemiological evidence to suggest that classical scrapie is zoonotic. The epidemiological data are too limited to conclude whether the atypical scrapie agent has a zoonotic potential. Transmission experiments to human PrP transgenic mice or primates suggest that some TSE agents other than the classical BSE agent in cattle (namely L-type atypical BSE, classical BSE in sheep, TME, CWD agents) might have zoonotic potential and indicate that that of the L-type atypical BSE agent appears similar or even higher than that of the classical BSE agent. A single study reported efficient transmission of a natural sheep classical scrapie isolate to primates.

Commentary ---------- Following to a request from the European Commission, the Panel on Biological Hazards (BIOHAZ) and the European Centre for Disease Prevention and Control (ECDC) were asked to deliver a scientific opinion on any possible epidemiological or molecular association between transmissible spongiform encephalopathies (TSEs) in animals and humans. The opinion reviews and discusses the existing scientific evidence that links animal and human TSEs currently known.

The opinion first considers the definition of zoonoses and the principles for the identification of zoonotic diseases, which can be based on evidence gathered from both epidemiological and laboratory studies. The opinion describes the challenges involved in identifying TSEs as zoonoses, due to the specific characteristics of TSE infections/diseases, such as the nature of TSE agents, the occurrence of animal and human TSEs, and the type of monitoring applied, the long incubation period of TSEs etc. The example of the process that led to establishing a link between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) is reviewed. The epidemiological and laboratory criteria that can be used to investigate such a link are described in detail, since those criteria might be useful for the identification of links between other animal and human TSEs.

The opinion discusses the strain diversity of the TSE agents described in sheep, goats, cattle, cervids, and humans, based on the current knowledge, which highlights that multiple TSE agents exist in each species. The factors influencing the capacity of TSE agents to cross the species transmission barrier are then considered in detail, including the variability in host and donor PrP gene and protein, the TSE strain type involved and its interaction with the host PrP, and the route of infection.

The opinion critically assesses the tools and methodologies currently available to study and evaluate the possible association between animal and human TSEs. The use of epidemiology is discussed for TSEs in both animals and humans, and the possibility to compare the 2 sources of information is presented as a possible method to study the possible links.

Both in vivo and in vitro laboratory methods are considered and discussed, including neuropathology, transmission experiments involving different animal models (wild type and transgenic mice, primates and other species), biochemical methods, cell-free conversion assays, protein misfolding cyclic amplification (PMCA), and cell culture assays. Characteristics, advantages, and disadvantages of the different methods are reviewed, including the opportunity to collate data from different types of experiments for the study of potential associations between animal and human TSEs.

The opinion then reviews the scientific evidence currently available for the different animal and human TSEs, including classical BSE, atypical BSE (H-type and L-type), classical scrapie, atypical scrapie, chronic wasting disease (CWD), transmissible mink encephalopathy (TME), and human TSEs. In particular, the following aspects are systematically discussed for each TSE agent: epidemiology, pathogenesis, and in vivo and in vitro transmission experiments.

The opinion concludes that, at present, the only TSE agent demonstrated to be zoonotic is the classical BSE agent. With regard to human TSEs, detected cases of sporadic CJD are randomly distributed in time and geographical location. These observations have been interpreted as a supportive argument that sporadic CJD is not environmentally acquired. However, the epidemiological evidence in relation to sporadic CJD cannot be regarded as definitive, and the possibility that a small proportion of cases are zoonotic cannot be excluded.

It also concludes that a series of uncertainties in relation to the epidemiological patterns of animal and human TSEs indicate that even a rough comparison of the present epidemiological patterns of human and animal TSEs other than classical BSE is unlikely to be informative. Because of these uncertainties, it is an imperative to continue to carry out systematic surveillance of human TSE diseases, and to continue and improve the surveillance of animal TSE diseases.

The opinion highlights that the active screening has allowed the identification of 3 new forms of animal TSEs (L-type atypical BSE, H-type atypical BSE, and atypical scrapie), but that the information obtained has major limitations due to the unknown sensitivity of the current monitoring system for these TSEs.

There is no epidemiological evidence to suggest that classical scrapie is zoonotic. The epidemiological data are too limited to conclude whether the atypical scrapie agent has a zoonotic potential.

Transmission experiments to human PrP transgenic mice suggest that some TSE agents other than the classical BSE agent in cattle (namely L-type atypical BSE and classical BSE in sheep agents) might have zoonotic potential, whereas for other agents there is no evidence provided of a zoonotic potential (H-type atypical BSE and CWD), or no published studies are available (classical and atypical scrapie). In addition, transmission experiments to primates suggest that some TSE agents other than the classical BSE agent in cattle (namely L-type atypical BSE, classical BSE in sheep, TME, CWD agents) might have zoonotic potential. In particular, primates are highly permissive to L-type atypical BSE, even by the oral route.

The opinion emphasizes that laboratory transmission experiments indicate that the L-type atypical BSE agent has a significant zoonotic potential, which appears similar or even higher than that of the classical BSE agent. While transmission data for evaluating the zoonotic potential of classical scrapie in primates and human PrP transgenic mice are extremely limited or not yet available, a single study reported efficient transmission of a natural sheep classical scrapie isolate to primates.

The opinion concludes that human PrP transgenic mice and primates are currently the most relevant models for investigating the human transmission barrier, but the extent to which such models are informative for measuring the zoonotic potential of an animal TSE under field exposure conditions is unknown. It is unpredictable whether a TSE agent will transmit to a new host, and if the transmission principally occurs, what the transmission rate will be.

Based on the results obtained with in vitro conversion assays, the opinion concludes that there is probably no absolute molecular barrier to transmission of TSE agents between mammalian species. Results also suggest that these assays may be developed as a tool for quantifying the transmission barriers between species for different TSE agent strains; however, there is no means at the moment to transpose in vitro results into the likelihood of in vivo interspecies transmission.

-- Communicated by: Terry S Singeltary Sr

[ProMED-mail thanks Terry S Singeltary Sr for drawing attention to this comprehensive document which provides a current evaluation of experimental work designed to explore the zoonotic potential of the various recently recognised TSEs of domestic and other animals.

It is concluded that at present the only TSE agent demonstrated to be zoonotic is the classical BSE agent. Nor can it be entirely excluded at the present time that a small proportion of cases of sporadic CJD may be environmentally acquired. - Mod.CP]

******

http://www.promedmail.org/direct.php?id=20110607.1736

USDA FDA FAILED BSE TRIPLE FIRE WALLS, a feed ban and surveillance system that was nothing more than ink on paper ;

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)

http://prionpathy.blogspot.com/2010/08/bse-case-associated-with-prion-protein.html

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

RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II

___________________________________

PRODUCT

Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007

CODE

Cattle feed delivered between 01/12/2007 and 01/26/2007

RECALLING FIRM/MANUFACTURER

Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.

Firm initiated recall is ongoing.

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

___________________________________

PRODUCT

Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007

CODE

The firm does not utilize a code - only shipping documentation with commodity and weights identified.

RECALLING FIRM/MANUFACTURER

Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete.

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

http://www.fda.gov/Safety/Recalls/EnforcementReports/2007/ucm120446.htm

Monday, September 12, 2011

BSE PRION Agriculture Animal Feed Question House of Lords Thursday, 8 September 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/09/bse-prion-agriculture-animal-feed.html

Saturday, July 23, 2011

CATTLE HEADS WITH TONSILS, BEEF TONGUES, SPINAL CORD, SPECIFIED RISK MATERIALS (SRM's) AND PRIONS, AKA MAD COW DISEASE

http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/cattle-heads-with-tonsils-beef-tongues.html

Saturday, November 6, 2010

TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU Berne, 2010 TAFS

INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation

http://madcowfeed.blogspot.com/2010/11/tafs1-position-paper-on-position-paper.html

Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject PRO/AH/EDR> Prion disease update 2010 (11)

PRION DISEASE UPDATE 2010 (11)

http://www.promedmail.org/direct.php?id=20101206.4364

Sunday, September 25, 2011

Mad Cow Scaremongers

Mad Cow Scaremongers by Terry S. Singeltary Sr. a review of the TSE prion agent 2003-2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/09/mad-cow-scaremongers.html

Friday, November 30, 2007

CJD QUESTIONNAIRE USA CWRU AND CJD FOUNDATION

http://cjdquestionnaire.blogspot.com/2007/11/cjd-questionnaire.html

http://cjdquestionnaire.blogspot.com/

LAYPERSON

Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518

Can Mortality Data Provide Reliable Indicators for Creutzfeldt-Jakob Disease Surveillance? A Study in France from 2000 to 2008

2011-11-08T19:01:00.000-08:00

Vol. 37, No. 3-4, 2011

Original Paper

Can Mortality Data Provide Reliable Indicators for Creutzfeldt-Jakob Disease Surveillance? A Study in France from 2000 to 2008

Jean-Philippe Brandela–e, Arlette Welaratnea, Dominique Salomonf, g, Isabelle Capekh, Véronique Vaillanth, Albertine Aouabai, Stéphane Haïka–e, Annick Alpérovitchf, g

aAP-HP, Cellule Nationale de Référence des Maladies de Creutzfeldt-Jakob, Groupe Hospitalier Pitié-Salpêtrière, bINSERM, UMR-S 975, Equipe Maladie d’Alzheimer – Maladies à prions, cCNRS, UMR 7225, dUniversité Pierre et Marie Curie Paris 06, UMR 7225, S-975, Centre de Recherche de l’Institut Cerveau-Moelle (CRICM), eCNR des ATNC, fINSERM, U708, Neuroépidémiologie, gUPMC Université Paris 06, UMR S708, Paris, hInstitut de Veille Sanitaire, Saint-Maurice, et iINSERM-CépiDc, Le Vésinet, France

Address of Corresponding Author

Neuroepidemiology 2011;37:188-192 (DOI: 10.1159/000332764)

--------------------------------------------------------------------------------

Key Words

Creutzfeldt-Jakob disease Mortality register Active surveillance Evaluation of surveillance systems

--------------------------------------------------------------------------------

Abstract

Background: Surveillance of Creutzfeldt-Jakob disease (CJD) is still an important issue because of the variant CJD epidemic, which is in decline and also because of the emergence of novel forms of animal transmissible spongiform encephalopathy with zoonotic potential and the risk of nosocomial and blood transfusion-related transmission. Active surveillance has been implemented in most European countries and requires important human resources and funding. Here, we studied whether national mortality and morbidity statistics can be used as reliable indicators. Methods: CJD data collected by the French national CJD surveillance centre were compared with data registered in the national mortality statistics. Results: From 2000 to 2008, the two sources reported fairly similar numbers of CJD deaths. However, analysis of individual data showed important between-sources disagreement. Nearly 24% of CJD reported by the mortality register were false-positive diagnoses and 21.6% of the CJD cases diagnosed by the surveillance centre were not registered as CJD in the national mortality statistics. One out of 22 variant CJD cases was not reported as having any type of CJD in the mortality statistics. Conclusions:These findings raise doubt about the possibility of a reliable CJD surveillance only based on mortality data.

Copyright © 2011 S. Karger AG, Basel

--------------------------------------------------------------------------------

Author Contacts

Jean-Philippe Brandel Cellule Nationale de Référence des Maladies de Creutzfeldt-Jakob Groupe Hospitalier Pitié-Salpêtrière, 47–83 boulevard de l’Hôpital FR–75013 Paris (France) Tel. +33 14 216 2626, E-Mail jean-philippe.brandel@psl.aphp.fr

--------------------------------------------------------------------------------

© 2011 S. Karger AG, Basel

http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=332764&Ausgabe=255660&ProduktNr=224263

"Conclusions:These findings raise doubt about the possibility of a reliable CJD surveillance only based on mortality data."

i been saying it for a decade. however, as with the USDA et al BSE aka mad cow surveillance and testing there from, the CJD surveillance program was set up the same way, NOT TO FIND CASES OF HUMAN TSE AKA CJD from any source of livestock in the USA $$$

Views & Reviews

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States

Ermias D. Belay, MD, Ryan A. Maddox, MPH, Pierluigi Gambetti, MD and Lawrence B. Schonberger, MD

+ Author Affiliations

From the Division of Viral and Rickettsial Diseases (Drs. Belay and Schonberger and R.A. Maddox), National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA; and National Prion Disease Pathology Surveillance Center (Dr. Gambetti), Division of Neuropathology, Institute of Pathology, Case Western Reserve University, Cleveland, OH.

Address correspondence and reprint requests to Dr. Ermias D. Belay, 1600 Clifton Road, Mailstop A-39, Atlanta, GA 30333.

http://www.neurology.org/content/60/2/176

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?

http://www.neurology.org/content/60/2/176/reply#neurology_el_535

Reply to Singletary

Ryan A. Maddox, MPH Ermias D. Belay, MD, Lawrence B. Schonberger, MD Centers for Disease Control and Prevention Atlanta GA

Mr. Singletary raises several issues related to current Creutzfeldt- Jakob disease (CJD) surveillance activities. Although CJD is not a notifiable disease in most states, its unique characteristics, particularly its invariably fatal outcome within usually a year of onset, make routine mortality surveillance a useful surrogate for ongoing CJD surveillance.[1] In addition, because CJD is least accurately diagnosed early in the course of illness, notifiable-disease surveillance could be less accurate than, if not duplicative of, current mortality surveillance.[1] However, in states where making CJD officially notifiable would meaningfully facilitate the collection of data to monitor for variant CJD (vCJD) or other emerging prion diseases, CDC encourages the designation of CJD as a notifiable disease.[1] Moreover, CDC encourages physicians to report any diagnosed or suspected CJD cases that may be of special public health importance (e.g., vCJD, iatrogenic CJD, unusual CJD clusters).

As noted in our article, strong evidence is lacking for a causal link between chronic wasting disease (CWD) of deer and elk and human disease,[2] but only limited data seeking such evidence exist. Overall, the previously published case-control studies that have evaluated environmental sources of infection for sporadic CJD have not consistently identified strong evidence for a common risk factor.[3] However, the power of a case-control study to detect a rare cause of CJD is limited, particularly given the relatively small number of subjects generally involved and its long incubation period, which may last for decades. Because only a very small proportion of the US population has been exposed to CWD, a targeted surveillance and investigation of unusual cases or case clusters of prion diseases among persons at increased risk of exposure to CWD is a more efficient approach to detecting the possible transmission of CWD to humans. In collaboration with appropriate local and state health departments and the National Prion Disease Pathology Surveillance Center, CDC is facilitating or conducting such surveillance and case- investigations, including related laboratory studies to characterize CJD and CWD prions.

Mr. Singletary also expresses concern over a recent publication by Asante and colleagues indicating the possibility that some sporadic CJD cases may be attributable to bovine spongiform encephalopathy (BSE).[4] The authors reported that transgenic mice expressing human prion protein homozygous for methionine at codon 129, when inoculated with BSE prions, developed a molecular phenotype consistent with a subtype of sporadic CJD. Although the authors implied that BSE might cause a sporadic CJD-like illness among persons homozygous for methionine, the results of their research with mice do not necessarily directly apply to the transmission of BSE to humans. If BSE causes a sporadic CJD-like illness in humans, an increase in sporadic CJD cases would be expected to first occur in the United Kingdom, where the vast majority of vCJD cases have been reported. In the United Kingdom during 1997 through 2002, however, the overall average annual mortality rate for sporadic CJD was not elevated; it was about 1 case per million population per year. In addition, during this most recent 6-year period following the first published description of vCJD in 1996, there was no increasing trend in the reported annual number of UK sporadic CJD deaths.[3, 5] Furthermore, surveillance in the UK has shown no increase in the proportion of sporadic CJD cases that are homozygous for methionine (Will RG, National CJD Surveillance Unit, United Kingdom, 2003; personal communication).

References

1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Diagnosis and reporting of Creutzfeldt-Jakob disease. JAMA 2001;285:733-734.

2. Belay ED, Maddox RA, Gambetti P, Schonberger LB. Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States. Neurology 2003;60:176-181.

3. Belay ED. Transmissible spongiform encephalopathies in humans. Annu Rev Microbiol 1999;53:283-314.

4. Asante EA, Linehan JM, Desbruslais M, et al. BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein. EMBO J 2002;21:6358-6366.

5. The UK Creutzfeldt-Jakob Disease Surveillance Unit. CJD statistics. Available at: http://www.cjd.ed.ac.uk/figures.htm. Accessed February 18, 2003.

http://www.neurology.org/content/60/2/176/reply#neurology_el_582

Human Prion Diseases in the United States

Robert C. Holman1*, Ermias D. Belay1, Krista Y. Christensen1, Ryan A. Maddox1, Arialdi M. Minino2, Arianne M. Folkema1, Dana L. Haberling1, Teresa A. Hammett1, Kenneth D. Kochanek2, James J. Sejvar1, Lawrence B. Schonberger1

1 Division of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-borne and Enteric Diseases, Centers for Disease Control and Prevention (CDC), U.S. Department of Health and Human Services (USDHHS), Atlanta, Georgia, United States of America, 2 Division of Vital Statistics, National Center for Health Statistics, Centers for Disease Control and Prevention (CDC), U.S. Department of Health and Human Services (USDHHS), Hyattsville, Maryland, United States of America

Abstract Top

Background

Prion diseases are a family of rare, progressive, neurodegenerative disorders that affect humans and animals. The most common form of human prion disease, Creutzfeldt-Jakob disease (CJD), occurs worldwide. Variant CJD (vCJD), a recently emerged human prion disease, is a zoonotic foodborne disorder that occurs almost exclusively in countries with outbreaks of bovine spongiform encephalopathy.

This study describes the occurrence and epidemiology of CJD and vCJD in the United States.

Methodology/Principal Findings

Analysis of CJD and vCJD deaths using death certificates of US residents for 1979–2006, and those identified through other surveillance mechanisms during 1996–2008. Since CJD is invariably fatal and illness duration is usually less than one year, the CJD incidence is estimated as the death rate. During 1979 through 2006, an estimated 6,917 deaths with CJD as a cause of death were reported in the United States, an annual average of approximately 247 deaths (range 172–304 deaths). The average annual age-adjusted incidence for CJD was 0.97 per 1,000,000 persons. Most (61.8%) of the CJD deaths occurred among persons =65 years of age for an average annual incidence of 4.8 per 1,000,000 persons in this population. Most deaths were among whites (94.6%); the age-adjusted incidence for whites was 2.7 times higher than that for blacks (1.04 and 0.40, respectively). Three patients who died since 2004 were reported with vCJD; epidemiologic evidence indicated that their infection was acquired outside of the United States.

Conclusion/Significance

Surveillance continues to show an annual CJD incidence rate of about 1 case per 1,000,000 persons and marked differences in CJD rates by age and race in the United States. Ongoing surveillance remains important for monitoring the stability of the CJD incidence rates, and detecting occurrences of vCJD and possibly other novel prion diseases in the United States.

Citation: Holman RC, Belay ED, Christensen KY, Maddox RA, Minino AM, et al. (2010) Human Prion Diseases in the United States. PLoS ONE 5(1): e8521. doi:10.1371/journal.pone.0008521

Editor: Mick F. Tuite, University of Kent, United Kingdom

Received: July 21, 2009; Accepted: October 30, 2009; Published: January 1, 2010

Holman et al. This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.

Funding: The authors have no support or funding to report.

Competing interests: The authors have declared that no competing interests exist.

* E-mail: rholman@cdc.gov

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0008521&annotationId=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd;jsessionid=42A8AB7D8AE8305E793259D57C0F5DCF.ambra02

2 responses

re-Human Prion Diseases in the United States

Posted by flounder on 01 Jan 2010 at 18:11 GMT

Most recent response on 02 Jan 2011 at 20:00 GMT

http://www.plosone.org/article/fetchArticleComments.action?annotationId=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd&articleURI=info%3Adoi%2F10.1371%2Fjournal.pone.0008521

my comments to PLosone here ;

re-Human Prion Diseases in the United States Posted by flounder on 01 Jan 2010 at 18:11 GMT

I kindly disagree with your synopsis for the following reasons ;

No competing interests declared.

RE: re-Human Prion Diseases in the United States part 2

flounder replied to flounder on 02 Jan 2010 at 21:26 GMT

I would kindly like to add to my initial concerns, something I brought up years ago, and I believe that still hold true today, more so even than when I first stated these concerns in 2003 ;

routine passive mortality CJD surveillance USA ?

THIS has been proven not to be very useful in the U.K.;

THE EPIDEMIOLOGY OF CJD RG WILL 1984 (182 PAGES)

snip...

One reason for this was the _inaccuracy_ in coding of cases correctly certified as CJD Coding is carried out by staff who are not medically qualified and it is not surprising that coding errors occur in the processing of large numbers of certificates. In 1982, 12,000 certificates per week were processed at the office of population censuses and surveys by 15 coders and 6 checkers (Alderson et al., 1983). The occurrence of both inter- and intra-observer coding errors has been described (Curb et al., 1983) and the _inaccuracies_ of BOTH certification and coding discovered in this study _support_ the introduction of a more accurate system of death certificates and a more detailed and specific coding system...

snip...

http://web.archive.org/web/20040521215716/http://www.bseinquiry.gov.uk/files/mb/m26/tab01.pdf

Draft Proposal For The Monitoring of Creutzfeldt-Kakob Disease 1989 Dr. R. Will

snip...

IDENTIFICATION OF CASES

Cases of CJD may be identified from death certificates, but this alone is unlikely to provide adequate monitoring. ERRORS are made in certification and diagnosis; in the Oxford study death certificates were obtained on a series of known confirmed cases and CJD was mentioned in only 66% of certificates. In another series of 175 certified cases, 42 patients were judged not to have suffered from CJD after examination of case notes (7)...

full text;

http://web.archive.org/web/20050526035006/http://www.bseinquiry.gov.uk/files/yb/1989/05/00005001.pdf

AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease.

snip...

http://web.archive.org/web/20060307063542/http://www.bseinquiry.gov.uk/files/yb/1991/01/04004001.pdf

Confucius is confused again? how in 1996 and earlier can the 28 sporadic CJD victims and the one-in-a-million there from, how can it still be one in a million in 2008, with the sporadic CJD count rising to 205, still be one-in-a-million? and the years in-between, steady rise just about every year, and it still be only one-in-a-million, year after year after years? I suppose just more of that fuzzy math, which you can see here;

http://www.cjdsurveillance.com/pdf/case-table.pdf

Please see my complete comment to this synopsis here ;

Saturday, January 2, 2010

Human Prion Diseases in the United States January 1, 2010

http://prionunitusaupdate2008.blogspot.com/2010/01/human-prion-diseases-in-united-states.html

No competing interests declared.

RE: RE: re-Human Prion Diseases in the United States part 2

flounder replied to flounder on 02 Jan 2011 at 20:00 GMT

Wednesday, December 29, 2010

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY PRION END OF YEAR REPORT DECEMBER 29, 2010

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/transmissible-spongiform-encephalopathy.html

Wednesday, December 29, 2010

CWD Update 99 December 13, 2010

http://chronic-wasting-disease.blogspot.com/2010/12/cwd-update-99-december-13-2010.html

Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518

No competing interests declared.

Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: an updated classification

Piero Parchi Æ Rosaria Strammiello Æ Silvio Notari Æ Armin Giese Æ Jan P. M. Langeveld Æ Anna Ladogana Æ Inga Zerr Æ Federico Roncaroli Æ Patrich Cras Æ Bernardino Ghetti Æ Maurizio Pocchiari Æ Hans Kretzschmar Æ Sabina Capellari

Received: 30 June 2009 / Revised: 16 August 2009 / Accepted: 17 August 2009 / Published online: 29 August 2009

The Author(s) 2009. This article is published with open access at Springerlink.com

Abstract

Six subtypes of sporadic Creutzfeldt-Jakob disease with distinctive clinico-pathological features have been identified largely based on two types of the abnormal prion protein, PrPSc, and the methionine (M)/valine (V) polymorphic codon 129 of the prion protein. The existence of affected subjects showing mixed phenotypic features and concurrent PrPSc types has been reported but with inconsistencies among studies in both results and their interpretation. The issue currently complicates diagnosis and classification of cases and also has implications for disease pathogenesis. To explore the issue in depth, we carried out a systematic regional study in a large series of 225 cases. PrPSc types 1 and 2 concurrence was detected in 35% of cases and was higher in MM than in MV or VV subjects. The deposition of either type 1 or 2, when concurrent, was not random and always characterized by the coexistence of phenotypic features previously described in the pure subtypes. PrPSc type 1 accumulation and related pathology predominated in MM and MV cases, while the type 2 phenotype prevailed in VVs. Neuropathological examination best identified the mixed types 1 and 2 features in MMs and most MVs, and also uniquely revealed the cooccurrence of pathological variants sharing PrPSc type 2. In contrast, molecular typing best detected the concurrent PrPSc types in VV subjects and MV cases with kuru plaques. The present data provide an updated disease classification and are of importance for future epidemiologic and transmission studies aimed to identify etiology and extent of strain variation in sporadic Creutzfeldt-Jakob disease.

snip...

Discussion

Previous studies have addressed the issue of PrPSc types 1 and 2 co-occurrence in sCJD. Most of them raised the question of the influence of the number of cases and brain areas analyzed and emphasized the possibility that the cooccurrence of PrPSc types 1 and 2 is underestimated [13, 18, 20, 30, 37, 40, 43]. On the other hand, the use of a novel, potentially very sensitive approach, later shown to have pitfalls related to the detection of unspecific bands generated by partially digested PrPSc fragments [25], likely led other investigators to overestimate the incidence of the concurrent PrPSc types [35, 45]. Thus, the overall results on the phenomenon of the coexistence of molecular and clinico-pathological sCJD subtypes are at present inconclusive with respect to incidence, effect on disease phenotype and criteria for disease classification. To contribute to the full understanding of these issues, in the present study, we combined a systematic analysis of several brain regions in a large series of case including all codon 129 genotypes and the rarest phenotypes with the use of a refined methodology for the detection of the PrPSc type concurrence, which provides good sensitivity combined with high specificity [25].

After screening about 4,200 samples from a largely consecutive series of 200 cases, we estimated that PrPSc types 1 and 2 coexist in about 35% of sCJD cases, which is overall consistent with figures from some of the previous studies [13, 37, 43] in which the number of cases and areas analyzed were significantly lower. This finding supports the idea that PrPSc types co-occurrence involves a relevant but limited group of sCJD subjects and indicates that the incidence of the phenomenon had not been significantly underestimated.

As far as the characteristics of the CJD population with mixed phenotypes are concerned, our data show that the PrPSc types 1 and 2 co-occur more frequently in the MM than in the MV and VV genotypes. More specifically, the large majority of sCJD cases with concurrent PrPSc types combines features of the MM and MM 2C sCJD subtypes, in variable proportions. Most commonly, in such cases, the MM1 phenotype is predominant over the MM 2C phenotype, but the opposite situation also rarely occurs. The latter results significantly differ from those obtained in most previous studies. Indeed, Head et al. [13] mainly found a focal type 1 co-occurrence in MM and MV subjects with dominant type 2, Schoch et al. [40] detected the mixed protein types mostly in MV2 cases showing the type 1 only focally in subcortical areas, and Uro-Coste et al. [43] mainly detected a random co-occurrence of type 1 in MV or VV cases with dominant type 2. Given that only our study was based on a large series of consecutive cases, we attribute such heterogeneity of previous results to case selection biases, although methodological differences may also have contributed [43].

snip...

Taken together, our data indicate that a protocol including the neuropathologic assessment of the eight brain regions mentioned above and PrPSc typing in four critical regions such as the temporal, parietal and occipital neocortices, and medial thalamus is strongly recommended for a reliable sCJD group classification addressing the issue of mixed phenotypes. Indeed, by applying this protocol instead of examining all 21 brain regions, we would have reached the same classification of cases in the present series.

We also wish to underline the importance of identifying correctly the sCJD cases with mixed features for transmission purposes. Indeed, the question of whether the concurrence of PrPSc types 1 and 2 in CJD reflects a coinfection by two prion strains related to specific undiscovered human genotypes, or determined by epigenetic factors remains unanswered and will largely rely on transmission studies in which the careful selection of samples will be of critical importance. Concerning this critical question, we find intriguing that the large, confluent vacuoles and the perivacuolar pattern of PrPSc deposition, we originally linked to sCJD MM 2C are also found in a subgroup of MV 2K subjects in addition to MM/MV 1?2C. In addition, we have described here the same morphological features in one case of fatal insomnia (i.e. the MM2-thalamic subtype or MM 2T) which adds to two previously reported cases [19, 30, 31]. Thus, it seems that large confluent vacuoles and the perivacuolar pattern of PrPSc deposition may be found in sCJD associated with all phenotypes linked to MM or MV at codon 129. Although this observation remains difficult to interpret at present, it appears relevant for our future understanding of the molecular basis and the extent of strain variation in sCJD. In any case, our observation strongly suggests that the phenomenon of mixed phenotypes in sCJD goes beyond PrPSc types 1 and 2 coexistence and also involves subtypes which shares the same PrPSc type. This, in turn, further underlines the importance of combining histopathological assessment and biochemical PrPSc typing for sCJD subtype characterization.

The present data also show that the association of two PrP27-30 fragments, which does not represent a bona-fide type 1 and 2 concurrence, may also be a feature of some sCJD cases. Thus, the PrP27-30 profile in VV2 cases in the cerebellum, thalamus and midbrain is sometime characterized by a doublet comprising a 18.5 kDa in addition to the typical 19 kDa band, while the western blot profile of PrP27-30 in the MV 2K cases appears almost invariably characterized by the association of two PrPSc core fragments including a classic 19 kDa type 2 band and a slower migrating band of about 20 kDa. Although these profiles truly represent concurrent PrPSc fragments, and the 20 and 18.5 kDa fragments likely reflect specific PK cleavage sites, the 20 and 18.5 kDa bands are distinguished from the type 1 and type 2 fragments because, at least to date, they were never detected independently from types 1 and 2, and are not markers of specific clinico-pathological phenotypes. Knowledge of these regional variations is nonetheless important to avoid misinterpreting a PrPSc profile as novel when only one brain region is analyzed [21].

Finally, the results obtained from the analyses of lesion profiles and clinical features in the subgroups of sCJD cases with mixed features deserve further comment. By showing that the relative load of each of the two PrPSc types significantly correlates with disease duration, the relative frequency of certain symptoms, and the ratio between cortical and cerebellar pathology, our study provides further strong evidence for the PrPSc type being a major biological determinant in human prion disease. In conclusion, the present data add to our knowledge of the prevalence and phenotypic spectrum of the sCJD variants with mixed molecular and pathological features, provide an updated molecular classification of the disease subtypes and will serve for future epidemiologic and transmission studies aimed at disclosing the etiology and extent of strain variation in sCJD.

Acknowledgments We wish to thank Barbara Polischi and Sabrina Boninsegna for her technical assistance. We also thank all the physicians who provided clinical data and helped in the collection of tissues and all family members who consented to the use of tissue for research. This study was funded in the frame of the bilateral Italy (ISS)-USA (NIH, Office for Rare Diseases) agreement on joint research on rare diseases, by the European Commission (FOOD-CT- 2004-506579), the Italian Ministry of University, Research and Technology (FIRB-2003-RBNE03FMCJ_006), the Federal Ministry of Health (ZV2-1369-340): grant PHS P30 AG010133, and the Gino Galletti Foundation.

Keywords Prion protein Brain mapping Molecular typing Neurodegeneration Classification

P. Parchi R. Strammiello S. Notari S. Capellari Dipartimento di Scienze Neurologiche, Universita` di Bologna, Bologna, Italy A. Giese H. Kretzschmar Institut fu¨r Neuropathologie, Ludwig-Maximilians-Universita¨t Mu¨nchen, Munich, Germany J. P. M. Langeveld Central Veterinary Institute of Wageningen UR, Lelystad, The Netherlands A. Ladogana M. Pocchiari Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita`, Rome, Italy I. Zerr Department of Neurology, National Reference Center for TSE Surveillance, Georg-August University, Go¨ttingen, Germany F. Roncaroli Division of Neuroscience and Mental Health, Department of Clinical Neuroscience, Imperial College, London, UK P. Cras Born-Bunge Institute (BBI), University of Antwerp (UA), Antwerp, Belgium B. Ghetti Department of Pathology, Indiana University, Indianapolis, IN, USA P. Parchi (&) Department of Neurological Sciences, Universtity of Bologna, Via Foscolo 7, 40123 Bologna, Italy e-mail: piero.parchi@unibo.it

http://www.springerlink.com/content/21552482u6761291/fulltext.pdf

MANY, MANY THANKS TO Parchi et al for this study, AND for the public access to full text. ...TSS

Tuesday, August 11, 2009

Characteristics of Established and Proposed Sporadic Creutzfeldt-Jakob Disease Variants

Brian S. Appleby, MD; Kristin K. Appleby, MD; Barbara J. Crain, MD, PhD; Chiadi U. Onyike, MD, MHS; Mitchell T. Wallin, MD, MPH; Peter V. Rabins, MD, MPH

Background: The classic Creutzfeldt-Jakob disease (CJD), Heidenhain, and Oppenheimer-Brownell variants are sporadic CJD (sCJD) phenotypes frequently described in the literature, but many cases present with neuropsychiatric symptoms, suggesting that there may be additional sCJD phenotypes.

Objective: To characterize clinical, diagnostic, and molecular features of 5 sCJD variants.

Design: Retrospective analysis.

Setting: The Johns Hopkins and Veterans Administration health care systems.

Participants: Eighty-eight patients with definite or probable sCJD.

Main Outcome Measures: Differences in age at onset, illness progression, diagnostic test results, and molecular subtype.

Results: The age at onset differed among sCJD variants (P=.03); the affective variant had the youngest mean age at onset (59.7 years). Survival time (P .001) and the time to clinical presentation (P=.003) differed among groups. Patients with the classic CJD phenotype had the shortest median survival time from symptom onset (66 days) and those who met criteria for the affective sCJD variant had the longest (421 days) and presented to clinicians significantly later (median time from onset to presentation, 92 days; P=.004). Cerebrospinal fluid analyses were positive for 14-3-3 protein in all of the affective variants, regardless of illness duration. Periodic sharp-wave complexes were not detected on any of the electroencephalography tracings in the Oppenheimer-Brownell group; basal ganglia hyperintensity was not detected on brain magnetic resonance imaging in this group either. All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.

Conclusions: The classic CJD phenotype and the Heidenhain, Oppenheimer-Brownell, cognitive, and affective sCJD variants differ by age at disease onset, survival time, and diagnostic test results. Characteristics of these 5 phenotypes are provided to facilitate further clinicopathologic investigation that may lead to more reliable and timely diagnoses of sCJD.

Arch Neurol. 2009;66(2):208-215

snip...

COMMENT

snip...see full text ;

http://creutzfeldt-jakob-disease.blogspot.com/2009/08/characteristics-of-established-and.html

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009

August 10, 2009

Greetings,

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. North America seems to have the most species with documented Transmissible Spongiform Encephalopathy's, most all of which have been rendered and fed back to food producing animals and to humans for years. If you look at the statistics, sporadic CJD seems to be rising in the USA, and has been, with atypical cases of the sCJD. I find deeply disturbing in the year of 2009, that Human Transmissible Spongiform Encephalopathy of any strain and or phenotype, of all age groups, and I stress all age groups, because human TSE's do not know age, and they do not know borders. someone 56 years old, that has a human TSE, that has surgery, can pass this TSE agent on i.e. friendly fire, and or passing it forward, and there have been documented nvCJD in a 74 year old. Remembering also that only sporadic CJD has been documented to transmit via iatrogenic routes, until recently with the 4 cases of blood related transmission, of which the origin is thought to be nvCJD donors. However most Iatrogenic CJD cases are nothing more than sporadic CJD, until the source is proven, then it becomes Iatrogenic. An oxymoron of sorts, because all sporadic CJD is, are multiple forms, or strains, or phenotypes of Creutzfeldt Jakob Disease, that the route and source and species have not been confirmed and or documented. When will the myth of the UKBSEnvCJD only theory be put to bed for good. This theory in my opinion, and the following there from, as the GOLD STANDARD, has done nothing more than help spread this agent around the globe. Politics and money have caused the terrible consequences to date, and the fact that TSEs are a slow incubating death, but a death that is 100% certain for those that are exposed and live long enough to go clinical. once clinical, there is no recourse, to date. But, while sub-clinical, how many can one exposed human infect? Can humans exposed to CWD and scrapie strains pass it forward as some form of sporadic CJD in the surgical and medical arenas? why must we wait decades and decades to prove this point, only to expose millions needlessly, only for the sake of the industries involved? would it not have been prudent from the beginning to just include all TSE's, and rule them out from there with transmission studies and change policies there from, as opposed to doing just the opposite? The science of TSE's have been nothing more than a political circus since the beginning, and for anyone to still believe in this one strain, one group of bovines, in one geographical location, with only one age group of human TSE i.e. nvCJD myth, for anyone to believe this today only enhances to spreading of these human and animal TSE's. This is exactly why we have been in this quagmire.

The ones that believe that there is a spontaneous CJD in 85%+ of all cases of human TSE, and the ones that do not believe that cattle can have this same phenomenon, are two of the same, the industry, and so goes the political science aspect of this tobacco and or asbestos scenario i.e. follow the money. I could go into all angles of this man made nightmare, the real facts and science, for instance, the continuing rendering technology and slow cooking with low temps that brewed this stew up, and the fact that THE USA HAD THIS TECHNOLOGY FIRST AND SHIPPED IT TO THE U.K. SOME 5 YEARS BEFORE THE U.S. STARTED USING THE SAME TECHNOLOGY, to save on fuel cost. This is what supposedly amplified the TSE agent via sheep scrapie, and spread via feed in the U.K. bovine, and other countries exporting the tainted product. BUT most everyone ignores this fact, and the fact that the U.S. has been recycling more TSE, from more species with TSEs, than any other country documented, but yet, it's all spontaneous, and the rise in sporadic CJD in the U.S. is a happenstance of bad luck ??? I respectfully disagree. To top that all off, the infamous BSE-FIREWALL that the USDA always brags about was nothing more than ink on paper, and I can prove this. YOU can ignore it, but this is FACT (see source, as late as 2007, in one recall alone, some 10,000,000 MILLION POUNDS OF BANNED MAD COW FEED WENT OUT INTO COMMERCE TO BE FED OUT, and most was never recovered. This was banned blood laced, meat and bone meal. 2006 was a banner year for banned mad cow protein going into commerce in the U.S. (see source of FDA feed ban warning letter below). I stress that the August 4, 1997 USA mad cow feed ban and this infamous BSE firewall, was nothing more than ink on paper, it was never enforceable.

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. 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. This would further have to be broken down to strain of species and then the route of transmission would further have to be broken down. Accumulation and Transmission are key to the threshold from sub- clinical to clinical disease, and key to all this, is to stop the amplification and transmission of this agent, the spreading of, no matter what strain. In my opinion, to continue with this myth that the U.K. strain of BSE one strain TSE in cows, and the nv/v CJD one strain TSE humans, and the one geographical location source i.e. U.K., and that all the rest of human TSE are just one single strain i.e. sporadic CJD, a happenstance of bad luck that just happens due to a twisted protein that just twisted the wrong way, IN 85%+ OF ALL HUMAN TSEs, when to date there are 6 different phenotypes of sCJD, and growing per Gambetti et al, and that no other animal TSE transmits to humans ??? With all due respect to all Scientist that believe this, I beg to differ. To continue with this masquerade will only continue to spread, expose, and kill, who knows how many more in the years and decades to come. ONE was enough for me, My Mom, hvCJD i.e. Heidenhain Variant CJD, DOD 12/14/97 confirmed, which is nothing more than another mans name added to CJD, like CJD itself, Jakob and Creutzfeldt, or Gerstmann-Straussler-Scheinker syndrome, just another CJD or human TSE, named after another human. WE are only kidding ourselves with the current diagnostic criteria for human and animal TSE, especially differentiating between the nvCJD vs the sporadic CJD strains and then the GSS strains and also the FFI fatal familial insomnia strains or the ones that mimics one or the other of those TSE? Tissue infectivity and strain typing of the many variants of the human and animal TSEs are paramount in all variants of all TSE. There must be a proper classification that will differentiate between all these human TSE in order to do this. With the CDI and other more sensitive testing coming about, I only hope that my proposal will some day be taken seriously. ...

please see history, and the ever evolving TSE science to date ;

Saturday, June 13, 2009

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009

http://cjdusa.blogspot.com/2009/06/monitoring-occurrence-of-emerging-forms.html

WHO WILL WATCH THE CHILDREN for CJD over the next 5 decades ?

SCHOOL LUNCH PROGRAM FROM DOWNER CATTLE UPDATE

http://downercattle.blogspot.com/2009/05/who-will-watch-children.html

http://downercattle.blogspot.com/

Monday, October 19, 2009

Atypical BSE, BSE, and other human and animal TSE in North America Update October 19, 2009

http://bse-atypical.blogspot.com/2009/10/atypical-bse-bse-and-other-human-and.html

Sunday, September 6, 2009

MAD COW USA 1997 SECRET VIDEO

http://madcowusda.blogspot.com/2009/09/mad-cow-usa-1997-video.html

U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ? see video at bottom

http://creutzfeldt-jakob-disease.blogspot.com/2009/07/usa-hiding-mad-cow-disease-victims-as.html

DAMNING TESTIMONY FROM STANLEY PRUSINER THE NOBEL PEACE PRIZE WINNER ON PRIONS SPEAKING ABOUT ANN VENEMAN see video

http://maddeer.org/

CVM Annual Report Fiscal Year 2008: October 1, 2007-September 30, 2008

PUTTING LIPSTICK ON A PIG AND TAKING HER TO A DANCE...TSS

BSE Feed Rule Enforcement: A Decade of Success OFF TO A FAST START

http://madcowfeed.blogspot.com/2008/06/texas-firm-recalls-cattle-heads-that.html

2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006

http://bse-atypical.blogspot.com/2006/08/bse-atypical-texas-and-alabama-update.html

Sent: Tuesday, November 03, 2009 9:07 PM

Subject: [BSE-L] re-FOIA REQUEST ON FEED RECALL PRODUCT contaminated with prohibited material Recall # V-258-2009 and Recall # V-256-2009 (CONFIRMED BSE RELATED, BOTH INCIDENCES)

http://madcowfeed.blogspot.com/2009/11/re-foia-request-on-feed-recall-product.html

Thursday, November 05, 2009

Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: an updated classification

http://creutzfeldt-jakob-disease.blogspot.com/2009/11/incidence-and-spectrum-of-sporadic.html

An Unusual Case of Variant CJD 18 December 2009

A Case Report published in this week's The Lancet, written by Professor John Collinge, MRC Prion Unit and National Prion Clinic, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, reports the particular genetic make-up of a 30-year old man who has died of variant Creutzfeldt-Jakob disease (vCJD). The case report suggests that there could be other people with the condition who at the moment have no symptoms.

vCJD is caused by infectious agents called prions, which are made primarily of protein. The prions which cause vCJD are the same as those that cause bovine spongiform encephalopathy (BSE, also known as mad cow disease) in cows. Prion diseases affect the structure of the brain or other neural tissue, and all are currently untreatable and eventually fatal. Disease-causing prions are thought to consist of abnormally folded proteins that spread by encouraging the normal healthy prion protein found on the surface of most cells in the body to change shape. Prion diseases share similar disease mechanisms with Alzheimer's, Parkinson's, and other neurodegenerative brain diseases.

The 30-year-old man was admitted to hospital in June, 2008, with a 13-month history of personality change, progressive unsteadiness, and intellectual decline. He complained of severe leg pain and poor memory. Two months later he developed visual hallucinations. His symptoms worsened over the next three months. An MRI scan and other tests led to a diagnosis of vCJD. The man died in January 2009.

The case is unusual because tests showed the man had a particular genotype at his human prion protein gene (PRNP 129 codon), which can code for the amino acids valine (V) or methionine (M). People can be VV (homozygous), MM (again homozygous), or MV (heterozygous). Since 1994, around 200 cases of vCJD have been identified worldwide, and all those tested have been MM homozygous. However, the man in this Case Report was heterozygous.

Other prion diseases such as kuru or CJD associated with the use of pituitary hormones tend to have longer incubation periods in people who are PRNP heterozygous than those who are MM homozygous. The authors have recently reported some heterozygous patients with kuru had been incubating the disease over 50 years. Thus the authors believe there could be other cases like this one in which people are infected with vCJD but experiencing a long incubation period.

The authors say:

"The majority of the UK population have potentially been exposed to BSE prions but the extent of clinically silent infection remains unclear. About a third of the UK population are PRNP codon 129 methionine homozygous. If individuals with other genotypes are similarly susceptible to developing prion disease after BSE prion exposure, but with longer incubation periods, further cases, which may or may not meet diagnostic criteria for vCJD, would be expected in these PRNP codon 129 genotypes."

They conclude:

"However, prion disease susceptibility and incubation periods are also affected by other genetic loci, and the possibility remains that cases of vCJD to date may have unusual combinations of genotypes at these loci, yet to be fully characterised."

Press contact: 020 7637 6011 press.office@headoffice.mrc.ac.uk

http://www.mrc.ac.uk/Newspublications/News/MRC006556

Case Report

Variant CJD in an individual heterozygous for PRNP codon 129

Diego Kaski, Simon Mead, Harpreet Hyare, Sarah Cooper, Ravi Jampana, James Overell, Richard Knight, John Collinge, Peter Rudge

A 30-year-old man was admitted to hospital in June, 2008, with a 13-month history of personality change, progressive unsteadiness, and intellectual decline. He complained of severe leg pain and poor memory. 2 months later he de-veloped visual hallucinations and falsely believed he had an abdominal tumour. Symptoms worsened over the next 3 months. In October, 2008, his score on the mini mental state examination was 26/30. Pursuit eye movements were saccadic. He had a pout reflex. There was mild ataxia in the arms. His legs were severely ataxic with brisk tendon reflexes and a left extensor plantar response. He needed two crutches to walk. Medical history included tonsillectomy and removal of a cervical lymph node 15 years previously but he had never had a blood trans-fusion or received implantation of other human tissues.

EEG showed slow wave activity. CSF protein, glucose, and cell count were normal but the 14-3-3 protein was positive. MRI of the brain was consistent with the pulvinar sign (figure A). Although not all neuroradiologists con-sulted considered the pulvinar sign positive, quantitative assessment showed symmetrical higher signal in the pul-vinar nuclei than the caudate nuclei (figure B). Extensive screens for genetic, metabolic, and autoimmune diseases, including those induced by neoplasia, were negative. PRNP analysis did not show any known disease-associated mutations; codon 129 was heterozygous. A clinical diag-nosis of variant Creutzfeldt-Jakob disease (vCJD) was made on the basis of a characteristic clinical onset and progres-sion, exclusion of other diagnoses, and MRI findings. Sporadic CJD was judged unlikely given the combination of young age, clinical features, MRI findings, and absence of pseudoperiodic complexes on EEG. His carers did not want further investigation. His condition deteriorated and he died in January, 2009. Autopsy was not done.

Human prion diseases have acquired, sporadic, and inherited aetiologies, show wide phenotypic heterogeneity, and are associated with propagation of infectious prions of many distinct strain types.1 Since 1994, about 200 cases of vCJD, causally related to exposure to bovine spongiform encephalopathy (BSE) prions, have been identified world-wide. vCJD is generally seen in young adults, has charac-teristic neuropathological features and tissue distribution of infectivity, and a distinctive type 4 (London classifica-tion) molecular strain type.1 A polymorphism at codon 129 (encoding methionine or valine) of the human prion protein gene (PRNP), constitutes a powerful susceptibility factor in all types of prion disease. In vCJD, every case genotyped to date has been methionine homozygous. In the other acquired prion diseases, cases have occurred in all genotypes but with different mean incubation periods,1 which can span decades;2 PRNP codon 129 heterozygotes generally have the longest incubation periods. There is a report of a recipient of a blood transfusion from a donor incubating vCJD who died of unrelated causes but showed signs of prion infection at autopsy and was PRNP codon 129 heterozygous.3 Animal studies have suggested that different clinicopathological phenotypes could occur in people with various PRNP codon 129 genotypes.4,5 The majority of the UK population have potentially been exposed to BSE prions but the extent of clinically silent infection remains unclear. About a third of the UK population are PRNP codon 129 methionine homozygous. If individuals with other genotypes are similarly susceptible to developing prion disease after BSE prion exposure, but with longer incubation periods, further cases, which may or may not meet diagnostic criteria for vCJD, would be expected in these PRNP codon 129 genotypes. However, prion disease susceptibility and incubation periods are also affected by other genetic loci, and the possibility remains that cases of vCJD to date may have unusual combinations of genotypes at these loci, yet to be fully characterised.

Figure: MRI (A) Increased signal intensity in the pulvinar nucleus bilaterally (arrow). (B) MR signal intensity in the pulvinar (Pu) is higher than in the head of the caudate nuclei (C), putamen (P), and right frontal white matter (FWM).

Contributors

All authors were involved in discussion about diagnosis, care of the patient, and preparation of the report. Written consent to publish was obtained.

Conflicts of interest

JC is a director and shareholder of D-Gen Ltd, an academic spin-out company in the field of prion disease diagnosis, decontamination, and therapy. The other authors declare that they have no conflicts of interest.

References

1 Collinge J. Prion diseases of humans and animals: their causes and molecular basis. Annu Rev Neurosci 2001; 24: 519-50.

2 Collinge J, Whitfield J, McKintosh E, et al. Kuru in the 21st century-an acquired human prion disease with very long incubation periods. Lancet 2006; 367: 2068-74.

3 Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW. Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 2004; 364: 527-29.

4 Asante E, Linehan J, Gowland I, et al. Dissociation of pathological and molecular phenotype of variant Creutzfeldt-Jakob disease in transgenic human prion protein 129 heterozygous mice. Proc Natl Acad Sci USA 2006; 103: 10759-64.

5 Wadsworth JD, Asante E, Desbruslais M, et al. Human prion protein with valine 129 prevents expression of variant CJD phenotype. Science 2004; 306: 1793-96.

http://press.thelancet.com/vcjd.pdf

Monday, December 14, 2009

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

http://nor-98.blogspot.com/2009/12/similarities-between-forms-of-sheep.html

Saturday, December 05, 2009

Molecular Model of Prion Transmission to Humans

http://creutzfeldt-jakob-disease.blogspot.com/2009/12/molecular-model-of-prion-transmission.html

Tuesday, August 11, 2009

Characteristics of Established and Proposed Sporadic Creutzfeldt-Jakob Disease Variants

http://creutzfeldt-jakob-disease.blogspot.com/2009/08/characteristics-of-established-and.html

Friday, December 11, 2009

Sporadic Creutzfeldt-Jakob disease causing a 2-years slowly progressive isolated dementia

http://creutzfeldt-jakob-disease.blogspot.com/2009/12/sporadic-creutzfeldt-jakob-disease.html

Sunday, August 09, 2009

CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009

http://creutzfeldt-jakob-disease.blogspot.com/2009/08/cjdstraight-talk-withjames.html

Thursday, December 17, 2009

An Unusual Case of Variant CJD 18 December 2009

http://creutzfeldt-jakob-disease.blogspot.com/2009/12/unusual-case-of-variant-cjd-18-december.html

(American Journal of Pathology. 2009;175:2566-2573.) © 2009 American Society for Investigative Pathology DOI: 10.2353/ajpath.2009.090623

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

Wiebke M. Wemheuer*, Sylvie L. Benestad, Arne Wrede*, Ulf Schulze-Sturm*, Wilhelm E. Wemheuer, Uwe Hahmann*, Joanna Gawinecka, Ekkehard Schütz, Inga Zerr, Bertram Brenig, Bjørn Bratberg, Olivier Andréoletti¶ and Walter J. Schulz-Schaeffer* From the Prion and Dementia Research Unit,* Department of Neuropathology, and the National Transmissible Spongiform Encephalopathies Reference Center, Department of Neurology, University Medical Center Goettingen, Goettingen, Germany; the Department of Pathology, National Veterinary Institute, Oslo, Norway; the Institute of Veterinary Medicine, Faculty for Agricultural Sciences, University of Goettingen, Goettingen, Germany; and Animal Health,¶ Interactions Hôte Agent Pathogène, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France

Transmissible spongiform encephalopathies such as scrapie in sheep, Creutzfeldt-Jakob disease (CJD) in humans, and bovine sporadic encephalopathy in cattle are characterized by the accumulation of a misfolded protein: the pathological prion protein. Ever since bovine sporadic encephalopathy was discovered as the likely cause of the new variant of CJD in humans, parallels between human and animal transmissible spongiform encephalopathies must be viewed under the aspect of a disease risk for humans. In our study we have compared prion characteristics of different forms of sheep scrapie with those of different phenotypes of sporadic CJD. The disease characteristics of sporadic CJD depend considerably on the prion type 1 or 2. Our results show that there are obvious parallels between sporadic CJD type 1 and the so-called atypical/Nor98 scrapie. These parelleles apply to the deposition form of pathological prion protein in the brain, detected by the paraffin-embedded-tissue blot and the prion aggregate stability with regard to denaturation by the chaotropic salt guanidine hydrochloride. The same applies to sporadic CJD type 2 and classical scrapie. The observed parallels between types of sporadic CJD and types of sheep scrapie demonstrate that distinct groups of prion disease exist in different species. This should be taken into consideration when discussing interspecies transmission.

snip...

UPDATE ON THIS STUDY, further into this study ;

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

snip...

Different Scrapie Prion Types Show Similarities to Human Prion Types: PrPsc Deposition Pattern and Western Blot Results

After proteinase K-digestion and Western blot analysis, two different prion protein types were detectable in clinically distinct human Creutzfeldt-Jakob diseases.30 Depending on the PrPSc types 1 or 2 (Figure 1C) a difference in the form of PrPSc aggregates and the neuroanatomical distribution in the brain could be observed similar to differences identified in sheep scrapie. In patients with CJD that accumulate PrPSc type 1, reticular/synaptic were detected in cortical structures (Figure 3F), subcortical nuclei, and the cerebellar cortex (Figure 4D). By contrast, prion aggregates in patients accumulating PrPSc type 2 appeared to be complex as they displayed in particular perivacuolar, intra- and perineuronal, and/or plaque-like forms (Figures 3C and 5B). These differences concerning the deposition form of PrPSc aggregates were independent of the methionine/valine polymorphism at codon 129 of the PRNP. The topographical pattern of PrPSc distribution between these two prion types differed as follows: type 1 deposits were typically restricted to gray matter structures, while all type 2 patients showed deposits in the white matter. In patients with type 1 PrPSc the midbrain and brain stem structures were relatively spared, but in patients with type 2 PrPSc brain stem and midbrain were heavily affected. Although these prion type-related topographical differences are not completely identical to those in sheep scrapie, a comparable connection between prion type and deposition pattern is evident.

Aggregate Stability Regarding Denaturation

Similar to scrapie in sheep, the stability of PrPSc aggregates of human sporadic CJD against denaturation with GdnHCl showed two groups: denaturation-resistant and denaturation-sensitive PrPSc aggregates. This property correlated with the prion protein type according to Parchi et al8 and is independent from the physiologically occurring methionine/valine polymorphism at codon 129 of the PRNP. By membrane adsorption after GdnHCl denaturation and proteinase K-digestion, human PrPSc type 1 proved to be less stable than human PrPSc type 2. While human PrPSc type 2 was detectable up to GdnHCl concentrations between 3M and 4M, human PrPSc type 1 was stable up to 2M GdnHCl. Neither methionine nor valine at codon 129 in type 1 or type 2 seemed to alter the stability of the prion protein aggregates (Figure 5).

Summarizing the results, striking parallels between human PrPSc type 1 and atypical/Nor98 scrapie as well as human PrPSc type 2 and classical scrapie are observed with regard to PrPSc deposition and stability of the prion aggregates.

Discussion

In humans, different prion types are linked with clinically and neuropathologically distinct prion diseases.8 The present work emphasizes that the differences in deposition characteristics and stability with regard to denaturation between atypical/Nor98 and classical scrapie also account for different prion types. Moreover, the two scrapie types that have been characterized show a number of striking similarities with human PrPSc types in sporadic CJD. Hence, we propose that the existence of different PrPSc types might be a common denominator of prion diseases in humans and animals. Since these two prion types show an across-the-species comparability with similar biochemical and pathological characteristics, it is most likely that they exist due to a different conformational pattern of the disease-related prion protein.

Prion Types Depend on Conformation

The interpretation that the conformation of PrPSc accounts for prion types is supported by different proteinase K-cleavage sites of human prion types9 and the propagation of mutation-associated prion characteristics in human transgenic mice without PRNP-point mutation. 31 However, differences in protein stability as they have been found in this study, provide direct evidence for a conformational distinction between these molecules.32 Further support for the relation between type and conformation is also given by experiments focusing on the size of prion protein aggregates. Using virus removal filters, Kobayashi et al33 were able to show differences in the size of CJD type 1 and type 2 aggregates: PrPSc type 2 forms larger aggregates than PrPSc type 1, independent of whether the disease was sporadic, iatrogenic or acquired. This difference is clearly reflected by the morphology of the PrPSc depositions we have found in sheep scrapie and human CJD. Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine (reticular) deposits, whereas CJD type 2 and classical scrapie display a complex aggregate pattern, regardless of the respective genotypes at the polymorphic positions of the PRNP that were investigated.

Prion Type Characteristics Versus Prion Strain Characteristics

Structural differences of the disease-associated protein have also been proposed as an explanation for the existence of strains. Partial digestion of the disease-associated protein with proteinase K as well as differences in antibody binding after the protein was partially denatured were used to identify structural characteristics in correlation with strain properties and different clinical TSE forms.23,34,35 It needs to be considered that the kinetics of proteinase K-digestion of PrPSc are markedly influenced by detergent effects in the buffer, demonstrating that the accessibility of the cleavage sites are variable.35 In contrast, differences in the stability against total unfolding of PrPSc seem to be a usable criterion to identify conformational differences or conformational motives. Whereas detergents affect the tertiary structure of a protein by interacting with hydrophilic and hydrophobic areas of protein molecules, chaotropic salts like GdnHCl destroy the hydrogen bonds in -helices and -sheets leading to an irregular coiled polypeptide chain.36 This is in line with the observation that detergents remove prion infectivity only partially, whereas chemicals that destroy secondary structures like chaotropic salts are highly effective. 37 However, detectable differences regarding the stability against denaturation with GdnHCl shown for various prion strains in hamsters seem to be very small compared with the ones that can be shown here for the prion types of human and ovine prion diseases. Strains could thus correspond to structural differences that are less marked than those defining types and are probably constant only under defined conditions. Influences of polymorphisms or interactions with other genetic factors like the promotor region, species-specific factors like the recently detected incorporation of polyanionic molecules into prions,38 glycosaminoglycans or other yet unknown factors of the original host may also lead to different strains in a new host within the prion types of the original species.5,39 The existence of prion types does not exclude the existence of strains. The same variations that account for strains might be the reason for differences in the clinical disease course of the natural host.

Two Different Prion Types also in BSE?

Parallel to human sporadic CJD and our results in sheep scrapie, there is increasing evidence that two prion types also exist in cattle BSE. Two presumably sporadic forms of BSE known as H-type BSE14 and bovine amyloidotic spongiform encephalopathy, also called L-type BSE,15 have been described in cattle in addition to typical/classical BSE.40 The small variation in the apparent molecular weight of the unglycosylated band of bovine amyloidotic spongiform encephalopathy is considered to be well within the range of classical BSE,41,42 which would leave H-type BSE with a considerably larger unglycosylated fragment in Western blot analysis than the second BSE type. Interestingly, bovine amyloidotic spongiform encephalopathy converts into classical BSE after serial passages in bovine-transgenic mice,43 although displaying clinically different diseases in cattle.44 From the latter experiment the authors concluded that different strains were responsible for different phenotypes. Obviously the different clinical diseases were generated by agents that belong to a single prion type. These results together with our observations emphasize the need to differentiate strictly between prion types and prion strains and demonstrate that even in cattle BSE, one prion type may contain different prion strains.

Prion Type Displays Parallels in the Pathophysiology of Disease between Species

Biochemical and morphological similarities have been used to draw parallels between forms of BSE and human prion diseases.15 Parallels between species can also be observed with regard to the route of prion infection: in classical BSE, variant CJD, and classical scrapie, all of which presumably belong to one class of prion type (type 2 in humans) according to the observations made above, the oral route of infection has been identified. These TSEs use the dorsal motor nucleus of the vagus nerve as an entry site into the brain.29,45,46 This observation suggests that distinct prion types in human and animal TSEs possibly have an impact on the pathogenesis of prion diseases.

Conclusion

As the prion protein is a highly conserved protein in terms of evolution, parallels between characteristics of prion types in TSEs of different species are of interest. In the present study, we report previously unknown similarities between sheep scrapie forms and human sporadic CJD types. We propose that the observed similarities between sheep scrapie and sporadic CJD in humans justify new interspecies groups of prion diseases in which prion types, not prion strains, are the major determinant for prion disease forms. While epidemiology implies that classical scrapie is not related to human TSEs,47 the atypical/Nor98 scrapie risk for human transmission has not yet been elucidated. Currently there is no compelling evidence that sCJD has a different origin than sporadic genesis. However, the finding of prion types with an across-the-species comparability might provide further understanding of the pathogenesis in prion diseases.

Acknowledgments We thank Tatjana Pfander, Nadine Rupprecht, and Kerstin Brekerbohm for their skillful technical assistance.

http://ajp.amjpathol.org/cgi/content/abstract/175/6/2566

hmmm, this is getting interesting now...

Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine (reticular) deposits,

see also ;

All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.

http://cjdusa.blogspot.com/2009/09/co-existence-of-scrapie-prion-protein.html

Tuesday, July 29, 2008

Heidenhain Variant Creutzfeldt Jakob Disease Case Report

snip...

Heidenhain Variant Creutzfeldt Jakob Disease autopsy case report 'MOM'

DIVISION OF NEUROPATHOLOGY University of Texas Medical Branch 114 McCullough Bldg. Galveston, Texas 77555-0785

FAX COVER SHEET

DATE: 4-23-98

TO: Mr. Terry Singeltary @ -------

FROM: Gerald Campbell

FAX: (409) 772-5315 PHONE: (409) 772-2881

Number of Pages (including cover sheet):

Message:

*CONFIDENTIALITY NOTICE*

This document accompanying this transmission contains confidential information belonging to the sender that is legally privileged. This information is intended only for the use of the individual or entry names above. If you are not the intended recipient, you are hereby notified that any disclosure, copying distribution, or the taking of any action in reliances on the contents of this telefaxed information is strictly prohibited. If you received this telefax in error, please notify us by telephone immediately to arrange for return of the original documents. -------------------------- Patient Account: 90000014-518 Med. Rec. No.: (0160)118511Q Patient Name: POULTER, BARBARA Age: 63 YRS DOB: 10/17/34 Sex: F Admitting Race: C

Attending Dr.: Date / Time Admitted : 12/14/97 1228 Copies to:

UTMB University of Texas Medical Branch Galveston, Texas 77555-0543 (409) 772-1238 Fax (409) 772-5683 Pathology Report

FINAL AUTOPSY DIAGNOSIS Autopsy' Office (409)772-2858

Autopsy NO.: AU-97-00435

AUTOPSY INFORMATION: Occupation: Unknown Birthplace: Unknown Residence: Crystal Beach Date/Time of Death: 12/14/97 13:30 Date/Time of Autopsy: 12/15/97 15:00 Pathologist/Resident: Pencil/Fernandez Service: Private Restriction: Brain only

FINAL AUTOPSY DIAGNOSIS

I. Brain: Creutzfeldt-Jakob disease, Heidenhain variant.

snip...see full text ;

http://creutzfeldt-jakob-disease.blogspot.com/2008/07/heidenhain-variant-creutzfeldt-jakob.html

P.5.21

Parallels between different forms of sheep scrapie and types of Creutzfeldt-Jakob disease (CJD)

Wiebke M. Wemheuer1, Sylvie L. Benestad2, Arne Wrede1, Wilhelm E. Wemheuer3, Tatjana Pfander1, Bjørn Bratberg2, Bertram Brenig3,Walter J. Schulz-Schaeffer1 1University Medical Center Goettingen, Germany; 2Institute of Veterinary Medicine Oslo, Norway; 3Institute of Veterinary Medicine Goettingen, Germany

Background: Scrapie in sheep and goats is often regarded as the archetype of prion diseases. In 1998, a new form of scrapie - atypical/Nor98 scrapie - was described that differed from classical scrapie in terms of epidemiology, Western blot profile, the distribution of pathological prion protein (PrPSc) in the body and its stability against proteinase K. In a similar way, distinct disease types exist in sporadic Creutzfeldt-Jakob disease (CJD). They differ with regard to their clinical outcome, Western blot profile and PrPSc deposition pattern in the central nervous system (CNS).

Objectives: The comparison of PrPSc deposits in sheep scrapie and human sporadic CJD.

Methods: Tissues of the CNS of sheep with classical scrapie, sheep with atypical/Nor98 scrapie and 20 patients with sporadic CJD were examined using the sensitive Paraffin Embedded Tissue (PET) blot method. The results were compared with those obtained by immunohistochemistry. With the objective of gaining information on the protein conformation, the PrPSc of classical and atypical/Nor98 sheep scrapie and sporadic CJD was tested for its stability against denaturation with guanidine hydrochloride (GdnHCl) using a Membrane Adsorption Assay.

Results: The PrPSc of atypical/Nor98 scrapie cases and of CJD prion type 1 patients exhibits a mainly reticular/synaptic deposition pattern in the brain and is relatively sensitive to denaturation with GdnHCl. In contrast classical scrapie cases and CJD prion type 2 patients have a more complex PrPSc deposition pattern in common that consists of larger PrPSc aggregates and the PrPSc itself is comparatively stable against denaturation.

Discussion: The similarity between CJD types and scrapie types indicates that at least two comparable forms of the misfolded prion protein exist beyond species barriers and can elicit prion diseases. It seems therefore reasonable to classify classical and atypical/Nor98 scrapie - in analogy to the existing CJD types - as different scrapie types.

http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf

Monday, November 30, 2009

USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE

http://nor-98.blogspot.com/2009/11/usda-and-oie-collaborate-to-exclude.html

Monday, December 1, 2008

When Atypical Scrapie cross species barriers

http://nor-98.blogspot.com/2008/12/when-atypical-scrapie-cross-species.html

EVIDENCE OF SCRAPIE IN SHEEP AS A RESULT OF FOOD BORNE EXPOSURE

This is provided by the statistically significant increase in the incidence of sheep scrape from 1985, as determined from analyses of the submissions made to VI Centres, and from individual case and flock incident studies. ........

http://web.archive.org/web/20010305222246/www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf

1: J Infect Dis 1980 Aug;142(2):205-8

Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.

snip...

The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.

PMID: 6997404

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract

12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY

snip...

A The Present Position with respect to Scrapie A] The Problem

Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries.

The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep.

It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible.

Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"

Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.

snip...

76/10.12/4.6

http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf

Nature. 1972 Mar 10;236(5341):73-4.

Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis). Gibbs CJ Jr, Gajdusek DC.

Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)

C. J. GIBBS jun. & D. C. GAJDUSEK

National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland

SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).

http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.html

Epidemiology of Scrapie in the United States 1977

http://web.archive.org/web/20030513212324/http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf

Tuesday, April 28, 2009

Nor98-like Scrapie in the United States of America

http://nor-98.blogspot.com/2009/04/nor98-like-scrapie-in-united-states-of.html

Scrapie USA

http://scrapie-usa.blogspot.com/

Like lambs to the slaughter 31 March 2001 by Debora MacKenzie Magazine issue 2284

FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.

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 ...

http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html

R.I.P. MOM hvCJD confirmed DECEMBER 14, 1997

Monday, December 14, 2009

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

http://nor-98.blogspot.com/2009/12/similarities-between-forms-of-sheep.html

Tuesday, August 18, 2009

BSE-The Untold Story - joe gibbs and singeltary 1999 - 2009 Greetings,

http://madcowusda.blogspot.com/2009/08/bse-untold-story-joe-gibbs-and.html

Wednesday, December 30, 2009

Is there evidence of vertical transmission of variant CJD ?

http://creutzfeldt-jakob-disease.blogspot.com/2009/12/is-there-evidence-of-vertical.html

Alzheimer's and CJD

http://betaamyloidcjd.blogspot.com/

Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA

Friday, January 01, 2010

Human Prion Diseases in the United States

http://creutzfeldt-jakob-disease.blogspot.com/2010/01/human-prion-diseases-in-united-states.html

-------------------- BSE-L@LISTS.AEGEE.ORG --------------------

No competing interests declared.

see full text ;

http://www.plosone.org/annotation/listThread.action?inReplyTo=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd&root=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd

http://www.plosone.org/annotation/listThread.action?inReplyTo=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd&root=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd

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. FREE FULL TEXT

http://jama.ama-assn.org/cgi/content/extract/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

http://jama.ama-assn.org/cgi/content/full/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

2 January 2000

British Medical Journal

U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well

http://www.bmj.com/cgi/eletters/320/7226/8/b#6117

15 November 1999

British Medical Journal

vCJD in the USA * BSE in U.S.

http://www.bmj.com/cgi/eletters/319/7220/1312/b#5406

Saturday, January 2, 2010

Human Prion Diseases in the United States January 1, 2010 ***FINAL***

http://prionunitusaupdate2008.blogspot.com/2010/01/human-prion-diseases-in-united-states.html

Manuscript Draft Manuscript Number: Title: HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory Article Type: Personal View Corresponding Author: Mr. Terry S. Singeltary, Corresponding Author's Institution: na First Author: Terry S Singeltary, none Order of Authors: Terry S Singeltary, none; Terry S. Singeltary Abstract: TSEs have been rampant in the USA for decades in many species, and they all have been rendered and fed back to animals for human/animal consumption. 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 2007.

http://www.regulations.gov/fdmspublic/ContentViewer?objectId=090000648027c28e&disposition=attachment&contentType=pdf

2011 NOVEMBER

Oral.42: Prion Seeding Activity in Cerebrospinal Fluid from Sporadic Creutzfeldt-Jakob Disease Patients Using Real-Time QuIC Analysis: A Potential New Diagnostic Test?

Lynne I. McGuire,1,† Alexander H. Peden,1 Nigel Appleford,2 Gary Mallinson,2 Christina Orru,3 Jason Wilham,3 Greg Raymond,3 Mary Andrews,1 Mark W. Head,1 Byron Caughey,3 Robert Will,1 Richard Knight1 and Alison Green,1

1 NCJDSU, University of Edinburgh; Edinburgh, UK; 2 Bristol Institute for Transfusion Sciences, NHS Blood and Transplant; Bristol, UK; 3 Laboratory of Persistent Viral Disease, NIAID Rocky Mountain Laboratories, National Institutes of Health; Hamilton, MT USA†Presenting author; Email: lmcguir1@staffmail.ed.ac.uk

Since its introduction into the diagnostic criteria for sporadic CJD in 1998, the analysis of cerebrospinal fluid (CSF) for 14-3-3 has become a widely accepted investigation in patients with suspected sporadic CJD. However, a number of reports have raised concerns about its lack of specificity. This has prompted the search for a more specific and disease-related pre-mortem diagnostic test for sporadic CJD. The ability of PrPSc to convert PrPC into protease-resistance isoforms has been exploited using a variety of techniques such as protein misfolding cyclic amplification (PMCA) and quaking induced conversion (QuIC). A recent adaptation of QuIC (real-time QuIC) has been described which incorporates thioflavin T (ThT) in the reaction mixture. The ThT binds to the aggregated PrP causing a change in the ThT emission spectrum that can be monitored in real-time. Recent studies have shown that CSF samples from hamsters inoculated with experimental scrapie, sheep with scrapie and patients with sporadic CJD can be correctly identified using real-time QuIC.1,2 We now describe the findings of an investigation into the value of real-time QuIC in the diagnosis of sCJD. A blinded panel of CSF samples from 56 neuropathologically confirmed cases of sCJD and from 53 patients who were initially suspected of having sCJD but who were found to have an alternative diagnosis were analyzed. Of the 56 patients with sCJD 51 were found to give a positive response with real-time QuIC. In contrast only one patient from the control group was found to be positive. The sensitivity and specificity was 91% and 98%, respectively. The corresponding sensitivity and specificity of CSF 14-3-3 was 91% and 55%, respectively. These results suggest that real-time QuIC has the potential to be a more specific pre-mortem CSF test for sCJD than CSF 14-3-3.

References

1. Atarashi R, Satoh K, Sano K, Fuse T, Yamanaka H, Yamaguchi N, et al. Ultrasensitive human prion detection in cerebrospinal fluids by real-time quaking induced conversion. Prion 2010; 4:214

2. Wilham JM, Orru CD, Benssen RA, Atarashi R, Sano K, Race B, et al. Rapid end-point quantitation of prion seeding activity with sensitivity comparable to bioassays. PLoS 2010; 6:1-15

http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION AKA MAD COW, BSE, CJD, CWD, SCRAPIE UPDATE

P.9.21

Molecular characterization of BSE in Canada

Jianmin Yang1, Sandor Dudas2, Catherine Graham2, Markus Czub3, Tim McAllister1, Stefanie Czub1 1Agriculture and Agri-Food Canada Research Centre, Canada; 2National and OIE BSE Reference Laboratory, Canada; 3University of Calgary, Canada

Background: Three BSE types (classical and two atypical) have been identified on the basis of molecular characteristics of the misfolded protein associated with the disease. To date, each of these three types have been detected in Canadian cattle.

Objectives: This study was conducted to further characterize the 16 Canadian BSE cases based on the biochemical properties of there associated PrPres. Methods: Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases was determined using modified Western blot analysis.

Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and changes in glycosylation similar to other atypical BSE cases. PK digestion under mild and stringent conditions revealed a reduced protease resistance of the atypical cases compared to the C-type cases. N terminal- specific antibodies bound to PrPres from H type but not from C or L type. The C-terminal-specific antibodies resulted in a shift in the glycoform profile and detected a fourth band in the Canadian H-type BSE.

Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada.

*** It also suggests a similar cause or source for atypical BSE in these countries.

http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf

STRICTLY PRIVATE AND CONFIDENTIAL 25, AUGUST 1995

snip...

To minimise the risk of farmers' claims for compensation from feed compounders.

To minimise the potential damage to compound feed markets through adverse publicity.

To maximise freedom of action for feed compounders, notably by maintaining the availability of meat and bone meal as a raw material in animal feeds, and ensuring time is available to make any changes which may be required.

snip...

THE FUTURE

4..........

MAFF remains under pressure in Brussels and is not skilled at handling potentially explosive issues.

5. Tests _may_ show that ruminant feeds have been sold which contain illegal traces of ruminant protein. More likely, a few positive test results will turn up but proof that a particular feed mill knowingly supplied it to a particular farm will be difficult if not impossible.

6. The threat remains real and it will be some years before feed compounders are free of it. The longer we can avoid any direct linkage between feed milling _practices_ and actual BSE cases, the more likely it is that serious damage can be avoided. ...

SEE full text ;

http://web.archive.org/web/20060517074958/http://www.bseinquiry.gov.uk/files/yb/1995/08/24002001.pdf

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)

http://prionpathy.blogspot.com/2010/08/bse-case-associated-with-prion-protein.html

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

RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II

___________________________________

PRODUCT

Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007

CODE

Cattle feed delivered between 01/12/2007 and 01/26/2007

RECALLING FIRM/MANUFACTURER

Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.

Firm initiated recall is ongoing.

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

___________________________________

PRODUCT

Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007

CODE

The firm does not utilize a code - only shipping documentation with commodity and weights identified.

RECALLING FIRM/MANUFACTURER

Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete.

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

http://www.fda.gov/Safety/Recalls/EnforcementReports/2007/ucm120446.htm

Monday, September 12, 2011

BSE PRION Agriculture Animal Feed Question House of Lords Thursday, 8 September 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/09/bse-prion-agriculture-animal-feed.html

Saturday, July 23, 2011

CATTLE HEADS WITH TONSILS, BEEF TONGUES, SPINAL CORD, SPECIFIED RISK MATERIALS (SRM's) AND PRIONS, AKA MAD COW DISEASE

http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/cattle-heads-with-tonsils-beef-tongues.html

Saturday, November 6, 2010

TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU Berne, 2010 TAFS

INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation

http://madcowfeed.blogspot.com/2010/11/tafs1-position-paper-on-position-paper.html

Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject PRO/AH/EDR; Prion disease update 2010 (11)

PRION DISEASE UPDATE 2010 (11)

http://www.promedmail.org/direct.php?id=20101206.4364

Saturday, June 25, 2011

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque

"BSE-L in North America may have existed for decades"

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html

Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.

snip...

The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...

http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf

Sunday, June 26, 2011

Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/risk-analysis-of-low-dose-prion.html

MAD COW DISEASE, TEXAS STYLE

http://www.organicconsumers.org/articles/article_23850.cfm

Wednesday, June 15, 2011

Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html

Sunday, May 01, 2011

STUDY OF ATYPICAL BSE 2010 Annual Report May 2011

http://bse-atypical.blogspot.com/2011/05/study-of-atypical-bse-2010-annual.html

Thursday, February 10, 2011

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY REPORT UPDATE CANADA FEBRUARY 2011 and how to hide mad cow disease in Canada Current as of: 2011-01-31

http://madcowtesting.blogspot.com/2011/02/transmissible-spongiform-encephalopathy.html

Friday, February 18, 2011

UNITED STATES OF AMERICA VS GALEN J. NIEHUES FAKED MAD COW FEED TEST ON 92 BSE INSPECTION REPORTS FOR APPROXIMATELY 100 CATTLE OPERATIONS ''PLEADS GUILTY"

http://bse-atypical.blogspot.com/2011/02/united-states-of-america-vs-galen-j.html

Wednesday, November 17, 2010

MAD COW TESTING FAKED IN USA BY Nebraska INSPECTOR Senator Mike Johanns STATE

http://madcowtesting.blogspot.com/2010/11/mad-cow-testing-faked-in-usa-by.html

Wednesday, February 16, 2011

IN CONFIDENCE

SCRAPIE TRANSMISSION TO CHIMPANZEES

IN CONFIDENCE

http://scrapie-usa.blogspot.com/2011/02/in-confidence-scrapie-transmission-to.html

Sunday, April 18, 2010

SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010

http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html

Monday, April 25, 2011

Experimental Oral Transmission of Atypical Scrapie to Sheep

Volume 17, Number 5-May 2011

http://nor-98.blogspot.com/2011/04/experimental-oral-transmission-of.html

Monday, November 30, 2009

USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE

http://nor-98.blogspot.com/2009/11/usda-and-oie-collaborate-to-exclude.html

Monday, June 27, 2011

Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates

http://chronic-wasting-disease.blogspot.com/2011/06/zoonotic-potential-of-cwd-experimental.html

Wednesday, September 21, 2011

Evidence for distinct CWD strains in experimental CWD in ferrets

http://chronic-wasting-disease.blogspot.com/2011/09/evidence-for-distinct-cwd-strains-in.html

UPDATED DATA ON 2ND CWD STRAIN

Wednesday, September 08, 2010

CWD PRION CONGRESS SEPTEMBER 8-11 2010

http://chronic-wasting-disease.blogspot.com/2010/09/cwd-prion-2010.html

Wednesday, January 5, 2011

ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011

Prions

David W. Colby1,* and Stanley B. Prusiner1,2

http://betaamyloidcjd.blogspot.com/2011/01/enlarging-spectrum-of-prion-like.html

Wednesday, July 06, 2011

Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation

http://chronic-wasting-disease.blogspot.com/2011/07/swine-are-susceptible-to-chronic.html

Thursday, April 03, 2008

A prion disease of cervids: Chronic wasting disease

2008 1: Vet Res. 2008 Apr 3;39(4):41

A prion disease of cervids: Chronic wasting disease

Sigurdson CJ.

snip...

*** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,

snip...

full text ;

http://chronic-wasting-disease.blogspot.com/2008/04/prion-disease-of-cervids-chronic.html

1989

IN CONFIDENCE

Perceptions of unconventional slow virus diseases of animals in the USA

Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or about that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep. Whether they were scrapie infected sheep or not is unclear.

http://collections.europarchive.org/tna/20080102193705/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf

http://wildlife.state.co.us/NR/rdonlyres/C82EB818-90C6-4D85-897E-9CE279546CCB/0/JWDEpiCWD.pdf

CJD9/10022

October 1994

Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane BerksWell Coventry CV7 7BZ

Dear Mr Elmhirst,

CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT

Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published.

The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication.

The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department.

The statistical results reqarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme.

I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all.

http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf

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.

http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf

Monday, May 23, 2011

Atypical Prion Diseases in Humans and Animals 2011

Top Curr Chem (2011)

DOI: 10.1007/128_2011_161

# Springer-Verlag Berlin Heidelberg 2011

Michael A. Tranulis, Sylvie L. Benestad, Thierry Baron, and Hans Kretzschmar

Abstract

Although prion diseases, such as Creutzfeldt-Jakob disease (CJD) in humans and scrapie in sheep, have long been recognized, our understanding of their epidemiology and pathogenesis is still in its early stages. Progress is hampered by the lengthy incubation periods and the lack of effective ways of monitoring and characterizing these agents. Protease-resistant conformers of the prion protein (PrP), known as the "scrapie form" (PrPSc), are used as disease markers, and for taxonomic purposes, in correlation with clinical, pathological, and genetic data. In humans, prion diseases can arise sporadically (sCJD) or genetically (gCJD and others), caused by mutations in the PrP-gene (PRNP), or as a foodborne infection, with the agent of bovine spongiform encephalopathy (BSE) causing variant CJD (vCJD). Person-to-person spread of human prion disease has only been known to occur following cannibalism (kuru disease in Papua New Guinea) or through medical or surgical treatment (iatrogenic CJD, iCJD). In contrast, scrapie in small ruminants and chronic wasting disease (CWD) in cervids behave as infectious diseases within these species. Recently, however, so-called atypical forms of prion diseases have been discovered in sheep (atypical/Nor98 scrapie) and in cattle, BSE-H and BSE-L. These maladies resemble sporadic or genetic human prion diseases and might be their animal equivalents. This hypothesis also raises the significant public health question of possible epidemiological links between these diseases and their counterparts in humans.

M.A. Tranulis (*)

Norwegian School of Veterinary Science, Oslo, Norway

e-mail: Michael.Tranulis@nvh.no

S.L. Benestad

Norwegian Veterinary Institute, Oslo, Norway

T. Baron

Agence Nationale de Se´curite´ Sanitaire, ANSES, Lyon, France

H. Kretzschmar

Ludwig-Maximilians University of Munich, Munich, Germany

Keywords Animal Atypical Atypical/Nor98 scrapie BSE-H BSE-L Human Prion disease Prion strain Prion type

http://resources.metapress.com/pdf-preview.axd?code=f433r34h34ugg617&size=largest

Wednesday, March 31, 2010

Atypical BSE in Cattle

To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE.

In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2

Thursday, August 12, 2010

Seven main threats for the future linked to prions

First threat

The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.

***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.

Second threat

snip...

http://www.neuroprion.org/en/np-neuroprion.html

Rural and Regional Affairs and Transport References Committee

The possible impacts and consequences for public health, trade and agriculture of the Government’s decision to relax import restrictions on beef Final report June 2010

2.66 Dr Fahey also told the committee that in the last two years a link has been established between forms of atypical CJD and atypical BSE. Dr Fahey said that: They now believe that those atypical BSEs overseas are in fact causing sporadic Creutzfeldt-Jakob disease. They were not sure if it was due to mad sheep disease or a different form. If you look in the textbooks it looks like this is just arising by itself. But in my research I have a summary of a document which states that there has never been any proof that sporadic Creutzfeldt-Jakob disease has arisen de novo—has arisen of itself. There is no proof of that. The recent research is that in fact it is due to atypical forms of mad cow disease which have been found across Europe, have been found in America and have been found in Asia. These atypical forms of mad cow disease typically have even longer incubation periods than the classical mad cow disease.50

http://www.aph.gov.au/senate/committee/rrat_ctte/mad_cows/report/report.pdf

Terry S. Singeltary Sr. has added the following comment:

"According to the World Health Organisation, the future public health threat of vCJD in the UK and Europe and potentially the rest of the world is of concern and currently unquantifiable. However, the possibility of a significant and geographically diverse vCJD epidemic occurring over the next few decades cannot be dismissed.

The key word here is diverse. What does diverse mean? If USA scrapie transmitted to USA bovine does not produce pathology as the UK c-BSE, then why would CJD from there look like UK vCJD?"

http://www.promedmail.org/direct.php?id=20100405.1091

When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2

The conclusions state that, at present, the only TSE agent demonstrated to be zoonotic is the classical BSE agent. Active screening has allowed the identification of 3 new forms of animal TSEs (H-type atypical BSE, L-type atypical BSE, and atypical scrapie), but the information obtained has major limitations due to the unknown sensitivity of the current monitoring system for these TSEs. There is no epidemiological evidence to suggest that classical scrapie is zoonotic. The epidemiological data are too limited to conclude whether the atypical scrapie agent has a zoonotic potential. Transmission experiments to human PrP transgenic mice or primates suggest that some TSE agents other than the classical BSE agent in cattle (namely L-type atypical BSE, classical BSE in sheep, TME, CWD agents) might have zoonotic potential and indicate that that of the L-type atypical BSE agent appears similar or even higher than that of the classical BSE agent. A single study reported efficient transmission of a natural sheep classical scrapie isolate to primates.

Commentary ---------- Following to a request from the European Commission, the Panel on Biological Hazards (BIOHAZ) and the European Centre for Disease Prevention and Control (ECDC) were asked to deliver a scientific opinion on any possible epidemiological or molecular association between transmissible spongiform encephalopathies (TSEs) in animals and humans. The opinion reviews and discusses the existing scientific evidence that links animal and human TSEs currently known.

The opinion first considers the definition of zoonoses and the principles for the identification of zoonotic diseases, which can be based on evidence gathered from both epidemiological and laboratory studies. The opinion describes the challenges involved in identifying TSEs as zoonoses, due to the specific characteristics of TSE infections/diseases, such as the nature of TSE agents, the occurrence of animal and human TSEs, and the type of monitoring applied, the long incubation period of TSEs etc. The example of the process that led to establishing a link between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) is reviewed. The epidemiological and laboratory criteria that can be used to investigate such a link are described in detail, since those criteria might be useful for the identification of links between other animal and human TSEs.

The opinion discusses the strain diversity of the TSE agents described in sheep, goats, cattle, cervids, and humans, based on the current knowledge, which highlights that multiple TSE agents exist in each species. The factors influencing the capacity of TSE agents to cross the species transmission barrier are then considered in detail, including the variability in host and donor PrP gene and protein, the TSE strain type involved and its interaction with the host PrP, and the route of infection.

The opinion critically assesses the tools and methodologies currently available to study and evaluate the possible association between animal and human TSEs. The use of epidemiology is discussed for TSEs in both animals and humans, and the possibility to compare the 2 sources of information is presented as a possible method to study the possible links.

Both in vivo and in vitro laboratory methods are considered and discussed, including neuropathology, transmission experiments involving different animal models (wild type and transgenic mice, primates and other species), biochemical methods, cell-free conversion assays, protein misfolding cyclic amplification (PMCA), and cell culture assays. Characteristics, advantages, and disadvantages of the different methods are reviewed, including the opportunity to collate data from different types of experiments for the study of potential associations between animal and human TSEs.

The opinion then reviews the scientific evidence currently available for the different animal and human TSEs, including classical BSE, atypical BSE (H-type and L-type), classical scrapie, atypical scrapie, chronic wasting disease (CWD), transmissible mink encephalopathy (TME), and human TSEs. In particular, the following aspects are systematically discussed for each TSE agent: epidemiology, pathogenesis, and in vivo and in vitro transmission experiments.

The opinion concludes that, at present, the only TSE agent demonstrated to be zoonotic is the classical BSE agent. With regard to human TSEs, detected cases of sporadic CJD are randomly distributed in time and geographical location. These observations have been interpreted as a supportive argument that sporadic CJD is not environmentally acquired. However, the epidemiological evidence in relation to sporadic CJD cannot be regarded as definitive, and the possibility that a small proportion of cases are zoonotic cannot be excluded.

It also concludes that a series of uncertainties in relation to the epidemiological patterns of animal and human TSEs indicate that even a rough comparison of the present epidemiological patterns of human and animal TSEs other than classical BSE is unlikely to be informative. Because of these uncertainties, it is an imperative to continue to carry out systematic surveillance of human TSE diseases, and to continue and improve the surveillance of animal TSE diseases.

The opinion highlights that the active screening has allowed the identification of 3 new forms of animal TSEs (L-type atypical BSE, H-type atypical BSE, and atypical scrapie), but that the information obtained has major limitations due to the unknown sensitivity of the current monitoring system for these TSEs.

There is no epidemiological evidence to suggest that classical scrapie is zoonotic. The epidemiological data are too limited to conclude whether the atypical scrapie agent has a zoonotic potential.

Transmission experiments to human PrP transgenic mice suggest that some TSE agents other than the classical BSE agent in cattle (namely L-type atypical BSE and classical BSE in sheep agents) might have zoonotic potential, whereas for other agents there is no evidence provided of a zoonotic potential (H-type atypical BSE and CWD), or no published studies are available (classical and atypical scrapie). In addition, transmission experiments to primates suggest that some TSE agents other than the classical BSE agent in cattle (namely L-type atypical BSE, classical BSE in sheep, TME, CWD agents) might have zoonotic potential. In particular, primates are highly permissive to L-type atypical BSE, even by the oral route.

The opinion emphasizes that laboratory transmission experiments indicate that the L-type atypical BSE agent has a significant zoonotic potential, which appears similar or even higher than that of the classical BSE agent. While transmission data for evaluating the zoonotic potential of classical scrapie in primates and human PrP transgenic mice are extremely limited or not yet available, a single study reported efficient transmission of a natural sheep classical scrapie isolate to primates.

The opinion concludes that human PrP transgenic mice and primates are currently the most relevant models for investigating the human transmission barrier, but the extent to which such models are informative for measuring the zoonotic potential of an animal TSE under field exposure conditions is unknown. It is unpredictable whether a TSE agent will transmit to a new host, and if the transmission principally occurs, what the transmission rate will be.

Based on the results obtained with in vitro conversion assays, the opinion concludes that there is probably no absolute molecular barrier to transmission of TSE agents between mammalian species. Results also suggest that these assays may be developed as a tool for quantifying the transmission barriers between species for different TSE agent strains; however, there is no means at the moment to transpose in vitro results into the likelihood of in vivo interspecies transmission.

-- Communicated by: Terry S Singeltary Sr

[ProMED-mail thanks Terry S Singeltary Sr for drawing attention to this comprehensive document which provides a current evaluation of experimental work designed to explore the zoonotic potential of the various recently recognised TSEs of domestic and other animals.

It is concluded that at present the only TSE agent demonstrated to be zoonotic is the classical BSE agent. Nor can it be entirely excluded at the present time that a small proportion of cases of sporadic CJD may be environmentally acquired. - Mod.CP]

******

http://www.promedmail.org/direct.php?id=20110607.1736

U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ? (see video at bottom)

http://creutzfeldt-jakob-disease.blogspot.com/2009/07/usa-hiding-mad-cow-disease-victims-as.html

2006

USA sporadic CJD cases rising ;

There is a growing number of human CJD cases, and they were presented last week in San Francisco by Luigi Gambatti(?) from his CJD surveillance collection.

He estimates that it may be up to 14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins.

http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm

http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf

2008

The statistical incidence of CJD cases in the United States has been revised to reflect that there is one case per 9000 in adults age 55 and older. Eighty-five percent of the cases are sporadic, meaning there is no known cause at present.

http://www.cjdfoundation.org/fact.html

CJD USA RISING, with UNKNOWN PHENOTYPE ;

5 Includes 41 cases in which the diagnosis is pending, and 17 inconclusive cases;

*** 6 Includes 46 cases with type determination pending in which the diagnosis of vCJD has been excluded.

http://www.cjdsurveillance.com/pdf/case-table.pdf

Thursday, August 4, 2011

Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011 (SEE VIDEO)

http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html

Sunday, August 21, 2011

The British disease, or a disease gone global, The TSE Prion Disease (SEE VIDEO)

http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/british-disease-or-disease-gone-global.html

Saturday, March 5, 2011

MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html

Friday, November 04, 2011

Diagnostic accuracy of cerebrospinal fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada: a 6-year prospective study Research article

http://creutzfeldt-jakob-disease.blogspot.com/2011/11/diagnostic-accuracy-of-cerebrospinal.html

WHO WILL FOLLOW THE CHILDREN FOR CJD SYMPTOMS ???

Saturday, May 2, 2009

U.S. GOVERNMENT SUES WESTLAND/HALLMARK MEAT OVER USDA CERTIFIED DEADSTOCK DOWNER COW SCHOOL LUNCH PROGRAM

http://downercattle.blogspot.com/2009/05/us-government-sues-westlandhallmark.html

http://downercattle.blogspot.com/

Tuesday, October 4, 2011

De novo induction of amyloid-ß deposition in vivo

Molecular Psychiatry advance online publication 4 October 2011; doi: 10.1038/mp.2011.120

Molecular Psychiatry advance online publication 4 October 2011; doi: 10.1038/mp.2011.120

De novo induction of amyloid-ß deposition in vivo

R Morales1,2, C Duran-Aniotz1,3, J Castilla2,4, L D Estrada2,5 and C Soto1,2

1Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, TX, USA 2University of Texas Medical Branch at Galveston, Galveston, TX, USA 3Universidad de Los Andes, Facultad de Medicina. Av. San Carlos de Apoquindo 2200, Las Condes, Santiago, Chile 4CIC bioGUNE, Parque Tecnologico de Biskaia, Ed 800, 48160 Derio and IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain

Correspondence: Dr C Soto, Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, 6431 Fannin St, Houston, TX 77030, USA. E-mail: Claudio.Soto@uth.tmc.edu

5Current address: Laboratorio de Señalización Celular, Centro de Envejecimiento y Regeneración. P. Universidad Catolica de Chile, Santiago, Chile.

Received 8 March 2011; Revised 15 August 2011; Accepted 25 August 2011; Published online 4 October 2011.

Abstract

Alzheimer's disease (AD), the most common type of senile dementia, is associated to the build-up of misfolded amyloid-ß (Aß) in the brain. Although compelling evidences indicate that the misfolding and oligomerization of Aß is the triggering event in AD, the mechanisms responsible for the initiation of Aß accumulation are unknown. In this study, we show that Aß deposition can be induced by injection of AD brain extracts into animals, which, without exposure to this material, will never develop these alterations. The accumulation of Aß deposits increased progressively with the time after inoculation, and the Aß lesions were observed in brain areas far from the injection site. Our results suggest that some of the typical brain abnormalities associated with AD can be induced by a prion-like mechanism of disease transmission through propagation of protein misfolding. These findings may have broad implications for understanding the molecular mechanisms responsible for the initiation of AD, and may contribute to the development of new strategies for disease prevention and intervention.

Keywords:

amyloid; prion; protein misfolding; disease transmission

http://www.nature.com/mp/journal/vaop/ncurrent/abs/mp2011120a.html

see more here ;

http://betaamyloidcjd.blogspot.com/2011/10/de-novo-induction-of-amyloid-deposition.html

http://transmissiblespongiformencephalopathy.blogspot.com/2011/10/alzheimers-disease-is-transmissible.html

Wednesday, September 21, 2011

PrioNet Canada researchers in Vancouver confirm prion-like properties in Amyotrophic Lateral Sclerosis (ALS)

http://transmissiblespongiformencephalopathy.blogspot.com/2011/09/prionet-canada-researchers-in-vancouver.html

POLITICAL BSe and CJD and THE WOW FACTOR $$$

Monday, September 26, 2011

Variably Protease-Sensitive Prionopathy, Prionpathy, Prionopathy, FFI, GSS, gCJD, hvCJD, sCJD, TSE, PRION, update 2011

http://prionopathy.blogspot.com/2011/09/variably-protease-sensitive-prionopathy.html

Mad Cow Scaremongers

Mad Cow Scaremongers by Terry S. Singeltary Sr. a review of the TSE prion agent 2003-2011

re-2003

"he also blindly insists upon a mad-cow with Alzheimer’s, Parkinson’s, and Lou Gehrig’s disease."

http://www.seac.gov.uk/pdf/hol-response091008.pdf

http://bse-atypical.blogspot.com/2009/10/seac-science-and-technology-committees.html

SNIP...SEE FULL TEXT ;

http://transmissiblespongiformencephalopathy.blogspot.com/2011/09/mad-cow-scaremongers.html

EFSA Journal 2011 The European Response to BSE: A Success Story

This is an interesting editorial about the Mad Cow Disease debacle, and it's ramifications that will continue to play out for decades to come ;

Monday, October 10, 2011

EFSA Journal 2011 The European Response to BSE: A Success Story

snip...

EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.

snip...

http://www.efsa.europa.eu/en/efsajournal/pub/e991.htm?emt=1

http://www.efsa.europa.eu/en/efsajournal/doc/e991.pdf

see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;

http://transmissiblespongiformencephalopathy.blogspot.com/2011/10/efsa-journal-2011-european-response-to.html

layperson

TSS

Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518

Diagnostic accuracy of cerebrospinal fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada: a 6-year prospective study

2011-11-04T19:33:00.000-07:00

Research article

Diagnostic accuracy of cerebrospinal fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada: a 6-year prospective study

Michael B Coulthart , Gerard H Jansen , Elina Olsen , Debra L Godal , Tim Connolly , Bernard CK Choi , Zheng Wang and Neil R Cashman

BMC Neurology 2011, 11:133doi:10.1186/1471-2377-11-133

Published:

27 October 2011

Abstract (provisional)

Background

To better characterize the value of cerebrospinal fluid (CSF) proteins as diagnostic markers in a clinical population of subacute encephalopathy patients with relatively low prevalence of sporadic Creutzfeldt-Jakob disease (sCJD), we studied the diagnostic accuracies of several such markers (14-3-3, tau and S100B) in 1000 prospectively and sequentially recruited Canadian patients with clinically suspected sCJD.

Methods

The study included 127 patients with autopsy-confirmed sCJD (prevalence = 12.7%) and 873 with probable non-CJD diagnoses. Standard statistical measure of diagnostic accuracy were employed, including sensitivity (Se), specificity (Sp), predictive values (PVs), likelihood ratios (LRs), and Receiver Operating Characteristic (ROC) analysis.

Results

At optimal cutoff thresholds (empirically selected for 14-3-3, assayed by immunoblot; 976 pg/mL for tau and 2.5 ng/mL for S100B, both assayed by ELISA), Se and Sp respectively were 0.88 (95% CI, 0.81-0.93) and 0.72 (0.69-0.75) for 14-3-3; 0.91 (0.84-0.95) and 0.88 (0.85-0.90) for tau; and 0.87 (0.80-0.92) and 0.87 (0.84-0.89) for S100B. The observed differences in Sp between 14-3-3 and either of the other 2 markers were statistically significant. Positive LRs were 3.1 (2.8-3.6) for 14-3-3; 7.4 (6.9-7.8) for tau; and 6.6 (6.1-7.1) for S100B. Negative LRs were 0.16 (0.10-0.26) for 14-3-3; 0.10 (0.06-0.20) for tau; and 0.15 (0.09-0.20) for S100B. Estimates of areas under ROC curves were 0.947 (0.931-0.961) for tau and 0.908 (0.888-0.926) for S100B. Use of interval LRs (iLRs) significantly enhanced accuracy for patient subsets [e.g., 41/120 (34.2%) of tested sCJD patients displayed tau levels >10,000 pg/mL, with an iLR of 56.4 (22.8-140.0)], as did combining tau and S100B [e.g., for tau >976 pg/mL and S100B >2.5 ng/mL, positive LR = 18.0 (12.9-25.0) and negative LR = 0.02 (0.01-0.09)].

Conclusions

CSF 14-3-3, tau and S100B proteins are useful diagnostic markers of sCJD even in a low-prevalence clinical population. CSF tau showed better overall diagnostic accuracy than 14-3-3 or S100B. Reporting of quantitative assay results and combining tau with S100B could enhance case definitions used in diagnosis and surveillance of sCJD.

Conclusions In summary, while acknowledging that CSF protein marker testing in the diagnostic investigation of sCJD should always be carefully linked to clinical context, our key finding is that quantitative CSF tau and S100B assays, particularly in combination, have significant value even in clinical settings where the pre-test probability of sCJD is relatively low, and may be an optimal choice for clinical investigations of sCJD, perhaps with prioritization of tau. It may also be timely to consider formally incorporating these markers into sCJD surveillance case definitions. True ante mortem laboratory diagnosis of human prion diseases may eventually be achieved with new approaches based for example on PrPSc [10, 11, 47], other markers suggested by CJD pathobiology [48] or discovered by systematic screening [49], or perhaps a combination of these. In the interim however, optimized application of known diagnostic markers will require judicious quantitative assessment of their performance in realistic clinical settings.

http://www.biomedcentral.com/content/pdf/1471-2377-11-133.pdf

Risk.10: CSF Proteins and Diagnosis of Sporadic Creutzfeldt-Jakob Disease in Canada

Michael B. Coulthart,1,† Gerard H. Jansen,2 Elina Olsen,3 Deborah L. Godal,1 Tim Connolly,3 Bernard C. Choi,3 Zheng Wang3 and Neil R. Cashman4

1Public Health Agency of Canada; Winnipeg, MB Canada; 2University of Ottawa; Ottawa, ON Canada; 3Public Health Agency of Canada; Ottawa, ON Canada; 4University of British Columbia; Vancouver, BC Canada†Presenting author; Email: michael.coulthart@phac-aspc.gc.ca

Background. With its range of initial symptoms that may accompany other conditions, and a frequent need for timely diagnosis, sporadic Creutzfeldt-Jakob disease (sCJD) can present the clinician with significant challenges. Particularly widely employed for this purpose are assays for certain brain proteins in cerebrospinal fluid (CSF). Data are needed to better support systematic revision of diagnostic probabilities for sCJD on the basis of CSF protein assay results, in patient populations that also include diverse subacute encephalopathies eliciting a clinical suspicion of sCJD.

Methods. CSF 14-3-3, total Tau and S-100B proteins were studied prospectively in 948 Canadian patients suspected of having sCJD, including 121 with autopsy-confirmed sCJD and 827 with probable non-CJD diagnoses. Various metrics of diagnostic accuracy including sensitivity, specificity, predictive values and likelihood ratios were estimated.

Results. Estimated diagnostic accuracy for individual markers were mostly consistent with those of previously published studies at optimal cutoff thresholds for this study population (empirically defined for 14-3-3 immunoblot; 976 pg/mL for Tau; 2.5 ng/mL for S-100B). Sensitivity and specificity estimates respectively at these thresholds were 0.88 (95% CI, 0.81–0.93) and 0.71 (0.68–0.74) for 14-3-3; 0.90 (0.83–0.95) and 0.87 (0.85–0.90) for Tau; and 0.86 (0.78–0.91) and 0.86 (0.84–0.89) for S-100B; thus, the only outlier was 14-3-3 specificity (~0.7). Positive likelihood ratio (LR+) estimates were low to moderate: 3.0 (2.8–3.3) for 14-3-3; 7.1 (6.6–7.6) for Tau and 6.3 (5.8–6.8) for S-100B at optimal cutoff thresholds. Negative likelihood ratios were moderate: 0.17 (0.10–0.30) for 14-3-3; 0.12 (0.07–0.2) for Tau; and 0.17 (0.10–0.30) for S-100B. Interval LR estimates strengthened accuracy for patient subsets—for example, 31.4% of sCJD patients displayed extreme CSF Tau levels (>12 000 pg/mL), associated with an LR of 64.0 (23.3–175.9). Combining Tau and S-100B results, even at intermediate values, also enhanced accuracy; e.g., LR+ = 55.6 (20.1–153.7) with Tau > 5000 pg/mL and S-100B > 5.0 ng/mL.

Conclusions. CSF Tau and S-100B show comparable or better diagnostic accuracy compared to 14-3-3 in a heterogeneous patient population with low average pre-test probability of sCJD. Tau and S-100B may be optimal choices for many sCJD case investigations. Reporting of quantitative assay results as well as combining Tau and S-100B could enhance the clinical utility of surveillance case definitions for sCJD.

================

Risk.49: Creutzfeldt-Jakob Disease in Canada, 1998–2009

Zheng Wang,1,† Gerard Jansen,1, 2 Elina Olsen,1 Stacy Sabourin,1 Rolande D’Amour,1 Tim Connolly,1 Jennifer Kruse,1 Neil Cashman3 and Michael Coulthart1

1The Canadian Creutzfeldt-Jakob Disease Surveillance System; Public Health Agency of Canada; Ottawa, ON Canada; 2Department of Pathology; Ottawa Hospital; Ottawa, ON Canada; 3Brain Research Centre; University of British Columbia; Vancouver, BC Canada†Presenting author; Email: zheng.wang@phac-aspc.gc.ca

Background. Creutzfeldt-Jakob Disease (CJD) is a fatal, transmissible neurodegenerative disease with sporadic, genetic and acquired forms. In 1998, Canada launched comprehensive national CJD surveillance to assess the characteristics of CJD in Canada and its risks to the health of Canadians. This study describes the broad characteristics of CJD in Canada from 1998–2009.

Methods. Case ascertainment was based on internationally accepted criteria. Demographic information and risk-factor data were collected by standardized questionnaire and medical chart review. Poisson regression, descriptive analysis, and case investigation were employed.

Results. A total of 453 CJD deaths in Canadian residents were registered from 1998–2009. Four hundred and fifteen (92%) were sporadic (sCJD), 33 (7%) were genetic and five (1%) were acquired. Average annual sCJD mortality was 1.1 per million population, increasing gradually from 0.9 in 1999 to 1.4 in 2009 (P = 0.27). All provinces saw average annual mortalities ranging from 1.0 to 1.5 (P = 0.85), except three territories where population is small (~25,000 to ~45,000), sCJD occurred equally in both genders at 1.1. sCJD was rare under 50 years of age with only 11 cases identified (2.7%). Mortality increased after 50 and peaked at 8 per million in the 70–74 age group. Median age at death was 69 and median duration of illness was 4 months. Genetic TSE accounted for 33 deaths: 19 were GSS (P102L: 5, D202N: 2, P105T: 2, Q217R:1, A117V: 1, unknown mutation: 8); 13 were familial CJD (E200K: 9, D178N: 2, V203I: 1, V189I:1); one was FFI (D178N). Median age for genetic TSE was 59 and median duration of illness was 27 months. For the five acquired cases of CJD, four were associated with dura mater procedures (3 Lyodura, 1 Tutoplast) and were identified from 1998–2003 in patients aged 14–59. Investigation indicated the infections possibly occurred from 1981–1992 with incubation times from 10–16 years. One biochemically and neuropathologically confirmed variant CJD death occurred in 2002 in a person under 40 years old, likely acquired overseas.

Discussion and Conclusion. Characteristics of CJD in Canada are consistent with those observed in other countries. The increase in sCJD mortality can be at least partly attributed to increased awareness of CJD among referring clinicians. The finding of four dura matter associated CJD cases and one imported vCJD case in Canada demonstrate risks to Canadians from acquired CJD exist. Continued surveillance for iatrogenic risks and novel forms of CJD is warranted.

====================

Envt.05: Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque

Emmanuel Comoy,1,† Valérie Durand,1 Evelyne Correia,1 Sophie Freire,1 Jürgen Richt,2 Justin Greenlee,3 Juan-Maria Torres,4 Paul Brown,1 Bob Hills5 and Jean-Philippe Deslys1

1Atomic Energy Commission; Fontenay-aux-Roses, France; 2Kansas State University; Manhattan, KS USA; 3USDA; Ames, IA USA; 4INIA; Madrid, Spain; 5Health Canada; Ottawa, ON Canada†Presenting author; Email: emmanuel.comoy@cea.fr

The epidemiology of Transmissible mink encephalopathy (TME) indicates an alimentary origin. Several inter-species transmission experiments have not succeeded in establishing with certainty any natural reservoir of this prion strain, although both ovine and bovine sources have been suspected. Cattle exposed to TME develop a spongiform encephalopathy that is distinct from classical Bovine Spongiform Encephalopathy (c-BSE).

Inoculation of c-BSE to cynomolgus macaque provided early evidence of a possible risk to humans, and remains an important model to define the risk of both primary (oral transmission from cattle to primate) and secondary (intravenous intra-species transmission) exposures. We have also evaluated the transmissibility of other cattle prion strains to macaques, including L- and H- atypical forms of BSE, namely BSE-L and BSE-H, and cattle-adapted TME.

BSE-L induced a neurological disease distinct from c-BSE. Peripheral exposures demonstrate the transmissibility of BSE-L by oral, intravenous, and intra-cerebral routes, with incubation periods similar to c-BSE. Cattle-adapted TME also induced a rapid disease in cynomolgus macaque. The clinical features, lesion profile, and biochemical signature of the induced disease was similar to the features observed in animals exposed to BSE-L, suggesting a link between the two prion strains. Secondary transmissions to a common host (transgenic mouse overexpressing bovine PrP) of cattle-TME and BSE-L before or after passage in primates induced diseases with similar incubation periods: like the c-BSE strain, these cattle strains maintained their distinctive features regardless of the donor species and passages.

If the link between TME and BSE-L is confirmed, our results would suggest that BSE-L in North America may have existed for decades, and highlight a possible preferential transmission of animal prion strains to primates after passage in cattle.

=====================

www.landesbioscience.com Prion

http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf

Thursday, October 27, 2011

Squirrel Monkeys (Saimiri sciureus) Infected with the Agent of Bovine Spongiform Encephalopathy Develop Tau Pathology

doi:10.1016/j.jcpa.2011.09.004 | How to Cite or Link Using DOI

Experimentally induced disease

http://transmissiblespongiformencephalopathy.blogspot.com/2011/10/squirrel-monkeys-saimiri-sciureus.html

EFSA Journal 2011 The European Response to BSE: A Success Story

This is an interesting editorial about the Mad Cow Disease debacle, and it's ramifications that will continue to play out for decades to come ;

Monday, October 10, 2011

EFSA Journal 2011 The European Response to BSE: A Success Story

snip...

EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.

snip...

http://www.efsa.europa.eu/en/efsajournal/pub/e991.htm?emt=1

http://www.efsa.europa.eu/en/efsajournal/doc/e991.pdf

see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;

http://transmissiblespongiformencephalopathy.blogspot.com/2011/10/efsa-journal-2011-european-response-to.html

Monday, September 26, 2011

L-BSE BASE prion and atypical sporadic CJD

http://bse-atypical.blogspot.com/2011/09/l-bse-base-prion-and-atypical-sporadic.html

Thursday, August 4, 2011

Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html

CANADA CJD UPDATE 2011

CJD Deaths Reported by CJDSS1, 1994-20112 As of January 31, 2011

3. Final classification of 49 cases from 2009, 2010, 2011 is pending.

snip...

http://www.phac-aspc.gc.ca/hcai-iamss/cjd-mcj/cjdss-ssmcj/pdf/stats_0111-eng.pdf

USA 2011

USA

National Prion Disease Pathology Surveillance Center

Cases Examined1

(November 1, 2010)

Year Total Referrals2 Prion Disease Sporadic Familial Iatrogenic vCJD

1996 & earlier 51 33 28 5 0 0

1997 114 68 59 9 0 0

1998 87 51 43 7 1 0

1999 121 73 65 8 0 0

2000 146 103 89 14 0 0

2001 209 119 109 10 0 0

2002 248 149 125 22 2 0

2003 274 176 137 39 0 0

2004 325 186 164 21 0 13

2005 344 194 157 36 1 0

2006 383 197 166 29 0 24

2007 377 214 187 27 0 0

2008 394 231 205 25 0 0

2009 425 258 215 43 0 0

2010 333 213 158 33 0 0

TOTAL 38315 22656 1907 328 4 3

1 Listed based on the year of death or, if not available, on year of referral;

2 Cases with suspected prion disease for which brain tissue and/or blood (in familial cases) were submitted;

3 Disease acquired in the United Kingdom;

4 Disease was acquired in the United Kingdom in one case and in Saudi Arabia in the other case;

5 Includes 18 cases in which the diagnosis is pending, and 18 inconclusive cases;

6 Includes 23 (22 from 2010) cases with type determination pending in which the diagnosis of vCJD has been excluded.

http://www.cjdsurveillance.com/pdf/case-table.pdf

Please notice where sporadic CJD cases in 1996 went from 28 cases, to 215 cases in 2009, the highest recorded year to date. sporadic CJD is on a steady rise, and has been since 1996.

I also urge you to again notice these disturbing factors in lines 5 and 6 ;

5 Includes 18 cases in which the diagnosis is pending, and 18 inconclusive cases;

6 Includes 23 (22 from 2010) cases with type determination pending in which the diagnosis of vCJD has been excluded.

========end=====tss=====2011

Saturday, March 5, 2011

MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html

Sunday, August 21, 2011

The British disease, or a disease gone global, The TSE Prion Disease

(see video here)

http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/british-disease-or-disease-gone-global.html

U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ?

(see video at bottom)

http://creutzfeldt-jakob-disease.blogspot.com/2009/07/usa-hiding-mad-cow-disease-victims-as.html

Sunday, September 6, 2009

MAD COW USA 1997

(SEE SECRET VIDEO)

http://madcowusda.blogspot.com/2009/09/mad-cow-usa-1997-video.html

Tuesday, November 01, 2011

Could we face the return of CJD? Experts fear it may lie dormant in thousands

http://creutzfeldt-jakob-disease.blogspot.com/2011/11/could-we-face-return-of-cjd-experts.html

Monday, September 26, 2011

L-BSE BASE prion and atypical sporadic CJD

http://bse-atypical.blogspot.com/2011/09/l-bse-base-prion-and-atypical-sporadic.html

Monday, September 26, 2011

Variably Protease-Sensitive Prionopathy, Prionpathy, Prionopathy, FFI, GSS, gCJD, hvCJD, sCJD, TSE, PRION, update 2011

http://prionopathy.blogspot.com/2011/09/variably-protease-sensitive-prionopathy.html

Sunday, September 25, 2011

Mad Cow Scaremongers

Mad Cow Scaremongers by Terry S. Singeltary Sr. a review of the TSE prion agent 2003-2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/09/mad-cow-scaremongers.html

tss

Could we face the return of CJD? Experts fear it may lie dormant in thousands

2011-11-01T13:17:00.000-07:00

Could we face the return of CJD? Experts fear it may lie dormant in thousands

By Lois Rogers

Last updated at 8:09 AM on 1st November 2011

Holly Mills, aged 15 - three years before she developed the full-blown symptoms of CJD Holly Mills was a lively teenager about to start university. But with her whole life ahead of her, she suddenly found herself in the grip of tragedy.

Within the space of just a few months, the gregarious 18-year-old had become so severely brain damaged that she was unable to move or communicate.

Eight years on, Holly has to be fed through a tube into her stomach and shows no emotion or awareness of her tragic predicament. Her days are spent in heartbreaking, silent immobility.

Holly is one of only three people still alive after developing the full-blown symptoms of Creutzfeldt–Jakob disease (also known as new variant CJD, or vCJD) — the human form of mad cow disease.

Holly’s parents Peter and Linda, both 61, are devoting themselves to their daughter’s full-time care and to a programme of daily mental stimulation, in the belief they are keeping her brain alive until a treatment emerges that will help her.

While they and their three older children live in hope of a cure for Holly, there is growing concern that another CJD outbreak may be imminent.

New evidence collected by the Health Protection Agency (HPA) suggests that one in 4,000 people who were eating meat before 1996 is probably carrying CJD (after that date, cattle infected with mad cow disease were, theoretically, removed from the food chain).

That could mean that as many as 15,000 people nationwide could be affected. While this is in line with a previous survey, the latest findings suggest CJD might be more prevalent in older people.

The findings — which received little publicity when published a few weeks ago — are mid-way results of a programme testing 30,000 samples of tonsil and appendix tissue removed during routine operations across the country.

The aim was to look for evidence of ‘silent’ or symptom-free infection, though scientists admit the method used in the tests cannot identify CJD with total accuracy.

Until recently, a definite diagnosis of the disease in people who have the symptoms could be made only after death, because brain tissue analysis was required.

Holly with her mother Linda, who is devoting herself to her daughter's full-time care and to a programme of daily mental stimulation However, John Collinge, a professor of neurology and a leading expert at the Government’s CJD research unit at University College, London, has developed a blood test which can check if the disease is present by detecting evidence of the so-called prions or infectious proteins known to cause the disease.

He believes the number of people infected could be as high as one in 1,000 and says the CJD situation is ‘very worrying indeed’.

So far, there’s little official interest in investing the several million pounds needed to turn the blood test into the high-speed screening tool needed to bring it into routine use. Critics say this is because the Government fears what it might find.

Mad cow disease, or bovine spongiform encephalopathy (BSE), first emerged in Britain in 1986 as a result of ‘cannibalism’, when beef offal was fed to cattle, which are natural grass-eaters.

The proteins, called prions, that cause BSE were found in large quantities in the brains, spinal cords and spleens of cattle (although they were also subsequently discovered in meat tissue, too). When animal carcasses were ground down to form feed stuff for other cattle, prions were passed on.

They then colonised the brains of the cattle which ate them, and were passed to humans via cheap, mechanically-recovered meat — such as processed sinews and offal that were used at the time in school dinners and baby food.

In humans, the prions triggered the development of a new form of fatal human dementia called new variant CJD, which was first identified in 1996. These prions are entirely new infectious agents, completely different from viruses, bacteria or parasites.

Basically, they are faulty versions of healthy proteins in brain and nervous tissue that then induce their neighbours to become faulty. As a result, the brain cannot function: all signals are disrupted or shut down completely, leading to almost certain death.

Holly was a lively teenager about to start university, but now her days are spent in heartbreaking, silent immobility A ban on using animal remains in livestock feed was imposed in 1989, and 4.4 million cattle were slaughtered to eliminate the disease. At the same time, a ban was imposed on the use of mechanically-recovered meat in products for human consumption.

By the mid-Nineties, when CJD fears were at their height, up to 3.5 million people were believed to possibly be affected. The risk appeared to be greater in younger people, although the reason isn’t clear.

But as new cases failed to materialise (according to official statistics, 168 people have died from CJD in the UK), the view of the Government and medical establishment was that the danger had passed.

However, the new data from the Health Protection Agency suggests the rate of infection is much higher than currently thought.

‘We do not know how many infected people there are or how many of them will develop it,’ Professor Collinge says.

‘The incubation period, where there are no symptoms, can last for decades.’

But it is not only the threat of a widescale re-emergence of the infection that worries experts. There is also the possibility of a new generation being exposed to the disease, as a result of a European Union decision to change the rules on animal feed.

Although CJD emerged from beef, experts say there is evidence of related diseases affecting other meat-producing animals if they are forced into cannibalismContrary to popular belief, BSE has not been wiped out. In fact, 11 cattle were diagnosed with it in Britain last year, although none entered the food chain.

Most young cattle slaughtered for meat are not believed to have developed sufficient infectivity to pose a risk to humans. Any animal more than 30 months old destined for the food chain is checked for BSE after it has been slaughtered.

The new concern is not cattle, however, but pigs and chicken. Earlier this summer, the European Commission announced it was relaxing the ban on using animal remains in livestock feed.

From next year, chicken meat will be used in pig feed and vice versa, to cut costs for farmers who otherwise have to rely on expensive imported soya beans for growth-promoting protein-based animal foods.

Although CJD emerged from beef, experts say there is evidence of related diseases affecting other meat-producing animals if they are forced into cannibalism.

Now a group of CJD-affected families, led by former Labour health secretary Frank Dobson, is to challenge the Government to hasten the development of the new blood test to give people the chance to check if they are infected.

The proposal has been given added urgency by the latest findings about CJD-infected tonsil and appendix tissue, but the Government has been dragging its feet, says Mr Dobson.

‘The projections I was given when I was health secretary in 1998 were that the total number of CJD cases could be anything between a few hundred and 3.5 million people,’ he said.

‘Until now, the only certain way of diagnosing CJD in people who have not yet developed symptoms is to analyse tissue after death.

'Trials show John Collinge’s blood test works, but it needs investment to turn it into a proper screening tool that can quickly deal with a high volume of blood samples.

‘You would have thought the Government would want it to test blood supplies and get an accurate picture of how many people are infected. I can’t understand why they’re not getting on with this.’ Anxiety about CJD transcends party boundaries, with Tory MP Sir Paul Beresford joining Mr Dobson’s cause. The reason Holly and the other two surviving CJD victims are alive is probably because their families fought court battles to be allowed to give them pentosan polysulphate‘We need to find out the extent of the problem and what we need to do about it,’ he said.

‘Otherwise we will potentially see a flood of cases in our grandchildren.’

The parents of Holly, from Thornton Dale in North Yorks, are among those backing the campaign. ‘It’s too big an issue to ignore,’ said Peter Mills. ‘The evidence suggests there will be a second bout of this infection and we need the measures in place to test blood. There is clearly a risk from infected people who have no symptoms. Even if they don’t develop the disease, they can pass it on.’

Normal sterilising techniques do not remove the abnormal proteins which cause CJD from surgical or dental instruments because they survive high temperatures.

There have been at least six transmissions from hospital operations and four cases of CJD infections passed from three different blood donors. All those infected in these ways have died.

In the meantime, Peter and Linda are fully engaged in caring for their sick daughter. When she was diagnosed with the disease aged 18, she was within weeks of leaving home to study midwifery. In fact, her symptoms had been emerging over the previous two years.

At first the family put her fatigue and anxiety down to teenage depression. She had fainting fits two or three times at school when she was 16, but her GP assumed she would grow out of them.

But when Holly began losing weight and having difficulty walking, her parents realised something was wrong.

Her condition quickly worsened, but the CJD diagnosis — based on ruling out everything else — was a dreadful shock.

‘We were devastated,’ says Peter. ‘We think she caught it from the mechanically-recovered meat they used to put in baby food.

'Once Holly became ill, it all happened very fast. Within a few weeks of the diagnosis she couldn’t walk or talk. We treat it like a head injury.

‘We want to stimulate her as much as possible. We talk to her all the time and, although she doesn’t respond, we are convinced she still has some functions.’

Every morning, a system of hoists and pulleys allows Linda to transport Holly from bed to a specially-built bath tub. Once she is washed and dressed, the three embark on an outing into the countryside. Come rain or shine, Holly’s parents guide her wheelchair along the cliff-top paths in the nearby seaside resort of Scarborough, or through the elegant surroundings of one of the local National Trust mansions.

The reason Holly and the other two surviving CJD victims are alive is probably because their families fought court battles to be allowed to give them pentosan polysulphate, an experimental drug currently unlicenced in the UK, injected into the brain which seems to prevent the final stages of the disease.

What lies ahead for Holly and the thousands of other CJD carriers remains to be seen. Campaigning with Frank Dobson, Sir Paul Beresford and the Mills family is Christine Lord, from Southsea, Hampshire, whose son Andy, a radio sports commentator, died aged 24 from CJD three years ago.

Other experts believe up to 60,000 could be affected ‘In one of the last conversations we had, Andy asked me to find out how he got ill and I promised I would,’ says Christine, a BBC journalist who is writing a book about what she believes has been a political cover-up of the extent of the CJD risk. ‘I want to know where this came from. I stopped him eating beef from the age of six because of BSE, but he still got the disease.’

She is organising a protest next month to demand access to the blood test. ‘I think the Government doesn’t want the test out there because of people finding out how prevalent CJD is,’ she says.

A spokesman for the NHS Blood Service said it was in talks with Professor Collinge about using his test to screen the 7,000 blood donations collected daily across the country, but could not say when the work would be done to develop a tool capable of bulk screening.

‘We are spending £40?million a year on a process to remove white blood cells and £200?million a year on synthetic blood-clotting factors to minimise the risk of CJD transmission via blood,’ she told the Mail.

Professor Collinge says blood will certainly already have been donated by infected donors. ‘I think the possibility of a lethal infection in one in 4,000 blood donors is very worrying. People wouldn’t accept that level of risk if it was HIV.’

The Government’s experts have extrapolated the Health Protection Agency’s data and suggested at least 15,000 people are carrying CJD, though they agree the exact figure is unknown and other experts believe up to 60,000 could be affected.

Meanwhile, Azra Ghani, professor of infectious disease epidemiology at London’s Imperial College, says the potential harm from symptom-free CJD carriers is impossible to predict.

‘It’s a waiting game with any new infection. We just don’t know if these people will be infectious or not.’

http://www.dailymail.co.uk/health/article-2055904/Could-face-return-CJD-Experts-fear-lie-dormant-thousands.html

Cow aged over 72 months enters food supply without being tested for BSE Wednesday 26 October 2011

The Agency has been notified that meat has entered the food supply from a cow aged over 72 months that had not been tested for BSE. A negative BSE test result is mandatory for cattle slaughtered for human consumption at over 72 months of age.

It is very unlikely that the cow was infected with BSE and as specified risk material (SRM) was removed, any risk to human health is extremely low. SRM is the parts of cattle most likely to carry BSE infectivity.

The cow, aged 74 months and 11 days, was slaughtered at Anglo Dutch Meats (Charing) Ltd’s abattoir in Kent, on 11 August 2011. The error was discovered on 6 October in the course of routine cross-checks of slaughter and BSE test data.

According to BSE regulations, the untested cow, plus the one slaughtered before and the two after should not have entered the food supply. However, by the time the failure was discovered, the associated carcases had left the premises.

Subsequent checks indicate that the meat from the carcases was mixed with a large volume of other meat which is no longer in the food supply and is likely to have been eaten.

http://www.food.gov.uk/news/newsarchive/2011/oct/anglodutch

Cow aged over 48 months enters food supply without being tested for BSE

Tuesday 23 February 2010

The Agency has been notified that meat from a cow aged over 48 months has entered the food supply without being tested for BSE.

It is very unlikely that the cow was infected with BSE and, as specified risk material (SRM) was removed, any risk to human health is extremely low. However, testing is mandatory for cattle slaughtered for human consumption at over 48 months of age.

The cow was slaughtered at Pickstock Ashby Ltd's abattoir in Hartshorne, Derbyshire, on 4 November 2009 aged almost 57 months. The failure was discovered on 28 January during routine cross checks of slaughter and BSE test data. By the time the failure was discovered all of the affected carcasses and offal had left the premises.

The affected carcasses, some edible co-products and offal had been exported. Some meat returned to Britain after processing and some went to other countries. Other edible co-products remained in Britain. Subsequent checks indicate that all of the meat and edible co-product that remained in Britain or that returned to Britain is no longer in the food supply chain. The authorities in the countries that received the exported material have been informed.

Background to BSE testing The BSE testing age was raised to 48 months at the beginning of last year. Cattle aged over 48 months are allowed to enter the food supply provided they have tested negative for BSE. If there is no BSE test, all parts of the carcase must be condemned.

Specified risk material (SRM) is those parts of the animal that contain almost all BSE infectivity, if the animal is infected with BSE.

http://www.food.gov.uk/news/newsarchive/2010/feb/over48monthcow

Cow aged over 48 months enters food supply without being tested for BSE

Tuesday 14 September 2010

The Agency has been notified that meat has entered the food supply from a cow aged over 48 months that had not been tested for BSE.

It is very unlikely that the cow was infected with BSE and, as specified risk material was removed, any risk to human health is extremely low. Nevertheless, a negative BSE test result is mandatory for cattle over 48 months of age slaughtered for human consumption.

The cow was aged one day over 48 months when slaughtered on 9 July at G & GB Hewitt Ltd abattoir in Chester. The error was discovered on 24 August in the course of routine cross-checks of slaughter and BSE test data.

According to BSE regulations, the untested cow, the animal slaughtered before and the two slaughtered after must not enter the food supply. However, by the time the failure was discovered, all of the associated carcasses had left the premises.

Subsequent checks traced one small batch of meat that has since been destroyed and indicate that the rest of the meat from the carcasses is no longer in the food supply chain.

http://www.food.gov.uk/news/newsarchive/2010/sep/otmuntested

Cow aged over 48 months enters food supply without being tested for BSE Monday 2 November 2009

The Agency has been notified that a 58 months old cow has entered the food supply without being tested for BSE. BSE testing is mandatory for cattle slaughtered for human consumption at over 48 months of age.

However, as all the specified risk material (SRM) was removed, and it is unlikely that the cow was infected with BSE, any risk to human health is very low. SRM is those parts of the animal that contain almost all BSE infectivity.

The cow was slaughtered on 28 July 2009 at Dunbia abattoir in Dungannon. The error was discovered by Northern Ireland's Department of Agriculture and Rural Development (DARD) when a routine annual herd TB test revealed that the cow had been misidentified.

DARD has now established the correct identity and age of the cow slaughtered on 28 July. Checks indicate that all the meat and other products from the untested cow are likely to have been eaten.

http://www.food.gov.uk/news/newsarchive/2009/nov/over48

Monday, May 12, 2008

BSE YOUNGEST AGE STATISTICS UNDER 30 MONTHS

http://bseyoungestage.blogspot.com/

Sunday, May 18, 2008

BSE, CJD, and Baby foods (the great debate 1999 to 2005)

http://bseinquiry.blogspot.com/2008/05/bse-cjd-and-baby-foods-great-debate.html

NORTH AMERICA USA

PLEASE be aware, for 4 years, the USDA fed our children all across the Nation (including TEXAS) dead stock downer cows, the most high risk cattle for BSE aka mad cow disease and other dangerous pathogens.

who will watch our children for CJD for the next 5+ decades ???

WAS your child exposed to mad cow disease via the NSLP ???

SCHOOL LUNCH PROGRAM FROM DOWNER CATTLE UPDATE

http://downercattle.blogspot.com/2009/05/who-will-watch-children.html

http://downercattle.blogspot.com/

DID YOUR CHILD CONSUME SOME OF THESE DEAD STOCK DOWNER COWS, THE MOST HIGH RISK FOR MAD COW DISEASE ???

you can check and see here ;

http://www.fns.usda.gov/fns/safety/pdf/Hallmark-Westland_byState.pdf

Wednesday, June 15, 2011

Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html

MAD COW DISEASE, TEXAS STYLE

http://www.organicconsumers.org/articles/article_23850.cfm

with an incubation period of up to 50 years or more, we will all just have to wait and see...

Saturday, June 25, 2011

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque

"BSE-L in North America may have existed for decades"

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html

Saturday, July 23, 2011

CATTLE HEADS WITH TONSILS, BEEF TONGUES, SPINAL CORD, SPECIFIED RISK MATERIALS (SRM's) AND PRIONS, AKA MAD COW DISEASE

http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/cattle-heads-with-tonsils-beef-tongues.html

Sunday, June 26, 2011

Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/risk-analysis-of-low-dose-prion.html

Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.

snip...

The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...

http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf

Wednesday, March 31, 2010

Atypical BSE in Cattle

To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE.

In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2

2006

USA sporadic CJD cases rising ;

There is a growing number of human CJD cases, and they were presented last week in San Francisco by Luigi Gambatti(?) from his CJD surveillance collection.

He estimates that it may be up to 14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins.

http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm

http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf

2008

The statistical incidence of CJD cases in the United States has been revised to reflect that there is one case per 9000 in adults age 55 and older. Eighty-five percent of the cases are sporadic, meaning there is no known cause at present.

http://www.cjdfoundation.org/fact.html

CJD USA RISING, with UNKNOWN PHENOTYPE ;

5 Includes 41 cases in which the diagnosis is pending, and 17 inconclusive cases;

*** 6 Includes 46 cases with type determination pending in which the diagnosis of vCJD has been excluded.

http://www.cjdsurveillance.com/pdf/case-table.pdf

Thursday, August 12, 2010

Seven main threats for the future linked to prions

First threat

The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.

***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.

Second threat

snip...

http://www.neuroprion.org/en/np-neuroprion.html

Rural and Regional Affairs and Transport References Committee

The possible impacts and consequences for public health, trade and agriculture of the Government’s decision to relax import restrictions on beef Final report June 2010

2.66 Dr Fahey also told the committee that in the last two years a link has been established between forms of atypical CJD and atypical BSE. Dr Fahey said that: They now believe that those atypical BSEs overseas are in fact causing sporadic Creutzfeldt-Jakob disease. They were not sure if it was due to mad sheep disease or a different form. If you look in the textbooks it looks like this is just arising by itself. But in my research I have a summary of a document which states that there has never been any proof that sporadic Creutzfeldt-Jakob disease has arisen de novo—has arisen of itself. There is no proof of that. The recent research is that in fact it is due to atypical forms of mad cow disease which have been found across Europe, have been found in America and have been found in Asia. These atypical forms of mad cow disease typically have even longer incubation periods than the classical mad cow disease.50

http://www.aph.gov.au/senate/committee/rrat_ctte/mad_cows/report/report.pdf

Published Date: 2010-04-05 17:00:02

Subject: PRO/AH/EDR> Prion disease update 1010 (04) Archive Number: 20100405.1091

PRION DISEASE UPDATE 2010 (04)

Communicated by: Terry S Singeltary Sr

[Terry S. Singeltary Sr. has added the following comment:

"According to the World Health Organisation, the future public health threat of vCJD in the UK and Europe and potentially the rest of the world is of concern and currently unquantifiable. However, the possibility of a significant and geographically diverse vCJD epidemic occurring over the next few decades cannot be dismissed . The key word here is diverse. What does diverse mean? If USA scrapie transmitted to USA bovine does not produce pathology as the UK c-BSE, then why would CJD from there look like UK vCJD?"

http://www.promedmail.org/direct.php?id=20100405.1091

Thursday, August 4, 2011

Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011

(see video here) ;

http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html

Sunday, August 21, 2011

The British disease, or a disease gone global, The TSE Prion Disease

(see video here)

http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/british-disease-or-disease-gone-global.html

U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ?

(see video at bottom)

http://creutzfeldt-jakob-disease.blogspot.com/2009/07/usa-hiding-mad-cow-disease-victims-as.html

Sunday, September 6, 2009

MAD COW USA 1997

(SEE SECRET VIDEO)

http://madcowusda.blogspot.com/2009/09/mad-cow-usa-1997-video.html

2010-2011

When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2

Published Date: 2011-06-07 11:47:33

Subject: PRO/AH/EDR> Prion disease update 2011 (06) Archive Number: 20110607.1736

PRION DISEASE UPDATE 2011 (06) ******************************

A ProMED-mail post http://www.promedmail.org

The conclusions state that, at present, the only TSE agent demonstrated to be zoonotic is the classical BSE agent. Active screening has allowed the identification of 3 new forms of animal TSEs (H-type atypical BSE, L-type atypical BSE, and atypical scrapie), but the information obtained has major limitations due to the unknown sensitivity of the current monitoring system for these TSEs. There is no epidemiological evidence to suggest that classical scrapie is zoonotic. The epidemiological data are too limited to conclude whether the atypical scrapie agent has a zoonotic potential. Transmission experiments to human PrP transgenic mice or primates suggest that some TSE agents other than the classical BSE agent in cattle (namely L-type atypical BSE, classical BSE in sheep, TME, CWD agents) might have zoonotic potential and indicate that that of the L-type atypical BSE agent appears similar or even higher than that of the classical BSE agent. A single study reported efficient transmission of a natural sheep classical scrapie isolate to primates.

Commentary ---------- Following to a request from the European Commission, the Panel on Biological Hazards (BIOHAZ) and the European Centre for Disease Prevention and Control (ECDC) were asked to deliver a scientific opinion on any possible epidemiological or molecular association between transmissible spongiform encephalopathies (TSEs) in animals and humans. The opinion reviews and discusses the existing scientific evidence that links animal and human TSEs currently known.

The opinion first considers the definition of zoonoses and the principles for the identification of zoonotic diseases, which can be based on evidence gathered from both epidemiological and laboratory studies. The opinion describes the challenges involved in identifying TSEs as zoonoses, due to the specific characteristics of TSE infections/diseases, such as the nature of TSE agents, the occurrence of animal and human TSEs, and the type of monitoring applied, the long incubation period of TSEs etc. The example of the process that led to establishing a link between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) is reviewed. The epidemiological and laboratory criteria that can be used to investigate such a link are described in detail, since those criteria might be useful for the identification of links between other animal and human TSEs.

The opinion discusses the strain diversity of the TSE agents described in sheep, goats, cattle, cervids, and humans, based on the current knowledge, which highlights that multiple TSE agents exist in each species. The factors influencing the capacity of TSE agents to cross the species transmission barrier are then considered in detail, including the variability in host and donor PrP gene and protein, the TSE strain type involved and its interaction with the host PrP, and the route of infection.

The opinion critically assesses the tools and methodologies currently available to study and evaluate the possible association between animal and human TSEs. The use of epidemiology is discussed for TSEs in both animals and humans, and the possibility to compare the 2 sources of information is presented as a possible method to study the possible links.

Both in vivo and in vitro laboratory methods are considered and discussed, including neuropathology, transmission experiments involving different animal models (wild type and transgenic mice, primates and other species), biochemical methods, cell-free conversion assays, protein misfolding cyclic amplification (PMCA), and cell culture assays. Characteristics, advantages, and disadvantages of the different methods are reviewed, including the opportunity to collate data from different types of experiments for the study of potential associations between animal and human TSEs.

The opinion then reviews the scientific evidence currently available for the different animal and human TSEs, including classical BSE, atypical BSE (H-type and L-type), classical scrapie, atypical scrapie, chronic wasting disease (CWD), transmissible mink encephalopathy (TME), and human TSEs. In particular, the following aspects are systematically discussed for each TSE agent: epidemiology, pathogenesis, and in vivo and in vitro transmission experiments.

The opinion concludes that, at present, the only TSE agent demonstrated to be zoonotic is the classical BSE agent. With regard to human TSEs, detected cases of sporadic CJD are randomly distributed in time and geographical location. These observations have been interpreted as a supportive argument that sporadic CJD is not environmentally acquired. However, the epidemiological evidence in relation to sporadic CJD cannot be regarded as definitive, and the possibility that a small proportion of cases are zoonotic cannot be excluded.

It also concludes that a series of uncertainties in relation to the epidemiological patterns of animal and human TSEs indicate that even a rough comparison of the present epidemiological patterns of human and animal TSEs other than classical BSE is unlikely to be informative. Because of these uncertainties, it is an imperative to continue to carry out systematic surveillance of human TSE diseases, and to continue and improve the surveillance of animal TSE diseases.

The opinion highlights that the active screening has allowed the identification of 3 new forms of animal TSEs (L-type atypical BSE, H-type atypical BSE, and atypical scrapie), but that the information obtained has major limitations due to the unknown sensitivity of the current monitoring system for these TSEs.

There is no epidemiological evidence to suggest that classical scrapie is zoonotic. The epidemiological data are too limited to conclude whether the atypical scrapie agent has a zoonotic potential.

Transmission experiments to human PrP transgenic mice suggest that some TSE agents other than the classical BSE agent in cattle (namely L-type atypical BSE and classical BSE in sheep agents) might have zoonotic potential, whereas for other agents there is no evidence provided of a zoonotic potential (H-type atypical BSE and CWD), or no published studies are available (classical and atypical scrapie). In addition, transmission experiments to primates suggest that some TSE agents other than the classical BSE agent in cattle (namely L-type atypical BSE, classical BSE in sheep, TME, CWD agents) might have zoonotic potential. In particular, primates are highly permissive to L-type atypical BSE, even by the oral route.

The opinion emphasizes that laboratory transmission experiments indicate that the L-type atypical BSE agent has a significant zoonotic potential, which appears similar or even higher than that of the classical BSE agent. While transmission data for evaluating the zoonotic potential of classical scrapie in primates and human PrP transgenic mice are extremely limited or not yet available, a single study reported efficient transmission of a natural sheep classical scrapie isolate to primates.

The opinion concludes that human PrP transgenic mice and primates are currently the most relevant models for investigating the human transmission barrier, but the extent to which such models are informative for measuring the zoonotic potential of an animal TSE under field exposure conditions is unknown. It is unpredictable whether a TSE agent will transmit to a new host, and if the transmission principally occurs, what the transmission rate will be.

Based on the results obtained with in vitro conversion assays, the opinion concludes that there is probably no absolute molecular barrier to transmission of TSE agents between mammalian species. Results also suggest that these assays may be developed as a tool for quantifying the transmission barriers between species for different TSE agent strains; however, there is no means at the moment to transpose in vitro results into the likelihood of in vivo interspecies transmission.

-- Communicated by: Terry S Singeltary Sr

[ProMED-mail thanks Terry S Singeltary Sr for drawing attention to this comprehensive document which provides a current evaluation of experimental work designed to explore the zoonotic potential of the various recently recognised TSEs of domestic and other animals.

It is concluded that at present the only TSE agent demonstrated to be zoonotic is the classical BSE agent. Nor can it be entirely excluded at the present time that a small proportion of cases of sporadic CJD may be environmentally acquired. - Mod.CP]

******

http://www.promedmail.org/direct.php?id=20110607.1736

EFSA Journal 2011 The European Response to BSE: A Success Story

This is an interesting editorial about the Mad Cow Disease debacle, and it's ramifications that will continue to play out for decades to come ;

Monday, October 10, 2011

EFSA Journal 2011 The European Response to BSE: A Success Story

snip...

EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.

snip...

http://www.efsa.europa.eu/en/efsajournal/pub/e991.htm?emt=1

http://www.efsa.europa.eu/en/efsajournal/doc/e991.pdf

see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;

http://transmissiblespongiformencephalopathy.blogspot.com/2011/10/efsa-journal-2011-european-response-to.html

Saturday, January 2, 2010

Human Prion Diseases in the United States January 1, 2010 ***FINAL***

http://prionunitusaupdate2008.blogspot.com/2010/01/human-prion-diseases-in-united-states.html

Manuscript Draft Manuscript Number: Title: HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory Article Type: Personal View Corresponding Author: Mr. Terry S. Singeltary, Corresponding Author's Institution: na First Author: Terry S Singeltary, none Order of Authors: Terry S Singeltary, none; Terry S. Singeltary Abstract: TSEs have been rampant in the USA for decades in many species, and they all have been rendered and fed back to animals for human/animal consumption. 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 2007.

http://www.regulations.gov/fdmspublic/ContentViewer?objectId=090000648027c28e&disposition=attachment&contentType=pdf

my comments to PLosone here ;

http://www.plosone.org/annotation/listThread.action?inReplyTo=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd&root=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd

Sunday, August 09, 2009

CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009

http://creutzfeldt-jakob-disease.blogspot.com/2009/08/cjdstraight-talk-withjames.html

Tuesday, August 18, 2009

BSE-The Untold Story - joe gibbs and singeltary 1999 - 2009

http://madcowusda.blogspot.com/2009/08/bse-untold-story-joe-gibbs-and.html

another question, just how long have these atypical BSE TSEs been around in the bovine ???

Subject: atypical BSE reported in 1992 and conviently slaughterd and incinerated and then swept under rug for about 12 years

Date: April 26, 2007 at 1:08 pm PST 1992

NEW BRAIN DISORDER

3. WHAT ABOUT REPORTS OF NEW FORM OF BSE?

THE VETERINARY RECORD HAS PUBLISHED AN ARTICLE ON A NEW BRAIN DISORDER OF CATTLE DISCOVERED THROUGH OUR CONTROL MEASURES FOR BSE. ALTHOUGH IT PRESENTS SIMILAR CLINICAL SIGNS TO BSE THERE ARE MAJOR DIFFERENCES IN THE HISTOPATHOLOGY AND INCUBATION PERIODS BETWEEN THE TWO. MUST EMPHASISE THAT THIS IS NOT BSE.

4. IS THIS NEW BRAIN DISORDER A THREAT?

WE DO NOT EVEN KNOW WHETHER THE AGENT OF THIS DISEASE IS TRANSMISSIBLE. IN ANY CASE, CASES SO FAR IDENTIFIED HAD SHOWN SIMILAR SYMPTOMS TO THOSE OF BSE, AND THEREFORE HAVE BEEN SLAUGHTERED AND INCINERATED, SO THAT IF A TRANSMISSIBLE AGENT WERE INVOLVED IT WOULD HAVE BEEN ELIMINATED. .......

http://web.archive.org/web/20030714222309/www.bseinquiry.gov.uk/files/yb/1992/10/26001001.pdf

2. The Collinge/Will dispute appears to rumble on. Dr. Collinge had told Dr. Tyrrell that Dr. Will's response to his criticism about sharing material had been ''quite unacceptable'' (in spite of it's apparently conciliatory tone). Apparently Professor Allen was now going to try and arrange a meeting to resolve the dispute. No action here for MAFF, although Mr. Murray may be interested.

3. Dr. Tyrrell regretted that the Committee had not seen the article on BBD. However he felt that for the time being NO specific action was called for. The most important need was to consider the possibility that the condition might be transmissible. As we have discussed, I suggested that we might circulate a paper to the members of the committee giving our appreciation of this condition (and perhaps of other non-BSE neurological conditions that had been identified in negative cases) and of any necessary follow up action. IF any Committee member felt strongly about this, or if the issue CAME TO A HEAD, we would call an interim meeting. He was happy with this approach. I would be grateful if Mr. Maslin could, in discussion with CVL and veterinary colleagues draft such a note, which will presumably very largely follow what Mr. Bradley's briefing paper has already said, taking account of DOH comments, We can then clear a final version with DOH before circulating it to Committee members.

http://web.archive.org/web/20030714222309/www.bseinquiry.gov.uk/files/yb/1992/10/29005001.pdf

IN CONFIDENCE

This is a highly competitive field and it really will be a pity if we allow many of the key findings to be published by overseas groups while we are unable to pursue our research findings because of this disagreement, which I hope we can make every effort to solve.

http://web.archive.org/web/20030714222309/www.bseinquiry.gov.uk/files/yb/1992/10/26002001.pdf

COLLINGE THREATENS TO GO TO MEDIA

http://web.archive.org/web/20030714222309/www.bseinquiry.gov.uk/files/yb/1992/12/16005001.pdf

Wednesday, August 20, 2008

Bovine Spongiform Encephalopathy Mad Cow Disease typical and atypical strains, was there a cover-up ?

http://bse-atypical.blogspot.com/2008/08/bovine-spongiform-encephalopathy-mad.html

Saturday, February 28, 2009

NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS

"All of the 15 cattle tested showed that the brains had abnormally accumulated PrP"

2009 SEAC 102/2

http://bse-atypical.blogspot.com/2009/02/new-results-on-idiopathic-brainstem.html

Wednesday, July 28, 2010

Atypical prion proteins and IBNC in cattle DEFRA project code SE1796 FOIA Final report

http://bse-atypical.blogspot.com/2010/07/atypical-prion-proteins-and-ibnc-in.html

USA MAD COW FEED IN COMMERCE

FDA TRIPLE FIREWALL MAD COW FEED BAN WAS NOTHING MORE THAN INK ON PAPER

10 YEARS (one decade) POST USA FDA MAD COW FEED BAN OF AUGUST 4, 1997, USA STILL FEEDING COWS TO COWS

Date: March 21, 2007 at 2:27 pm PST

RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II

___________________________________

PRODUCT

Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007

CODE

Cattle feed delivered between 01/12/2007 and 01/26/2007

RECALLING FIRM/MANUFACTURER

Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.

Firm initiated recall is ongoing.

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

___________________________________

PRODUCT

Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007

CODE

The firm does not utilize a code - only shipping documentation with commodity and weights identified.

RECALLING FIRM/MANUFACTURER

Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete.

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

http://www.fda.gov/Safety/Recalls/EnforcementReports/2007/ucm120446.htm

Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject PRO/AH/EDR; Prion disease update 2010 (11)

PRION DISEASE UPDATE 2010 (11)

http://www.promedmail.org/direct.php?id=20101206.4364

SEE TONNAGE OF MAD COW FEED IN COMMERCE IN 2007 ALONE, A DECADE POST PARTIAL AND VOLUNTARY MAD COW FEED BAN ;

Saturday, November 6, 2010

TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU Berne, 2010 TAFS

INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation

http://madcowfeed.blogspot.com/2010/11/tafs1-position-paper-on-position-paper.html

Saturday, July 23, 2011

CATTLE HEADS WITH TONSILS, BEEF TONGUES, SPINAL CORD, SPECIFIED RISK MATERIALS (SRM's) AND PRIONS, AKA MAD COW DISEASE

http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/cattle-heads-with-tonsils-beef-tongues.html

Mad Cow Scaremongers

Mad Cow Scaremongers by Terry S. Singeltary Sr. a review of the TSE prion agent 2003-2011

re-2003

"he also blindly insists upon a mad-cow with Alzheimer’s, Parkinson’s, and Lou Gehrig’s disease."

http://www.seac.gov.uk/pdf/hol-response091008.pdf

http://bse-atypical.blogspot.com/2009/10/seac-science-and-technology-committees.html

SNIP...SEE FULL TEXT ;

http://transmissiblespongiformencephalopathy.blogspot.com/2011/09/mad-cow-scaremongers.html

Tuesday, October 4, 2011

De novo induction of amyloid-ß deposition in vivo

Molecular Psychiatry advance online publication 4 October 2011; doi: 10.1038/mp.2011.120

http://betaamyloidcjd.blogspot.com/2011/10/de-novo-induction-of-amyloid-deposition.html

layperson

TSS

Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518 flounder9@verizon.net