The oral secretion of infectious scrapie prions occurs in pre-clinical sheep with a range of PRNP genotypes

JVI Accepts, published online ahead of print on 19 October 2011

J. Virol. doi:10.1128/JVI.05579-11 Copyright © 2011,American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The oral secretion of infectious scrapie prions occurs in pre-clinical sheep with a range of PRNP genotypes

Kevin C. Gough1, Claire A. Baker2, Helen C. Rees2, Linda A. Terry3, John Spiropoulos3, Leigh Thorne3, and Ben C. Maddison2,* 1. School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, College Road, Sutton Bonington, Leicestershire, LE12 5RD. UK 2. ADAS UK, School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, College Road, Sutton Bonington, Leicestershire, LE12 5RD. UK 3. Animal Health and Veterinary Laboratories Agency, Woodham Lane, New Haw, Addlestone, Surrey. KT15 3NB. UK

* Corresponding author: Dr B. C. Maddison, ADAS-UK, School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, College Road, Sutton Bonington, Leicestershire, LE12 5RD. UK. Telephone: +44-115-9516272; FAX: +44-115-9516440; E-mail: Ben.Maddison@adas.co.uk

ABSTRACT

Preclinical sheep with the highly scrapie-susceptible VRQ/VRQ PRNP genotype secrete prions from the oral cavity. In order to further understand the significance of orally available prions, buccal swabs were taken from sheep with a range of PRNP genotypes and analysed by protein misfolding cyclic amplification reaction (sPMCA). Prions were detected in buccal swabs from scrapie-exposed sheep of genotypes that are linked to high (VRQ/VRQ and ARQ/VRQ) and low (ARR/VRQ and AHQ/VRQ) lymphoreticular involvement in scrapie pathogenesis. For both groups, the levels of prion detection were significantly higher than that for the scrapie-resistant ARR/ARR sheep which were kept in the same farm environment and acted as sentinel controls for prions derived from the environment which might contaminate the oral cavity. In addition, sheep with no exposure to the scrapie agent did not contain any measurable prion within their oral cavity. Furthermore, prion was detected in sheep of a wide age range representing various stages of preclinical disease. These data demonstrate that orally available scrapie prions may be a common feature in sheep incubating scrapie, regardless of the PRNP genotype and any associated high level accumulation of PrPSc within lymphoreticular tissues. PrPSc was present in buccal swabs from a high proportion of sheep with PRNP genotypes associated with relatively low disease-penetrance; indicating that subclinical scrapie infection is likely to be a common occurrence. The significance of positive sPMCA reactions was confirmed by the transmission of infectivity in buccal swab extracts to Tg338 mice, illustrating the likely importance of orally available prions in the horizontal transmission of scrapie.

http://jvi.asm.org/cgi/content/short/JVI.05579-11v1


[2] UK: SEAC position statement on dentistry

Date: Sat 30 Jun 2007

Source: Position Statement vCJD and Dentistry, Spongiform Encephalopathy Advisory Committee (SEAC) Update, June 2007 [edited]

Position Statement vCJD and Dentistry ------------------------------------- Issue -----

1. The Department of Health (DH) asked SEAC to advise on the findings of preliminary research aimed at informing estimates of the risk of variant Creutzfeldt-Jakob Disease (vCJD) transmission via dentistry.

Background ----------

2. Prions are more resistant than other types of infectious agents to the conventional cleaning and sterilization practices used to decontaminate dental instruments (1). Appreciable quantities of residual material may remain adherent to the surface after normal cleaning and sterilization (2). Therefore, if dental tissues are both infectious and susceptible to infection, the dental instruments are a potential mechanism for the secondary transmission of vCJD. Dentistry could be a particularly significant route of transmission for the population as a whole, due to the large number of routine procedures undertaken and also because dental patients have a normal life expectancy.

This is in contrast with other transmission routes, such as blood transfusion and neurosurgery, where procedures are often carried out in response to some life-threatening condition. Additionally, the ubiquity of dental procedures and the lack of central records on dental procedures means that should such transmission occur, then it would be difficult to detect and control.

3. No cases of vCJD transmission arising from dental procedures have been reported to date (3). Previous DH risk assessments (4,5) have focused on 2 possible mechanisms for the transfer of vCJD infectivity via dental instruments; accidental abrasion of the lingual tonsil and endodontic procedures that involve contact with dental pulp. In considering these assessments, SEAC agreed that the risk of transmission via accidental abrasion of the lingual tonsil appears very low. However, the risk of transmission via endodontic procedures may be higher and give rise to a self sustaining vCJD epidemic under circumstances where (i) dental pulp is infective, (ii) transmission via endodontic instruments is efficient and (iii) a large proportion of vCJD infections remain in a subclinical carrier state (SEAC 91, February 2006). In light of this, SEAC advised that restricting endodontic files and reamers to single use be considered (6). SEAC recommended reassessment of these issues as new data emerge.

New research ------------

4. Preliminary, unpublished results of research from the Health Protection Agency, aimed at addressing some of the uncertainties in the risk assessments, were reviewed by SEAC (SEAC 97, May 2007). The prion agent used in these studies is closely related to the vCJD agent. This research, using a mouse model, shows that following inoculation of mouse-adapted bovine spongiform encephalopathy (BSE) directly into the gut, infectivity subsequently becomes widespread in tissues of the oral cavity, including dental pulp, salivary glands and gingiva, during the preclinical as well as clinical stage of disease.

5. It is not known how closely the level and distribution of infectivity in the oral cavity of infected mice reflects those of humans infected with vCJD, as there are no comparable data from oral tissues, in particular dental pulp and gingiva, from human subclinical or clinical vCJD cases (7). Although no abnormal prion protein was found in a study of human dental tissues, including dental pulp, salivary glands and gingiva from vCJD cases, the relationship between levels of infectivity and abnormal prion protein is unclear (8). Infectivity studies underway using the mouse model and oral tissues that are presently available from human vCJD cases will provide some comparable data. On the basis of what is currently known, there is no reason to suppose that the mouse is not a good model for humans in respect to the distribution of infectivity in oral tissues. Furthermore, the new data are consistent with published results from experiments using a hamster scrapie model (9).

6. A 2nd set of experiments using the same mouse model showed that non-invasive and transient contact between gingival tissue and fine dental files contaminated with mouse-adapted BSE brain homogenate transmits infection very efficiently. It is not known how efficient gingival transmission would be if dental files were contaminated with infectious oral tissues and then subsequently cleaned and sterilized, a situation which would more closely model human dental practice. Further studies using the mouse model that would be more representative of the human situation, comparing oral tissues with a range of doses of infectivity, cleaned and sterilized files and the kind of tissue contact with instruments that occurs during dentistry, should be considered.

7. SEAC considered that the experiments appear well designed and the conclusions justified and reliable, while recognizing that the research is incomplete and confirmatory experiments have yet to be completed. It is recommended that the research be completed, submitted for peer-review and widely disseminated as soon as possible so others can consider the implications. Nevertheless, these preliminary data increase the possibility that some oral tissues of humans infected with vCJD may potentially become infective during the preclinical stage of the disease. In addition, they increase the possibility that infection could potentially be transmitted not only via accidental abrasion of the lingual tonsil or endodontic procedures but a variety of routine dental procedures.

Implications for transmission risks -----------------------------------

8. The new findings help refine assumptions made about the level of infectivity of dental pulp and the stage of incubation period when it becomes infective in the risk assessment of vCJD transmission from the reuse of endodontic files and reamers (10). For example, if one patient in 10 000 were to be carrying infection (equivalent to about 6000 people across the UK, the best current estimate (11), the data suggest that in the worst case scenario envisaged in the risk assessment, reuse of endodontic files and reamers might lead to up to 150 new infections per annum. It is not known how many of those infected would go on to develop clinical vCJD. In addition, transmission via the reuse of endodontic files and reamers could be sufficiently efficient to cause a self-sustaining vCJD epidemic arising via this route.

9. These results increase the importance of obtaining reliable estimates of vCJD infection prevalence. Data that will soon be available from the National Anonymous Tonsil Archive may help refine this assessment and provide evidence of the existence and extent of subclinical vCJD infection in tonsillectomy patients. Further data, such as from post mortem tissue or blood donations, will be required to assess prevalence in the general UK population (12).

10. Recent guidance issued by DH to dentists to ensure that endodontic files and reamers are treated as single use (13) is welcomed and should, as long as it is effectively and quickly implemented, prevent transmission and a self-sustaining epidemic arising via this route. However, the extent and monitoring of compliance with this guidance in private and National Health Service dental practice is unclear.

11. The new research also suggests that dental procedures involving contact with other oral tissues, including gingiva, may also be capable of transmitting vCJD. In the absence of a detailed risk assessment examining the potential for transmission via all dental procedures, it is not possible to come to firm conclusions about the implications of these findings for transmission of vCJD. However, given the potential for transmission by this route, serious consideration should be given to assessing the options for reducing transmission risks, such as improving decontamination procedures and practice or the implementation of single use instruments.

12. The size of the potential risk from interactions between the dental and other routes of secondary transmission, such as blood transfusion and hospital surgery, to increase the likelihood of a self-sustaining epidemic is unclear.

13. It is likely to be difficult to distinguish clinical vCJD cases arising from dietary exposure to BSE from secondary transmissions via dental procedures, should they arise, as a large proportion of the population is likely both to have consumed contaminated meat and undergone dentistry.

However, an analysis of dental procedures by patient age may provide an indication of the age group in which infections, if they occur, would be most likely to be observed. Should the incidence of clinical vCJD cases in this age group increase significantly, this may provide an indication that secondary transmission via dentistry is occurring. Investigation of the dental work for these cases may provide supporting data. There is no clear evidence, to date, based on surveillance or investigations of clinical vCJD cases, that any vCJD cases have been caused by dental procedures, but this possibility cannot be excluded.

Conclusions -----------

14. Preliminary research findings suggest that the potential risk of transmission of vCJD via dental procedures may be greater than previously anticipated. Although this research is incomplete, uses an animal model exposed to relatively high doses of infectivity, and there are no data from infectivity studies on human oral tissues, these findings suggest an increased possibility that vCJD may be relatively efficiently transmitted via a range of dental procedures. Ongoing infectivity studies using human oral tissues and the other studies suggested here will enable more precise assessment of the risks of vCJD transmission through dental procedures.

15. Guidance was issued to dentists earlier this year [2007] recommending that endodontic files and reamers be treated as single use, which, provided this policy is adhered to, will remove any risk of a self-sustaining epidemic arising from reuse of these instruments. To minimize risk, it is critical that appropriate management and audit is in place, both for NHS and private dentistry.

16. It is also critical that a detailed and comprehensive assessment of the risks of all dental procedures be conducted as a matter of urgency. While taking into account the continuing scientific uncertainties, this will allow a more thorough consideration of the possible public health implications of vCJD transmission via dentistry and the identification of possible additional precautionary risk reduction measures. The assessment will require continued updating as more evidence becomes available on the transmissibility of vCJD by dental routes, and on the prevalence of infection within the population. A DH proposal to convene an expert group that includes dental professionals to expedite such an assessment is welcomed. Given the potential for transmission via dentistry, consideration should be given to the urgent assessment of new decontamination technologies which, if proven robust and effective, could significantly reduce transmission risks.

References ----------

(1) Smith et al. (2003) Prions and the oral cavity. J. Dent. Res. 82, 769-775. (2) Smith et al. (2005) Residual protein levels on reprocessed dental instruments. J. Hosp. Infect. 61, 237-241. (3) Everington et al. (2007) Dental treatment and risk of variant CJD - a case control study. Brit. Den. J. 202, 1-3. (4) Department of Health. (2003) Risk assessment for vCJD and dentistry. (5) Department of Health (2006) Dentistry and vCJD: the implications of a carrier-state for a self-sustaining epidemic. Unpublished. (6) SEAC (2006) Position statement on vCJD and endodontic dentistry . (7) Head et al. (2003) Investigation of PrPres in dental tissues in variant CJD. Br. Dent. J. 195, 339-343. (8) SEAC 90 reserved business minutes. (9) Ingrosso et al. (1999) Transmission of the 263K scrapie strain by the dental route. J. Gen. Virol. 80, 3043-3047. (10) Department of Health (2006) Dentistry and vCJD: the implications of a carrier-state for a self-sustaining epidemic. Unpublished. (11) Clarke & Ghani (2005) Projections of future course of the primary vCJD epidemic in the UK: inclusion of subclinical infection and the possibility of wider genetic susceptibility R. J. Soc. Interface. 2, 19-31. (12) SEAC Epidemiology Subgroup (2006) position statement of the vCJD epidemic . (13) DH (2007) Precautionary advice given to dentists on re-use of instruments .

-- Communicated by Terry S. Singletary, Sr.

******

http://creutzfeldt-jakob-disease.blogspot.com/2010/02/creutzfeldt-jakob-disease-cjd-biannual.html


Subject: CJD: update for dental staff Date: November 12, 2006 at 3:25 pm PST

1: Dent Update. 2006 Oct;33(8):454-6, 458-60.

CJD: update for dental staff.

http://seac992007.blogspot.com/2008/06/seac-2008-one-hundredth-meeting-of.html


SEAC Position Statement

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

Position statement vCJD and Endodontic dentistry Issue

1. The Department of Health (DH) asked SEAC to advise on the findings and implications of a preliminary risk assessment of potential vCJD transmission via endodontic procedures (dental procedures involved in the maintenance of dental pulp and the treatment of the pulp cavity) 1. This is particularly pertinent because of the large number of endodontic procedures undertaken in the UK.

Background

2. There are no reported definite or suspected cases of vCJD transmission arising from dental procedures. However, prions are more resistant than other types of infectious agent to the conventional cleaning and sterilisation practices used to decontaminate dental instruments 2. Therefore, should dental instruments become contaminated from tissues in the oral cavity of infected individuals, there is a risk of transmission to subsequent patients.

3. A quantitative DH risk assessment 3, accepted by SEAC in 2003, considered two possible mechanisms for the transfer of vCJD infectivity via dental instruments: (i) accidental abrasion of the lingual tonsil, known to carry infectivity in vCJD cases; and (ii) contact with dental pulp that evidence from animal studies suggested may be infective. On the basis of the information available, the DH analysis suggested that the risk of transmission to individual patients via accidental abrasion of the lingual tonsil is very low. Furthermore, should dental pulp be infective, the risk of transmission via endodontic procedures, although higher, is also low. Although a very large number of dental procedures are conducted, the relative risk to public health from potential transmission via dental, compared with hospital, surgery was considered to be relatively low.

4. In 2006, SEAC considered a new preliminary risk assessment by DH of the risks of vCJD transmission via endodontic procedures, taking into account new information on decontamination of dental instruments, the potential infectivity of dental pulp, and the possible existence of subclinical vCJD carrier cases.

Endodontic instruments

5. Evidence suggests that the files and reamers used in endodontic procedures are reused and are difficult to reliably decontaminate 4. Appreciable quantities of residual material remain adherent to the surface after normal cleaning and sterilisation 5. Thus, there is potential for transfer of dental pulp between patients undergoing endodontic procedures.

vCJD infectivity in dental tissues

6. There are no data on vCJD infectivity in dental pulp. Although no abnormal prions were found in a study of dental tissues, including dental pulp, from vCJD cases 6, dental pulp includes blood and peripheral nerve tissue known to carry vCJD infectivity 7,8. In addition, appreciable infectivity has been found in the dental pulp of hamsters with hamster scrapie 9. Although it is possible that the peripheral nerve may only become infective close to, or after, the onset of clinical vCJD, inflammation may promote the propagation of prions 10. Thus, although the data are limited and indirect, it is reasonable to assume that the dental pulp of individuals subclinically-infected with vCJD may be infectious although the level of infectivity is unknown. Studies underway will provide direct data on the infectivity in dental tissues from vCJD cases.

Subclinical carrier state

7. A study of humanised mice showed that vCJD infections may not always progress to clinical disease within the normal lifespan of the animals 11. Another study suggested that prion infections in mice that remain at a subclinical level can be transmitted to other mice, resulting in clinical disease 12. Thus, there is evidence to suggest that individuals infected with the BSE / vCJD agent may remain in a subclinical infection carrier state instead of developing vCJD. A discrepancy between prevalence estimates based on a survey of abnormal prion protein in appendix and tonsil tissue and data on vCJD cases supports this hypothesis 13. As no diagnostic test exists to identify such individuals, they could over the course of their lives be potential sources of numerous secondary infections arising from invasive medical or dental procedures.

8. The prevalence of subclinical infection in the UK population is uncertain. A recent estimate suggests the number of subclinical carriers may be of the order of several thousand 14. SEAC has strongly recommended that further studies to ascertain better the prevalence of vCJD infection be urgently considered 15.

Transmission risks

9. The new DH analysis suggests that, on the basis that residual dental pulp on endodontic files and reamers is transferred relatively efficiently to patients on reuse, dental pulp is as infective as peripheral nerve tissue and a subclinical carrier population for vCJD exists, a self-sustaining vCJD epidemic arising from endodontic surgery is plausible. There are uncertainties about the efficiency of vCJD transmission via endodontic procedures, the vCJD infectivity of dental pulp and the existence of a subclinical infection carrier state. However, even if a self-sustaining epidemic were not possible, clusters of vCJD infections could arise from the use of instruments contaminated with the vCJD agent from endodontic procedures on infected patients. Interactions between this and other routes of secondary transmission, such as blood transfusion and hospital surgery, would make a self-sustaining epidemic more likely.

Potential risk reduction measures

10. Endodontic files and reamers have a limited lifespan, restricting the number of possible secondary transmissions. Improving the effectiveness of procedures used to decontaminate dental instruments would reduce the risk of transmission. Restricting endodontic files and reamers to single use would prevent potential secondary transmission via these instruments.

Conclusions

11. A preliminary risk assessment produced by DH suggests that vCJD transmission via endodontic dentistry may, under certain hypothetical but plausible scenarios, be sufficient to sustain a secondary vCJD epidemic. However, there are uncertainties around the data and assumptions underpinning the assessment. Research underway will address some of these uncertainties and allow the risk assessment to be refined. Once the research is complete and / or other data become available, the risks should be reassessed. A watching brief should be maintained.

12. It is unclear whether or not vCJD infectivity can be transmitted via endodontic files and reamers. However, given the plausibility of such a scenario and the large number of procedures undertaken annually, it would be prudent to consider restricting these instruments to single use as a precautionary measure. Since sufficiently rigorous decontamination of these instruments is difficult, single use of these instruments would eliminate this risk, should it exist.

SEAC May 2006

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

1. Department of Health. Dentistry and vCJD: the implications of a “carrier state” for a self-sustaining epidemic due to endodontic dentistry. A Preliminary Risk Assessment. Unpublished. 2. Smith et al. (2003) Prions and the oral cavity. J. Dent. Res. 82, 769-775. 3. Department of Health. (2003) Risk assessment for vCJD and dentistry. 4. Letters et al. (2005) A study of visual and blood contamination on reprocessed endodontic files from general dental practice. Br. Dent. J. 199, 522-525. 5. Smith et al. (2005) Residual protein levels on reprocessed dental instruments. J. Hosp. Infect. 61, 237-241. 6. Head et al. (2003) Investigation of PrPres in dental tissues in variant CJD. Br. Dent. J. 195, 339-343. 7. SEAC 91 minutes paragraph 9. www.seac.gov.uk/papers/papers.htm
 8. Department of Health (2005) Assessing the risk of vCJD transmission via surgery: an interim view. Unpublished. 9. Ingrosso et al. (1999) Transmission of the 263K scrapie strain by the dental route. J. Gen. Virol. 80, 3043-3047. 10. Heikenwalder et al. (2005) Chronic lymphocytic inflammation specifies the organ tropism of prions. Science. 307, 1107-1110. 11. Bishop et al. (2006) Predicting susceptibility and incubation time of human-to-human transmission of vCJD. Lancet Neurology. 12. Hill et al. (2000) Species-barrier-independent prion replication in apparently resistant species. Proc. Natl. Acad. Sci. USA. 97, 10248-10253. 13. SEAC Epidemiology Subgroup (2005) Position statement on the vCJD epidemic. www.seac.gov.uk/statements/state260106subgroup.htm
14. Clarke & Ghani. (2005) Projections of future course of the primary vCJD epidemic in the UK: inclusion of subclinical infection and the possibility of wider genetic susceptibility. R. J. Soc. Interface. 15. SEAC (2005) SEAC response to the SEAC Epidemiology Subgroup statement on the vCJD epidemic. www.seac.gov.uk/statements/state260106.htm


Page updated: 8th May 2006

http://www.seac.gov.uk/statements/statement0506.htm


Subject: MASTER DENTIST FALLS VICTIM TO CJD Date: March 31, 2007 at 1:27 pm PST

Subject: MASTER DENTIST FALLS VICTIM TO CJD Date: March 31, 2007 at 1:27 pm PST

''It was in the cards a long time ago,'' she says. ''We've put it in the hands of God.''

- Crystal Harmon can be reached at 894-9643 or by e-mail at charmon@bc-times.com.

http://www.mlive.com/news/bctimes/index.ssf?/base/news-9/1175181333132150.xml&coll=4

see full text ;

http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0703&L=sanet-mg&T=0&F=&S=&P=106052


http://neurotalk.psychcentral.com/archive/index.php/t-13173.html


Monday, December 31, 2007

Risk Assessment of Transmission of Sporadic Creutzfeldt-Jakob Disease in Endodontic Practice in Absence of Adequate Prion Inactivation

http://creutzfeldt-jakob-disease.blogspot.com/2007_12_01_archive.html


Subject: CJD: update for dental staff Date: November 12, 2006 at 3:25 pm PST

1: Dent Update. 2006 Oct;33(8):454-6, 458-60.

CJD: update for dental staff.

http://seac992007.blogspot.com/2008/06/seac-2008-one-hundredth-meeting-of.html


Tuesday, August 12, 2008

Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007 (occupational exposure to prion diseases)

http://creutzfeldt-jakob-disease.blogspot.com/2008/08/biosafety-in-microbiological-and.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, March 16, 2010

Transmissible Spongiform Encephalopathy Agents: Safe Working and the Prevention of Infection: Part 4 REVISED FEB. 2010

http://creutzfeldt-jakob-disease.blogspot.com/2010/03/transmissible-spongiform-encephalopathy.html


Tuesday, December 14, 2010

Infection control of CJD, vCJD and other human prion diseases in healthcare and community settings part 4, Annex A1, Annex J, UPDATE DECEMBER 2010

http://creutzfeldt-jakob-disease.blogspot.com/2010/12/infection-control-of-cjd-vcjd-and-other.html


Saturday, January 16, 2010

Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to Bramble et al Evidence For CJD/TSE Transmission Via Endoscopes

http://creutzfeldt-jakob-disease.blogspot.com/2010/01/evidence-for-cjd-tse-transmission-via.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


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


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


I strenuously urge the USDA and the OIE et al to revoke the exemption of the legal global trading of atypical Nor-98 scrapie TSE. ...TSS


Friday, February 11, 2011

Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues

http://nor-98.blogspot.com/2011/02/atypicalnor98-scrapie-infectivity-in.html


Thursday, June 2, 2011

USDA scrapie report for April 2011 NEW ATYPICAL NOR-98 SCRAPIE CASES Pennsylvania AND California

http://nor-98.blogspot.com/2011/06/usda-scrapie-report-for-april-2011-new.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


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


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


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


Thursday, December 23, 2010

Molecular Typing of Protease-Resistant Prion Protein in Transmissible Spongiform Encephalopathies of Small Ruminants, France, 2002-2009 Volume 17, Number 1 January 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/molecular-typing-of-protease-resistant.html


Sunday, December 12, 2010

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

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/efsa-reviews-bsetse-infectivity-in.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


BSE: TIME TO TAKE H.B. PARRY SERIOUSLY

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



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


snip...SEE MORE HERE ;

http://bse-atypical.blogspot.com/2011/05/atypical-prion-diseases-in-humans-and.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


Tuesday, April 26, 2011

sporadic CJD RISING Text and figures of the latest annual report of the NCJDRSU covering the period 1990-2009 (published 11th March 2011)

http://creutzfeldt-jakob-disease.blogspot.com/2011/04/sporadic-cjd-rising-text-and-figures-of.html


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




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, October 10, 2011

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

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


TSS