EFSA BIOHAZ Scientific Opinion on the revision of the quantitative risk assessment (QRA) of the BSE risk posed by processed animal proteins (PAPs)

EFSA Journal 2011;9(1):1947

Suggested citation: EFSA Panel on Biological Hazards (BIOHAZ); Scientific Opinion on the revision of the quantitative risk assessment (QRA) of the BSE risk posed by processed animal proteins (PAPs). EFSA Journal 2011;9(1):1947. [80 pp.]

doi:10.2903/j.efsa.2011.1947. Available online: www.efsa.europa.eu/efsajournal


© European Food Safety Authority, 2011

SCIENTIFIC OPINION

Scientific Opinion on the revision of the quantitative risk assessment (QRA) of the BSE risk posed by processed animal proteins (PAPs)1

EFSA Panel on Biological Hazards (BIOHAZ)2, 3

European Food Safety Authority (EFSA), Parma, Italy

ABSTRACT

The cattle Bovine Spongiform Encephalopathy (BSE) risk posed by bovine derived Processed Animal Proteins (PAPs) in feed was estimated, the diagnostic methods and their sensitivity to detect animal proteins in feed and compared different risk assessment methods for animal proteins in feed was reviewed. It was concluded that the current global limit of detection for PAPs in feed is still considered to be 0.1%. Data related to BSE monitoring and PAP production in the European Union (EU) were considered. A model (EFSA QRA PAP model) was developed to study the magnitude of the total BSE infectivity in PAPs and in ruminant feed under a certain scenario assuming some specific crosscontaminations. On the basis of the 2009 BSE surveillance data in the EU, assuming a 0.1% contamination (the limit of detection for PAP in feed) with non-ruminant PAPs and according to the EFSA QRA PAP model, the total BSE infectivity load that could enter in cattle feed per year in the EU would be equivalent to 0.2 Cattle oral Infectious Dose 50%4 (Co ID50) (9 x 10-5 – 1.3 CI95%) (that would mean that less than one additional BSE infected cattle could be expected in the EU cattle population per year with an upper 95% confidence). The specific scenario described by the model and the related assumptions and uncertainties are discussed in this scientific opinion.

© European Food Safety Authority, 2011

KEY WORDS

Bovine Spongiform Encephalopathy (BSE), quantitative risk assessment, Processed Animal Proteins (PAP), Cat 3 Animal By-Products

1 On request from the European Commission, Question No EFSA-Q-2010-00001, adopted on 09 December 2010.

2 Panel members: Olivier Andreoletti, Herbert Budka, Sava Buncic, John D Collins, John Griffin, Tine Hald, Arie Havelaar, James Hope, Günter Klein, James McLauchlin, Christine Müller-Graf, Christophe Nguyen-The, Birgit Noerrung, Luisa Peixe, Miguel Prieto Maradona, Antonia Ricci, John Sofos, John Threlfall, Ivar Vågsholm and Emmanuel Vanopdenbosch. Correspondence:

biohaz@efsa.europa.eu

3 Acknowledgement: The Panel wishes to thank the members of the Working Group on the review of the QRA of the residual BSE risk of MBM: Amie Adkin, Olivier Andreoletti, Philip Comer, Christian Ducrot, Michael Gravenor, Matthias Greiner, James Hope, Christine Müller-Graf and Emmanuel Vanopdenbosch for the preparatory work on this scientific opinion.

4 The oral dose which infects 50% of cattle in an experimental test.

Suggested citation: EFSA Panel on Biological Hazards (BIOHAZ); Scientific Opinion on the revision of the quantitative risk assessment (QRA) of the BSE risk posed by processed animal proteins (PAPs). EFSA Journal 2011;9(1):1947. [80 pp.]

doi:10.2903/j.efsa.2011.1947. Available online: www.efsa.europa.eu/efsajournal


SNIP...

CONCLUSIONS AND RECOMMENDATIONS

CONCLUSIONS

• The current global limit of detection for PAPs in feed is still considered to be 0.1%.

• The EFSA 2004 QRA model was reviewed and compared with other published similar risk assessments. The structure of the model is considered to be still suitable for purpose of assessing the residual exposure from Classical BSE for cattle posed by bovine derived processed animal proteins at European Union level.

• For more specific questions and questions concerning particular countries, a more specific or different model should be considered.

• An updated version of the EFSA 2004 QRA model was developed (called EFSA QRA PAP model) to answer the specific terms of reference of this mandate.

• Scientific input data were reviewed and updated. Certain parameters were considered to be conservative and uncertainties were identified.

• The EFSA QRA PAP model relies on the continuation of the current SRM policy and TSE monitoring system. It also assumes that only Category 3 Animal By-Product material is allowed to enter in PAP produced from ruminant material.

• The EFSA QRA PAP model relies on the specific scenario described and on specific assumptions like homogenous mixing. While conservative values are used, uncertainties of certain parameters (i.e. the ratio of detected vs undetected infected animals, the probability of incomplete SRM removal and the amount of infectious tissue remaining after incomplete SRM removal) were identified. Changes in scientific knowledge would require an adjustment of the model.

• The EFSA QRA PAP model calculations are based on the present available data, including unofficial data about PAP production communicated directly by industry. Changes in PAP and feed production would require adjustment of the model input data.

• Based on 2009 BSE surveillance data and according to the EFSA QRA PAP model, assuming a 0.1% contamination (which is the limit of detection for PAPs in feed) with non-ruminant PAPs, the total BSE infectivity load that could enter in cattle feed in the EU would be equivalent to 0.2 Co ID50 (9 x 10-5 – 1.3 CI95%) (that would mean that less than one additional BSE infected cattle could be expected in the EU cattle population per year with an upper 95% confidence).

• Considering the many uncertainties related to Atypical BSE L and H (prevalence, tissue distribution of the infectious agent, efficacy of rendering process for agent inactivation) the risk of Atypical BSE transmission through PAPs cannot be assessed. It should however not be disregarded.

RECOMMENDATIONS

• In order to improve the limit of detection of animal proteins in feed the development of analytical methods should be continued.

• Considering the limitations of the model (including the scenario and the uncertainties), if the use of some mammalian PAPs for feeding animals should be reintroduced the risk of (re-)emergence of TSEs in cattle should be taken into account.

• In case of modification of the mitigation measures against BSE this assessment should be updated. The most important measures that were assumed in the EFSA QRA PAP model are the removal of SRMs and strict separation of ruminant and non-ruminant sources in the production and distribution of PAPs.

• Specific data related to the PAP production system and their distribution and use should be collected.

• Specific knowledge related to Atypical BSE should be expanded. In particular with regard to its prevalence, pathogenesis in natural host, capacity to propagate in other animal species and resistance to inactivation processes applied in rendering plants.

• When appropriate information on Atypical BSE will be available the present assessment should be revised.


http://www.efsa.europa.eu/en/efsajournal/doc/1947.pdf



> When appropriate information on Atypical BSE will


> be available the present assessment should be revised.




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://collections.europarchive.org/tna/20080102153800/http://www.bseinquiry.gov.uk/files/yb/1995/08/24002001.pdf


THIS is what happens when you have the industry run the government $$$

WE now know that atypical BSE is more virulent than typical BSE, but the USA is still feeding cows to cows (see banned product in commerce to 2008), and that the infamous August 4, 1997, partial and voluntary mad cow feed ban in the USA was nothing more than ink on paper, so why has the SRM regulations not changed yet $$$

Saturday, June 12, 2010

PUBLICATION REQUEST AND FOIA REQUEST Project Number: 3625-32000-086-05 Study of Atypical Bse

http://bse-atypical.blogspot.com/2010/06/publication-request-and-foia-request.html


Wednesday, July 28, 2010

re-Freedom of Information Act Project Number 3625-32000-086-05, Study of Atypical BSE UPDATE July 28, 2010

http://bse-atypical.blogspot.com/2010/07/re-freedom-of-information-act-project.html


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



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


BANNED MAD COW FEED IN COMMERCE IN ALABAMA (where h-g-BSEalabama mad cow was documented)

Date: September 6, 2006 at 7:58 am PST PRODUCT

a) EVSRC Custom dairy feed, Recall # V-130-6;

b) Performance Chick Starter, Recall # V-131-6;

c) Performance Quail Grower, Recall # V-132-6;

d) Performance Pheasant Finisher, Recall # V-133-6.

CODE None RECALLING FIRM/MANUFACTURER Donaldson & Hasenbein/dba J&R Feed Service, Inc., Cullman, AL, by telephone on June 23, 2006 and by letter dated July 19, 2006. Firm initiated recall is complete.

REASON

Dairy and poultry feeds were possibly contaminated with ruminant based protein.

VOLUME OF PRODUCT IN COMMERCE 477.72 tons

DISTRIBUTION AL

______________________________

http://www.fda.gov/bbs/topics/enforce/2006/ENF00968.html


PRODUCT Bulk custom dairy pre-mixes,

Recall # V-120-6 CODE None RECALLING FIRM/MANUFACTURER Ware Milling Inc., Houston, MS, by telephone on June 23, 2006. Firm initiated recall is complete. REASON Possible contamination of dairy animal feeds with ruminant derived meat and bone meal.

VOLUME OF PRODUCT IN COMMERCE 350 tons

DISTRIBUTION AL and MS

______________________________

PRODUCT

a) Tucker Milling, LLC Tm 32% Sinking Fish Grower, #2680-Pellet, 50 lb. bags, Recall # V-121-6;

b) Tucker Milling, LLC #31120, Game Bird Breeder Pellet, 50 lb. bags, Recall # V-122-6;

c) Tucker Milling, LLC #31232 Game Bird Grower, 50 lb. bags, Recall # V-123-6;

d) Tucker Milling, LLC 31227-Crumble, Game Bird Starter, BMD Medicated, 50 lb bags, Recall # V-124-6;

e) Tucker Milling, LLC #31120, Game Bird Breeder, 50 lb bags, Recall # V-125-6;

f) Tucker Milling, LLC #30230, 30 % Turkey Starter, 50 lb bags, Recall # V-126-6;

g) Tucker Milling, LLC #30116, TM Broiler Finisher, 50 lb bags, Recall # V-127-6

CODE All products manufactured from 02/01/2005 until 06/20/2006 RECALLING FIRM/MANUFACTURER Recalling Firm: Tucker Milling LLC, Guntersville, AL, by telephone and visit on June 20, 2006, and by letter on June 23, 2006. Manufacturer: H. J. Baker and Brothers Inc., Stamford, CT. Firm initiated recall is ongoing.

REASON Poultry and fish feeds which were possibly contaminated with ruminant based protein were not labeled as "Do not feed to ruminants".

VOLUME OF PRODUCT IN COMMERCE 7,541-50 lb bags

DISTRIBUTION AL, GA, MS, and TN

END OF ENFORCEMENT REPORT FOR AUGUST 9, 2006

###

http://www.fda.gov/bbs/topics/ENFORCE/2006/ENF00964.html


Subject: MAD COW FEED RECALL AL AND FL VOLUME OF PRODUCT IN COMMERCE 125 TONS Products manufactured from 02/01/2005 until 06/06/2006

Date: August 6, 2006 at 6:16 pm PST PRODUCT

a) CO-OP 32% Sinking Catfish, Recall # V-100-6;

b) Performance Sheep Pell W/Decox/A/N, medicated, net wt. 50 lbs, Recall # V-101-6;

c) Pro 40% Swine Conc Meal -- 50 lb, Recall # V-102-6;

d) CO-OP 32% Sinking Catfish Food Medicated, Recall # V-103-6;

e) "Big Jim's" BBB Deer Ration, Big Buck Blend, Recall # V-104-6;

f) CO-OP 40% Hog Supplement Medicated Pelleted, Tylosin 100 grams/ton, 50 lb. bag, Recall # V-105-6;

g) Pig Starter Pell II, 18% W/MCDX Medicated 282020, Carbadox -- 0.0055%, Recall # V-106-6;

h) CO-OP STARTER-GROWER CRUMBLES, Complete Feed for Chickens from Hatch to 20 Weeks, Medicated, Bacitracin Methylene Disalicylate, 25 and 50 Lbs, Recall # V-107-6;

i) CO-OP LAYING PELLETS, Complete Feed for Laying Chickens, Recall # 108-6;

j) CO-OP LAYING CRUMBLES, Recall # V-109-6;

k) CO-OP QUAIL FLIGHT CONDITIONER MEDICATED, net wt 50 Lbs, Recall # V-110-6;

l) CO-OP QUAIL STARTER MEDICATED, Net Wt. 50 Lbs, Recall # V-111-6;

m) CO-OP QUAIL GROWER MEDICATED, 50 Lbs, Recall # V-112-6 CODE

Product manufactured from 02/01/2005 until 06/06/2006

RECALLING FIRM/MANUFACTURER Alabama Farmers Cooperative, Inc., Decatur, AL, by telephone, fax, email and visit on June 9, 2006. FDA initiated recall is complete.

REASON Animal and fish feeds which were possibly contaminated with ruminant based protein not labeled as "Do not feed to ruminants".

VOLUME OF PRODUCT IN COMMERCE 125 tons

DISTRIBUTION AL and FL

END OF ENFORCEMENT REPORT FOR AUGUST 2, 2006

###

http://www.fda.gov/bbs/topics/enforce/2006/ENF00963.html


MAD COW FEED RECALL USA EQUALS 10,878.06 TONS NATIONWIDE Sun Jul 16, 2006 09:22 71.248.128.67

RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINE -- CLASS II

______________________________

PRODUCT

a) PRO-LAK, bulk weight, Protein Concentrate for Lactating Dairy Animals, Recall # V-079-6;

b) ProAmino II, FOR PREFRESH AND LACTATING COWS, net weight 50lb (22.6 kg), Recall # V-080-6;

c) PRO-PAK, MARINE & ANIMAL PROTEIN CONCENTRATE FOR USE IN ANIMAL FEED, Recall # V-081-6;

d) Feather Meal, Recall # V-082-6 CODE

a) Bulk

b) None

c) Bulk

d) Bulk

RECALLING FIRM/MANUFACTURER H. J. Baker & Bro., Inc., Albertville, AL, by telephone on June 15, 2006 and by press release on June 16, 2006. Firm initiated recall is ongoing.

REASON

Possible contamination of animal feeds with ruminent derived meat and bone meal.

VOLUME OF PRODUCT IN COMMERCE 10,878.06 tons

DISTRIBUTION Nationwide

END OF ENFORCEMENT REPORT FOR July 12, 2006

###

http://www.fda.gov/bbs/topics/enforce/2006/ENF00960.html


Tuesday, March 2, 2010

Animal Proteins Prohibited in Ruminant Feed/Adulterated/Misbranded Rangen Inc 2/11/10 USA

http://madcowfeed.blogspot.com/2010/03/animal-proteins-prohibited-in-ruminant.html


Monday, March 1, 2010

ANIMAL PROTEIN I.E. MAD COW FEED IN COMMERCE A REVIEW 2010

http://madcowfeed.blogspot.com/2010/03/animal-protien-ie-mad-cow-feed-in.html


Terry S. Singeltary Sr. (Submitted question): Monday, April 5, 2010

Update on Feed Enforcement Activities to Limit the Spread of BSE April 5, 2010

http://madcowfeed.blogspot.com/2010/04/update-on-feed-enforcement-activities.html


Friday, April 23, 2010

Upcoming BSE Webinar on Thursday, April 22, 2010 a review

http://bseusa.blogspot.com/2010/04/upcoming-bse-webinar-on-thursday-april.html


Friday, October 8, 2010

Scientific reasons for a feed ban of meat-and-bone meal, applicable to all farmed animals including cattle, pigs, poultry, farmed fish and pet food

http://madcowfeed.blogspot.com/2010/10/scientific-reasons-for-feed-ban-of-meat.html


O.4.3

Spread of BSE prions in cynomolgus monkeys (Macaca fascicularis) after oral transmission

Edgar Holznagel1, Walter Schulz-Schaeffer2, Barbara Yutzy1, Gerhard Hunsmann3, Johannes Loewer1 1Paul-Ehrlich-Institut, Federal Institute for Sera and Vaccines, Germany; 2Department of Neuropathology, Georg-August University, Göttingen, Germany, 3Department of Virology and Immunology, German Primate Centre, Göttingen, Germany

Background: BSE-infected cynomolgus monkeys represent a relevant animal model to study the pathogenesis of variant Creutzfeldt-Jacob disease (vCJD).

Objectives: To study the spread of BSE prions during the asymptomatic phase of infection in a simian animal model.

Methods: Orally BSE-dosed macaques (n=10) were sacrificed at defined time points during the incubation period and 7 orally BSE-dosed macaques were sacrificed after the onset of clinical signs. Neuronal and non-neuronal tissues were tested for the presence of proteinase-K-resistant prion protein (PrPres) by western immunoblot and by paraffin-embedded tissue (PET) blot technique.

Results: In clinically diseased macaques (5 years p.i. + 6 mo.), PrPres deposits were widely spread in neuronal tissues (including the peripheral sympathetic and parasympathetic nervous system) and in lymphoid tissues including tonsils. In asymptomatic disease carriers, PrPres deposits could be detected in intestinal lymph nodes as early as 1 year p.i., but CNS tissues were negative until 3 – 4 years p.i. Lumbal/sacral segments of the spinal cord and medulla oblongata were PrPres positive as early as 4.1 years p.i., whereas sympathetic trunk and all thoracic/cervical segments of the spinal cord were still negative for PrPres. However, tonsil samples were negative in all asymptomatic cases.

Discussion: There is evidence for an early spread of BSE to the CNS via autonomic fibres of the splanchnic and vagus nerves indicating that trans-synaptical spread may be a time-limiting factor for neuroinvasion. Tonsils were predominantly negative during the main part of the incubation period indicating that epidemiological vCJD screening results based on the detection of PrPres in tonsil biopsies may mostly tend to underestimate the prevalence of vCJD among humans.

P.4.23

Transmission of atypical BSE in humanized mouse models

Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1 1Case Western Reserve University, USA; 2Instituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University (Previously at USDA National Animal Disease Center), USA

Background: Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Atypical BSE cases have been discovered in three continents since 2004; they include the L-type (also named BASE), the H-type, and the first reported case of naturally occurring BSE with mutated bovine PRNP (termed BSE-M). The public health risks posed by atypical BSE were largely undefined.

Objectives: To investigate these atypical BSE types in terms of their transmissibility and phenotypes in humanized mice. Methods: Transgenic mice expressing human PrP were inoculated with several classical (C-type) and atypical (L-, H-, or Mtype) BSE isolates, and the transmission rate, incubation time, characteristics and distribution of PrPSc, symptoms, and histopathology were or will be examined and compared.

Results: Sixty percent of BASE-inoculated humanized mice became infected with minimal spongiosis and an average incubation time of 20-22 months, whereas only one of the C-type BSE-inoculated mice developed prion disease after more than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse brains was biochemically different from bovine BASE or sCJD. PrPSc was also detected in the spleen of 22% of BASE-infected humanized mice, but not in those infected with sCJD. Secondary transmission of BASE in the humanized mice led to a small reduction in incubation time. The atypical BSE-H strain is also transmissible with distinct phenotypes in the humanized mice, but no BSE-M transmission has been observed so far.

Discussion: Our results demonstrate that BASE is more virulent than classical BSE, has a lymphotropic phenotype, and displays a modest transmission barrier in our humanized mice.

BSE-H is also transmissible in our humanized Tg mice.

The possibility of more than two atypical BSE strains will be discussed.

Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.

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


P03.137

Transmission of BSE to Cynomolgus Macaque, a Non-human Primate; Development of Clinical Symptoms and Tissue Distribution of PrPSC

Yamakawa, Y1; Ono, F2; Tase, N3; Terao, K3; Tannno, J3; Wada, N4; Tobiume, M5; Sato, Y5; Okemoto-Nakamura, Y1; Hagiwara, K1; Sata, T5 1National Institure of Infectious diseases, Cell biology and Biochemistry, Japan; 2Corporation for Production and Research Laboratory Primates., Japan; 3National Institure of Biomedical Innovation, Tsukuba Primate Reserch Center, Japan; 4Yamauchi Univ., Veterinary Medicine, Japan; 5National Institure of Infectious diseases, Pathology, Japan

Two of three cynomolgus monkeys developed abnormal neuronal behavioral signs at 30-(#7) and 28-(#10) months after intracerebral inoculation of 200ul of 10% brain homogenates of BSE affected cattle (BSE/JP6). Around 30 months post inoculation (mpi), they developed sporadic anorexia and hyperekplexia with squeal against environmental stimulations such as light and sound. Tremor, myoclonic jerk and paralysis became conspicuous during 32 to 33-mpi, and symptoms become worsened according to the disease progression. Finally, one monkey (#7) fell into total paralysis at 36-mpi. This monkey was sacrificed at 10 days after intensive veterinary care including infusion and per oral supply of liquid food. The other monkey (#10) had to grasp the cage bars to keep an upright posture caused by the sever ataxia. This monkey was sacrificed at 35-mpi. EEG of both monkeys showed diffuse slowing. PSD characteristic for sporadic CJD was not observed in both monkeys. The result of forearm movement test showed the hypofunction that was observed at onset of clinical symptoms. Their cognitive function determined by finger maze test was maintained at the early stage of sideration. However, it was rapidly impaired followed by the disease progression. Their autopsied tissues were immunochemically investigated for the tissue distribution of PrPSc. Severe spongiform change in the brain together with heavy accumulation of PrPSc having the type 2B/4 glycoform profile confirmed successful transmission of BSE to Cynomolgus macaques. Granular and linear deposition of PrPSC was detected by IHC in the CNS of both monkeys. At cerebral cortex, PrPSC was prominently accumulated in the large plaques. Sparse accumulation of PrPSc was detected in several peripheral nerves of #7 but not in #10 monkey, upon the WB analysis. Neither #7 nor #10 monkey accumulated detectable amounts of PrPSc in their lymphatic organs such as tonsil, spleen, adrenal grands and thymus although PrPSc was barely detected in the submandibular lymph node of #7 monkey. Such confined tissue distribution of PrPSc after intracerebral infection with BSE agent is not compatible to that reported on the Cynomolgus macaques infected with BSE by oral or intra-venous (intra-peritoneal) routs, in which PrPSc was accumulated at not only CNS but also widely distributed lymphatic tissues.

P04.27

Experimental BSE Infection of Non-human Primates: Efficacy of the Oral Route

Holznagel, E1; Yutzy, B1; Deslys, J-P2; Lasmézas, C2; Pocchiari, M3; Ingrosso, L3; Bierke, P4; Schulz-Schaeffer, W5; Motzkus, D6; Hunsmann, G6; Löwer, J1 1Paul-Ehrlich-Institut, Germany; 2Commissariat à l´Energie Atomique, France; 3Instituto Superiore di Sanità, Italy; 4Swedish Institute for Infectious Disease control, Sweden; 5Georg August University, Germany; 6German Primate Center, Germany

Background: In 2001, a study was initiated in primates to assess the risk for humans to contract BSE through contaminated food. For this purpose, BSE brain was titrated in cynomolgus monkeys.

Aims: The primary objective is the determination of the minimal infectious dose (MID50) for oral exposure to BSE in a simian model, and, by in doing this, to assess the risk for humans. Secondly, we aimed at examining the course of the disease to identify possible biomarkers.

Methods: Groups with six monkeys each were orally dosed with lowering amounts of BSE brain: 16g, 5g, 0.5g, 0.05g, and 0.005g. In a second titration study, animals were intracerebrally (i.c.) dosed (50, 5, 0.5, 0.05, and 0.005 mg).

Results: In an ongoing study, a considerable number of high-dosed macaques already developed simian vCJD upon oral or intracerebral exposure or are at the onset of the clinical phase. However, there are differences in the clinical course between orally and intracerebrally infected animals that may influence the detection of biomarkers.

Conclusions: Simian vCJD can be easily triggered in cynomolgus monkeys on the oral route using less than 5 g BSE brain homogenate. The difference in the incubation period between 5 g oral and 5 mg i.c. is only 1 year (5 years versus 4 years). However, there are rapid progressors among orally dosed monkeys that develop simian vCJD as fast as intracerebrally inoculated animals.

The work referenced was performed in partial fulfilment of the study “BSE in primates“ supported by the EU (QLK1-2002-01096).

http://www.neuroprion.org/resources/pdf_docs/conferences/prion2007/abstract_book.pdf


Simian vCJD can be easily triggered in cynomolgus monkeys on the oral route using less than 5 g BSE brain homogenate.

http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf


WE know now, and we knew decades ago, that 5.5 grams of suspect feed in TEXAS was enough to kill 100 cows.

look at the table and you'll see that as little as 1 mg (or 0.001 gm) caused 7% (1 of 14) of the cows to come down with BSE;

Risk of oral infection with bovine spongiform encephalopathy agent in primates

Corinne Ida Lasmézas, Emmanuel Comoy, Stephen Hawkins, Christian Herzog, Franck Mouthon, Timm Konold, Frédéric Auvré, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Nicole Salès, Gerald Wells, Paul Brown, Jean-Philippe Deslys Summary The uncertain extent of human exposure to bovine spongiform encephalopathy (BSE)--which can lead to variant Creutzfeldt-Jakob disease (vCJD)--is compounded by incomplete knowledge about the efficiency of oral infection and the magnitude of any bovine-to-human biological barrier to transmission. We therefore investigated oral transmission of BSE to non-human primates. We gave two macaques a 5 g oral dose of brain homogenate from a BSE-infected cow. One macaque developed vCJD-like neurological disease 60 months after exposure, whereas the other remained free of disease at 76 months. On the basis of these findings and data from other studies, we made a preliminary estimate of the food exposure risk for man, which provides additional assurance that existing public health measures can prevent transmission of BSE to man.

snip...

BSE bovine brain inoculum

100 g 10 g 5 g 1 g 100 mg 10 mg 1 mg 0·1 mg 0·01 mg

Primate (oral route)* 1/2 (50%)

Cattle (oral route)* 10/10 (100%) 7/9 (78%) 7/10 (70%) 3/15 (20%) 1/15 (7%) 1/15 (7%)

RIII mice (ic ip route)* 17/18 (94%) 15/17 (88%) 1/14 (7%)

PrPres biochemical detection

The comparison is made on the basis of calibration of the bovine inoculum used in our study with primates against a bovine brain inoculum with a similar PrPres concentration that was inoculated into mice and cattle.8 *Data are number of animals positive/number of animals surviving at the time of clinical onset of disease in the first positive animal (%). The accuracy of bioassays is generally judged to be about plus or minus 1 log. ic ip=intracerebral and intraperitoneal.

Table 1: Comparison of transmission rates in primates and cattle infected orally with similar BSE brain inocula

Published online January 27, 2005

http://www.thelancet.com/journal/journal.isa


It is clear that the designing scientists must also have shared Mr Bradleys surprise at the results because all the dose levels right down to 1 gram triggered infection.

http://web.archive.org/web/20040523230128/www.bseinquiry.gov.uk/files/ws/s145d.pdf


it is clear that the designing scientists must have also shared Mr Bradleyâs surprise at the results because all the dose levels right down to 1 gram triggered infection.

http://web.archive.org/web/20030526212610/http://www.bseinquiry.gov.uk/files/ws/s147f.pdf


Docket No, 04-047-l Regulatory Identification No. (RIN) 091O-AF46 NEW BSE SAFEGUARDS (comment submission)

http://madcowfeed.blogspot.com/2008/07/docket-no-04-047-l-regulatory.html


BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01

http://www.regulations.gov/fdmspublic/ContentViewer?objectId=09000064801f8152&disposition=attachment&contentType=msw8


Docket No. 2003N-0312 Animal Feed Safety System [TSS SUBMISSION]

http://www.fda.gov/ohrms/dockets/dockets/03n0312/03N-0312_emc-000001.txt


Docket Management Docket: 02N-0273 - Substances Prohibited From Use in

Animal Food or Feed; Animal Proteins Prohibited in Ruminant Feed

Comment Number: EC -10

Accepted - Volume 2

http://www.fda.gov/ohrms/dockets/dailys/03/Jan03/012403/8004be07.html


PART 2

http://www.fda.gov/ohrms/dockets/dailys/03/Jan03/012403/8004be09.html


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


Tuesday, December 14, 2010 TAFS1ripmomdod12-14-97hvcjd

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

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/tafs1-position-paper-on-relaxation-of.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/pls/apex/f?p=2400:1001:5492868805159684::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,86129


Monday, January 17, 2011

MAD COW Update on Feed Enforcement Activities to Limit the Spread of BSE January 13, 2011

January 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/mad-cow-update-on-feed-enforcement.html


Thursday, November 18, 2010

UNITED STATES OF AMERICA VS GALEN J. NIEHUES FAKED MAD COW FEED TEST ON 92 BSE INSPECTION REPORTS FOR APPROXIMATELY 100 CATTLE OPERATIONS

http://bse-atypical.blogspot.com/2010/11/united-states-of-america-vs-galen-j.html


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, June 16, 2010

Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties

http://creutzfeldt-jakob-disease.blogspot.com/2010/06/defining-sporadic-creutzfeldt-jakob.html


Tuesday, January 18, 2011

Agent strain variation in human prion disease: insights from a molecular and pathological review of the National Institutes of Health series of experimentally transmitted disease

http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/agent-strain-variation-in-human-prion.html




Wednesday, January 19, 2011


EFSA and ECDC review scientific evidence on possible links between TSEs in animals and humans Webnachricht 19 Januar 2011



http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/efsa-and-ecdc-review-scientific.html




DID EVERYONE FILL OUT THEIR CJD QUESIONNAIRE FROM THE CDC AND OR THE CJD FOUNDATION ???

Friday, November 30, 2007

CJD QUESTIONNAIRE USA CWRU AND CJD FOUNDATION

http://cjdquestionnaire.blogspot.com/



Thursday, November 15, 2007

EFSA opinion on the BSE related public health risks of certain animal proteins in animal feed

http://efsaopinionbseanimalprotein.blogspot.com/2007/11/efsa-opinion-on-bse-related-public.html



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

EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2 December 2010

EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2 December 2010

EFSA has published today a scientific opinion on Transmissible Spongiform Encephalopathy (TSE)[1] infectivity in the tissues of small ruminants such as goats and sheep[2]. Based on new scientific evidence and taking into account the current situation with respect to the occurrence of TSEs in animals in the EU, EFSA’s Biological Hazards (BIOHAZ) panel has reviewed the distribution of TSE infectivity in small ruminant tissues and has provided for the first time a quantification of the impact of current SRM measures in managing TSE-related risks in small ruminants. The removal of Specified Risk Materials (SRM)[3] such as the brain and spinal cord from animals going into the food chain protects consumers from TSE-related risks. EFSA’s advice will help inform risk managers in the implementation of measures outlined in the TSE Road Map 2[4].

In this opinion, EFSA’s Biological Hazards (BIOHAZ) Panel reviews the latest scientific data on the infectivity of different small ruminant tissues for Classical scrapie, Atypical scrapie and BSE and takes into consideration aspects such as the age and genetic makeup of the animals. With the exception of Bovine Spongiform Encephalopathy (BSE), other TSEs in animals such as scrapie have not been found to be transmissible to humans.

The Panel noted that only one single case[5] of naturally occurring BSE has ever been identified in small ruminants worldwide. Moreover, the opinion provides a set of simulations quantifying for the first time the impact of different SRM options on reducing the risk from the possible presence of BSE in small ruminants. The Panel says that, should a BSE-infected small ruminant ever enter the food chain[6], the current SRM policy would allow a 10-fold reduction of the infectivity load, that is the level of TSE agent present in an infected animal. Experts also advise that the use of the dressed carcass only (excluding the head and the spinal cord) would allow a greater reduction of the BSE exposure risk than the current SRM measures.

With respect to classical scrapie, the panel concludes that, as for BSE, the current SRM policy allows a 10-fold reduction of the infectivity load. The Panel points out that a modification of the SRM list based only on considerations for BSE will also have an impact on human exposure to Classical and Atypical scrapie agents. In addition, the Panel adds that the infectivity of goat kids below 3 months of age is negligible, even if they come from infected herds.

For Atypical scrapie in sheep and goats, the Panel says that since some infectivity, albeit at low levels, can be found in other tissues[7] than those specified in the SRM list, it cannot be assumed that the current SRM measures will prevent the entry of the Atypical scrapie agent into the food chain.

The Panel recommends further improving data collection and risk assessment in this area of work. In particular, it recommends updating this opinion when data from ongoing experiments, such as those concerning the development of BSE in goats, become available. The Panel specifies that the development of specific assessment models could provide a more precise estimate of the impact of SRM removal policies on managing risks from TSEs.

Scientific Opinion on BSE/TSE infectivity in small ruminant tissues

Opinion on TSE Infectivity distribution in ruminant tissues issued by the Scientific Steering Committee (SSC) of the European Commission of 2002 For media enquiries, please contact: Ian Palombi, Press Officer or Steve Pagani, Head of Press Office Tel: +39 0521 036 149 Email: Press@efsa.europa.eu

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

[1] Transmissible Spongiform Encephalopathies (TSEs) are a family of diseases that affect the brain and nervous system of humans and animals. The diseases are characterised by a degeneration of brain tissue giving it a sponge-like appearance. TSEs include Bovine Spongiform Encephalopathy (BSE) principally found in cattle, scrapie in sheep and goats, as well as variant Creutzfeldt Jakob Disease (vCJD) and other diseases in humans. Whilst scrapie (classical and atypical) has been known for centuries as a disease affecting sheep and goats , to date only one single case of naturally occurring BSE has ever been identified in small ruminants. More information on TSEs

[2] This opinion updates a previous opinion on TSE Infectivity distribution in ruminant tissues issued by the Scientific Steering Committee (SSC) of the European Commission of 2002.

[3] Specified risk materials are the tissues containing the highest risk of BSE infectivity. In the EU the removal of SRM, which is the most important public health measure to protect consumers from BSE risk, is mandatory since 2000. Various tissues including the brain, spinal cord, vertebral column, tonsils and ileum are classified and then consequently removed as SRM with specific rules defined by animal species and according to age. The list of SRM is indicated in Annex 5 of Regulation EC 999/2001.

[4] The road map is a strategic document of the European Commission which outlines possible future changes to measures in place in the EU to manage the risk of BSE and other TSEs and ensure a high level of consumer protection. On 16 July 2010 the Commission adopted a Communication to the European Parliament and the Council outlining areas where future possible changes to EU TSE-related measures could be made. The TSE Road Map 2 – A strategy paper on Transmissible Spongiform Encephalopathies for 2010-2015

[5] One goat slaughtered in 2002.

[6] In the EU, sheep and goats found to be infected with TSEs are excluded from the food and feed chain.

[7] Atypical scrapie infectivity can be found for instance in lymphoid tissues, nerves and skeletal muscles.

http://www.efsa.europa.eu/en/press/news/biohaz101202.htm?WT.mc_id=EFSAHL01&emt=1


Scientific Opinion on BSE/TSE infectivity in small ruminant tissues Question number: EFSA-Q-2010-00052

Adopted: 21 October 2010

http://www.efsa.europa.eu/en/scdocs/doc/s1875.pdf


http://www.efsa.europa.eu/en/scdocs/doc/s1875.pdf


please see ;

http://www.goatbse.eu/site/index.php


Scientific Opinion on BSE/TSE infectivity in small ruminant tissues Question number: EFSA-Q-2010-00052 Adopted: 21 October 2010

Summary (0.1 Mb)

Opinion (0.6 Mb)

Summary

Following a request from the European Commission (EC), the Panel on Biological Hazards (BIOHAZ Panel) was asked to deliver a scientific opinion on BSE/TSE infectivity in small ruminant tissues.

The most recent scientific opinion on TSE infectivity distribution in small ruminant tissues was published in January 2002 by the Scientific Steering Committees (SSC) and last amended in November 2002[1]. In recent years new scientific data relating to the infectivity of some tissues in small ruminants became available. Some of those findings related to the tissues from sheep and goats might have an impact to the current measures in relation to the Specified Risk Material (SRM) list of the Regulation (EC) 999/2001[2].

Therefore, the EC asked EFSA: i) to update, as regards small ruminants and on the basis of the most recent scientific data, the SSC scientific opinion from 2002 on TSE infectivity distribution in ruminant tissues; ii) to indicate based on the current epidemiological situation as regards BSE in the small ruminant population in EU, whether a review of the existing SRM list for small ruminants should be envisaged with regard to the potential exposure to the BSE agent.

The BIOHAZ Panel addressed the mandate by reviewing individually for Classical scrapie, BSE and Atypical scrapie in small ruminants aspects related to: i) tissue infectivity distribution according to the age and the genotype of sheep and goats; and ii) the infectious load in the different tissues.

In order to perform the assessment all the currently available scientific results were reviewed. Data about the TSE monitoring in small ruminants in the EU were provided by the European Commission and information on small ruminants slaughtered by species and age category in each EU Member State were provided by the EFSA Focal Points Network.

It was emphasized that this assessment required several assumptions. Moreover, the estimates of the infectious load are based on a simple approach using computations based on a low and a high estimate of each of the parameters. This provides order of magnitude estimates of the infectious load of TSE agents entering into the food chain at EU 27 level. This approach could be replaced by a probabilistic model to provide more insight into the uncertainties. However, due to time and resources constraints it was not possible for the BIOHAZ Panel to develop and validate such a probabilistic model within the framework of this mandate.

Considering Classical scrapie in small ruminants it was concluded that the current SRM policy allows a reduction of the relative infectivity associated to the carcass of an infected animal of about 1 log10 (infectious load as expressed in IC ID50[3] in C57Bl6 mice). The infectivity load as expressed in the opinion (IC ID50 in C57Bl6 mice) cannot be related to any quantifiable dietary transmission risk in farmed animals or humans.

As regards to Classical scrapie in goats, it was further concluded that, according to the currently available knowledge, goat kids below 3 months of age, even coming from infected herds, represent a negligible source of infectivity for the food chain.

On the basis of data collected between 2007 and 2009, the total number of Classical scrapie infected animals that could enter yearly into the food chain in the EU27 as a whole was estimated to approximately range between 16,000 and 67,000 (most probable estimate 29, 000) for sheep and between 10,000 and 34,000 (most probable estimate 13,000) for goats.

The Panel pointed out that Classical scrapie is present in a majority of EU member states. However because differences in the prevalence of the disease, population size and production system (age at slaughter), there are significant differences between certain member states with regards to Classical scrapie infectivity load that may enter the food chain. This heterogeneity and the differences in consumption pattern between countries and regions mean that the dietary exposure to Classical scrapie cannot be considered to be homogeneous in the EU27.

It was furthermore concluded that at the EU27 level, the current SRM policy in force allows a global reduction of the potential exposure to Classical scrapie which can be estimated to be around 1 log10 (infectious load as expressed in IC ID50 in C57Bl6 mice).

When considering BSE in small ruminants, the Panel concluded that with 95% confidence the the number of BSE cases that could enter yearly into the food chain in the EU is ranging between 0 and 240 for sheep and between 0 and 381 for goats. This estimate argues against any current widespread BSE epidemic within the EU small ruminant population.

The BIOHAZ Panel indicated that the current SRM policy allows a reduction of the relative infectivity associated to the carcass of a BSE infected animal of about 1 log10 (infectious load as expressed in IC ID50 in C57Bl6 mice). The infectivity load as expressed in the opinion (IC ID50 in C57Bl6 mice) cannot be related to any quantifiable dietary transmission risk in farmed animals or humans.

It was further emphasized that preliminary biochemical and immunohistochemical data in goats suggest that there might be no major involvement of the lymphoid tissues in preclinical and clinical phase of the disease after oral experimental challenge. Before more complete information becomes available it is not possible to provide reliable specific estimates of the impact of SRM removal measures on the BSE exposure that would be associated with an infected goat entering into the food chain. The Panel highlighted that in this context the estimates of the impact of SRM removal measures on the BSE exposure provided for BSE in sheep could be considered as a worst case scenario for BSE in goats.

As regards to Atypical scrapie both in sheep and goats it was concluded that low levels of infectivity can be present in peripheral tissues (lymphoid tissues, nerves, skeletal muscle) in preclinical and clinical cases of Atypical scrapie harbouring various genotypes. Consequently SRM measures cannot be assumed to prevent the entry of the Atypical scrapie agent into the food chain.

It was highlighted that there is currently no data on the kinetics of distribution of the Atypical scrapie agent into peripheral tissues of incubating small ruminants and that there are uncertainties on the Atypical scrapie pathogenesis and its true prevalence in the EU small ruminant population. Therefore, the Panel was not in position to provide an assessment of the current Atypical scrapie infectious load entering into the food chain.

In answering to the first Term of Reference, the BIOHAZ Panel revised the TSE tissue infectivity distribution in small ruminants and provided updated information within the body of the opinion (section 2, tables 1 to 12).

Considering the second Term of Reference, the BIOHAZ Panel provided a set of simulations illustrating the impact of different policy options on the BSE infectious load potentially present in an infected sheep. According to these simulations, the use of the dressed carcass[4] only would allow a greater reduction of the BSE exposure risk than the current SRM policy measures. The elimination of the ileum has a major impact on the relative reduction of the BSE infectivity load that might enter in the food chain from an animal aged below 12 months. The CNS (Central Nervous System) removal is the most efficient measure to reduce the relative infectivity load associated with a BSE infected small ruminant older than 12 months entering into the food chain.

It was finally indicated that a modification of the SRM list driven only by consideration about BSE will also impact on the dietary exposure to Classical scrapie and Atypical scrapie agents.

The BIOHAZ Panel recommended: i) to update the assessment once data from ongoing experiments will become available; ii) to develop a specific probabilistic model in order to provide more precise estimates of the impact of SRM removal on the infectious load of TSE agents entering into the food chain at EU 27 level; iii) to improve the quality of the data collected on the small ruminant population (e.g. age category and destination of the animal); and iv) to expand the current data collected in the context of the TSE surveillance activities by recording the tested animal age category and the type of rapid test used.

Published: 2 December 2010

http://www.efsa.europa.eu/en/scdocs/scdoc/1875.htm


http://www.efsa.europa.eu/en/scdocs/doc/s1875.pdf


3.2.1. Conclusions • According to the model developed by EFSA in its opinion of January 2007 the maximum number of BSE cases in the EU27 sheep population is equal to or below 4.2 per million sheep with a most probable value of 0, under the assumption of a 50% sensitivity of the screening test. • According to the model developed by EFSA in its opinion of January 2007 the maximum number of BSE cases in the EU27 goat population is equal to or below 53.7 per million goats with a most probable value of 14.7, under the assumption of a 50% sensitivity of the screening test. • There are uncertainties related to the technical limits of the methodology applied to detect BSE in sheep (discriminatory assay).

snip...

2.3. BSE

BSE agent possible spread in small ruminants has been considered as a major threat over the last 15

years.

To date, there has been:

• no report of naturally occurring BSE in sheep in the commercial situation,

• one confirmed case of natural BSE in a goat was reported in France 2002 (Eloit et al., 2005).

Both sheep and goats have been shown to be susceptible to the BSE agent and in the absence of natural cases to be studied, all the knowledge related to BSE pathogenesis in small ruminants relies on experimental challenges in sheep (Bellworthy et al., 2008; Bellworthy et al., 2005b; Gonzalez et al., 2005; Jeffrey et al., 2001b; van Keulen et al., 2008a) and goats EU “goatBSE project (FOOD-CT-2006-36353)8.

Like the situation in natural scrapie, PRNP polymorphisms have a major impact on BSE susceptibility and dissemination of the agent in the organs. However, PRNP genotypes that are associated with the highest susceptibility in the context of BSE in sheep are different from those observed for natural scrapie. Moreover it is now well documented that BSE agent can propagate in sheep bearing the ARR/ARR genotype after oral exposure (Andreoletti et al., 2006; Lantier et al., 2008).

The low natural prevalence of BSE in a number of species (including human) other than cattle that were exposed to cattle BSE suggests the existence of real barrier to transmission of this disease under natural conditions. However, recently the BSE agent in sheep was described to harbour a higher virulence and capacities to cross the transmission barrier than the original BSE cattle agent (Espinosa et al., 2007; Espinosa et al., 2009). These observations suggest that exposure to small ruminant passaged BSE agent might result in a higher transmission rate in a third species compared to that observed with cattle BSE.

8 Details available at http://www.goatbse.eu


BSE/TSE infectivity in small ruminant tissues

EFSA Journal 2010;8(11):1875 26

Recently presented data suggest that BSE adapted in small ruminants might have a higher efficacy to cross the human species barrier (as modelled in transgenic mice expressing the human PrP Met 129 gene) than cattle BSE (Plinstone et al., 2010). Currently the minimum BSE infectious dose that would allow to infect a human being remains unknown.

2.3.1. BSE in sheep

The distribution of PrPSc in sheep experimentally infected with BSE is very similar to that observed in sheep with Classical scrapie. It involves the lymphoreticular system, the peripheral nervous system, enteric nervous system, muscle, blood and Central nervous system (Foster et al., 1993; Jeffrey et al., 2001b; van Keulen et al., 2008b). More recently scant PrPSc deposits have been detected in the liver of clinical and preclinical and ARQ/ARQ BSE (Everest et al., 2009), which is consistent with earliest report of infectivity presence in this tissue (Bellworthy et al., 2005b).

The presence of PrPSc was described in lymphoreticular tissues from sheep clinically affected with ARR/ARR and VRQ/VRQ genotype (Andreoletti et al., 2006; Bellworthy et al., 2008) although with greatly prolonged incubation periods compared to ARQ/ARQ or AHQ/AHQ sheep. Together studies published by (Bellworthy et al., 2005b; van Keulen et al., 2008a) and the data presented by Lantier et al. (Lantier et al., 2008) provides an overall picture of the dissemination kinetics of the BSE agent in the organs of orally challenged ARQ/ARQ sheep (see Table 11).

snip...

2.3.2. BSE in goats

Until recently, there was no specific data describing the pathogenesis of the BSE agent following oral exposure of goats. In that context, BSE risk assessments undertaken so far in that species have relied on the assumption that BSE in goats would behave similarly to natural scrapie in goats and experimental BSE in sheep (EFSA, 2005a).

Within the framework of the European GoatBSE project (FOOD-CT-2006-36353; www.goatBSE.eu), oral challenge experiments of BSE to goats were performed using either cattle BSE isolate or experimental goat BSE isolate (INRA; the University of Edinburgh; Friedrich-Loeffler Institute).

Animals harbouring various PRNP genotypes were inoculated; the (expected) susceptible wild-type I142R211Q222/IRQ, the animals with lower susceptibility genotypes I142Q211Q222/IRQ, I142R211K222/IRQ and M142R211Q222/IRQ were used (EFSA Panel on Biological Hazards (BIOHAZ), 2009).

BSE/TSE infectivity in small ruminant tissues

EFSA Journal 2010;8(11):1875 29

Serial kills of a defined number of animals were performed at 6 and 12 and 24 months post infection. To date, PrPSc was detected in the brainstem (PTA-immunoblot and imunohistochemistry) of four wild-type goats 24 months post infection, which indicates a BSE-infection.

Additionally in these animals PrPSc deposition (Immunohistochemistry) was found in the gut (GALT) and the peripheral nervous system of the time point killed animals, but not in other lymphoid tissues.

These PrPSc detection results (Immunohistochemistry) are consistent with a lack of major involvement of the lymphoreticular tissues. In order to confirm these results, a panel of relevant tissues are currently being tested by bioassay ovine PrP overexpressing mice (TgshpXV).

In the meanwhile available results remain too preliminary to draw definitive conclusions. However, if confirmed, they would signify that BSE pathogenesis in sheep and goats might be dissimilar. Under such scenario the use of data collected in sheep infected with BSE could not anymore be considered pertinent to assess BSE risk in goat, other than to assume that extrapolating from sheep data would give a worst case scenario.

2.3.3. BSE conclusions

• In sheep:

Dissemination and distribution of PrPSc in the organs of orally challenged sheep bearing the ARQ/ARQ genotype is well documented.

The kinetics of distribution of the BSE agent in sheep harbouring other genotypes is less or not documented.

There is little information available on the infectivity titer in the tissues of BSE affected sheep at the different stages of the disease.

• In goats:

Preliminary data, after oral experimental challenge, suggest that there is apparently no major involvement of the lymphoid tissues in the preclinical and clinical phase. However, these data need to be completed and confirmed.

Pathogenesis data collected in sheep can be considered as a worst case scenario for BSE in goats.

There is no information available on the infectivity titer in the tissues of BSE affected goats at the different stages of the disease.

snip...

http://www.efsa.europa.eu/en/scdocs/doc/1875.pdf


SCIENTIFIC OPINION

Scientific Opinion on BSE/TSE infectivity in small ruminant tissues1

EFSA Panel on Biological Hazards (BIOHAZ)2, 3

European Food Safety Authority (EFSA), Parma, Italy

ABSTRACT

The objectives addressed were i) to provide an update on TSE (Transmissible Spongiform Encephalopathy) infectivity distribution in small ruminant tissues; and ii) to indicate based on the current epidemiological situation as regards to BSE (Bovine Spongiform Encephalopathy) in the small ruminant population in the EU (European Union), whether a review of the existing SRM (Specified Risk Materials) list for small ruminants should be envisaged with regard to the potential exposure to the BSE agent. The appraisal was addressed by reviewing for Classical scrapie, BSE and Atypical scrapie in small ruminants aspects related to: i) tissue infectivity distribution according to the age and the genotype of sheep and goats; and ii) the infectious load in the different tissues. In order to perform the assessment all the currently available scientific results were reviewed, and data on TSE monitoring in small ruminants in the EU and on small ruminants slaughtered by species and age category in each EU Member State were considered. The reduction of the infectivity associated to the carcass of an infected individual achieved by the current SRM policy in small ruminants for Classical scrapie and BSE was estimated. The total number of Classical scrapie infected sheep and goats that could enter yearly into the food chain was provided. Moreover, considerations about Atypical scrapie were given. A set of simulations allowing estimating the impact of different policy options on the BSE infectious load potentially present in an infected sheep was provided.

© European Food Safety Authority, 2010

KEY WORDS

Bovine Spongiform Encephalopathy (BSE), Classical scrapie, Atypical scrapie, Transmissible Spongiform Encephalopathies (TSEs), Specified Risk Material (SRM), Small Ruminants

snip...

When considering BSE in small ruminants, the Panel concluded that with 95% confidence the the number of BSE cases that could enter yearly into the food chain in the EU is ranging between 0 and 240 for sheep and between 0 and 381 for goats. This estimate argues against any current widespread BSE epidemic within the EU small ruminant population.

http://www.goatbse.eu/site/images/stories/diverse/opinion%20on%20bse-tse%20infectivity%20in%20sruminants.pdf


BSE has been detected in two goats. One case was a French goat which was born in 2000 and died in 2002. The second was a British goat which was born in 1987 and died in 1990.

http://www.defra.gov.uk/foodfarm/farmanimal/diseases/atoz/bse/othertses/scrapie/


http://www.defra.gov.uk/foodfarm/farmanimal/diseases/atoz/bse/science-research/sheep-goats/experimental.htm


http://www.defra.gov.uk/foodfarm/farmanimal/diseases/atoz/bse/science-research/projects-table.htm#3d


http://www.defra.gov.uk/foodfarm/farmanimal/diseases/atoz/bse/science-research/documents/bse-sheep-goats.pdf


Thursday, November 18, 2010

Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep

http://bse-atypical.blogspot.com/2010/11/increased-susceptibility-of-human-prp.html


One of these isolates (TR316211) behaved like the CH1641 isolate, with PrPres features in mice similar to those in the sheep brain. From two other isolates (O100 and O104), two distinct PrPres phenotypes were identified in mouse brains, with either high (h-type) or low (l-type) apparent molecular masses of unglycosylated PrPres, the latter being similar to that observed with CH1641, TR316211, or BSE. Both phenotypes could be found in variable proportions in the brains of the individual mice. In contrast with BSE, l-type PrPres from "CH1641-like" isolates showed lower levels of diglycosylated PrPres. From one of these cases (O104), a second passage in mice was performed for two mice with distinct PrPres profiles. This showed a partial selection of the l-type phenotype in mice infected with a mouse brain with predominant l-type PrPres, and it was accompanied by a significant increase in the proportions of the diglycosylated band. These results are discussed in relation to the diversity of scrapie and BSE strains.

http://jvi.asm.org/cgi/content/full/81/13/7230?view=long&pmid=17442721


In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q (AAQQ) and the disease phenotype is similar to that seen with experimental strain CH1641.

http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=182469


4.2.9 A further hypothesis to explain the occurrence of BSE is the emergence or selection of a strain or strains of the scrapie agent pathogenic for cattle. Mutations of the scrapie agent. which can occur after a single passage in mice. have been well documented (9). This phenomenon cannot be dismissed for BSE. but given the form of the epidemic and the geographically widespread occurrence of BSE, such a hypothesis" would require the emergence of a mutant scrapie strain simultaneously in a large . number of sheep flocks, or cattle. throughout the country. Also. if it resulted "from a localised chance transmission of the scrapie strain from sheep to cattle giving rise , . to a mutant. a different pattern of disease would have been expected: its range would '. have increased with time. Thus the evidence from Britain is against the disease being due to a new strain of the agent, but we note that in the United States from 1984 to 1988 outbreaks of scrapie in sheep flocks are reported to have Increased markedly. now being nearly 3 times as high as during any previous period (18).

http://collections.europarchive.org/tna/20080102132706/http://www.bseinquiry.gov.uk/files/ib/ibd1/tab02.pdf


If the scrapie agent is generated from ovine DNA and thence causes disease in other species, then perhaps, bearing in mind the possible role of scrapie in CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the notifiable disease. ...


http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1988/06/08004001.pdf

http://scrapie-usa.blogspot.com/2007/12/scrapie-hb-parry-seriously-yb886841.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


RISK OF BSE TO SHEEP VIA FEED


http://collections.europarchive.org/tna/20090114022605/http://www.bseinquiry.gov.uk/files/sc/seac31/tab01.pdf


Marion Simmons communicated surprising evidence for oral transmissibility of Nor98/atypical scrapie in neonatal sheep and although bioassay is ongoing, infectivity of the distal ileum of 12 and 24 month infected sheep is positive in Tg338 mice.


http://www.goatbse.eu/site/index.php?option=com_content&view=article&id=94:minutes-workshop-2010&catid=9:popular&Itemid=22


SUMMARY REPORTS OF MAFF BSE TRANSMISSION STUDIES AT THE CVL ;


http://collections.europarchive.org/tna/20090114023010/http://www.bseinquiry.gov.uk/files/sc/seac18/tab02b.pdf



THE RISK TO HUMANS FROM SHEEP;


http://collections.europarchive.org/tna/20090114022915/http://www.bseinquiry.gov.uk/files/sc/seac24/tab03.pdf



EXPERIMENTAL TRANSMISSION OF BSE TO SHEEP


http://collections.europarchive.org/tna/20090114023211/http://www.bseinquiry.gov.uk/files/sc/seac25/tab05.pdf



SHEEP AND BSE

PERSONAL AND CONFIDENTIAL

SHEEP AND BSE

A. The experimental transmission of BSE to sheep.

Studies have shown that the ''negative'' line NPU flock of Cheviots can be experimentally infected with BSE by intracerebral (ic) or oral challenge (the latter being equivalent to 0.5 gram of a pool of four cow brains from animals confirmed to have BSE).

http://collections.europarchive.org/tna/20090506010048/http://www.bseinquiry.gov.uk/files/sc/seac33/tab02.pdf



RB264

BSE - TRANSMISSION STUDIES

http://collections.europarchive.org/tna/20090113230127/http://www.bseinquiry.gov.uk/files/sc/Seac06/tab06.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


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



One of these isolates (TR316211) behaved like the CH1641 isolate, with PrPres features in mice similar to those in the sheep brain. From two other isolates (O100 and O104), two distinct PrPres phenotypes were identified in mouse brains, with either high (h-type) or low (l-type) apparent molecular masses of unglycosylated PrPres, the latter being similar to that observed with CH1641, TR316211, or BSE. Both phenotypes could be found in variable proportions in the brains of the individual mice. In contrast with BSE, l-type PrPres from "CH1641-like" isolates showed lower levels of diglycosylated PrPres. From one of these cases (O104), a second passage in mice was performed for two mice with distinct PrPres profiles. This showed a partial selection of the l-type phenotype in mice infected with a mouse brain with predominant l-type PrPres, and it was accompanied by a significant increase in the proportions of the diglycosylated band. These results are discussed in relation to the diversity of scrapie and BSE strains.

http://jvi.asm.org/cgi/content/full/81/13/7230?view=long&pmid=17442721


In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q (AAQQ) and the disease phenotype is similar to that seen with experimental strain CH1641.

http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=182469


PR-26

NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS

R. Nonno1, E. Esposito1, G. Vaccari1, E. Bandino2, M. Conte1, B. Chiappini1, S. Marcon1, M. Di Bari1, S.L. Benestad3, U. Agrimi1 1 Istituto Superiore di Sanità, Department of Food Safety and Veterinary Public Health, Rome, Italy (romolo.nonno@iss.it); 2 Istituto Zooprofilattico della Sardegna, Sassari, Italy; 3 National Veterinary Institute, Department of Pathology, Oslo, Norway

Molecular variants of PrPSc are being increasingly investigated in sheep scrapie and are generally referred to as “atypical” scrapie, as opposed to “classical scrapie”. Among the atypical group, Nor98 seems to be the best identified. We studied the molecular properties of Italian and Norwegian Nor98 samples by WB analysis of brain homogenates, either untreated, digested with different concentrations of proteinase K, or subjected to enzymatic deglycosylation. The identity of PrP fragments was inferred by means of antibodies spanning the full PrP sequence. We found that undigested brain homogenates contain a Nor98-specific PrP fragment migrating at 11 kDa (PrP11), truncated at both the C-terminus and the N-terminus, and not N-glycosylated. After mild PK digestion, Nor98 displayed full-length PrP (FL-PrP) and N-glycosylated C-terminal fragments (CTF), along with increased levels of PrP11. Proteinase K digestion curves (0,006-6,4 mg/ml) showed that FL-PrP and CTF are mainly digested above 0,01 mg/ml, while PrP11 is not entirely digested even at the highest concentrations, similarly to PrP27-30 associated with classical scrapie. Above 0,2 mg/ml PK, most Nor98 samples showed only PrP11 and a fragment of 17 kDa with the same properties of PrP11, that was tentatively identified as a dimer of PrP11. Detergent solubility studies showed that PrP11 is insoluble in 2% sodium laurylsorcosine and is mainly produced from detergentsoluble, full-length PrPSc. Furthermore, among Italian scrapie isolates, we found that a sample with molecular and pathological properties consistent with Nor98 showed plaque-like deposits of PrPSc in the thalamus when the brain was analysed by PrPSc immunohistochemistry. Taken together, our results show that the distinctive pathological feature of Nor98 is a PrP fragment spanning amino acids ~ 90-155. This fragment is produced by successive N-terminal and C-terminal cleavages from a full-length and largely detergent-soluble PrPSc, is produced in vivo and is extremely resistant to PK digestion. Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.

119

http://www.neuroprion.com/pdf_docs/conferences/prion2006/abstract_book.pdf


P03.141

Aspects of the Cerebellar Neuropathology in Nor98

Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute,

Norway Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

http://www.neuroprion.com/pdf_docs/conferences/prion2007/abstract_book.pdf


A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes

Annick Le Dur*,?, Vincent Béringue*,?, Olivier Andréoletti?, Fabienne Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶, Jean-Luc Vilotte?, Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,?? +Author Affiliations

*Virologie Immunologie Moléculaires and ?Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France; ?Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066 Toulouse, France; §Agence Française de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon, France; **Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway

Edited by Stanley B. Prusiner, University of California, San Francisco, CA (received for review March 21, 2005)

Abstract Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.

http://www.pnas.org/content/102/44/16031.abstract


Monday, December 1, 2008

When Atypical Scrapie cross species barriers

Authors

Andreoletti O., Herva M. H., Cassard H., Espinosa J. C., Lacroux C., Simon S., Padilla D., Benestad S. L., Lantier F., Schelcher F., Grassi J., Torres, J. M., UMR INRA ENVT 1225, Ecole Nationale Veterinaire de Toulouse.France; ICISA-INlA, Madrid, Spain; CEA, IBiTec-5, DSV, CEA/Saclay, Gif sur Yvette cedex, France; National Veterinary Institute, Postboks 750 Sentrum, 0106 Oslo, Norway, INRA IASP, Centre INRA de Tours, 3738O Nouzilly, France.

Content

Atypical scrapie is a TSE occurring in small ruminants and harbouring peculiar clinical, epidemiological and biochemical properties. Currently this form of disease is identified in a large number of countries. In this study we report the transmission of an atypical scrapie isolate through different species barriers as modeled by transgenic mice (Tg) expressing different species PRP sequence.

The donor isolate was collected in 1995 in a French commercial sheep flock. inoculation into AHQ/AHQ sheep induced a disease which had all neuro-pathological and biochemical characteristics of atypical scrapie. Transmitted into Transgenic mice expressing either ovine or PrPc, the isolate retained all the described characteristics of atypical scrapie.

Surprisingly the TSE agent characteristics were dramatically different v/hen passaged into Tg bovine mice. The recovered TSE agent had biological and biochemical characteristics similar to those of atypical BSE L in the same mouse model. Moreover, whereas no other TSE agent than BSE were shown to transmit into Tg porcine mice, atypical scrapie was able to develop into this model, albeit with low attack rate on first passage.

Furthermore, after adaptation in the porcine mouse model this prion showed similar biological and biochemical characteristics than BSE adapted to this porcine mouse model. Altogether these data indicate.

(i) the unsuspected potential abilities of atypical scrapie to cross species barriers

(ii) the possible capacity of this agent to acquire new characteristics when crossing species barrier

These findings raise some interrogation on the concept of TSE strain and on the origin of the diversity of the TSE agents and could have consequences on field TSE control measures.

http://www.neuroprion.org/resources/pdf_docs/conferences/prion2008/abstract-book-prion2008.pdf


Gerstmann-Straussler's disease, atypical multiple sclerosis and carcinomas in a family of sheepbreeders. Acta Neuropath. 56: 87-92, 1982. Peiffer (1982) described a family of sheepbreeders in which a father and 2 sons had GSS. All 3 also had congenital hip dysplasia, as did at least 3 other members of the kindred, all females. Atactic symptoms, dysarthria, and personality changes characterized the clinical course of this disorder, which might be labeled atypical multiple sclerosis. Like CJD , GSS is a form of subacute spongiform encephalopathy. Cases of GSS are clinically similar to the atactic type of CJD. Although there are many neuropathologic similarities, GSS differs from CJD by the presence of kuru-plaques and numerous multicentric, floccular plaques in the cerebral and cerebellar cortex, basal ganglia, and white matter. Whereas only 5 to 15% of CJD cases are familial, most cases of GSS are familial.

http://www.mad-cow.org/Alzheimer_cjd.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.

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

NATUREVol 45726 February 2009

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


Thursday, October 07, 2010

Experimental Transmission of H-type Bovine Spongiform Encephalopathy to Bovinized Transgenic Mice

http://bse-atypical.blogspot.com/2010/10/experimental-transmission-of-h-type.html


The most recent assessments (and reassessments) were published in June 2005 (Table I; 18), and included the categorisation of Canada, the USA, and Mexico as GBR III. Although only Canada and the USA have reported cases, the historically open system of trade in North America suggests that it is likely that BSE is present also in Mexico.

http://www.oie.int/boutique/extrait/06heim937950.pdf


Rare BSE mutation raises concerns over risks to public health

SIR — Atypical forms (known as H- and L-type) of bovine spongiform encephalopathy (BSE) have recently appeared in several European countries as well as in Japan, Canada and the United States. This raises the unwelcome possibility that variant Creutzfeldt–Jakob disease (vCJD) could increase in the human population. Of the atypical BSE cases tested so far, a mutation in the prion protein gene (PRNP) has been detected in just one, a cow in Alabama with BSE;

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


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


Thursday, November 18, 2010

Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep

http://bse-atypical.blogspot.com/2010/11/increased-susceptibility-of-human-prp.html


Monday, November 22, 2010

Atypical transmissible spongiform encephalopathies in ruminants: a challenge for disease surveillance and control

REVIEW ARTICLES

http://transmissiblespongiformencephalopathy.blogspot.com/2010/11/atypical-transmissible-spongiform.html


Tuesday, November 02, 2010

BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992

http://bse-atypical.blogspot.com/2010/11/bse-atypical-lesion-distribution-rbse.html


Saturday, December 11, 2010

Species-barrier-independent prion replication in apparently resistant species

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/species-barrier-independent-prion.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


http://bseusa.blogspot.com/2010/04/usda-and-oie-out-of-touch-with-risk.html


Sunday, March 28, 2010

Nor-98 atypical Scrapie, atypical BSE, spontaneous TSE, trade policy, sound science ?

http://nor-98.blogspot.com/2010/03/nor-98-atypical-scrapie-atypical-bse.html


TSS