Saturday, February 13, 2016

The Risk of Prion Infection through Bovine Grafting Materials in dentistry

The Risk of Prion Infection through Bovine Grafting Materials in dentistry
 
Original Article Hessamnowzari@gmail.com;
 
The Risk of Prion Infection through Bovine Grafting Materials
 
Yeoungsug Kim DDS, MSD1, Angel Emmanuel Rodriguez DDS2 and Hessam Nowzari DDS, PhD3,*
 
Article first published online: 8 FEB 2016
 
DOI: 10.1111/cid.12391 Keywords cCJD; EU; FDA; IHC; PMCA; PK-sensitive; PrPC, PrPSc; PrP 27–30; SAF; sCJD; WB
 
Abstract
 
Background
 
Bovine-derived grafting materials are frequently used in a variety of bone augmentation techniques. The aim of this paper is to assess the unique safety issue of bovine-derived grafting materials that is rarely addressed in dental literature: risk of bovine spongiform encephalopathy (BSE).
 
Methods
 
The validity of the current BSE diagnostic methods, surveillance and epidemiological trends in affected countries, and BSE infectivity in bovine bone before and after manufacturing processing were reviewed and analyzed.
 
Results
 
Prion screening has significant limits. Humans are not safe from the infection of prion disease of other species. Prions can and do break the species barrier. There is evidence there may be tens of thousands of infectious carriers in the western countries alone. This raises concern about the potential for perpetuation of infection via medical procedures.
 
Conclusion
 
The limited ability to screen prions within the animal genome, along with a long latency period to manifestation of the disease (1 to over 50 years) in infected patients, provides a framework for discussing posible long-term risks of the xenografts that are used so extensively in dentistry. We suggest abolishing the use of bovine bone.
 
 
 
BSE TSE PRION RISK FACTORS AND DENTAL
 
Clin Implant Dent Relat Res. 2011 Dec 15. doi: 10.1111/j.1708-8208.2011.00407.x. [Epub ahead of print]
 
Risk of Prion Disease Transmission through Bovine-Derived Bone Substitutes: A Systematic Review.
 
Kim Y, Nowzari H, Rich SK. Source Resident, Advanced Education in Periodontics Program, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA professor, Clinical Dentistry and director, Advanced Education in Periodontics Program, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA associate professor, Advanced Education in Periodontics Program, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.
 
Abstract Background: Despite the causal association between variant Creutzfeldt - Jakob disease and bovine spongiform encephalopathy (BSE), bovine origin graft materials are widely used during dental surgical procedures. The aim of this study was to assess the risk of BSE transmission through anorganic bovine bone substitutes.
 
Methods: Electronic database of MEDLINE was searched to identify relevant studies regarding our focused questions, presence of BSE prion infectivity in raw bovine bone, BSE prion inactivation by bone substitute manufacturing process, protein contents in anorganic bovine bone substitutes, and validity of current BSE diagnostic methods. Search terms yielded 1,704 titles. After title/abstract screening and duplicates removal, 36 full-text articles were screened for inclusion.
 
Results: A total of 16 studies were included in the final analysis. No eligible studies were identified regarding the efficacy of BSE prion inactivation by the treatments used for anorganic bovine bone manufacturing. BSE infectivity and PrP(Sc) , pathological prion, were detected in bovine bone marrow and serum samples. Proteins were detected in Tutoplast® (bovine), Bio-Oss®, and tibia samples treated at the similar condition for Bio-Oss deproteinization. Inconsistent results of different BSE diagnostic tests were not unusual findings (Iwata et al. 2006; Arnold et al. 2007; Murayama et al. 2010), and a study by Balkema-Buschmann and colleagues showed an apparent discrepancy between BSE infectivity and detection of PrP(27-30), the current surrogate marker for prion disease infectivity.
 
*** Conclusion: This review indicates that bovine-derived graft biomaterials may carry a risk of prion transmission to patients.
 
© 2011 Wiley Periodicals, Inc. PMID: 22171533 [PubMed - as supplied by publisher]
 
 
Aerosols Transmit Prions to Immunocompetent and Immunodeficient Mice
 
Johannes Haybaeck1.¤a, Mathias Heikenwalder1.¤b, Britta Klevenz2., Petra Schwarz1, Ilan Margalith1, Claire Bridel1, Kirsten Mertz1,3, Elizabeta Zirdum2, Benjamin Petsch2, Thomas J. Fuchs4, Lothar Stitz2*, Adriano Aguzzi1* 1 Department of Pathology, Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland, 2 Institute of Immunology, Friedrich-Loeffler-Institut, Tu¨ bingen, Germany, 3 Department of Pathology, Clinical Pathology, University Hospital Zurich, Zurich, Switzerland, 4 Department of Computer Science, Machine Learning Laboratory, ETH Zurich, Zurich, Switzerland
 
Abstract Prions, the agents causing transmissible spongiform encephalopathies, colonize the brain of hosts after oral, parenteral, intralingual, or even transdermal uptake. However, prions are not generally considered to be airborne. Here we report that inbred and crossbred wild-type mice, as well as tga20 transgenic mice overexpressing PrPC, efficiently develop scrapie upon exposure to aerosolized prions. NSE-PrP transgenic mice, which express PrPC selectively in neurons, were also susceptible to airborne prions. Aerogenic infection occurred also in mice lacking B- and T-lymphocytes, NK-cells, follicular dendritic cells or complement components. Brains of diseased mice contained PrPSc and transmitted scrapie when inoculated into further mice. We conclude that aerogenic exposure to prions is very efficacious and can lead to direct invasion of neural pathways without an obligatory replicative phase in lymphoid organs. This previously unappreciated risk for airborne prion transmission may warrant re-thinking on prion biosafety guidelines in research and diagnostic laboratories.
 
SNIP...
 
In summary, our results establish aerosols as a surprisingly efficient modality of prion transmission. This novel pathway of prion transmission is not only conceptually relevant for the field of prion research, but also highlights a hitherto unappreciated risk factor for laboratory personnel and personnel of the meat processing industry. In the light of these findings, it may be appropriate to revise current prion-related biosafety guidelines and health standards in diagnostic and scientific laboratories being potentially confronted with prion infected materials. While we did not investigate whether production of prion aerosols in nature suffices to cause horizontal prion transmission, the finding of prions in biological fluids such as saliva, urine and blood suggests that it may be worth testing this possibility in future studies.
 
Citation: Haybaeck J, Heikenwalder M, Klevenz B, Schwarz P, Margalith I, et al. (2011) Aerosols Transmit Prions to Immunocompetent and Immunodeficient Mice. PLoS Pathog 7(1): e1001257. doi:10.1371/journal.ppat.1001257 Editor: David Westaway, University of Alberta, Canada Received March 22, 2010; Accepted December 13, 2010; Published January 13, 2011
 
PLEASE SEE FULL TEXT, AND AGAIN, many thanks to PLOS for open access !!!
 
 
Journal of Neurology, Neurosurgery, and Psychiatry 1982;45:235-238
 
Evidence for case-to-case transmission of Creutzfeldt-Jakob disease
 
RG WILL, WB MATTHEWS
 
From the University Department of Clinical Neurology, The Radcliffe Infirmary, Oxford SUMMARY Three cases of probable iatrogenic transmission of Creutzfeldt-Jakob disease by neurosurgery are detailed together with a cluster of three cases in Eastern England possibly connected by dental procedures, and the development of Creutzfeldt-Jakob disease in a patient who had been in social contact with a familial case. snip... SPATIO-TEMPORAL CLUSTER
 
In 1965 a patient died of Creutzfeldt-Jakob disease, confirmed at necropsy. In 1968 a patient who lived within 250 m also died of the disease. These two patients shared the same general practitioner but unfortunately it has been impossible to examine the medical records which have been destroyed. In 1980 a patient who lived midway between the two previous patients and within sight of both houses died of pathologically proven Creutzfeldt-Jakob disease. This last patient worked as a dentist from 1950-1q77 and used his house as a surgery. The dental records have been examined but are incomplete and do not include either of the two previous patients. It has been impossible to obtain details of dental history by other means, and the possibility that the patients were treated by the dentist cannot be further explored. snip... In the close geographical group of three cases possible modes of transmission can be suggested, either iatrogenic or through dental procedures, but these must remain conjectural. It is known, however, that the similar scrapie agent can be transmitted from the gums in animals.10 Such close spatial clustering of cases is extremely unusual, being previously reported by Matthews,'1 but not detected even in'the study of the epidemiology of Creutzfeldt- Jakob disease in urban Paris, where the incidence was found to be relatively high.12 snip... Known examples of iatrogenic transmission of Creutzfeldt-Jakob disease have all involved actual or presumed implantation of tissue into brain or eye. In most cases of the disease no such opportunities of infection are found, but it remains unknown whether minor medical or dental procedures, or even simple contact, could also effect transmission. If so, a prolonged incubation period, perhaps extending over decades as in kuru,3 would render the detection of the means of transmission in individual patients inordinately difficult.
 
 
this pretty much sums it up for me, with regards to how indestructible this tse prion agent is ;
 
Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery.
 
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC. Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
 
Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.
 
 
Thursday, January 23, 2014
 
Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices) [Docket No. FDA–2013–D–1574]
 
 
Thursday, November 14, 2013
 
Prion diseases in humans: Oral and dental implications
 
 
LET US look at some history of science and debate there from of the potential/likelihood of TSE prion transmission via the dental route, some of the SEAC links no longer work, and then towards the bottom, the latest on the BSE, CWD, Scrapie, TSE PRION risk factor to human updates from PRION2015 conference...
 
 
SEAC
 
Spongiform Encephalopathy Advisory Committee
 
 
Thursday, December 22, 2011
 
Risk of Prion Disease Transmission through Bovine-Derived Bone Substitutes: A Systematic Review Clin Implant Dent Relat Res. 2011 Dec 15. doi: 10.1111/j.1708-8208.2011.00407.x. [Epub ahead of print]
 
 
 SEAC REVIEW ;
 
Saturday, February 27, 2010 SEAC Agenda 104th meeting on Friday 5th March 2010
 
 
Thursday, August 12, 2010
 
SEAC August 2010 Drayton Farm report update and more
 
 
Saturday, December 12, 2009
 
103RD MEETING OF THE SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE
 
 
Thursday, February 26, 2009
 
SEAC 102nd Meeting on Wednesday 4 March 2009 (SEE DH risk assessment on sourcing and pooling plasma)
 
 
Thursday, January 31, 2008
 
SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE Draft minutes of the 99th meeting held on 14th December 2007
 
snip...
 
ITEM 8 – PUBLIC QUESTION AND ANSWER SESSION
 
40. The Chair explained that the purpose of the question and answer session was to give members of the public an opportunity to ask questions related to the work of SEAC. Mr Terry Singeltary (Texas, USA) had submitted a question prior to the meeting, asking: “With the Nor-98 now documented in five different states so far in the USA in 2007, and with the two atypical BSE H-base
 
13 © SEAC 2007
 
cases in Texas and Alabama, with both scrapie and chronic wasting disease (CWD) running rampant in the USA, is there any concern from SEAC with the rise of sporadic CJD in the USA from ''unknown phenotype'', and what concerns if any, in relations to blood donations, surgery, optical, and dental treatment, do you have with these unknown atypical phenotypes in both humans and animals in the USA? Does it concern SEAC, or is it of no concern to SEAC? Should it concern USA animal and human health officials?”
 
41. A member considered that this question ............
 
 
 
Thursday, October 23, 2008
 
ONE HUNDRED AND FIRST MEETING OF THE SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE
 
 
 
Subject: PrPSc in salivary glands of scrapie-affected sheep
 
Date: February 15, 2007 at 9:33 am PST
 
J. Virol. doi:10.1128/JVI.02148-06 Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.
 
PrPSc in salivary glands of scrapie-affected sheep
 
Marta Vascellari*, Romolo Nonno, Franco Mutinelli, Michela Bigolaro, Michele Angelo Di Bari, Erica Melchiotti, Stefano Marcon, Claudia D'Agostino, Gabriele Vaccari, Michela Conte, Luigi De Grossi, Francesca Rosone, Francesco Giordani, and Umberto Agrimi Istituto Zooprofilattico Sperimentale delle Venezie, Histopathology Department, Viale dell'Università 10, 35020 Legnaro (PD), Italy; Istituto Superiore di Sanità, Department of Food Safety and Animal Health, Viale Regina Elena 299, 00161 Roma, Italy; Istituto Zooprofilattico Sperimentale delle Regioni Lazio e Toscana, Strada Terme, 01100 Viterbo, Italy
 
* To whom correspondence should be addressed. Email: mvascellari@izsvenezie.it .
 
Abstract
 
The salivary glands of scrapie-affected sheep and healthy controls were investigated for the presence of the pathological prion protein (PrPSc). PrPSc was detected in major (parotid and mandibular) and minor (buccal, labial and palatine) salivary glands of naturally and experimentally infected sheep. By western blot, PrPSc concentration in glands was estimated as 0.02-0.005% of brain. Immunohistochemistry revealed intracellular deposition of PrPSc in ductal and acinar epithelium and occasional labeling into the lumen of salivary ducts. The presence of PrPSc in salivary glands highlights the possible role of saliva in the horizontal transmission of scrapie.
 
 
 
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.
 
Scully C, Smith AJ, Bagg J. Eastman Dental Institute, University of London.
 
It is almost a decade since the recognition of the emergence of a new infectious disease termed variant Creutzfeldt-Jakob disease (vCJD) caused by prions (PrPTSE), abnormal variants of a normal human cell surface protein (PrP).This disease has a number of similarities to other forms of CJD--lethal disorders characterized by a prolonged incubation period, and progressive mental deterioration. In relation to oral tissues, PrPTSE have been found in neural, gingival, pulpal, lingual, lymphoreticular and salivary gland tissue in animal models. In both sporadic and variant CJD, PrPTSE is detectable in the trigeminal ganglion and, in vCJD, in lymphoreticular tissues, but infectivity has not been tested in other human oral tissues. CLINICAL RELEVANCE: PrPTSE is much more resistant to the common methods of inactivation than conventional pathogens, and it adheres avidly to steel whilst retaining its infectivity. Particular attention must be paid to cleaning and sterilizing re-usable dental instruments. Single-use devices, such as endodontic files and matrix bands, must never be re-used. Advice on the reprocessing of dental instruments used on known CJD patients must be obtained from local infection control teams. Research into effective methods of prion inactivation appears promising, although further work on the applicability to general dental practice is required.
 
PMID: 17087448 [PubMed - in process]
 
 
 
SEAC 99th meeting on Friday 14th December 2007
 
snip...
 
© SEAC 2007
 
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. Although no abnormal prion protein was found in a study of human dental tissues, including dental pulp, salivary glands and gingiva from vCJD cases22, the relationship between levels of infectivity and abnormal prion protein is unclear23. 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 model24.
 
6. A second 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 sterilised, 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 sterilised 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 recognising 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.
 
20 Department of Health (2006) Dentistry and vCJD: the implications of a carrier-state for a self-sustaining epidemic. Unpublished. 21 SEAC (2006) Position statement on vCJD and endodontic dentistry.
 
 
22 Head et al. (2003) Investigation of PrPres in dental tissues in variant CJD. Br. Dent. J. 195, 339-343. 23 SEAC 90 reserved business minutes.
 
Implications for transmission risks
 
snip...PLEASE SEE DISTURBING FINDINGS FULL TEXT HERE ;
 
 
A RE-ASSESSMENT OF THE POTENTIAL RISK OF VCJD TRANSMISSION VIA DENTISTRY ISSUE
 
1. The Department of Health (DH) has asked SEAC to consider an interim assessment of the potential risk of vCJD transmission via dental procedures. This work builds on previous risk assessments on possible dental transmission considered by SEAC.
 
BACKGROUND
 
Previous SEAC considerations of vCJD transmission via dentistry
 
snip...
 
The New DH Risk Assessment
 
8. The research on infectivity just noted forms one strand of a wider programme at the HPA, which is also intended to quantify protein residues found on dental instruments and the effectiveness of sterilisation in reducing infectivity. Following SEAC 97 (May 2007), DH commissioned a comprehensive re-assessment of the potential risks of vCJD transmission associated with dentistry to take account of research at the HPA and elsewhere. The assessment aims to clarify the range of plausible scenarios for vCJD transmission via dental instruments that could occur, given what is currently known, and to identify the most important factors affecting this risk. The assessment will be used to identify the most important areas of further work to address the uncertainties and any robust ways of cost effectively reducing risks further.
 
9. This new interim risk assessment has been produced by DH analysts (annex 3) in collaboration with a Scientific Reference Group of independent experts (Chaired by Professor Graham Medley). Members of the Group have expertise in dentistry, instrument decontamination, human and animal prion diseases, anatomy, public health, risk assessment modelling and epidemiology. This group met three times to review and refine the modelling framework and agree the risk assessment. The group provided advice on the inputs and assumptions incorporated into the risk assessment, particularly where expert judgement was required due to a lack of hard data. Under circumstances where key data are absent, precautionary assumptions were agreed. As a number of large uncertainties that strongly influence the quantification of risk remain, the risk assessment is considered as interim and will be updated in the future when new scientific evidence becomes available.
 
10. The assessment examines the risk that vCJD may be transmitted via dental procedures by establishing plausible ranges for key parameters, including (see sections 2 and 3 of the risk assessment):
 
• the vCJD infectivity of tissues of the oral cavity of infected patients
 
• the deposition of that material onto different types of dental instruments and the effectiveness of standard cleaning and sterilisation processes used in dental practice
 
• the mechanisms and efficiency of transfer of vCJD infectivity from contaminated instruments used on subsequent patients
 
• the probability of transmission based on assessments of the number and types of dental procedure conducted and the number of people who might be carrying an asymptomatic vCJD infection.
 
Findings 11.
 
As there is lack of substantial data with which to accurately quantify many of these parameters, plausible ranges for these parameters have been established to take account of the often large uncertainties in the data. The large uncertainties in many of these parameters strongly influence the quantification of the risk.
 
12. Plausible scenarios built up using ranges for each of these factors include many in which dental transmission would have no detectable effect on the course of the vCJD outbreak (see section 4 of the risk assessment). However, there are some which include a combination of pessimistic assumptions as regards the infectivity of dental / oral tissues and the effects of instrument decontamination which suggest that:
 
• there could be some hundreds of vCJD transmissions per annum via dentistry - albeit against a background of several thousand existing vCJD infections (not clinical cases of vCJD), or where
 
• dental transmission could generate a self-sustaining reservoir of vCJD infection within the population.
 
13. The distinction between vCJD infections and clinical cases of vCJD is important. If a large proportion of secondary transmissions result in subclinical infections (either never developing into clinical disease or doing so over an extended time-scale) and those infected are infectious, the likelihood of a self-sustaining epidemic increases. The proportion of individuals who might enter such a subclinical “carrier state” is unknown. Key Assumptions and areas of uncertainty
 
14. Work on the risk assessment is on-going and new data should enable some of the inputs and assumptions underpinning these scenarios to be revised. Key areas of uncertainty are:
 
• Infectivity in relevant tissues. Of all the unknowns, that of overriding importance is whether dental/oral tissues in patients incubating vCJD would be infective, and if so at what level.
 
There are as yet no results of studies using human gingival and dental pulp tissues, and these studies may extend into 2009 and 2010 respectively. This is examined in section 2.3 of the risk assessment.
 
• Protein Residues on dental instruments. This is examined in section 2.2 of the risk assessment.
 
• Efficacy of Autoclaving. This is examined in section 2.3 of the risk assessment.
 
• Current prevalence of vCJD infection. This is examined in section 3.3 of the risk assessment.
 
• Epidemiology of vCJD. This is examined in section 4 of the risk assessment.
 
15. Suggested areas of further work to reduce the uncertainty in these key areas are described in section 5 of the risk assessment together with a preliminary analysis of possible interventions and risk reduction measures.
 
ADVICE SOUGHT FROM THE COMMITTEE
 
snip...
 
POSITION STATEMENT vCJD AND ENDODONTIC DENTISTRY
 
snip...
 
Endodontic instruments
 
5. Evidence suggests that the files and reamers used in endodontic procedures are reused and are difficult to reliably decontaminate4. Appreciable quantities of residual material remain adherent to the surface after normal cleaning and sterilisation5. 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 cases6, dental pulp includes blood and peripheral nerve tissue known to carry vCJD infectivity7,8. In addition, appreciable infectivity has been found in the dental pulp of hamsters with hamster scrapie9. 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 prions10. 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. level of infectivity is unknown.
 
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.
 
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 animals11. Another study suggested that prion infections in mice that remain at a subclinical level can be transmitted to other mice, resulting in clinical disease12. 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 hypothesis13. 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 thousand14. SEAC has strongly recommended that further studies to ascertain better the prevalence of vCJD infection be urgently considered15.
 
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
 
===================================
 
© SEAC 2007
 
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. Although no abnormal prion protein was found in a study of human dental tissues, including dental pulp, salivary glands and gingiva from vCJD cases22, the relationship between levels of infectivity and abnormal prion protein is unclear23. 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 model24.
 
6. A second 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 sterilised, 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 sterilised 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 recognising 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.
 
20 Department of Health (2006) Dentistry and vCJD: the implications of a carrier-state for a self-sustaining epidemic. Unpublished. 21 SEAC (2006) Position statement on vCJD and endodontic dentistry.
 
 
22 Head et al. (2003) Investigation of PrPres in dental tissues in variant CJD. Br. Dent. J. 195, 339-343. 23 SEAC 90 reserved business minutes.
 
Implications for transmission risks
 
snip...
 
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 recommending that endodontic files and reamers be treated as single use which, provided it is adhered to, will remove any risk of a self-sustaining epidemic arising from re-use of these instruments. To minimise 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 proved robust and effective, could significantly reduce transmission risks.
 
SEAC June 2007
 
27 SEAC Epidemiology Subgroup (2006) position statement of the vCJD epidemic.
 
 
 
 
28 DH (2007) Precautionary advice given to dentists on re-use of instruments
 
 
see full text 17 pages ;
 
 
SEAC 99th meeting on Friday 14th December 2007
 
DECEMBER 14, 2007, 10 year Anniversary of my Moms death 'confirmed' from Heidenhain Variant Creutzfeldt Jakob Disease
 
Greetings,
 
AS one of them _lay_ folks, one must only ponder ;
 
"WITH the Nor-98 now documented in five different states so far in the USA in 2007, and with the TWO atypical BSE H-BASE cases in Texas and Alabama, with both scrapie and CWD running rampant in the USA, IS there any concern from SEAC with the rise of sporadic CJD in the USA from ''UNKNOWN PHENOTYPE'', and what concerns if any, in relations to blood donations, surgery, optical, and dental, do you have with these unknown atypical phenotypes in both humans and animals in the USA ???"
 
"Does it concern SEAC, or is it of no concern to SEAC?"
 
"Should it concern USA animal and human health officials?"
 
snip...
 
 
13 DH (2007) Precautionary advice given to dentists on re-use of instruments
 
 
 
 
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.
 
 
 -------- Original Message --------
 
Subject: 26th June 2003 - The 78th SEAC meeting took place on the 24th June
 
Date: Sun, 29 Jun 2003 09:30:36 –0500
 
From: "Terry S. Singeltary Sr." flounder@wt.net
 
Reply-To: Bovine Spongiform Encephalopathy BSE-L@uni-karlsruhe.de
 
To: BSE-L@uni-karlsruhe.de
 
######## Bovine Spongiform Encephalopathy #########
 
26th June 2003 - The 78th SEAC meeting took place on the 24th June, a summary <http://www.seac.gov.uk/summaries/summ_0603.htm> of that meeting is available. At this meeting the minutes from the 77th meeting in February were approved and are now available in the previous meetings <http://www.seac.gov.uk/papers/papers.htm> section of this website. Additionally available is an updated document (PDF) listing the commercial and non-commercial interests <http://www.seac.gov.uk/committee/interest.pdf>of the SEAC members...
 
Summary of the 78th SEAC meeting on 24th June 2003
 
------------------------------------------------------------------------
 
The Spongiform Encephalopathy Advisory Committee (SEAC) held its 78th meeting in London on 24 June 2003, when it discussed the following matters:
 
Risk Assessment on Ox Tongue and Associate Tonsil Tissue
 
At an earlier meeting SEAC considered a new finding of BSE infectivity in ox tongue. SEAC recommended that a risk assessment be conducted and this was commissioned by the Food Standards Agency, and presented at the June 2003 meeting. The risk assessment considered the possible range of human exposure to BSE infectivity from the consumption of ox tongue. The Committee concluded that it was not possible to advise the FSA precisely on the magnitude of the risk due to the substantial scientific uncertainty inherent in the risk assessment. However, the Committee agreed that the scientific evidence indicated that the potential risk of infectivity from eating tongue was likely to be very small. The Committee identified further scientific work that would help to refine the risk estimates.
 
Review of the use of MMBM in fertiliser
 
The Department of the environment, food and rural affairs (Defra) asked SEAC to provide scientific advice on the animal health implications of proposed changes to UK fertiliser controls. SEAC agreed that the proposed use of ash from the incineration of meat and bone meal (MBM) derived from category 2 and category 3 material without restriction on land would not result in significant additional risk to animal health. SEAC confirmed its earlier advice that mammalian MBM should not be permitted in fertilisers likely to be spread on agricultural land or land where animals may graze.
 
VLA Survey – Scrapie Surveillance in Sheep
 
The Committee noted the preliminary results of a report from the Veterinary Laboratories Agency estimating the prevalence of scrapie in the national flock. The Committee also noted that a full report would be available in due course, containing all of the data from the study.
 
vCJD Update
 
The National CJD surveillance unit reported that 136 vCJD cases have been confirmed in the UK with 4 cases still alive. All vCJD cases tested to date are of the same genotype (Methionine homozygous at codon 129 of the PrP gene). All vCJD cases so far identified in 2003 have reported the onset of clinical signs in 2002. Therefore the total number of onsets in 2002 cannot yet be confirmed.
 
Report from the SEAC Epidemiology sub-group
 
The Chairman of this specialist sub-group reported to SEAC that there continues to be statistical evidence that the vCJD epidemic is no longer increasing at the rate seen previously and that the underlying incidence may have reached or be reaching a peak. However the possibility of susceptible genotypes other than methionine homozygotes and the theoretical possibility of other clinical manifestations of infection with the BSE agent other than vCJD means that prediction of the evolution of the epidemic is uncertain and continued surveillance is essential.
 
Expert Group on Strain Differentiation
 
SEAC received a report from the Chairman of an expert group of the EU Community TSE Reference Laboratory Committee, which met on 23 June 2003 to review progress on a trial to evaluate rapid TSE tests.
 
Quinquennial Review of SEAC
 
The Committee welcomed the recommendations outlined in the SEAC Quinquennial Review Report published in March 2003...END...TSS
 
12-31-2007, 01:09 PM
 
Risk Assessment of Transmission of Sporadic Creutzfeldt-Jakob Disease in Endodontic Practice in Absence of Adequate Prion Inactivation
 
Nadège Bourvis1,2, Pierre-Yves Boelle1,2,3, Jean-Yves Cesbron4,5,6, Alain-Jacques Valleron1,2,3*
 
1 Université Pierre et Marie Curie-Paris6, Unité de Recherche Epidémiologie-Systèmes d'information-Modélisation, UMR S 707, Paris, France, 2 INSERM, U707, Paris, France, 3 Assistance Publique-Hôpitaux de Paris (AP-HP), Unité de Santé Publique, Hôpital St Antoine, Paris, France, 4 Laboratoire Adaptation et de Pathogénie des Micro-organismes, Université Joseph Fourier, UMR 5163, Grenoble, France, 5 Centre National de la Recherche Scientifique (CNRS), UMR 5163, Grenoble, France, 6 Centre hospitalier universitaire (CHU) de Grenoble, Laboratoire d'Immunologie, Grenoble, France
 
Abstract
 
Background
 
Experimental results evidenced the infectious potential of the dental pulp of animals infected with transmissible spongiform encephalopathies (TSE). This route of iatrogenic transmission of sporadic Creutzfeldt-Jakob disease (sCJD) may exist in humans via reused endodontic instruments if inadequate prion decontamination procedures are used.
 
Methodology/Principal Findings
 
To assess this risk, 10 critical parameters in the transmission process were identified, starting with contamination of an endodontic file during treatment of an infectious sCJD patient and ending with possible infection of a subsequent susceptible patient. It was assumed that a dose-risk response existed, with no-risk below threshold values. Plausible ranges of those parameters were obtained through literature search and expert opinions, and a sensitivity analysis was conducted. Without effective prion-deactivation procedures, the risk of being infected during endodontic treatment ranged between 3.4 and 13 per million procedures. The probability that more than one case was infected secondary to endodontic treatment of an infected sCJD patient ranged from 47% to 77% depending on the assumed quantity of infective material necessary for disease transmission. If current official recommendations on endodontic instrument decontamination were strictly followed, the risk of secondary infection would become quasi-null.
 
Conclusion
 
The risk of sCJD transmission through endodontic procedure compares with other health care risks of current concern such as death after liver biopsy or during general anaesthesia. These results show that single instrument use or adequate prion-decontamination procedures like those recently implemented in dental practice must be rigorously enforced.
 
Citation: Bourvis N, Boelle P-Y, Cesbron J-Y, Valleron A-J (2007) Risk Assessment of Transmission of Sporadic Creutzfeldt-Jakob Disease in Endodontic Practice in Absence of Adequate Prion Inactivation. PLoS ONE 2(12): e1330. doi:10.1371/journal.pone.0001330
 
Academic Editor: Alison Galvani, Yale University, United States of America
 
Received: April 30, 2007; Accepted: November 26, 2007; Published: December 26, 2007
 
Copyright: © 2007 Bourvis et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
 
Funding: EU contract INFTRANS
 
Competing interests: The authors have declared that no competing interests exist.
 
* To whom correspondence should be addressed. E-mail: alain-jacques.valleron@upmc.fr
 
snip...
 
Discussion
 
The results of this modelling approach show that the risk of sCJD transmission due to the reuse of instruments during ET may not be ignored in absence of effective prion-decontamination procedures.
 
How should our conclusions be used in a public health assessment? First note that this risk is already of concern to national health agencies as well as to health professionals [25]–[27]. Our work makes it possible to go beyond a qualitative assessment, towards more quantitative predictions where all hypotheses are clearly stated. The conclusions of this approach may easily be updated as new data accrue.
 
The details of ET were obtained from the latest official reports in France and UK or from experts. We conducted a literature search to collect the best estimates available of the possible quantities of infectious material left on the instruments, and subsequently partially removed by the classical disinfection procedures used until the last years of the 20th century. We obtained similarly estimates of the values of brain infectivity and of the ratio of brain infectivity to pulp infectivity. These parameters were obtained from animal experiments as they are clearly unknown in humans.
 
A comparable approach can be found in the HPA report on vCJD transmission in dentistry with two notable differences [25]. First, the route of instrument contamination and subsequent transmission considered in the HPA report was a very rare accidental process: the abrasion of tonsillar tissue during dental care. On the contrary, we considered the process of accessing the dental pulp during ET as certain, which obviously leads to a higher risk. Second, the HPA report considered infectivity of tonsils to be 106–107 i/c ID50 per gram, while we used dental pulp with a slightly lower range of infectivity from 104-106i/c ID50 per gram ( = BI* BPR).
 
The hypotheses we used concerning the relationship between the estimated inoculums and the probability of infection are obviously critical. In our assessment, we postulated that too small an inoculum (below 10−1 and 10−2 ID50 were considered with functions ϕ1 and ϕ2) would not lead to infection, and that there was a linear dose–response relationship above this threshold. This effectively complies with the “zero risk below a threshold” hypothesis rather than with the “single infectious particle” hypothesis. There is indeed experimental evidence that even very small quantities of infectious material may trigger infection in mice [13], [28], and this hypothesis was previously used in assessing decontamination procedures[29]. However, we adopted a more conservative risk estimate.
 
The duration of the infectious period of CJD is unknown but could be very long. We used as a reference the incubation period estimated from hGH iatrogenic cases [30]. To make comparison easier, and for want of better or more recent evidence, the duration of the infectious period relative to incubation was the same as in the HPA report, i.e. 40% of the incubation period [25].
 
Our risk assessment should have used the prevalence of infectious sCJD in those undergoing ET instead of that in the general population. Presumably, the former is the largest and the risk was therefore minimized. Indeed, children, who do not develop sCJD are taken into account in the general population estimate, when that in ET patients concerns only adults.
 
The ranges of values of risk assessment generated with our model were broad. They mirror the current lack of knowledge and the uncertainties concerning data and hypotheses. However, our model makes it clear that the ET of the 20th century were not risk-free in terms of CJD. Therefore, our model suggests that patients may well have been contaminated at the end of 20th century, and still be in the latency period and at risk of transmitting the disease.
 
The estimated individual risk of sCJD transmission during ET was low in our assessment. However, these values compared with the mortality rates in general anaesthesia [31], transcutaneous liver biopsy [32] or voluntary abortion [33] which are of concern in the modern health care.
 
We also studied the possible impact of ET at a population level and showed that there was a high probability that the reproduction rate R exceeded 1 in the absence of effective prion decontamination of the instruments: one of the conditions for the initiation of an epidemic process is fulfilled. To date, epidemiological surveillance data did not evidence such an epidemic process. However, would our hypothesis be true, the increase in incidence could remain modest and hard to identify for dozens of years because the incidence of sCJD is low, the incubation period long and in competition with all mortality causes present. CJD surveillance systems is too recent to show such trends.
 
Vacuum autoclaving and porous-load autoclaving for 18 min at 134°C are currently recognised as appropriate methods for prion decontamination, leading to a reduction of the infectivity load by of 3–5 log10 or more. According to our model, this decontamination would prevent CJD transmission in dental practice, even considering that the residual infectivity is not strictly reduced to zero. These methods are recommended in official reports in various countries. However, in a US study conducted in 1996 [34], only 53% of dentists used autoclaves to decontaminate root-canal files. In a survey conducted in France in 2004, only 79% of dentists used an autoclave [35]. The problem of correct use of the autoclaves and regular checking of their efficacy has also been raised by many authors in several countries [34]. A recent survey on dental practice also showed that other elementary precautionary measures against CJD transmission were not widely respected. For example, the vast majority of dentists did not actively seek out patients at-risk for any form of CJD (sporadic, iatrogenic or familial) [36]. Therefore, in the current situation and despite recommended decontamination procedures, the risk of sCJD transmission during dental care might still not be zero. In any case, our findings constitute a strong argument for the strict respect of the official recommendations on decontamination procedures in dentistry, and even suggest that the cost-benefit of single-use endodontic instruments should be re-evaluated.
 
The risk analysis approach we have used relies on a “problem dissection” in which all components to a risk are identified and linked to the available scientific data, knowledge, and expert opinion. It may be of help in other emerging diseases, when data on the natural history of the disease and transmission are still scarce and clinical events cannot be observed directly. In all these cases, the output of the work will always be questionable, because of the lack of data, but the strength of the method is that its results and final statements are refutable as data accrues.
 
snip... end... tss
 
 
 
Tuesday, August 12, 2008
 
Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007 (occupational exposure to prion diseases)
 
 
Monday, August 17, 2009
 
Transmissible Spongiform Encephalopathy Agents: Safe Working and the Prevention of Infection: Annex J,K, AND D Published: 2009
 
 
Friday, July 17, 2009
 
Revision to pre-surgical assessment of risk for vCJD in neurosurgery and eye surgery units Volume 3 No 28; 17 July 2009
 
 
Published Date: 2010-03-04 16:00:03
 
Subject: PRO/AH/EDR> Prion disease update (03)
 
Archive Number: 20100304.0709
 
 
Tuesday, March 16, 2010
 
Transmissible Spongiform Encephalopathy Agents: Safe Working and the Prevention of Infection: Part 4 REVISED FEB. 2010
 
 
Tuesday, May 11, 2010
 
Current risk of iatrogenic Creutzfeld-Jakob disease in the UK: efficacy of available cleaning chemistries and reusability of neurosurgical instruments
 
 
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
 
 
Tuesday, March 29, 2011
 
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY EXPOSURE SPREADING VIA HOSPITALS AND SURGICAL PROCEDURES AROUND THE GLOBE
 
 
Monday, May 16, 2011
 
Does Poor Dental Health Have a Role in the Emergence of Variant Creutzfeldt Jakob Disease in the United Kingdom?
 
 
Sunday, October 23, 2011
 
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
 
 
Wednesday, August 24, 2011
 
All Clinically-Relevant Blood Components Transmit Prion Disease following a Single Blood Transfusion: A Sheep Model of vCJD
 
 
Wednesday, August 24, 2011
 
There Is No Safe Dose of Prions
 
 
CDC Morbidity and Mortality Weekly Report Recommendations and Reports December 19, 2003 / Vol. 52 / No. RR-17
 
Guidelines for Infection Control in Dental Health-Care Settings — 2003
 
36 MMWR December 19, 2003 Creutzfeldt-Jakob Disease and Other Prion Diseases Creutzfeldt-Jakob disease (CJD) belongs to a group of rapidly progressive, invariably fatal, degenerative neurological disorders, transmissible spongiform encephalopathies (TSEs) that affect both humans and animals and are thought to be caused by infection with an unusual pathogen called a prion. Prions are isoforms of a normal protein, capable of self-propagation although they lack nucleic acid. Prion diseases have an incubation period of years and are usually fatal within 1 year of diagnosis. Among humans, TSEs include CJD, Gerstmann-Straussler- Scheinker syndrome, fatal familial insomnia, kuru, and variant CJD (vCJD). Occurring in sporadic, familial, and acquired (i.e., iatrogenic) forms, CJD has an annual incidence in the United States and other countries of approximately 1 case/ million population (445–448). In approximately 85% of affected patients, CJD occurs as a sporadic disease with no recognizable pattern of transmission. A smaller proportion of patients (5%–15%) experience familial CJD because of inherited mutations of the prion protein gene (448). vCJD is distinguishable clinically and neuropathologically from classic CJD, and strong epidemiologic and laboratory evidence indicates a causal relationship with bovine spongiform encephalopathy (BSE), a progressive neurological disorder of cattle commonly known as mad cow disease (449–451). vCJD, was reported first in the United Kingdom in 1996 (449) and subsequently in other European countries (452). Only one case of vCJD has been reported in the United States, in an immigrant from the United Kingdom (453). Compared with CJD patients, those with vCJD are younger (28 years versus 68 years median age at death), and have a longer duration of illness (13 months versus 4.5 months). Also, vCJD patients characteristically exhibit sensory and psychiatric symptoms that are uncommon with CJD. Another difference includes the ease with which the presence of prions is consistently demonstrated in lymphoreticular tissues (e.g., tonsil) in vCJD patients by immunohistochemistry (454). CJD and vCJD are transmissible diseases, but not through the air or casual contact. All known cases of iatrogenic CJD have resulted from exposure to infected central nervous tissue (e.g., brain and dura mater), pituitary, or eye tissue. Studies in experimental animals have determined that other tissues have low or no detectable infectivity (243,455,456). Limited experimental studies have demonstrated that scrapie (a TSE in sheep) can be transmitted to healthy hamsters and mice by exposing oral tissues to infectious homogenate (457,458). These animal models and experimental designs might not be directly applicable to human transmission and clinical dentistry, but they indicate a theoretical risk of transmitting prion diseases through perioral exposures. According to published reports, iatrogenic transmission of CJD has occurred in humans under three circumstances: after use of contaminated electroencephalography depth electrodes and neurosurgical equipment (459); after use of extracted pituitary hormones (460,461); and after implant of contaminated corneal (462) and dura mater grafts (463,464) from humans. The equipment-related cases occurred before the routine implementation of sterilization procedures used in healthcare facilities. Case-control studies have found no evidence that dental procedures increase the risk of iatrogenic transmission of TSEs among humans. In these studies, CJD transmission was not associated with dental procedures (e.g., root canals or extractions), with convincing evidence of prion detection in human blood, saliva, or oral tissues, or with DHCP becoming occupationally infected with CJD (465–467). In 2000, prions were not found in the dental pulps of eight patients with neuropathologically confirmed sporadic CJD by using electrophoresis and a Western blot technique (468). Prions exhibit unusual resistance to conventional chemical and physical decontamination procedures. Considering this resistance and the invariably fatal outcome of CJD, procedures for disinfecting and sterilizing instruments potentially contaminated with the CJD prion have been controversial for years. Scientific data indicate the risk, if any, of sporadic CJD transmission during dental and oral surgical procedures is low to nil. Until additional information exists regarding the transmissibility of CJD or vCJD, special precautions in addition to Vol. 52 / RR-17 Recommendations and Reports 37 standard precautions might be indicated when treating known CJD or vCJD patients; the following list of precautions is provided for consideration without recommendation (243,249,277,469):
 
• Use single-use disposable items and equipment whenever possible.
 
• Consider items difficult to clean (e.g., endodontic files, broaches, and carbide and diamond burs) as single-use disposables and discard after one use.
 
• To minimize drying of tissues and body fluids on a device, keep the instrument moist until cleaned and decontaminated.
 
• Clean instruments thoroughly and steam-autoclave at 134ºC for 18 minutes. This is the least stringent of sterilization methods offered by the World Health Organization. The complete list (469) is available at http://www.who.int/emcdocuments/tse/whocdscsraph2003c.html.
 
• Do not use flash sterilization for processing instruments or devices. Potential infectivity of oral tissues in CJD or vCJD patients is an unresolved concern. CDC maintains an active surveillance program on CJD. Additional information and resources are available at http://www.cdc.gov/ncidod/diseases/cjd/cjd.htm.
 
snip...
 
 
PRACTICE
 
BRITISH DENTAL JOURNAL VOLUME 197 NO. 2 JULY 24 2004 75
 
Presentation of a case of variant CJD in general dental practice
 
A. J. Smith1, D. I. Russell2, J. Greene3, A. Lowman4 and J. W. Ironside5
 
This case report describes the initial presentation of variant CJD to a general dental practitioner. The case highlights the importance of prompt referral of patients presenting with a history of atypical facial symptoms.
 
1Senior Lecturer, Microbiology, Glasgow Dental Hospital & School; 2Consultant Oral & Maxillofacial Surgeon, Glasgow Dental Hospital & School; 3Consultant Neurologist, Institute of Neurological Sciences, Southern General Hospital, Glasgow; 4Registrar in Neurology, National CJD Surveillance Unit, University of Edinburgh, Western General Hospital, Edinburgh; 5Professor of Clinical Neuropathology, National CJD Surveillance Unit, University of Edinburgh, Western General Hospital, Edinburgh Correspondence to: A. J. Smith, Infection Research Group, Glasgow Dental Hospital & School, 378 Sauchiehall Street, Glasgow G2 3JZ, Scotland Email: a.smith@dental.gla.ac.uk Refereed Paper doi:10.1038/sj.bdj.4811468 Received 13.10.03; Accepted 16.01.04 © British Dental Journal 2004; 197: 75 76
 
CASE REPORT
 
A 28-year-old patient presented to their general dental practitioner with a 4-week history of paraesthesia of the left side of the face including the lower lip. The patient was referred for an oral surgery consultant clinic appointment for a more detailed appraisal of the patient s signs and symptoms. Examination at the consultant clinic revealed an unremarkable past dental and medical history. The patient complained of a pins and needles sensation in the left cheek, left lower lip and chin and the skin of the left hand. Extra-oral examination demonstrated a partial loss of sensation as demonstrated by an impaired response to pin prick and light touch, as well as two point discrimination. This was evident in the areas of the left face supplied by the infra-orbital and mental nerves and the palm and back of the hand (C6, C7, C8). There was no weakness of the facial muscles and the right side was unaffected. Intra-oral examination revealed a healthy intact dentition with no obvious signs of dental disease. Due to the unusual distribution of the sensory abnormalities the patient was referred for an urgent neurological examination. On presentation to the neurology clinic for a detailed neurological examination, 3 months after initial presentation to the dental practitioner, some change in the patients personality were noted. These included becoming increasingly withdrawn with episodes of confusion. Clinical examination revealed that the patient's sensory impairment on the left side had extended to include the left arm, leg and trunk. No other neurological signs and symptoms were observed. Approximately 1 month later further diagnostic tests were performed as follows:
 
" EEG mild diffuse slowing " MRI brain scan bilateral diffuse areas of signal hypersensitivity affecting the pulvinar region of the brain " CSF 14-3-3 protein negative " CSF white cell count normal
 
On the basis of the clinical presentation of the sensory symptoms, psychiatric features and the MRI results a diagnosis of probable variant CJD was made. Eight months after presentation to the dental practitioner the patient died and the clinical diagnosis of variant CJD was confirmed following autopsy.
 
DISCUSSION
 
Psychiatric symptoms are common in the early stages of vCJD. Typical presentations are depression, anxiety and behavioural change.1 Neurological symptoms such as pain, paraesthesia and numbness precede psychiatric symptoms in 15% of cases and are present in combination with psychiatric symptoms in 22% of cases from the onset of disease. The most common early neurological (< 4 months onset) features are persistent pain affecting the limbs, trunk and face but not associated with sensory symptoms. Within 4 6 months of onset paraes-
 
? A description of a patient presenting with vCJD to a general dental practitioner. ? vCJD can present with atypical facial symptons such as paraesthesia. ? The case highlights the importance of medical history taking at each visit and the prompt referral of any patients with atypical signs and symptoms.
 
I N B R I E F
 
PRACTICE
 
76 BRITISH DENTAL JOURNAL VOLUME 197 NO. 2 JULY 24 2004
 
thesia and numbness in a similar distribution to, and often associated with pain is common.2,3 A diagnosis of CJD has been confirmed following autopsy in all cases where a post-mortem examination has been performed.4
 
DIAGNOSIS OF VCJD
 
An ante-mortem diagnosis of vCJD can be difficult in the early stages of the disease. However, diagnosis can be facilitated by use of a number of diagnostic criteria based on a detailed clinical history of the nature of the symptoms, pattern of progression and duration of the illness and diagnostic tests, and can lead to a clinical diagnosis with a high degree of accuracy.4 A number of tests and investigations can contribute to a diagnosis:
 
1. Blood tests In addition to excluding other forms of illness, blood tests collected with informed consent can be performed for any of the genetic mutations already identifiable in inherited prion diseases. Blood can also be tested for genetic susceptibility to vCJD by detecting the presence of methionine/ methionine homozygosity at codon 129. To date, all cases of vCJD are homozygous for methionine at this location.
 
2. EEG This can be a useful test for the diagnosis of sporadic CJD. In other forms of CJD the EEG may be normal or there may be nonspecific abnormalities.
 
3.Cranial MRI An MRI scan can be useful in assisting a diagnosis. In vCJD, abnormal changes can be observed in the posterior thalamic area of the brain (pulvinar sign) and in sCJD there are occasional changes in the basal ganglia.5
 
4. CSF Analysis of CSF is useful to exclude some types of infection. An increase in the neuronal protein 14-3-3 in the CSF can be of considerable help in the diagnosis of sCJD, but it is less helpful in vCJD.6
 
5. BIOPSY Brain biopsy is not recommended for any form of CJD unless an alternative treatable condition is suspected in the differential diagnosis. In vCJD, PrPSc also accumulates outside of the CNS in lymphoid tissues, so that biopsy of tonsillar tissue can provide a means of a probable diagnosis of vCJD. Within the UK, the use of tonsil biopsy for diagnosis of vCJD has been developed and validated.7
 
CONCLUSION
 
Although sensory disturbances in one or more divisions of the fifth cranial nerve is a rare presentation for vCJD, this possibility should be considered, particularly if the sensory symptoms progress to other areas. Some of the early clinical features of vCJD such as personality change, loss of concentration or sensory symptoms may occur in psychiatric conditions (sometimes as side effects of psychotropic drugs), or in the early stages of multiple sclerosis, However, the persistence of these symptoms over a number of weeks with no apparent cause should alert the practitioner to the presence of a more serious underlying cause and urgent referral for further investigation should be instituted. In particular, the emergence of ataxia (unsteady gait), myoclonus (sudden muscle spasms) or other movement disorders should strongly alert the clinician to suspect a progressive neurodegenerative condition such as vCJD. The authors wish to acknowledge the kind support of the patient's family to allow us the opportunity to publish this report.
 
1. Spencer M D, Knight R S G, Will R G. First hundred cases of variant CJD: retrospective case note review of early psychiatric and neurological features. Br Med J 2002; 324: 1479-1482. 2. Henry C, Knight R. Clinical features of variant Creutzfeldt-Jakob disease. Rev Med Virol 2002; 12: 143-150. 3. Macleod M A, Knight R, Stewart G, Zeidler M, Will R. Sensory features of variant Creutzfeldt-Jakob disease. J Neurol Neurosurg Psychiatry 2000; 69: 413-414. 4. Will R G, Zeidler M, Stewart G E et al. Diagnosis of new variant Creutzfeldt-Jakob disease. Annals of Neurology 2000; 47: 575-582. 5. Zeidler M, Sellar R J, Collier D A et al. The pulvinar sign on magnetic resonance imaging in variant Creutzfeldt-Jakob disease. Lancet 2000; 355: 1412- 1418. 6. Hsich G, Kennedy K, Gibbs C J, Lee K H, Harrington M G. The 14-3-3 brain protein in cerebrospinal fluid as a marker for transmissible spongiform encephalopathies. N Engl J Med 1996; 335: 924-930. 7. Hill A F, Butterworth R J, Joiner S et al. Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 1999; 353: 183-189.
 
BRITISH DENTAL JOURNAL VOLUME 197 NO. 2 JULY 24, 2004
 
 
Evidence For CJD/TSE Transmission Via Dental Instruments
 
From Terry S. Singletary, Sr flounder@wt.net 1-24-3
 
J Hosp Infect 2002 Jul;51(3):233-5 Related Articles, Links [Click here to read] Contaminated dental instruments.
 
Smith A, Dickson M, Aitken J, Bagg J.
 
Infection Research Group, Glasgow Dental Hospital & School, 378 Sauchiehall Street, Glasgow, UK. a.smith@dental.gla.ac.uk
 
There is current concern in the UK over the possible transmission of prions via contaminated surgical instruments. Some dental instruments (endodontic files) raise particular concerns by virtue of their intimate contact with terminal branches of the trigeminal nerve. A visual assessment using a dissecting light microscope and scanning electron microscopy of endodontic files after clinical use and subsequent decontamination was performed. The instruments examined were collected from general dental practices and from a dental hospital. Seventy-six per cent (22/29) of the files retrieved from general dental practices remained visibly contaminated, compared with 14% (5/37) from the dental hospital. Current methods for decontaminating endodontic instruments used in dentistry may be of an insufficient standard to completely remove biological material. Improved cleaning methods and the feasibility of single use endodontic instruments require further investigation.
 
PMID: 12144804 [PubMed - indexed for MEDLINE]
 
 
J Gen Virol 1999 Nov;80 ( Pt 11):3043-7
 
Transmission of the 263K scrapie strain by the dental route.
 
Ingrosso L, Pisani F, Pocchiari M
 
Laboratory of Virology, lstituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome, Italy.
 
Apart from a few cases of iatrogenic and familial human transmissible spongiform encephalopathies (TSEs) or prion diseases, the cause of Creutzfeldt-Jakob disease (CJD) remains unknown. In this paper we investigated the possibility that dental procedures may represent a potential route of infection. This was assessed by using the experimental model of scrapie in hamster. In the first part of this study we found that after intraperitoneal inoculation, oral tissues commonly involved in dental procedures (gingival and pulp tissues) bore a substantial level of infectivity. We also found high scrapie infectivity in the trigeminal ganglia, suggesting that the scrapie agent had reached the oral tissues through the sensitive terminal endings of the trigeminal nerves. In the second part of the study we inoculated a group of hamsters in the tooth pulp and showed that all of them developed scrapie disease. In these animals, we detected both infectivity and the pathological prion protein (PrPsc) in the trigeminal ganglion homolateral to the site of injection but not in the controlateral one. This finding suggests that the scrapie agent, and likely other TSE agents as well, spreads from the buccal tissues to the central nervous system through trigeminal nerves. Although these findings may not apply to humans affected by TSEs, they do raise concerns about the possible risk of transmitting these disorders through dental procedures. Particular consideration should be taken in regard to new variant CJD patients because they may harbour more infectivity in peripheral tissues than sporadic CJD patients.
 
PMID: 10580068
 
 
a simple auto-claving just will not kill this agent, considering the fact this agent can survive ashing to 600 degrees celsius;
 
New studies on the heat resistance of hamster-adapted scrapie agent: Threshold survival after ashing at 600°C suggests an inorganic template of replication Paul Brown*,dagger , Edward H. RauDagger , Bruce K. Johnson*, Alfred E. Bacote*, Clarence J. Gibbs Jr.*, and D. Carleton Gajdusek§
 
* Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, and Dagger Environmental Protection Branch, Division of Safety, Office of Research Services, National Institutes of Health, Bethesda, MD 20892; and § Institut Alfred Fessard, Centre National de la Recherche Scientifique, 91198 Gif sur Yvette, France
 
Contributed by D. Carleton Gajdusek, December 22, 1999
 
Abstract
 
One-gram samples from a pool of crude brain tissue from hamsters infected with the 263K strain of hamster-adapted scrapie agent were placed in covered quartz-glass crucibles and exposed for either 5 or 15 min to dry heat at temperatures ranging from 150°C to 1,000°C. Residual infectivity in the treated samples was assayed by the intracerebral inoculation of dilution series into healthy weanling hamsters, which were observed for 10 months; disease transmissions were verified by Western blot testing for proteinase-resistant protein in brains from clinically positive hamsters. Unheated control tissue contained 9.9 log10LD50/g tissue; after exposure to 150°C, titers equaled or exceeded 6 log10LD50/g, and after exposure to 300°C, titers equaled or exceeded 4 log10LD50/g. Exposure to 600°C completely ashed the brain samples, which, when reconstituted with saline to their original weights, transmitted disease to 5 of 35 inoculated hamsters. No transmissions occurred after exposure to 1,000°C. These results suggest that an inorganic molecular template with a decomposition point near 600°C is capable of nucleating the biological replication of the scrapie agent.
 
transmissible spongiform encephalopathy | scrapie | prion | medical waste | incineration
 
Introduction
 
The infectious agents responsible for transmissible spongiform encephalopathy (TSE) are notoriously resistant to most physical and chemical methods used for inactivating pathogens, including heat. It has long been recognized, for example, that boiling is ineffective and that higher temperatures are most efficient when combined with steam under pressure (i.e., autoclaving). As a means of decontamination, dry heat is used only at the extremely high temperatures achieved during incineration, usually in excess of 600°C. It has been assumed, without proof, that incineration totally inactivates the agents of TSE, whether of human or animal origin. It also has been assumed that the replication of these agents is a strictly biological process (1), although the notion of a "virus" nucleant of an inorganic molecular cast of the infectious beta -pleated peptide also has been advanced (2). In this paper, we address these issues by means of dry heat inactivation studies.
 
see full text:
 
 
Greetings again,
 
please believe me when i tell you this goes far far beyond the hamburger/deerburger/elkburger/sheepburger. Pandora's box of the demented has been opened for decades, closing it will be most impossible with current safeguards. until they can perfect a test, not only to confirm TSE agent, but also to differentiate between the many differnt strains (there are over 20 in sheep scrapie, and sheep scrapie is the sole model for CJD studies), they then will have to perfect a test that will differentiate between the many different routes. so, as you can see, this could very well take many more decades to answer these questions. but in the mean time, i will not now or ever accept the 'spontaneous/sporadic' theory without any source and route. i plan to continue to fan the fire until we know what killed our loved ones...
 
CJD/TSEs MUST BE MADE REPORTABLE NATIONALLY, SUPPORTED WITH A CJD QUESTIONNAIRE TO EVERY VICTIM/FAMILY THAT ASK REAL QUESTIONS PERTAINING TO ROUTE/SOURCE...TSS
 
Diagnosis and Reporting of Creutzfeldt-Jakob Disease T. S. Singeltary, Sr; D. E. Kraemer; R. V. Gibbons, R. C. Holman, E. D. Belay, L. B. Schonberger
 
 
kind regards, terry
 
----- Original Message -----
 
From: "Terry S. Singeltary Sr."
 
To:
 
Sent: Tuesday, July 26, 2005 8:00 AM
 
Subject: Information for dentists about the management of patients with, or ‘at risk’ of, Creutzfeldt-Jakob Disease (CJD) including variant CJD (vCJD)
 
##################### Bovine Spongiform Encephalopathy #####################
 
Gateway Approval Reference Number: 4463
 
Professor Raman Bedi
 
Chief Dental Officer – England
 
Room 332 Wellington House
 
133-135 Waterloo Road
 
London
 
SE1 8UG
 
Direct Line: 020 7 972 3995
 
Fax: 020 7972 3999
 
E-mail: raman.bedi@dh.gsi.gov.uk
 
4 February 2005
 
Dear Colleague
 
Information for dentists about the management of patients with, or ‘atrisk’
 
of, Creutzfeldt-Jakob Disease (CJD) including variant CJD (vCJD)
 
The aim of this letter is to clarify the situation with respect to the Primary
 
Dental Care of patients who have been diagnosed with CJD, or identified as
 
‘at-risk’ of CJD for public health purposes.
 
The clinical care – including dental care - of these patients, should not be
 
compromised in any way. As for all patients, satisfactory standards of
 
decontamination are required. Should dental treatment progress to head and
 
neck surgery, special precautionary measures may need to be taken to
 
reduce any possible transmission of CJD.
 
The possibility that CJD may be spread from patient to patient in healthcare
 
settings arises from knowledge that the CJD agent can be detected in certain
 
tissues, and that any infectivity transferred on instruments in the course of
 
their use may not be entirely removed (nor inactivated) by normal
 
decontamination processes.
 
Information about the appropriate management of these patients’ dental
 
treatment is summarised below. The Annex (Annex A) attached to this letter
 
provides supporting information and sources for further information.
 
KEY MESSAGES
 
Please ensure that:
 
- Patients with CJD, or identified as ‘at-risk’ of CJD for public health
 
purposes, (or their relatives) are not refused routine dental treatment
 
- Satisfactory standards of decontamination are observed
 
Gateway Approval Reference Number: 4463
 
- Information about patients who are ‘at-risk’ of CJD is included in any
 
referrals for surgery, and recorded in your records.
 
Actions for all Primary Dental Carers
 
When treating a patient with CJD, or a patient who informs you that he/she
 
has been identified as ‘at-risk’ of CJD, you should:
 
• Ensure that satisfactory standards of decontamination are observed.
 
Under these conditions, routine dentistry is understood to be low-risk, and
 
therefore no special infection control precautions are advised for the
 
instruments used on symptomatic or ‘at-risk’ patients.
 
The recommendations of the British Dental Association1 should be
 
followed at all times, and for all patients.
 
Further information on infection control procedures specifically for patients
 
with CJD or ‘at-risk’ of CJD is available in the guidance developed by the
 
Advisory Committee on Dangerous Pathogens (ACDP) Transmissible
 
Spongiform Encephalopathy (TSE) Working Group, Transmissible
 
spongiform encephalopathy agents: safe working and the prevention of
 
infection2.
 
For a patient who informs you that he/she has been identified as ‘at-risk’ of
 
CJD, you should also:
 
• Ensure that information about the patient’s ‘at-risk’ status is included
 
in any referrals for surgery. Head and neck surgery may involve contact
 
with tissues of high or medium infectivity, for which special infection control
 
precautions are advised. Please also record this information in your
 
records for this patient.
 
PROFESSOR RAMAN BEDI
 
Chief Dental Officer – England
 
Gateway Approval Reference Number: 4463
 
References
 
1 British Dental Association (February 2003) Advice sheet A12 Infection
 
Control in Dentistry
 
 
2 Transmissible spongiform encephalopathy agents: safe working and the
 
prevention of infection. Guidance from the Advisory Committee on
 
Dangerous Pathogens and the Spongiform Encephalopathy Advisory
 
Committee. 1998, 2003 and 2004
 
 
ANNEX A
 
Further information on managements of patients with, or at
 
risk of, CJD in Primary Dental Care
 
1. Categories of patients for whom this information applies
 
Details of the classification of patients with symptomatic CJD disease and
 
patients who are considered ‘at risk’ of CJD while asymptomatic can be found
 
in Table 4a of the guidance developed by the Advisory Committee on
 
Dangerous Pathogens (ACDP) Transmissible Spongiform Encephalopathy
 
(TSE) Working Group, Transmissible spongiform encephalopathy agents:
 
safe working and the prevention of infection2. This table is reproduced below.
 
Table 4a of TSE Infection Control Guidelines: Categorisation of patients by risk
 
1. Symptomatic patients 1.1 Patients who fulfil the diagnostic criteria for definite,
 
probable or possible CJD or vCJD (see Annex B for
 
diagnostic criteria).
 
1.2 Patients with neurological disease of unknown
 
aetiology who do not fit the criteria for possible CJD or
 
vCJD, but where the diagnosis of CJD is being actively
 
considered
 
2. Asymptomatic patients at risk from familial forms of
 
CJD linked to genetic mutations
 
2.1 Individuals who have or have had two or more blood
 
relatives affected by CJD or other prion disease, or a
 
relative known to have a genetic mutation indicative of
 
familial CJD.
 
2.2 Individuals who have been shown by specific
 
genetic testing to be at significant risk of developing
 
CJD or other prion disease.
 
3. Asymptomatic patients potentially at risk from
 
iatrogenic exposure##
 
3.1 Recipients of hormone derived from human pituitary
 
glands, e.g. growth hormone, gonadotrophin.
 
3.2 Individuals who have received a graft of dura mater.
 
(People who underwent neurosurgical procedures or
 
operations for a tumour or cyst of the spine before
 
August 1992 may have received a graft of dura mater,
 
and should be treated as at risk, unless evidence can be
 
provided that dura mater was not used).
 
3.3 Patients who have been contacted as potentially at
 
risk because of exposure to instruments used on, or
 
receipt of blood, plasma derivatives, organs or tissues
 
donated by, a patient who went on to develop CJD or
 
vCJD*.
 
## NB: A decision on the inclusion of corneal graft recipients in the "iatrogenic at risk" category is
 
pending completion of a risk assessment.
 
* The CJD Incidents Panel, which gives advice to the local team on what action needs to be taken when
 
a patient who is diagnosed as having CJD or vCJD underwent surgery or donated blood, organs or
 
tissues before CJD/vCJD was identified, will identify contacts who are potentially at risk.
 
- 1 -
 
ANNEX A
 
- 2 -
 
2. Dentistry in the TSE Infection Control Guidelines2
 
Part 4, page 16 of this guidance states that:
 
"The risks of transmission of infection from dental instruments are
 
thought to be very low provided optimal standards of infection control and
 
decontamination are maintained. General advice on the decontamination
 
of dental instruments can be found in guidance prepared by the British
 
Dental Association (BDA) on ‘Infection control in dentistry’2. This
 
document (known as the ‘A12’) is available from the BDA and can be
 
accessed on their website at www.bda-dentistry.org.uk. Dental
 
instruments used on patients defined in Table 4a can be handled in the
 
same way as those used in any other low risk surgery i.e. these
 
instruments can be reprocessed according to best practice and returned to
 
use. Optimal reprocessing standards must be observed. Additionally,
 
dentists are reminded that any instruments labelled by manufacturers as
 
‘single use’ should not be re-used under any circumstances.
 
"There is no reason why any of the categories of patients defined in
 
Table 4a or their relatives should be refused routine dental treatment.
 
They can be treated in the same way as any member of the general
 
public."
 
3. Tissues of high or medium infectivity for CJD and vCJD
 
In sporadic (and familial) CJD, significant infectivity is assumed to exist in the
 
central nervous system, olfactory epithelium and eye.
 
In variant CJD, significant infectivity is assumed to exist in these same tissues
 
and also in gastrointestinal lymphoid tissue and peripheral lymphoid tissue.
 
When patients ‘at-risk’ of CJD/vCJD undergo maxillio-facial surgery that may
 
disrupt certain cranial nerves, or lymphoid tissues of the head and neck,
 
special infection control precautions may need to be taken, as described in
 
the TSE Infection Control Guidance2.
 
4. Patients identified as ‘at-risk’ of CJD for public health purposes
 
There are several groups of patients who are identified as being at an
 
additional risk of CJD (i.e. a risk over and above the risk in the general UK
 
population that is around 1 in a million for sporadic CJD and is currently
 
unknown for vCJD). These patients are considered ‘at-risk’ of CJD for public
 
health purposes.
 
Over the past year, there has been a considerable increase in the number of
 
patients classified as ‘at-risk’ of vCJD due to the notification of patients
 
considered at risk due to receipt of UK blood products. This number may
 
increase further if more blood donors develop vCJD.
 
ANNEX A
 
- 3 -
 
Patients identified as ‘at-risk’ of CJD (including vCJD) for public health
 
purposes are asked to take the following precautions to reduce any possible
 
risk of spreading CJD:
 
Not to donate blood, organs or tissues
 
To inform healthcare staff before they undergo medical, surgical or dental
 
treatment
 
To inform their families in case they need emergency surgery in the future.
 
The health care professionals who notify these patients of their ‘at-risk’ status
 
have been asked to arrange for the information to be recorded in patients’
 
hospital medical records and/or primary care notes.
 
The responsibility for informing Primary Dental Carers lies with the patients
 
themselves.
 
5. The risk of vCJD transmission during dentistry
 
In 2003 a study was undertaken to assess the risk of transmitting vCJD
 
through routine, or ‘high-street’, dentistry3. It was concluded that any risk of
 
vCJD transmission by routine dental procedures was ‘low’. (There is
 
evidence of vCJD infectivity in tonsillar tissue prior to the onset of symptoms,
 
and tonsils are considered a tissue of ‘medium-infectivity’. The possible risk
 
due to abrasion of the tonsils (particularly the lingual tonsils) was therefore
 
examined specifically: this risk appeared to be remote. The possibility of
 
infectivity in other tissues (e.g. dental pulp) was also explored, and even for
 
pessimistic scenarios, it was estimated that the risks of transmitting vCJD
 
would be low.)
 
Many inputs to this risk assessment are subject to large ranges of uncertainty.
 
It was noted that the findings might not apply if decontamination procedures
 
(involving cleaning and autoclaving) used in high-street dentistry are less
 
efficient than assumed.
 
As stated in the report:
 
"As for hospital surgery, the key consideration in minimising any risk of
 
transmission is assuring the efficiency of instrument decontamination, even
 
though current methods cannot remove such risks completely. In line with
 
SEAC [Spongiform Encephalopathy Advisory Committee] advice, potential
 
risks can be further reduced by introduction of more single-use instruments
 
where appropriate, especially for difficult-to-clean items."
 
6. Advice from the CJD Incidents Panel
 
Despite the low estimated risk, one of the recommendations of the CJD
 
Incidents Panel (the expert committee set up by the Chief Medical Officer in
 
2000 to advise hospitals, trusts and public health teams on how to manage
 
incidents involving possible transmission of CJD between patients) is that
 
patients inform their dentists of their ‘at-risk’ status. This is to enable Primary
 
ANNEX A
 
- 4 -
 
Dental Carers to take the two appropriate actions of a) ensuring satisfactory
 
standards of decontamination are observed, and b) ensuring information
 
about patients’ CJD status is included in any referrals for head and neck
 
surgery.
 
7. Sources of further information
 
The TSE Infection Control Guidance2 includes a review and summary of what
 
is known about the distribution of CJD/vCJD infectivity in human (and animal)
 
tissues.
 
Information relating specifically to patients identified as ‘at-risk’ of vCJD due to
 
receipt of plasma products – including background information on vCJD, the
 
assessment of risk, special public health precautions, infection control issues
 
for these patients, and where to find further advice - is available at
 
 
Information about the CJD Incidents Panel is available at
 
 
Other information about CJD, and further links, can be found at
 
 
You may also contact your local infection control department for further
 
advice.
 
8. References
 
1 British Dental Association (February 2003) Advice sheet A12 Infection
 
Control in Dentistry
 
 
2 Transmissible spongiform encephalopathy agents: safe working and the
 
prevention of infection. Guidance from the Advisory Committee on
 
Dangerous Pathogens and the Spongiform Encephalopathy Advisory
 
Committee. 1998, 2003 and 2004
 
 
3 Department of Health (July 2003) Risk Assessment for vCJD and Dentistry
 
 
 
A12 Infection control.qxd (2003)
 
 
 
*** Subject: MASTER DENTIST FALLS VICTIM TO CJD
 
Date: March 31, 2007 at 1:27 pm PST
 
'In the hands of God' Thursday, March 29, 2007 By CRYSTAL HARMON TIMES WRITER Dr. Gregory J. Bever, 54, died Tuesday morning, at his home on Linwood Beach, surrounded by his family. His death was the result of a rare neurological malady called Creutzfeldt-Jakob disease. It struck suddenly and progressed rapidly.
 
Greg's sense of humor and selfless attitude persevered until the end, loved ones say.
 
Those who knew Greg best say he lived his life according to his heart's desires, mastering the endeavors he enjoyed most. He was a family man, a master dentist, a guitar player, a hockey booster and a sharp-shooter.
 
''He never denied himself anything,'' his wife, Lynne, says. ''He balanced his band, his work, the gun club. He loved his practice, his patients, and he did what he loved.''
 
Says brother Michaell Bever, of Atlanta, Ga.: ''He was focused on his family, his kids and his wife.''
 
He made time for others, leading groups of kids on Jet-Ski outings, or taking in relatives who needed temporary shelter. ''I never have known any human being that is so generous,'' Michaell says.
 
Molly Ballor, who's been office manager for Bever's practice for 22 years, says the staff at the bustling practice was part of his family, too.
 
''We feel like we've been kicked in the stomach,'' she said Tuesday. ''But we're doing what he'd want us to do: We're taking care of our patients.''
 
nnn
 
When Greg returned from the Mayo Clinic less than a month ago, word spread about the gravity of his condition, and well-wishers came calling at a rate of 30 to 40 a day.
 
Page 2 of 10 Pharmacist Tom Zsenyuk, Greg's best friend since they were freshmen at the University of Detroit, came from California.
 
''He was a special guy, very happy-go-lucky guy, and everybody liked him,'' Zsenyuk says. ''We used to play jokes on each other, and it was even better if there was a third party befooled.''
 
The two friends didn't speak of the illness during their final visit.
 
''It was just amazing to see him surrounded by so much love, from his family, his extended family,'' Zsenyuk says. ''I gave him a guitar pick that said 'We'll be friends forever.'''
 
The outpouring from friends and neighbors did not let up.
 
Greg was touched by the displays of friendship, but retained his levity.
 
''He turned to me and said, 'Lynne, this funeral is taking too long,''' says his wife of 26 years.
 
It's that sense of humor that's helped Greg and his family - which includes Gregory Jr., 19, a sophomore at Albion College; and All Saints students Alyson, 16, and Ian, 14 - face the grim diagnosis with grace.
 
''They're strong,'' Lynne says. ''They'll get through this.''
 
nnn
 
Page 3 of 10 Creutzfeldt-Jakob disease, according to the Centers of Disease Control and Prevention, strikes one person in a million worldwide.
 
The diagnosed disease was ''sporadic,'' which means it was not caused by anything that researchers have been able to pinpoint. It is not contagious. Most patients live less than a year after diagnosis, experts say.
 
For some unknown reason, proteins in CJD patients' brains fold in upon themselves, becoming something doctors call ''prions,'' and eat away at the healthy brain tissue.
 
Saturday, discussing her husband's illness with a Times reporter, Lynne held a brain-scan transparency up on a living room window overlooking the Saginaw Bay.
 
''You can see it so clearly when you know what you're looking for,'' she says, indicating porous-looking edges and an almost triangle-shaped white spot on the brain's right lobe. ''It turns brain tissue into sponge.''
 
nnn
 
Looking back, Lynne says, Greg's first symptoms probably appeared during a 10-day sailing trip to the British Virgin Islands in January. The first three days of the trip marked the first time the couple vacationed apart from their children since the first one came along 20 years ago.
 
Then the entire crew of family and friends arrived, and the group chartered three sailboats for a weeklong Caribbean island-hopping adventure. The sailing was rough, the weather hot, and the sleeping quarters were cramped.
 
''Greg's job was to man one side of the ropes, something he's done many times before,'' Lynne says. ''But he really couldn't do it. He'd loosen when he was supposed to tighten, or tighten when he was supposed to release. I thought, 'Wow, this lack of sleep is really affecting him.' He just kind of laughed it off.''
 
After returning to Linwood, Greg canceled his dental appointments and tried to get some rest.
 
Page 4 of 10 But his confusion persisted, so Greg drove himself to the emergency room at Beaumont Hospital in Troy.
 
Doctors there said Greg had suffered a stroke.
 
But his symptoms grew worse. He was sleeping 20 hours a day. He began having odd twitches and spasms, first with a thumb, then the whole hand. His arm torqued wildly one day when he and Lynne were sitting on the couch.
 
''What just happened?'' he asked her.
 
By early February, Greg's weight loss had reached 30 pounds. But a doctor assured the Bevers that within weeks, maybe months, he'd be back to normal.
 
After a Valentine's Day return to Beaumont, where more tests and a change of medication were ordered, Lynne says she became a bit pushy. She wanted an answer. She wanted her husband well.
 
The doctors said they had nothing more to offer.
 
nnn
 
One day toward the end of February, Lynne took Greg to the emergency room in Midland. A neurologist told Lynne that the lesion on the left side of Greg's brain was not from a stroke.
 
''It could be Creutzfeldt-Jakob disease,'' the neurologist said.
 
Page 5 of 10 A referral was made to Mayo Clinic, in Rochester, Minn.
 
Lynne packed her bags with two weeks of clothes. Surely, she thought, it's something else. Maybe Parkinson's, something curable. Or at least treatable.
 
''They were going to find out what was wrong with him, and he'd get some intensive rehab,'' she says, recalling her mindset as she made plans to go to Minnesota.
 
When they arrived in Rochester, they were met by a man who'd been arranged by Lynne's employer, AstraZeneca Pharmaceuticals, to rush them to the hospital. Greg's stiffness and uncontrolled movements had grown worse.
 
''Doctors and nurses were all over him, like something from a movie,'' Lynne says.
 
Doctors tried three different medications, to no avail. Greg spun and thrashed in the bed, asking ''What's happening to me?''
 
A day later, a brain scan led doctors at Mayo to diagnose CJD, Lynne says. It's fatal, doctors told them. There is no treatment, no cure.
 
''I guess it sucks to be me,'' Greg responded, mostly to break the tension in the room.
 
Doctors were concerned about Greg's rapid deterioration.
 
''How close are your kids?'' one asked.
 
Page 6 of 10 nnn
 
A few phone calls later, the Bever children, along with Lynne's brother, John Zessin were on a small plane, piloted by one of Greg's dental patients and family friend Mark VanBenschoten. Through snow squalls, they sped across Lake Michigan toward their father.
 
The teens already knew their dad was sick.
 
''What you don't know is that there's no cure for this disease,'' the doctor said. ''He's going to die.''
 
The tears came, and then the hugs. And these words from Lynne, words that the family has lived by since.
 
''This disease is so rare,'' she said, ''let's look at it as a gift.''
 
''We have time to say good-bye. Just think, if he was killed in a car accident on the way home from work one day, we wouldn't have been given this time.''
 
And so the good-byes began, the teens taking turns having time alone with their dad in the hospital room.
 
''Fourteen years was not enough time to have together,'' Ian told his dad.
 
''Buddy,'' Greg said, ''if I had 40 more years to spend with you, that still wouldn't be enough.''
 
Page 7 of 10 Greg wanted to go home.
 
The return trip was arduous. Greg was so stiff, Lynne says - ''basically, 180 pounds of immovable man'' - he had to be loaded into his seat through the cargo door.
 
Before leaving Rochester, Lynne called a friend who's a state trooper, asking if he could line up a stretcher. When they arrived at the airport, an ambulance and three attendants were waiting to take Greg home.
 
When he saw the hospital bed they had waiting for him, he wanted no part of it.
 
''I'm not using that,'' he said.
 
He never did.
 
nnn
 
The dentist started a rock band at the age of 44, when he and three friends formed the classic-oldies group The Sinclairs.
 
''It was his vision and passion for oldies music that led us to start the band,'' says guitar player Rod Loomis, of Midland. ''His vast library of nostalgia, facts, dates, and details for '60s music... The man was a walking library. He was amazing.''
 
The band, including drummer Ken Gloss and singer Dennis Beson, worked up a set of such standards as ''Secret Agent Man'' and ''I Fought the Law.'' They grew popular, playing up to 15 weekends a year.
 
Page 8 of 10 ''Greg had boundless energy,'' Loomis says.
 
Greg's ''guitar room'' is where he'd practice, with a half-dozen classic instruments housed among an array of memorabilia of the Beatles, his favorite band.
 
The last time Greg picked up a six-string - as the illness was taking hold - he came back downstairs, disgusted.
 
''He said he couldn't find the chords,'' Lynne says.
 
Shooting was another of Bever's passions. A member of the Linwood-Bay Sportsman's Club, Greg earned titles in skeet-shooting and shared his passion by teaching newcomers the sport.
 
An annual pheasant-hunting trip to South Dakota with brother Bruce each October was a 34-year tradition and a bright spot on Greg's calendar.
 
''We were hunting and motorcycle buddies,'' says Bruce, of Marietta, Ga. ''We made an awesome team.''
 
When someone suggests that Greg was a perfectionist, Michaell sets the record straight.
 
''No, that's not right,'' Michaell says. ''He's a person who believed in excellence. He didn't expect perfection from himself or from anyone. He's a man who knew the difference between perfection and excellence.''
 
''But,'' adds Lynne, ''he was a master at everything he did.''
 
Page 9 of 10 In 1999, Greg became the 19th dentist in Michigan to obtain the prestigious designation as ''master dentist'' from the Academy of General Dentistry, the culmination of 10 years - 1,100 hours - of study beyond his dentistry doctorate.
 
Greg told a Times reporter in 1999 where his work-ethic came from.
 
''My mother always said if you're going to be a ditch digger, be the best ditch digger,'' Greg said.
 
''It's just a commitment to excellence. I think excellence is an attitude that pervades all through your life.''
 
nnn
 
Lynne met Greg, a Plymouth native, at her father's dairy near Detroit when she was just 17. Greg, six years her senior, was completing a biology degree. They were married in 1980, and Greg graduated from dental school at Marquette University in Milwaukee, Wis., in 1984.
 
Greg went into partnership with dentist Jack Dee in Freeland and a year later, opened his own practice in Linwood.
 
''From the very first day,'' Lynne says, ''he was booked three weeks out.''
 
The Bevers fell in love with Linwood, and bought a little place on the beach. They've since built a new house - a sunny brick-faced home with windows looking out on the bay.
 
Greg bought out a small practice in Bay City, then, 15 years ago, merged the two offices into the current location, at 3926 Traxler Court, in Monitor Township.
 
Page 10 of 10 Lisa Moss, a dentist from Novi, has been seeing patients there since February and will continue to treat his patients until another dentist purchases the practice, Ballor says.
 
nnn
 
Greg's family will receive visitors from 2 p.m. until 8:30 p.m. today at the W.A. Trahan Funeral Chapel, 256 N. Madison. A prayer vigil is planned for 7 p.m. On Friday, the Rev. Robert DeLand will lead the funeral Mass at 10 a.m. at St. James Church, 710 Columbus Ave.
 
Lynne recalls a bit of advice one of her friends offered shortly after Greg's diagnosis.
 
''I hope you're not trying to find an answer,'' the friend said. ''Because there is no answer to find.''
 
Lynne decided to waste no time with the torture of ''Why?''
 
''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.
 
 
 
 
 
 
 
 
 
 
 
Subject: SEAC Position statement vCJD and Endodontic dentistry
 
Date: May 8, 2006 at 6:45 am PST
 
CJD WATCH MESSAGE BOARD TSS
 
2005 SEAC Position statement vCJD and Endodontic dentistry
 
Mon May 8, 2006 09:08 68.238.108.206
 
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
 
 
Dental treatment and risk of variant CJD – a case control study
 
D. Everington,1 A. J. Smith,2 H. J. T. Ward,3 S. Letters,4 R. G. Will5 and J. Bagg6
 
Objective Knowledge of risk factors for variant CJD (vCJD) remains
 
limited, but transmission of prion proteins via re-useable medical devices,
 
including dental instruments, or enhanced susceptibility following trauma
 
to the oral cavity is a concern. This study aimed to identify whether
 
previous dental treatment is a risk factor for development of vCJD.
 
Design Case control study.
 
Methods Risk factor questionnaires completed by interview with
 
relatives of 130 vCJD patients and with relatives of 66 community and
 
53 hospital controls were examined by a dental surgeon. Responses
 
regarding dental treatments were analysed.
 
Results We did not find a statistically significant excess of risk of vCJD
 
associated with dental treatments with the exception of extractions in
 
an unmatched analysis of vCJD cases with community controls
 
(p = 0.02). However, this result may be explained by multiple testing.
 
Conclusions This is the first published study to date to examine
 
potential links between vCJD and dental treatment. There was no
 
convincing evidence found of an increased risk of variant CJD
 
associated with reported dental treatment. However, the power of the
 
study is restricted by the number of vCJD cases to date and does not
 
preclude the possibility that some cases have resulted from secondary
 
transmission via dental procedures. Due to the limitations of the data
 
available, more detailed analyses of dental records are required to fully
 
exclude the possibility of transmission via dental treatment.
 
snip...
 
DISCUSSION
 
Many studies have searched for risk factors for the development
 
of different types of CJD, such as diet, exposure to
 
animals, surgical treatment, including dentistry, and occupational
 
exposures. A retrospective case control study 15 of 60
 
definite cases of sporadic CJD, occurring in Japan between
 
1975 and 1977 found no association with extractions of maxillary
 
or mandibular teeth. An analysis of 26 sporadic CJD
 
cases and 40 matched controls from the United States 16 failed
 
to discover a significant odds ratio for endodontic surgery,
 
though these workers did note statistically significant odds
 
ratios for intraocular pressure testing, injury to or surgery on
 
the head, face or neck and trauma to other parts of the body.
 
However, these findings suffer from low statistical power and,
 
in the case of the Japanese paper, information was requested
 
for extractions only during the five year period prior to onset.
 
This paper attempts to identify an association between vCJD
 
and reported dental treatment.
 
Comparison of the reported dental histories of cases and
 
controls found that extractions were the only dental risk factor
 
that reached statistical significance (at the 5% level) in the
 
unmatched analysis with community controls. This may be a
 
result of multiple testing especially as there are fewer extractions
 
in the cases than in the hospital controls. It is likely that
 
the majority of vCJD cases in this cohort were infected through
 
eating BSE contaminated meat products. Therefore, it is diffi -
 
cult to detect a small subgroup that may have been infected by
 
secondary transmission, as in this study, through dentistry.
 
There are a number of limitations to this study, most importantly
 
relying on reported data from relatives and the relatively
 
small numbers of cases and controls resulting in low
 
power to detect statistical differences. Recruitment of controls
 
has been problematic,17 although every effort was made to
 
maximise this group. Selection of controls was not matched for
 
demographic and socio-economic factors for dental attendance
 
and this may have resulted in bias. It is possible that some of
 
the responses of ‘no known treatment’ reflect poor knowledge
 
or recall on the part of the relatives. This would reduce the
 
power of the study to pick up significant differences between
 
groups, but not necessarily introduce bias.
 
Whilst these preliminary data on a topic of great concern
 
for public health do not provide evidence supporting reported
 
dental work as being a major route of transmission of the BSE
 
agent to humans to date, they do not preclude the possibility
 
that some vCJD cases have been infected by this route.
 
Furthermore, the incubation period following infection by
 
a peripheral route may be relatively long and therefore the
 
period of observation to date of potential secondary transmission
 
of vCJD may be too short to detect cases.
 
A more detailed study of previous treatment based on reviewing
 
actual dental records rather than relying on reported treatments
 
is required to gain a wider insight into the dental history
 
of both cases and controls. We are currently investigating the
 
possibility of examining dental records of vCJD cases and a
 
larger group of unmatched controls.18
 
The National CJD Surveillance Unit is funded by the Department of Health
 
and the Scottish Executive Department of Health. The sponsors of the study
 
had no role in study design, data collection, data analysis, data interpretation,
 
or in the writing of the report. We are also grateful to the families of
 
cases, without whose co-operation this study would not have been possible.
 
FULL TEXT ;
 
 
Subject: PrPSc in salivary glands of scrapie-affected sheep Date: February 15, 2007 at 9:33 am PST
 
J. Virol. doi:10.1128/JVI.02148-06 Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.
 
PrPSc in salivary glands of scrapie-affected sheep
 
Marta Vascellari*, Romolo Nonno, Franco Mutinelli, Michela Bigolaro, Michele Angelo Di Bari, Erica Melchiotti, Stefano Marcon, Claudia D'Agostino, Gabriele Vaccari, Michela Conte, Luigi De Grossi, Francesca Rosone, Francesco Giordani, and Umberto Agrimi Istituto Zooprofilattico Sperimentale delle Venezie, Histopathology Department, Viale dell'Università 10, 35020 Legnaro (PD), Italy; Istituto Superiore di Sanità, Department of Food Safety and Animal Health, Viale Regina Elena 299, 00161 Roma, Italy; Istituto Zooprofilattico Sperimentale delle Regioni Lazio e Toscana, Strada Terme, 01100 Viterbo, Italy
 
* To whom correspondence should be addressed. Email: mvascellari@izsvenezie.it .
 
Abstract
 
The salivary glands of scrapie-affected sheep and healthy controls were investigated for the presence of the pathological prion protein (PrPSc). PrPSc was detected in major (parotid and mandibular) and minor (buccal, labial and palatine) salivary glands of naturally and experimentally infected sheep. By western blot, PrPSc concentration in glands was estimated as 0.02-0.005% of brain. Immunohistochemistry revealed intracellular deposition of PrPSc in ductal and acinar epithelium and occasional labeling into the lumen of salivary ducts. The presence of PrPSc in salivary glands highlights the possible role of saliva in the horizontal transmission of scrapie.
 
 
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.
 
Scully C, Smith AJ, Bagg J. Eastman Dental Institute, University of London.
 
It is almost a decade since the recognition of the emergence of a new infectious disease termed variant Creutzfeldt-Jakob disease (vCJD) caused by prions (PrPTSE), abnormal variants of a normal human cell surface protein (PrP).This disease has a number of similarities to other forms of CJD--lethal disorders characterized by a prolonged incubation period, and progressive mental deterioration. In relation to oral tissues, PrPTSE have been found in neural, gingival, pulpal, lingual, lymphoreticular and salivary gland tissue in animal models. In both sporadic and variant CJD, PrPTSE is detectable in the trigeminal ganglion and, in vCJD, in lymphoreticular tissues, but infectivity has not been tested in other human oral tissues. CLINICAL RELEVANCE: PrPTSE is much more resistant to the common methods of inactivation than conventional pathogens, and it adheres avidly to steel whilst retaining its infectivity. Particular attention must be paid to cleaning and sterilizing re-usable dental instruments. Single-use devices, such as endodontic files and matrix bands, must never be re-used. Advice on the reprocessing of dental instruments used on known CJD patients must be obtained from local infection control teams. Research into effective methods of prion inactivation appears promising, although further work on the applicability to general dental practice is required.
 
PMID: 17087448 [PubMed - in process]
 
 
18 January 2007 - Draft minutes of the SEAC 95 meeting (426 KB) held on 7 December 2006 are now available.
 
snip...
 
64. A member noted that at the recent Neuroprion meeting, a study was presented showing that in transgenic mice BSE passaged in sheep may be more virulent and infectious to a wider range of species than bovine derived BSE.
 
Other work presented suggested that BSE and bovine amyloidotic spongiform encephalopathy (BASE) MAY BE RELATED. A mutation had been identified in the prion protein gene in an AMERICAN BASE CASE THAT WAS SIMILAR IN NATURE TO A MUTATION FOUND IN CASES OF SPORADIC CJD.
 
snip...
 
 
3:30 Transmission of the Italian Atypical BSE (BASE) in Humanized Mouse
 
Models Qingzhong Kong, Ph.D., Assistant Professor, Pathology, Case Western Reserve University
 
Bovine Amyloid Spongiform Encephalopathy (BASE) is an atypical BSE strain discovered recently in Italy, and similar or different atypical BSE cases were also reported in other countries. The infectivity and phenotypes of these atypical BSE strains in humans are unknown. In collaboration with Pierluigi Gambetti, as well as Maria Caramelli and her co-workers, we have inoculated transgenic mice expressing human prion protein with brain homogenates from BASE or BSE infected cattle. Our data shows that about half of the BASE-inoculated mice became infected with an average incubation time of about 19 months; in contrast, none of the BSE-inoculated mice appear to be infected after more than 2 years.
 
***These results indicate that BASE is transmissible to humans and suggest that BASE is more virulent than classical BSE in humans.***
 
6:30 Close of Day One
 
 
SEE STEADY INCREASE IN SPORADIC CJD IN THE USA FROM 1997 TO 2006. SPORADIC CJD CASES TRIPLED, with phenotype of 'UNKNOWN' strain growing. ...
 
 
There is a growing number of human CJD cases, and they were presented last week in San Francisco by Luigi Gambatti(?) from his CJD surveillance collection.
 
He estimates that it may be up to 14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins.
 
 
 
Chronology
 
1988
 
30. I cannot recall now when I first became aware of the new bovine disease but on
 
the 16th November 1988 I attended the CDSM to present two papers on dental products
 
[YB88/11.16/6.1-6.7]. At that meeting and the Committee noted a paper which provided
 
a background to the problem of BSE (YB88/5.13/9.1).
 
1989
 
31. On the 15th March 1989 [YB89/3.15/7.1-7.3], I attended the CDSM because there
 
were two items (items 11 and 23) on the agenda of dental interest which I had prepared
 
papers for.
 
32. At this meeting the Joint CSM/VPC Guidelines [YB89/3.00/1.2] for Industry
 
paper relating to BSE was noted and the Southwood Report IBD 2[vol IBD1, tab 2] was
 
given to members to take away [YB89/3.15/7.2].
 
33. On the 16th March 1989, I wrote to Dr Adams (Principal Medical Officer,
 
Medicines Division with overall responsibility for the review of medicines and the
 
CDSM) [YB89/03.16/8.1]. I had read the Joint CSM/VPC Guidelines [YB89/3.00/1.2]
 
and asked for an explanation of the sterilization guidelines which were in excess of the
 
Department of Health guidelines for sterilisation of unwrapped instruments. The length of
 
time in the Joint Guideline for autoclaving using a porous load cycle at 134-138 degrees
 
was 18 minutes instead of the usual minimum of 3 minutes.
 
34. I suggested to Dr Adams in that minute that in view of the comments that were
 
made with regard to the undesirability of harvesting human dura, this had implications for
 
the sterilization of all instruments used routinely for cranial surgery. Because the Joint
 
CSM/VPC Guidelines for Industry were to be sent to overseas manufacturers, I
 
questioned whether the units for pressure should have been expressed in the international
 
SI (Standard International) units.
 
35. Dr Adams in his minute dated the 21st March 1989 [YB89/03.21/15.1], stated that
 
the sterilization details were provided by MAFF at the Central Veterinary Laboratory and
 
seen by the Expert Working Group on BSE. He stated that advice along similar lines had
 
been issued to the NHS in 1981. There had been a number of well documented cases
 
where CJD had been transmitted via the use of contaminated instruments. He stated that
 
he was sure that these cases would be known to neurosurgeons.
 
36. I was minuted by Dr Pickles on the 17th April 1989 [YB89/4.1/5.1]. She
 
mentioned some comments made by the Tyrrell committee when considering the CSM
 
Guidelines and Dr Will’s concern in relation to topical dental products. I cannot recall
 
whether I wrote in response to this minute. I believe that I took it to be a notification of
 
the need for vigilance should dental products that had bovine actives/intermediates
 
become available and application made for licenses.
 
1990
 
37. I attended the CDSM meeting on the 17th January 1990 [YB90/1.17/12.1-12.5]
 
because applications for licences for dental products were being considered by the
 
Committee. It was usual for assessors to be asked to report on anything of a general
 
nature at the end of the discussions on papers. On this occasion the Committee were
 
informed that an application had been received under the Committee for Proprietary
 
Medicinal Products arrangements and the UK would be taking the lead. This was an
 
arrangement whereby a simultaneous application for a product licence could be made by
 
a company to a number of European Countries. The Committee was advised that it would
 
have to consider this application later in the year.
 
1991
 
38. At the Meeting of the CDSM held on 20th November 1991 [YB91/11.20//6.1-6.4] I
 
presented my assessment of a product consisting of a mixture of bovine derived collagen
 
and hydroxyapatite for the augmentation of deficient alveolar ridges. CDSM were unable
 
to advise the grant of a product licence.
 
1993
 
39. I attended the meeting of the CDSM held on 21st July 1993 [YB93/07.21/4.1-4.7]
 
to present the assessment of a collagen based product. The Committee were unable to
 
advise the grant of product licence.
 
40. On 13th September 1993, Mr Eaton, another Senior Dental Officer (with
 
responsibility for hospital dental services and postgraduate and continuing dental
 
education) minuted me [YB93/9.13/2.1] in relation to a request he had received from Dr
 
Ailsa Wight which required comment on an CJD article in the Daily Express dated 4th
 
September [YB93/09.04/3.1]. Mr Eaton had contacted a Professsor of Dentistry who
 
stated that it was most unlikely that treatment procedures in General Practice could be
 
responsible for transmission of CJD. He asked me to comment on a brief paper about
 
CJD which had been prepared by Dr Wight.
 
41. On the 14th September 1993 I minuted Dr Ailsa Wight (Senior DH medical officer
 
and SEAC Observer) [YB93/09.14/5.1]. I wrote that it seemed extremely unlikely that a
 
dentist in General Practice could infect patients with CJD virus. This statement was based
 
on the fact that human dura was not used in general dentistry but had been used in
 
specialised oral surgery which would not be carried out by a dentist in general practice.
 
42. I also informed Dr Wight that collagen sponge of bovine origin was commonly
 
used at one time as a haemostat following dental extractions. I stated that as far as I was
 
aware, no such dental products were licensed in the UK at that time.
 
43. I was able to give the advice in this minute from knowledge of what constituted
 
the general practice of dentistry, knowledge of dental products which I had gained from
 
my work as a general practitioner and as a senior dental officer which involved keeping
 
"up-to-date" with dental practice.
 
44. On the 28th September, Mr. Gordon had written to Dr Wight in relation to a
 
proposed BDA publication [YB93/09.28/3.1-3.3]. Dr Wight sent me her draft reply to Mr
 
Gordon and I made two minor comments in a minute dated 1st November 1993
 
[YB93/11.01/5.1]. I recommended that her reply should include a suggestion that the
 
BDA paper on Iatrogenic Creutzfeldt-Jakob Disease, should include there were other
 
good reasons for considering many endodontic instruments as single use items and for
 
limiting the number of times others might be re-used.
 
45. I remember that these reasons included the fact that re-sterilization of these
 
instruments might affect the physical properties of the instrument. The re-sterilization
 
might increase the chances of fracture of such instruments in the root canal. This would
 
have given rise to considerable difficulty in achieving a satisfactory result as far as a
 
patient was concerned. There were other amendments and according to letters I was
 
copied, the BDA publication was amended by Mr Gordon [YB93/11.17/5.1-5.4].
 
1994
 
46. I left the Department of Health in May 1994.
 
Relevant interests
 
47. I have no links past or present with the farming community, renderers, feed stock
 
manufacturers, pet food manufacturers, trade associations. During my time at the
 
Department of Health I had contact with pharmaceutical companies in a solely
 
professional capacity. Since leaving the DH, I have done part time consultancy work for a
 
number of manufacturers who produce dental products though none have been involved
 
with products of bovine origin.
 
48. This Statement is true to the best of my knowledge and belief.
 
Issued on behalf of the witness by:
 
The BSE Inquiry Press Office
 
6th Floor Hercules House
 
Hercules Road
 
London SE1 7DU
 
Fax: 0171 803 0893
 
 
 
Possible occupational risks from TSEs
 
Although CJD has been documented in a neurosurgeon, two neuropathology technicians, an
 
orthopaedic surgeon and a pathologist, it is reassuring to note that in none of these individuals
 
was there a history of a definite infective event. The orthopaedic surgeon had however worked
 
with human and ovine dura mater 20 years prior to his illness. Case-control studies do not
 
suggest that individuals potentially exposed to the TSE agent in the health care setting are at an
 
increased risk of developing CJD. However, the possibility that cases of CJD have rarely
 
occurred in such circumstances cannot be confidently dismissed.
 
A statistically significant excess of cases of CJD in cattle farmers has been reported in the UK
 
since 1990. Of concern, four of these six cases were known to have had BSE-affected animals in
 
their herds. However, analysis of the clinical and pathological features of these cases showed that
 
none had the nvCJD phenotype. This observation has been strengthened by recent molecular
 
biological data that demonstrated that the PrP glycosylation pattern characteristic of both BSE
 
and nvCJD was not present in any of these cases. Furthermore analysis of the incidence of CJD
 
in dairy farmers from other European countries, in which BSE is rare or absent, reveals a similar
 
excess of cases. This observation suggests that dairy farmers may be at increased risk of CJD for
 
reasons other than exposure to the BSE agent. One possible explanation for the apparent excess
 
of cases in dairy farmers, particularly in the UK, is that case ascertainment in this group has been
 
better than in other groups because of concern of a possible link between the bovine and human
 
diseases.
 
SECTION 7: THE RISK TO PATIENTS UNDERGOING DENTAL
 
TREATMENT
 
It is of great concern that there may be a risk of becoming infected with nv-CJD in the dental
 
surgery due to cross infection from either the dentist or another patient. The two main sources of
 
infectious material in the dental surgery are blood and saliva. As shown in Table 7 these are of
 
relatively low infectivity compared to the tissues of the CNS.
 
As nv-CJD has only recently been discovered, few experiments have been carried out to discover
 
whether it can be transmitted. Therefore, we must look at the other TSEs to get an indication of
 
likely risk.
 
The risk of transmission via saliva
 
Studies to ascertain levels of PrP have shown that salivary gland tissue contains high levels of
 
infectivity, much earlier than in brain tissue (Sakaguchi 1993, Eklund 1967). Replication of the
 
infectious agent first appears in salivary tissue soon after inoculation, possibly indicating that the
 
salivary glands are one of the primary sites of replication, rather than the brain. It was also found
 
that infectivity declines with time, suggesting that greatest risk from transmission is likely to be
 
early in the disease, before clinical signs are present.
 
There has been no research into the risk of transmission from saliva, however we must assume
 
that if salivary gland is infected then so is the saliva it produces.
 
The effect of gingival scarification on transmission
 
If it is found that BSE has been transmitted to humans via the oral route it is essential to ascertain
 
any factors that may have increased susceptibility and therefore may have implications for
 
human to human transmission. Studies into the effect of gingival scarification on the
 
transmission of Scrapie (Carp 1982) have shown that a higher proportion of mice succumbed to
 
infection if their gingivae had been scarified compared to the controls (100% and 71%
 
respectively). It was also shown that the incubation period was significantly shorter.
 
Although it has not been possible to transmit Scrapie using dental burs (Adams 1978) it was
 
found that the gingivae of infected mice do contain a low level of Scrapie infection that can be
 
transmitted using an intra-cerebral approach.
 
The risk of transmission via blood products
 
Although most forms of CJD have been considered infectious by the mid-1960s its
 
transmissibility through the use of blood products is still controversial.
 
Sporadic CJD has been reported to be transmitted to mice by injecting blood from human
 
patients directly into mouse brain (Brown, 1994, Manuelidis, 1985). However this evidence has
 
not been reproduced and another review of research with non-human primates indicated that
 
sporadic CJD-infected human blood did not transmit the disease to primates (Tateishi, 1985).
 
Some evidence indicates that blood of experimentally infected animals contains an infective
 
agent. PrP infectivity resides predominately or exclusively in lymphocytes and monocytes rather
 
than granulocytes (Lavelle, 1972). There has been no evidence of infectivity in erythrocytes,
 
platelets or plasma, but low infectivity cannot be excluded. Animal studies have demonstrated
 
that the scrapie-agent replicates first in the spleen and other lymphoid tissues but reaches the
 
highest concentration in the brain, where it results in the clinical appearance of the disease
 
(Kurudail 1983). Hence, peripheral tissues in contact with blood also harbour PrP infectivity.
 
Animal transmission data indicate that human spleen, lymph nodes, serum and cord blood are
 
irregularly infective for animals, although few cord blood samples have been tested (Manuelidis,
 
1979). Studies of experimental sporadic CJD in guinea pigs and mice have shown that the
 
infectious agent is present in the brain, viscera and blood before clinical disease develops
 
(Lavelle, 1972 & Czub 1986).
 
Several factors must be considered in reviewing the animal evidence regarding transmission of
 
human TSEs in blood: the type of human TSE being tested, the level of PrP infectivity of the
 
study tissue, the species barrier, and the route of transmission.
 
The evidence from animal studies is inconclusive regarding transmission of sporadic CJD
 
between humans by transfusion.
 
Although case reports have provided evidence linking CJD to the receipt of dura mater and
 
human growth hormone, no human cases have yet been causatively linked to blood transfusion.
 
A number of cases have been seen where patients have undergone organ transplant and then
 
developed CJD. It is, however, impossible to determine whether the organ was the source of the
 
infection as insufficient information about each case is available.
 
If CJD is transmissible in blood, cases should occur in young patients, particularly if the
 
incubation period is short as in the other iatrogenic cases. Even if the incubation period were
 
many years, one would expect to see cases in young persons because of the transfusions given to
 
infants and young children. If CJD is transmitted in blood, a detectable increase in cases in blood
 
transfusion patients may be expected. There is a ban on the use and export of blood and blood
 
products from the UK (February 1998) as a precautionary measure and for the past two years any
 
donor with a family history of CJD has been prevented from donating blood. However this may
 
be unreliable, as many patients will not know the accurate diagnoses of a family member's
 
illness.
 
As noted by Brown (1996) in reference to blood products, "iatrogenic disease from this source
 
would dwarf in importance all other sources by virtue of the sheer numbers of people who
 
theoretically have been or could be at risk". The appearance of nvCJD raises new concerns. Due
 
to a possible oral route of infection and a novel strain of agent, the distribution of tissue
 
infectivity may differ from other forms of CJD. This is supported by evidence that suggested that
 
at the palatine tonsil might harbour PrP in nvCJD but not in sporadic CJD.
 
In view of the theoretical possibility that blood from patients incubating a TSE may harbour the
 
infective TSE agent the World Health Organisation recommends that the following groups
 
should be excluded as blood donors:
 
· Recipients of extracts derived from human pituitary glands (growth hormone and
 
gonadotropin).
 
· Those with a family history of CJD, GSS or FFI.
 
· Those who have received a human dura mater graft.
 
Animal studies indicate that the infective agent of human TSEs is present in blood in low titres,
 
and sufficient evidence of animal transmission suggests that the disease has the potential to be
 
transmitted through blood (Heye 1994). However, to date, epidemiological evidence indicates
 
that if blood transmission occurs it is likely to be rare. This may be due to polymorphism at
 
codon 129, which could restrict susceptibility. It is also possible that most transfusions may not
 
contain sufficient dose to cause infection.
 
There is no specific scientific evidence to date that nv-CJD will transmit through blood products.
 
This is due to the incubation period being many months in laboratory animals. As infectivity has
 
only been detected in white blood cells the potential risk from donated blood can be decreased by
 
a process known as leuko-depletion, removal white blood cells.
 
The knowledge that blood may be infected could change the views of both the medical
 
profession and patients. Transfusions may only be used if absolutely necessary and patients may
 
be given the option of donating their own blood for scheduled operations.
 
If CJD were transmitted in pooled blood products or saliva, clusters would be detected. Most
 
clusters have usually been attributed to familial disease (Masters, 1979 & Reingold 1996).
 
Surveillance systems have found cases of CJD among persons who have received blood
 
transfusions but none have been linked to blood transmission.
 
It must be remembered, however, that surveillance systems may not detect cases when unique
 
epidemiological or clinical features are present.
 
SECTION 8: CONCLUSIONS
 
A number of factors must be taken into consideration when assessing the risk of transmission of
 
nvCJD during dental treatment. Dental patients are at risk of infection from a number of sources,
 
the most significant being the consumption of infected animal products during the 1980s. A
 
small minority of patients will also be at increased risk in their place of work, such as
 
neuropathologists, neurosurgeons and laboratory technicians.
 
The most likely route of infection is via ineffectively sterilised instruments. If a patient is
 
suspected of having or has been diagnosed with nv-CJD further precautions can be taken. The
 
patient is likely to be showing clinical signs, which are likely to make dental treatment difficult,
 
therefore only emergency treatment is going to be appropriate. Where possible, a treatment
 
option that involves the least cross infection risk should be undertaken. . To reduce this risk, all
 
instruments that have been used on a patient with nvCJD should be disposable or discarded. This
 
includes oral surgery equipment, root planing hand instruments and ultrasonic tips in addition to
 
needles and blades. In the case of accidental inoculation it is unlikely that sufficient infective
 
material will be involved to transmit the disease. As discussed previously, the peripheral route of
 
infection is ineffective compared with intracerebral inoculation, and blood or saliva contains
 
little infectivity compared to central nervous tissue. All patients should be treated using universal
 
precautions, which should be employed in all dental practices as a matter of routine, providing
 
the maximum protection equally to clinical staff and patients. This includes the use of gloves,
 
masks and eye protection at all times. After each patient all instruments should be autoclaved and
 
disposable alternatives should be used where appropriate.
 
The number of patients likely to be incubating nv-CJD is impossible to predict at present. Much
 
depends on the average incubation time, the longer the time, the higher the figure is likely to be.
 
At present the average incubation time can not be calculated nor is it possible to estimate the
 
dose required to infect a human. With the possibility of a nationwide epidemic investigation
 
must be carried out to determine the risk from cross infection. Research has yet to prove that
 
there is a risk, however, until all possibility of this can be discounted caution must prevail.
 
The resistance of the TSE agent to standard medical sterilisation procedures is noteworthy.
 
Experimental evidence demonstrates that the agent shows resistance to the following: exposure
 
to boiling, freezing, ethanol, H2O2, permanganate, iodine, ethylene oxide vapour, detergents,
 
organic solvents, formaldehyde, UV and gamma irradiation, and standard autoclaving.
 
Since conventional methods of sterilisation and disinfection do not decontaminate the CJD
 
infectious agent, specific measures must be used, however, many of these are impractical in the
 
dental practice.
 
Although the TSE agent is known to be infectious it is not contagious in the usual sense.
 
Individuals exposed to patients with CJD: their spouses, nurses and doctors, do not appear to
 
have an increased risk of developing the disease. Furthermore, professionals who might be
 
considered 'high risk' in relation to exposure to TSE agents: e.g. pathologists, neurosurgeons,
 
butchers etc. also do not appear to be at an increased risk of developing CJD. No proven instance
 
of CJD contracted occupationally has yet been identified. However, over 170 cases of iatrogenic
 
CJD contracted through inoculation of contaminated CNS tissue or corneal transplantation serve
 
to remind those of us involved in the management of all CJD patients of the importance of safety
 
procedures in relation to the TSE agents.
 
REFERENCES
 
snip...
 
The BSE Inquiry / Statement No 201A Dr Helen Churchill (scheduled to give evidence Monday 26th October 1998)
 
SPECIALISED OPTION PROJECT 1998 THE RISK FROM A NEWLY EMERGING PATHOGEN TO PATIENTS UNDERGOING DENTAL TREATMENT
 
 
 
Date: January 18, 2007 at 8:32 am PST
 
Fourth case of transfusion-associated vCJD infection in the United Kingdom
 
Editorial team (eurosurveillance.weekly@hpa.org.uk), Eurosurveillance editorial office
 
A suspected case of variant Creutzfeldt-Jakob disease (vCJD) has recently been diagnosed in a patient in the United Kingdom (UK), who received a blood transfusion from a donor who later developed vCJD [1]. This is the fourth case of probable transfusion transmission of vCJD infection in the UK. Three of the four recipients developed symptoms of vCJD. The first symptomatic case of vCJD associated with blood transfusion was identified in December 2003. This individual developed vCJD six and a half years after transfusion of red cells donated by an individual who developed symptoms of vCJD three and a half years after donation.
 
A second case of vCJD 'infection' was identified a few months later in a person who had received red cells from a donor who developed symptoms of vCJD 18 months after donation. This patient (the second case) died from causes unrelated to vCJD five years after transfusion. Post-mortem investigations found abnormal prion protein in the spleen and a cervical lymph node., However, prion protein was not found in the brain, and no pathological features of vCJD were found.
 
A third case developed symptoms of vCJD six years after receiving a transfusion of red blood cells, and died two years and eight months later. The donor of the blood involved developed vCJD about 20 months after donating it.
 
These three cases have been published as case reports and in the findings of the ongoing collaborative study between the National Blood Services, the National CJD Surveillance Unit, and the Office for National Statistics. This study aims to collect evidence about transmission of CJD or vCJD via the blood supply [2,3,4,5].
 
The new, fourth case is in a patient who developed symptoms of vCJD eight and a half years after receiving a transfusion of red blood cells from a donor who developed vCJD about 17 months after this blood was donated [1]. The donor to this case also donated the vCJD-implicated blood transfused to the third case. As for all other reported clinical vCJD cases that have been tested for genotype, this patient is a methionine homozygote at codon 129 of the prion protein gene. The patient is currently alive.
 
All four cases had received transfusions of non-leucodepleted red blood cells between 1996 and 1999. Since October 1999, leucocytes have been removed from all blood used for transfusion in the UK. The effect of leucodepletion on the reduction of the risk of transmission of vCJD from an infective donation is uncertain.
 
This fourth case of vCJD infection associated with blood transfusion further increases the level of concern about the risk of vCJD transmission between humans by blood transfusion, although much remains unknown. This reinforces the importance of the existing precautions that have been introduced to reduce the risk of transmission of vCJD infection by blood and blood products [6]. No cases of vCJD have been associated with fractionated plasma products. The small group of living recipients of vCJD-implicated blood transfusion in the UK have been informed of their potential exposure to vCJD by blood transfusion, asked to take certain precautions to reduce the risk of onward person-to-person transmission of vCJD during health care, and offered specialist neurological evaluation and advice.
 
This article has been adapted from reference 1
 
References:
 
snip...
 
 
==============
 
Subject: CJD/BSE SUTURES??? (old document) * suture imports from known BSE countries
 
Date: Tue, 11 Apr 2000 13:33:00 –0700
 
From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy
 
To: BSE-L@uni-karlsruhe.de
 
######### Bovine Spongiform Encephalopathy #########
 
MF580439/2 0069
 
10 January 1990
 
COMMERCIAL IN CONFIDENCE
 
NOT FOR PUBLICATION
 
COMMITTEE ON SAFETY OF MEDICINES
 
WORKING PARTY ON BOVINE SPONGIFORM ENCEPHALOPATHY
 
SURGICAL CATGUT SUTURES
 
ACTION TAKEN IN RESPONSE TO CSM/VPC GUIDELINES FOR INDUSTRY, AND FURTHER PROPOSALS.
 
l. Introduction
 
1.1 This paper is to outline the steps taken in relation to XXXXX Surgical Catgut Sutures in response to the Joint CSM/VPC Guidelines for Industry.
 
1.2 The Company has now submitted further proposals.
 
2. Background
 
2.1 At the first meeting of the Working Party on Bovine Spongiform Encephalopathy on 6 September 1989, detailed consideration was given to XXXXX Surgical Catgut. This arose from the Company's response to the Letter to Licence Holders, indicating that the bovine small intestine source material was derived from UK cattle, unlike 8 other licenced catgut sutures. In contrast XXXXX Surgical Catgut was stated to hold over 90% share of the market for catgut sutures, and to constitute approximately 83% of all sutures used in U.K.
 
90/01.10/8.1
 
MF580439/2 0070
 
The proposal is that decontamination of equipment, disassembled components, remaining fixed plant and the working environment should be by one or more of the following procedures following detergent cleaning.
 
i. Porous load autoclaving at 134-138°C for 18 min.
 
ii. Immersion for 1 hour in sodium hypochlorite solution containing 2% available chlorine.
 
iii. Washing down with sodium hypochlorite solution containing 2% available chlorine.
 
iv. Immersion in IN sodium hydroxide for 2 hours followed by rinsing with water.
 
v. Washing down with IN sodium hydroxide (where sodium hypochlorite or autoclaving cannot be applied).
 
5. Secretariat Comment
 
5.1 The progress made by the Company in implementing the proposed changeover to Australasian sourced material has been rapid and in advance of predicted timescale.
 
5.2 Setting a date for changeover from UK to Australasian sourced production, with prior decontamination of manufacturing facilities, is prudent. The opinion of the Working Party is sought on the reassurance offered by the proposed strategy for decontamination.
 
It may be felt that the decontamination procedures should be more fully described for methods 2-5, in particular:-
 
a) The minimum temperature at which the decontamination is carried out should be stated and relate to the experimental work on which the procedure is based.
 
b) The sodium hypochlorite fluid should be freshly prepared and checked for available chlorine both at the beginning and end of the incubation period. A minimum free chlorine level at the end of the period should be defined.
 
e) Where washing of structures or equipment is to be performed rather than immersion, the contact time and temperature should be defined. The method of ensuring that the materials will remain wet for the specified period should be defined.
 
90/01.10/8.2
 
MF580439/2 0071
 
d) It may be safer to ask the Company to renew equipment rather than "wash down", where practicable [e.g. plastic carboys).
 
e) Work clothing should be decontaminated or renewed [e.g. gloves/shoes) to avoid contamination of the decontaminated environment.
 
5.3 The introduction of the heat-setting step may not be considered appropriate at this stage, with the imminent change to Australasian sourced material.
 
6. Secretariat Recommendation
 
The advice of the Working Party is sought on the secretariat view that, in the light of 5.1 above, further action by the Licensing Authority is not currently necessary.
 
J.M.Raine
 
J.S.Sloggem
 
90/01.10/8.3
 
-----------------------------------------------------------------------
 
in light of the findings of the PNAS on 'BSE to humans = CJD', the above statement would need further attention...TSS >The advice of the Working Party is sought on the secretariat view that, >in the light of 5.1 above, further action by the Licensing Authority is >not currently necessary.
 
IMPORTS OF SUTURES FROM THE KNOWN BSE COUNTRY;
 
3006.10.0000: STERILE SURGICAL CATGUT, SIMILAR STERILE SUTURE MATERIALS AND STERILETISSUE ADHESIVES FOR SURGICAL WOUND CLOSURE; AND SIMILAR STERILE MATERIAL U.S. Imports for Consumption: December 1998 and 1998 Year-to-Date (Customs Value, in Thousands of Dollars) (Units of Quantity: Kilograms)
 
<--- ---="" 1998="" dec=""> <--- ---="" 1998="" ytd=""> Country Quantity Value Quantity Value
 
=================================================================
 
WORLD TOTAL . . . . . . . 10,801 3,116 143,058 40,068
 
Australia . . . . . . . . 3,925 1,024 37,373 10,507
 
Austria . . . . . . . . . 400 707 8,147 9,687
 
Belgium . . . . . . . . . --- --- 107 14
 
Brazil . . . . . . . . . --- --- 987 334
 
Canada . . . . . . . . . --- --- 138 4
 
Federal Rep. of Germany 1,795 356 16,878 3,741
 
France . . . . . . . . . 81 49 2,727 1,132
 
Hong Kong . . . . . . . . --- --- 525 2
 
India . . . . . . . . . . 57 13 329 37
 
Ireland . . . . . . . . . --- --- 151 22
 
Italy . . . . . . . . . . 12 9 12 9
 
Japan . . . . . . . . . . 170 167 835 661
 
Korea, Republic Of . . . 18 15 476 357
 
Mexico . . . . . . . . . --- --- 1,041 72
 
Netherlands . . . . . . . 2,985 494 34,833 5,794
 
Norway . . . . . . . . . 138 35 970 249
 
Panama . . . . . . . . . --- --- 10 5
 
Peru . . . . . . . . . . --- --- 52 6
 
Spain . . . . . . . . . . 32 5 428 60
 
Swaziland . . . . . . . . --- --- 2 3
 
Sweden . . . . . . . . . --- --- 679 115
 
Switzerland . . . . . . . --- --- 1,357 1,693
 
United Kingdom . . . . . 1,188 242 35,001 5,564
 
-----------------------------------------------------------------
 
and to think i have been sewed up about 35 or 40 times, rather frightening.......
 
3.586 On 27 July 1989, Mr Maslin circulated a minute considering such issues as the use of bovine eyeballs for teaching purposes, surgical sutures produced from bovine intestines and the use of spinal cord, thymus and spleen for pharmaceutical products. 12 Chapter 9 of this volume deals with bovine eyeballs, while medical and surgical products are dealt with in vol. 7: Medicines and Cosmetics.
 
 
 
 
 
MF580391/2 0180
 
COMMERCIAL IN CONFIDENCE NOT FOR PUBLICATION COMMITTEE ON SAFETY OF MEDICINES WORKING PARTY ON BOVINE SPONGIFORM ENCEPHALOPATHY
 
SURGICAL CATGUT
 
UK sourced product, derived from bovine small intestine. Large scale production and extensive clinical use.
 
Advice is sought on Company proposals for action.
 
COMERCIAL IN CONFIDENCE COMMITTEE ON SAFETY OF MEDICINES WORKING PARTY ON BSE PAPER CATEGORY 3: DENTAL AND SURGICAL MATERIALS SURGICAL CATGUT SUTURES-
 
1. INTRODUCTION
 
Surgical Catgut_________________________ represents the most immediate problem arising from the review of tissue implants, wound dressings, dental and surgical products containing material of bovine origin. the reasons for concern are:
 
i. UK origin of the source material
 
ii. nature of the source material (aerosal layer of bovine small intestine) and proximity to lymphoid tissue
 
iii. large scale of production and use of product
 
The aim of this paper.......
 
snip...full text;
 
 
 
sutures
 
 
 
COMMERCIAL IN CONFIDENCE
 
6.79 Dr Rotblat and Dr Purves had prepared a paper summarising the questionnaire responses received so far. 3 As had been agreed on 12 June, the 574 products that used animal ingredients were divided into the following categories, in decreasing order of concern: 4
Products with bovine brain/lymphoid tissue as ingredients and administered by injection.
111
Products with bovine ingredients (other than brain/lymphoid tissue) and administered by injection.
135
Tissue implants, open wound dressings, surgical materials, dental and ophthalmic products with bovine ingredients.
27
Products with bovine ingredients and administered topically.
5
Products with bovine ingredients and administered orally.
9
Products with other animal/insect/bird ingredients.
131
Products with materials produced from animal material by chemical processes eg. stearic acid, gelatin and lanolin.
156
 
 
 
 
 
 
 
kind regards, Terry S. Singeltary Sr., Bacliff, Texas USA
 
================
 
5.3.3 The greatest risk, in theory, would be from parenteral injection of material derived from bovine brain or lymphoid tissue. Medicinal products for injection or surgical implantation which are prepared from bovine tissues, or which utilise bovine serum albumin or similar agents in their manufacture, might also be capable of transmitting infectious agents. All medicinal products are licensed under the Medicines Act by the Licensing Authority following guidance, for example from the Committee on Safety of Medicines (CSM), the Committee on Dental and Surgical Materials (CDSM) and their subcommittees. The Licensing Authority have been alerted to potential concern about BSE in medicinal products and will ensure that scrutiny of source materials and manufacturing processes now takes account of BSE agent.
 
 
BEFORE the BSE Inquiry went online, i was requesting the daily hearings and submissions, and they were sending them to me via air mail. then, when the BSE Inquiry finally went online, i was then able to go back and match up some of what i had with the YB numbers (above), with the official documents. ...TSS
 
BSE offals used in cosmetics, toiletry and perfume industry Sun, 3 Sep 2000. Unpublished Inquiry documents obtained by CJD activist Terry S. Singeltary Sr. of Bacliff, Texas Miss Marion Kelly Cosmetic, Toiletry and Perfumery Association 35 Dover Street London W1X3RA
 
Department of Trade and Industry 10-18 Victoria Street London SW1H ONN Enquiries 01-215 5000 Telex 8811074 DTHQ G 01 215 3324 1 February 1990
 
 
40,000 human heart valves a year from BSE herds Sun, 3 Sep 2000. Unpublished Inquiry documents obtained by CJD activist Terry S. Singeltary Sr. of Bacliff, Texas
 
Opinion (webmaster): Below are some shocking documents. Here is a British company preparing 40,000 heart valves a year from bovine pericardium, primarily for export, and they are not required to source this material from BSE-free herds even in peak epidemic years. It is amazing to watch health "authorities" grovelling on their bellies to wring petty concessions from middle management at obscure little companies. The main worry is not the practise of using 800 potentially infected cows a week for human heart transplant material but that the press or recipients will get wind of it, hurting business.
 
BSE wasn't the problem, it was awkward queries from importing countries like the US. The cows are stunned using brain penetration -- can't do anything about the chunks of bovine brain blasted into the circulatory system, it's the norm. Can't use younger lower-risk animals either, patch would not be big enough. It is fascinating to see the British government worrying about, but doing nothing, with pigs with BSE 10 years ago.
 
While scrapie was long used as an excuse for continuing with human use of BSE-tainted material, little sheep material was used medically. Bovine transplants, vaccines, insulin doeses, etc. are far more dangerous than dietary material as injections, and are done on a very wide scale. So scrapie was never a valid analogy to BSE, as MAFF knew full well.
 
The British government deferred to the manufacturer's rep for an opinion on how contaminated pericardium might be, just as this appeared showing that this tissue is extremely dangerous:
 
 
England worried briefly about infecting other countries 27 Aug 00 confidential correspondence obtained by Terry S. Singeltary Sr.
 
BSE11/2 020;
 
SC1337p
 
DEPARTMENT OF HEALTH AND SOCIAL SECURITY Richmond House, 79 Whitehall, London SWIA 2NS Telephone 01-210 3000 From the Chief Medical Officer Sir Donald Achson KBE DM DSc FRCP FFCM FFOM
 
Mr K C Meldrum Chief Veterinary Officer Ministry of Agriculture, Fisheries and Food Government Buildings Hook Rise South Tolworth Surbiton Surrey KT6 7NG 3 January 1990
 
Dear Mr Meldrum
 
BOVINE SPONGIFORM ENCEPHALOPATHY
 
You will recall that we have previously discussed the potential risks of BSE occurring in other countries as a result of the continuing export from the UK of meat and bone that may be contaminated by scrapie or possibly BSE.
 
I remain concerned that we are not being consistent in our attempts to contain the risks of BSE. Having banned the feeding of meat and bone meal to ruminamts in 1988, we should take steps to prevent these UK products being fed to ruminants in other countries. This could be achieved either through a ban on the export of meat and bone meal, or at least by the proper labelling of these products to make it absolutely clear they should not be fed to ruminants [or zoo animals, including rare and endangered primates -- webmaster]. Unless some such action is taken the difficult problems we have faced with BSE may well occur in other countries who import UK meat and bone meal. Surely it is short sighted for us to risk being seen in future as having been responsible for the introduction of BSE to the food chain in other countries.
 
 
The documents below were provided by Terry S. Singeltary Sr on 8 May 2000. They are optically character read (scanned into computer) and so may contain typos and unreadable parts.
 
TIP740203/l 0424 CONFIDENTIAL
 
Mr Cunningham CMP3 From: D O Hagger MBI Dr Salisbury MED/IMCD3 Mr Burton PD/STB/PG1B B/17/2 Date: 15.02.1989 Mr Dudley PD/AD4
 
BOVINE SPONGIFORM ENCEPHALOPATHY
 
 
Other US BSE risks: the imported products picture 24 Jul 00 Trade Statistics: UK to US Compiled by Terry S. Singeltary Sr of Bacliff, Texas
 
[Opinion (webmaster): The US has focused for years on tracing, containing, and eradicating live animal imports from the UK or other countries with acknowledged BSE like Belgium, including some 499 cattle and the Vermont sheep. This strategy does not acknowledge imports of rendered bovine products from England during the BSE period nor secondary products such as surgical catgut, which is to say surgical cowgut, or dairy cattle embryos, vaccines for veterinarian and human medicines. What has become of these?
 
Mr. Singeltary, who lost his mother to CJD of unexplained origin a few years back and went on to became a well-known TSE activist, has tracked down voluminous pertinent import data through correspondence with UK officials and searches of government web sites. Imports of such products are frequently cited by Europeans in rating BSE risks in the US and in shutting out US exports.
 
Many people's eyes glaze over when reviewing reams of sometimes older trade statistics. There is no proof that any of the imported products was contaminated with BSE nor if so, any evidence that any BSE product lead to infection in US livestock, surgical patients, or what not. Nonetheless, the data obtained by Mr. Singeltary establish that an appalling variety and tonnage of products that were imported by the US from the UK and othr BSE-affected countries during the peak of the BSE epidemic years.]
 
10 January 1990 COMMERCIAL IN CONFIDENCE
 
NOT FOR PUBLICATION
 
COMMITTEE ON SAFETY OF MEDICINES WORKING PARTY ON BOVINE SPONGIFORM ENCEPHALOPATHY
 
SURGICAL CATGUT SUTURES 2.1 At the first meeting of the Working Party on Bovine Spongiform Encephalopathy on 6 September 1989, detailed consideration was given to XXXXX Surgical Catgut. This arose from the Company's response to the Letter to Licence Holders, indicating that the bovine small intestine source material was derived from UK cattle, unlike 8 other licenced catgut sutures. In contrast XXXXX Surgical Catgut was stated to hold over 90% share of the market for catgut sutures, and to constitute approximately 83% of all sutures used in U.K. IMPORTS OF SUTURES FROM THE KNOWN BSE COUNTRY;
 
 
 The documents below were provided by Terry S. Singeltary Sr on 8 May 2000. They are optically character read (scanned into computer) and so may contain typos and unreadable parts.
 
TIP740203/l 0424 CONFIDENTIAL
 
Mr Cunningham CMP3 From: D O Hagger MBI Dr Salisbury MED/IMCD3 Mr Burton PD/STB/PG1B B/17/2 Date: 15.02.1989 Mr Dudley PD/AD4
 
BOVINE SPONGIFORM ENCEPHALOPATHY
 
1. The purpose of this minute is to alert you to recent developments on BSE as they affect medicines and to invite representatives to a meeting in Market Towers on 22 February 1989.
 
2. The report of the Working Party on Bovine Spongiform Encephalopathy (BSE) was submitted by the CMO to the Secretary of State for Health and Minister for Agriculturer on 9 February.
 
3. The summary at the end of the report records, inter alia: 'we have drawn the attention of the Licensing Authority to the potential of transfer of BSE agent in human and veterinary medicinal products. In paragraph 7 of his submission (Annex A), the CMO notes:
 
"I am also putting work urgently in hand to satisfy myself that everything possible has been done to ensure .... that transfer of the BBE agent in human and veterinary medicinal products does not occur."
 
4. The Veterinary products Committee meets on 16 February and The committee on Safety of Medicines on 23 February when each will be considering a draft of some joint guidelines for manufacturers of medicinal products which use bovine material as an ingredient or an intermediate in the manufacturing process (Annex B).....
 
6. Although a wide range of medicines may be implicated - and the present proposal is to write to companies for more information - an "instant" telephone survey of manufacturer of vaccines used for children has already been undertaken in response to a request from Dr Harris. The results are in Dr Adams' minute of 14 February (Annex C) - the proviso in his second paragraph, last sentence should be noted. 89/02.15/11.1
 
89/02.15/11.2 MF580439/1 0584 SOUTHWOOD REPORT: BSE AND MEDICINAL PRODUCTS
 
1. I attach a list of questions on BSE and medicines compiled with the aim of providing question and answer briefing to DH and MAFF Ministers upon publication of the Southwood Report. I have suggested names of those who may be able to provide answers. All recipients are invited to consider which if any important areas have been missed. Also attached is copy QA briefing being proposed by MAFF. I understand MAFF have produced General QA briefing on the reports as a whole. ..
 
MF580439/1 0585 Question
 
1. Which medicines are affected? (person to provide reply) Dr. Jefferys
 
2. Are the risks greater with some medicines than others? Dr. Jefferys
 
3. Why are medicines affected? Dr. Jefferys
 
4. Are some affected products available over the counter from pharmacies or shops? Dr. Purves
 
5. Are only UK products at risk? Dr. Jefferys
 
6. Are existing stocks safe? Dr. Jefferys
 
7. Are pre 1980 stocks available? Mr. Burton
 
8. Are these alternatives to the use of bovine material? Dr. Purves
 
9. Why can't we throw away suspect stock and import or manufacture safe medicines? Dr. Jefferys
 
10. Which patients are at risk? Dr. Jefferys
 
11. Are some patients particularly vulnerable? Dr Jefferys
 
12. What risks exist to those who have already used these medicines? Dr. Jefferys
 
13. HOW might patients be affected? Dr. Jefferys
 
14. Can BSE be transmitted to patients by medicines? Dr. Jefferys
 
15. How long will it be before risks are quantified? Dr. Jefferys
 
100 89/02.17/10.2 MF580439/1 0586
 
16. What research is going on to find out if medicines can transmit this disease and if any patients have been affected? Dr Jefferys
 
17. Could recent cases of Creuuzfeld Jacob Disease have been caused by transmission of BSE through medicines? Dr. Jefferys
 
18. What action is the Licensing Authority taking to ensure proper scrutinising of source materials and manufacturing processes? Dr. Jefferys/Dr. Purves
 
19. Are the guidelines practical? Dr. Jefferys/Dr. Purves
 
20. Will the guidelines remove the risk? Dr. Jefferys
 
21. How will the guidelines be enforced? Dr. Jefferys/Dr. Purves
 
22. How soon will they come into force? Dr. Jefferys
 
23. Will the guidelines be published? Mr. Hagger
 
24. What is being done to reassure patients, parents etc? Mr. Hagger/Dr. Salisbury
 
25. What advice is being given to doctors, pharmacists etc? Mr. Hagger
 
26. What advice is the Government giving about its vaccination programme? Dr. Salisbury
 
27. Is the vaccination programme put at risk because of BSE? Dr. Salisbury
 
89/02.17/10.3
 
Q. Will government act on this?
 
A. Yes - thymus is not used in preparation of baby foods but it is contacting all manufacturers to seek their urgent views on use of kidneys and liver from ruminants. Will consider any necessary measures in the light of their response.
 
VETERINARY MEDICINES
 
Q. Can medicines spread BSE to other cattle/animals?
 
A. The report describes any risks as remote.
 
Q. How can risks be avoided?
 
A. In liaison with the DOH the Veterinary Products Committee is examining guidelines for the veterinary pharmaceutical industry which will be issued shortly.
 
Q. What will Guidelines say?
 
A. In essence they call for non-bovine sources to be used if possible, including synthetic material of biotechnological origin. Where this is not possible the industry should look for sources which are free of BSE and which are collected in a manner which avoids risk of contamination by the BSE agent.
 
89/02.17/10.4 MF580439/1 0588
 
A. Bovine source material is used in [garbled, cannot read...TSS] and some other medicines.
 
Q. How many medicines are involved?
 
A. Computer records show that about 300 of the 3,050 veterinary medicines licensed in the U.K. are manufactured directly from bovine source material. However, other medicines may be produced from bovine sources and a letter is going to all license holders so that a comprehensive list can be drawn up.
 
89/06.19/8.1 BSE3/1 0191 Hr J Maslin (MAFF) Ref: Maslin3g
 
From: Dr H Pickles Med SEB/B Date: 3 July 1989
 
CATTLE BY-PRODUCTS AND BSE
 
I was interested to see the list of by-products sent to the HSE. Those of particular concern included:
 
* small intestines: sutures (I thought the source was ovine but you are checking this)
 
* spinal cord: pharmaceuticals
 
* thymus: pharmaceuticals
 
Are you able to give me more information on which UK manufacturers use these materials? Our proposed ban on bovine offal for human consumption would not affect these uses, I assume.
 
Id No. 1934/RD/1 89/08.10/6.1 117A
 
BOVINE SPONGIFORM ENCEPHALAPATHY MEETING HELD ON 21 AUGUST 1989 AT 2;15 IN ROOM 720 Miss M Duncan (Chairman) Mr W Burton Dr E Hoxey Mrs J Dhell Ms K Turner Dr S Whittle Mr N Weatherhead ... 5. The MCA had sent 2700 questionnaires out, 1,124 had made valid returns; of these 122 use animal material of some kind and there are 582 products involved. ... 6. The MCA/BSE working group will meet on 6th September. Their aim is to review responses from professional officers in MCA who have suggested seven categories of importance (with 1 being the most important} for medical products:
 
ID 2267/NRE/1 89/08.21/10.1
 
1. Products with Bovine brain/lymph tissue administered by injection.
 
2. Products with bovine tissue other than brain/lymph administered by inection.
 
3. Tissue implants/open wound dressing/surgical materials/dental and ophthlamic products with bovine ingredients.
 
4. Products with bovine ingredients administered topically.
 
5. Products with bovine ingredients administered orally.
 
6. Products with other animal/fish/insect/bird ingredients administered by injection/topically/oral routes.
 
7. Products with ingredients derived from animal material by chemical processing (eg stearic acid, gelatine, lanolin ext.
 
The BSE working group will decide which of these are important, and should be examined more closely, and which categories can be eliminated.
 
The responses by the companies were presented by Ms Turner and were categorised by MCA standards, the products that were discussed were all low volume usage products eg sutures, heart valves.
 
8. As the responses included some materials of human origin it was decided that more information should be sought about CJD. There had been 2 recent deaths reported associated with human growth hormone. These were being investigated.
 
9. Re-editing of the Paper on "Incubation of Scrapie-like Agents"
 
It was suggested that the document could be sent out to companies with the non-standard sterilization Document. The document could have severe implications on the companies whose products have a high risk factor as decided by the MCA working group....
 
11. The Need for a list of High Priority Implantables The commitee decided that no list is necessary as all implantables, including ones from a human source are of high priority. Concern was shown over Killingbeck who use human material but had not yet responded. The company will be chased for a response. Concern was shown over the fact that there may be other scrapie-like organisms in other animals and further enquiries should be made.
 
2334q/RD/4 89/08.21/10.7
 
BOVINE MATERIAL USED IN THE MANUFACTURE OF SURGICAL IMPLANTS AND BLOOD CONTACT MEDICAL DEVICES
 
Glutaraldehyde, formaldehyde, and ethylene oxide are used in the sterilization of these devices.
 
However, glutaraldehyde 4,10,12,19 formaldehyde 5,10,11,13,19 and ethylene oxide 19,23 are all reported to be ineffective methods for sterilization of material infected with the agents of CJD or scrapie.
 
Previous advice and research using the agents of CJD and scrapie, has concentrated on the decontamination of equipment; protection of health care workers from contaminated human material; human growth hormone; and dura mater. The methods developed may not be directly applicable or transferable to material of bovine origin for use in human implantation.
 
2334q/RD/7 89/08.21/10.10 BSE11/2 020 SC1337
 
DEPARTMENT OF HEALTH AND SOCIAL SECURITY Richmood House 79 Whitehall, London SW1A 2NS Telephone 01-210-3000 From the Chief Medical Officer Sir Donald Acheson KBE DM DSc FRCP FFCM FFOM
 
Mr K C Meldrum Chief Veterinary Officer Ministry of Agriculture, Fisheries and Food Government Buildings Hook Rise South Tolworth Surbiton Surrey KT6 7NG
 
3 January 1990
 
Dear Mr. Meldrum,
 
BOVINE SPONGIFORM ENCEPHALOPATHY
 
You will recall that we have previously discussed the potential risks of BSE occurring in other Countries as a result of the continuing export from the UK of meat and bone that may be contaminated by scrapie or possibly BSE.
 
I remain concerned that we are not being consistent in our attempts to contain the risks of BSE. Having banned the feeding of meat and bone meal to ruminants in 1988, we should take steps to prevent these UK products being fed to ruminants in other countries. This could be achieved either through a ban on the export of meat and bone meal, or at least by the proper labelling of these products to make it absolutely clear they should not be fed to ruminants. Unless some such action is taken the difficult problems we have faced with BSE may well occur in other countries who import UK meat and bone meal. Surely it is short sighted for us to risk being seen in future as having been responsible for the introduction of BSE to the food chain in other countries.
 
I would be very interested to hear how you feel this gap in the present prcautionary measures to eliminate BSE should be closed. We should be aiming at the global elimination of this new bovine disease. The export of our meat and bone meal is a continuing risk to other countries.
 
Signed Sincerely Donald Acheson
 
Did the US import fetal calf serum and vaccines from BSE-affected countries? 3002.10.0040: FETAL BOVINE SERUM (FBS) U.S. Imports for Consumption: December 1998 and 1998 Year-to-Date (Customs Value, in Thousands of Dollars) (Units of Quantity: Kilograms)
 
<--- ---="" 1998="" dec=""> <--- ---="" 1998="" ytd=""> Country Quantity Value Quantity Value
 
=================================================================
 
WORLD TOTAL . . . . . . . 2,727 233 131,486 8,502
 
Australia . . . . . . . . --- --- 19,637 2,623
 
Austria . . . . . . . . . --- --- 2,400 191
 
Belgium . . . . . . . . . --- --- 17 32
 
Canada . . . . . . . . . 900 110 30,983 3,220
 
Costa Rica . . . . . . . 500 20 4,677 169
 
Federal Rep. of Germany --- --- 105 21
 
Finland . . . . . . . . . 1 8 9 83
 
France . . . . . . . . . --- --- 73 7
 
Guatemala . . . . . . . . --- --- 719 42
 
Honduras . . . . . . . . --- --- 1,108 88
 
Israel . . . . . . . . . --- --- 24 165
 
Netherlands . . . . . . . --- --- 1 5
 
New Zealand . . . . . . . 26 5 65,953 913
 
Panama . . . . . . . . . --- --- 1,195 64
 
Switzerland . . . . . . . 971 8 1,078 23
 
United Kingdom . . . . . 329 82 743 756
 
Uruguay . . . . . . . . . --- --- 2,764 98
 
------------------------------------------------------------------
 
3002.20.0000: VACCINES FOR HUMAN MEDICINE U.S. Imports for Consumption: December 1998 and 1998 Year-to-Date (Customs Value, in Thousands of Dollars) (Units of Quantity: Kilograms)
 
<--- ---="" 1998="" dec=""> <--- ---="" 1998="" ytd=""> Country Quantity Value Quantity Value
 
=================================================================
 
WORLD TOTAL . . . . . . . 25,702 26,150 550,258 378,735
 
Austria . . . . . . . . . --- --- 45 225
 
Belgium . . . . . . . . . 14,311 12,029 248,041 199,036
 
Canada . . . . . . . . . 1,109 1,527 15,798 16,305
 
Denmark . . . . . . . . . 80 234 246 682
 
Federal Rep. of Germany 1,064 4,073 12,001 6,329
 
France . . . . . . . . . 3,902 4,859 87,879 92,845
 
Ireland . . . . . . . . . --- --- 120 478
 
Italy . . . . . . . . . . --- --- 2,359 81
 
Japan . . . . . . . . . . 445 1,903 11,350 11,298
 
Netherlands . . . . . . . --- --- 94 6
 
Republic Of South Africa --- --- 2 1
 
Spain . . . . . . . . . . --- --- 60 30
 
Switzerland . . . . . . . 716 353 9,303 4,271
 
United Kingdom . . . . . 4,075 1,172 162,960 47,148
 
------------------------------------------------------------------
 
3002.30.0000: VACCINES FOR VETRINARY MEDICINE U.S. Imports for Consumption: December 1998 and 1998 Year-to-Date (Customs Value, in Thousands of Dollars) (Units of Quantity: Kilograms)
 
<--- ---="" 1998="" dec=""> <--- ---="" 1998="" ytd=""> Country Quantity Value Quantity Value
 
=================================================================
 
WORLD TOTAL . . . . . . . 6,528 237 87,149 2,715
 
Canada . . . . . . . . . --- --- 2,637 305
 
Federal Rep. of Germany --- --- 104 5
 
Netherlands . . . . . . . 138 64 472 192
 
New Zealand . . . . . . . 6,390 173 83,882 1,895
 
United Kingdom . . . . . --- --- 54 318
 
 
 
 
***PRION 2015 RESEARCH ARS USDA BSE, SCRAPIE, CWD, TSE PRION LINKS TO HUMANS AS SPORADIC CJD
 
 
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
 
Title: Transmission of scrapie prions to primate after an extended silent incubation period
 
Authors
 
item Comoy, Emmanuel - item Mikol, Jacqueline - item Luccantoni-Freire, Sophie - item Correia, Evelyne - item Lescoutra-Etchegaray, Nathalie - item Durand, Valérie - item Dehen, Capucine - item Andreoletti, Olivier - item Casalone, Cristina - item Richt, Juergen item Greenlee, Justin item Baron, Thierry - item Benestad, Sylvie - item Hills, Bob - item Brown, Paul - item Deslys, Jean-Philippe -
 
Submitted to: Scientific Reports Publication Type: Peer Reviewed Journal Publication Acceptance Date: May 28, 2015 Publication Date: June 30, 2015 Citation: Comoy, E.E., Mikol, J., Luccantoni-Freire, S., Correia, E., Lescoutra-Etchegaray, N., Durand, V., Dehen, C., Andreoletti, O., Casalone, C., Richt, J.A., Greenlee, J.J., Baron, T., Benestad, S., Brown, P., Deslys, J. 2015. Transmission of scrapie prions to primate after an extended silent incubation period. Scientific Reports. 5:11573.
 
Interpretive Summary: The transmissible spongiform encephalopathies (also called prion diseases) are fatal neurodegenerative diseases that affect animals and humans. The agent of prion diseases is a misfolded form of the prion protein that is resistant to breakdown by the host cells. Since all mammals express prion protein on the surface of various cells such as neurons, all mammals are, in theory, capable of replicating prion diseases. One example of a prion disease, bovine spongiform encephalopathy (BSE; also called mad cow disease), has been shown to infect cattle, sheep, exotic undulates, cats, non-human primates, and humans when the new host is exposed to feeds or foods contaminated with the disease agent. The purpose of this study was to test whether non-human primates (cynomologous macaque) are susceptible to the agent of sheep scrapie. After an incubation period of approximately 10 years a macaque developed progressive clinical signs suggestive of neurologic disease. Upon postmortem examination and microscopic examination of tissues, there was a widespread distribution of lesions consistent with a transmissible spongiform encephalopathy. This information will have a scientific impact since it is the first study that demonstrates the transmission of scrapie to a non-human primate with a close genetic relationship to humans. This information is especially useful to regulatory officials and those involved with risk assessment of the potential transmission of animal prion diseases to humans. Technical Abstract: Classical bovine spongiform encephalopathy (c-BSE) is an animal prion disease that also causes variant Creutzfeldt-Jakob disease in humans. Over the past decades, c-BSE's zoonotic potential has been the driving force in establishing extensive protective measures for animal and human health.
 
*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.
 
*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.
 
*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.
 
 
***This information will have a scientific impact since it is the first study that demonstrates the transmission of scrapie to a non-human primate with a close genetic relationship to humans. This information is especially useful to regulatory officials and those involved with risk assessment of the potential transmission of animal prion diseases to humans.
 
***This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated. Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.
 
 
O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations
 
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France
 
Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.
 
*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,
 
***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),
 
***is the third potentially zoonotic PD (with BSE and L-type BSE),
 
***thus questioning the origin of human sporadic cases. We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.
 
===============
 
***thus questioning the origin of human sporadic cases***
 
===============
 
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
 
==============
 
 
===============
 
 PRION CONFERENCE 2014 HELD IN ITALY RECENTLY CWD BSE TSE UPDATE
 
> First transmission of CWD to transgenic mice over-expressing bovine prion protein gene (TgSB3985)
 
PRION 2014 - PRIONS: EPIGENETICS and NEURODEGENERATIVE DISEASES – Shaping up the future of prion research
 
Animal TSE Workshop 10.40 – 11.05 Talk Dr. L. Cervenakova First transmission of CWD to transgenic mice over-expressing bovine prion protein gene (TgSB3985)
 
 
Friday, August 14, 2015
 
Susceptibility of cattle to the agent of chronic wasting disease from elk after intracranial inoculation
 
 
Wednesday, January 20, 2016
 
Exportation of Live Animals, Hatching Eggs, and Animal Germplasm From the United States [Docket No. APHIS-2012-0049] RIN 0579-AE00 2016-00962
 
 
Thursday, January 14, 2016
 
*** EMERGING ANIMAL DISEASES Actions Needed to Better Position USDA to Address Future Risks Report to the Chairman, Committee on Energy and Commerce, House of Representatives December 2015 GAO-16-132
 
GAO
 
 
Friday, January 1, 2016
 
South Korea Lifts Ban on Beef, Veal Imports From Canada
 
 
US CONGRESS, another failed entity...tss
 
Tuesday, December 29, 2015
 
*** Congress repeals country-of-origin labeling rule for beef and pork
 
 
December 28, 2015 at 2:21am
 
*** Australian government assessing risk of importing beef from US, Japan and the Netherlands
 
 
Thursday, December 24, 2015
 
Infectious disease spread is fueled by international trade
 
 
Thursday, December 17, 2015
 
Annual report of the Scientific Network on BSE-TSE 2015 EFSA-Q-2015-00738 10 December 2015
 
 
Sunday, October 18, 2015
 
World Organisation for Animal Health (OIE) and the Institut Pasteur Cooperating on animal disease and zoonosis research
 
 
SSS SHOOT SHOVEL AND SHUT UP !
 
*** you can find some history of the BSE cases in Canada and Klein’s BSE SSS policy comment here ;
 
 
Tuesday, August 12, 2014
 
MAD COW USDA TSE PRION COVER UP or JUST IGNORANCE, for the record AUGUST 2014
 
 
Saturday, December 12, 2015
 
*** BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION REPORT DECEMBER 14, 2015
 
 
Thursday, October 22, 2015
 
*** Former Ag Secretary Ann Veneman talks women in agriculture and we talk mad cow disease USDA and what really happened ***
 
 
*** Needless conflict ***
 
Nature 485, 279–280 (17 May 2012) doi:10.1038/485279b
 
Published online 16 May 2012
 
Terry S. Singeltary Sr. said:
 
I kindly wish to submit the following please ;
 
 
Comments on technical aspects of the risk assessment were then submitted to FSIS.
 
Comments were received from Food and Water Watch, Food Animal Concerns Trust (FACT), Farm Sanctuary, R-CALF USA, Linda A Detwiler, and Terry S. Singeltary.
 
This document provides itemized replies to the public comments received on the 2005 updated Harvard BSE risk assessment. Please bear the following points in mind:
 
 
Owens, Julie
 
From: Terry S. Singeltary Sr. [flounder9@verizon.net]
 
Sent: Monday, July 24, 2006 1:09 PM
 
To: FSIS RegulationsComments
 
Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)
 
Page 1 of 98
 
 
FSIS, USDA, REPLY TO SINGELTARY
 
 
Singeltary to APHIS FDA USDA et al ;
 
 
 
Thursday, January 14, 2016
 
*** Preventable Tragedies: Superbugs and How Ineffective Monitoring of Medical Device Safety Fails Patients REPORT ***
 
*** how can it be, HOW CAN IT BE $$$ not a word about CJD GSS FFI VPSPR TSE Prions that I saw...absolutely crazy, WE ARE MISSING THE BIGGER PICTURE!
 
how many victims that will never be reported ???
 
 
Sunday, October 18, 2015
 
World Organisation for Animal Health (OIE) and the Institut Pasteur Cooperating on animal disease and zoonosis research
 
 
Saturday, December 12, 2015
 
*** BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION REPORT DECEMBER 14, 2015
 
 
Thursday, December 17, 2015
 
Annual report of the Scientific Network on BSE-TSE 2015 EFSA-Q-2015-00738 10 December 2015
 
 
Friday, January 1, 2016
 
South Korea Lifts Ban on Beef, Veal Imports From Canada
 
 
US CONGRESS, another failed entity...tss
 
Tuesday, December 29, 2015
 
*** Congress repeals country-of-origin labeling rule for beef and pork
 
 
December 28, 2015 at 2:21am
 
*** Australian government assessing risk of importing beef from US, Japan and the Netherlands
 
 
Thursday, December 24, 2015
 
Infectious disease spread is fueled by international trade
 
 
*** you can find some history of the BSE cases in Canada and Klein’s BSE SSS policy comment here ;
 
 
Thursday, January 14, 2016
 
*** EMERGING ANIMAL DISEASES Actions Needed to Better Position USDA to Address Future Risks Report to the Chairman, Committee on Energy and Commerce, House of Representatives December 2015 GAO-16-132
 
GAO
 
 
Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy
 
 
07 02:27 AM
 
Terry S. Singeltary Sr. said:
 
re-Evidence for human transmission of amyloid-? pathology and cerebral amyloid angiopathy
 
Nature 525, 247?250 (10 September 2015) doi:10.1038/nature15369 Received 26 April 2015 Accepted 14 August 2015 Published online 09 September 2015 Updated online 11 September 2015 Erratum (October, 2015)
 
 
*** I would kindly like to comment on the Nature Paper, the Lancet reply, and the newspaper articles.
 
snip...see full text ;
 
 
Subject: 1992 IN CONFIDENCE TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES POSSIBILITY ON A TRANSMISSIBLE PRION REMAINS OPEN
 
BSE101/1 0136
 
IN CONFIDENCE
 
CMO
 
From: . Dr J S Metiers DCMO
 
4 November 1992
 
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
 
1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have recognised the public sensitivity of these findings and intend to report them in their proper context. 'This hopefully will avoid misunderstanding and possible distortion by the media to portray the results as having more greater significance than the findings so far justify.
 
2. Using a highly unusual route of transmission (intra-cerebral injection) the researchers have demonstrated the transmission of a pathological process from two cases one of severe Alzheimer's disease the other of Gerstmann-Straussler disease to marmosets. However they have not demonstrated the transmission of either clinical condition as the "animals were behaving normally when killed". As the report emphasises the unanswered question is whether the disease condition would have revealed itself if the marmosets had lived longer. They are planning further research to see if the conditions, as opposed to the partial pathological process, is transmissible.
 
what are the implications for public health?
 
3. The route 'of transmission is very specific and in the natural state of things highly unusual. However it could be argued that the results reveal a potential risk, in that brain tissue from these two patients has been shown to transmit a pathological process. Should therefore brain tissue from such cases be regarded as potentially infective? Pathologists, morticians, neuro surgeons and those assisting at neuro surgical procedures and others coming into contact with "raw" human brain tissue could in theory be at risk. However, on a priori grounds given the highly specific route of transmission in these experiments that risk must be negligible if the usual precautions for handling brain tissue are observed.
 
1
 
92/11.4/1.1
 
BSE101/1 0137
 
4. The other dimension to consider is the public reaction. To some extent the GSS case demonstrates little more than the transmission of BSE to a pig by intra-cerebral injection. If other prion diseases can be transmitted in this way it is little surprise that some pathological findings observed in GSS were also transmissible to a marmoset. But the transmission of features of Alzheimer's pathology is a different matter, given the much greater frequency of this disease and raises the unanswered question whether some cases are the result of a transmissible prion. The only tenable public line will be that "more research is required’’ before that hypothesis could be evaluated. The possibility on a transmissible prion remains open. In the meantime MRC needs carefully to consider the range and sequence of studies needed to follow through from the preliminary observations in these two cases. Not a particularly comfortable message, but until we know more about the causation of Alzheimer's disease the total reassurance is not practical.
 
J S METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH 832 llllYc!eS 2 92/11.4/1.2
 
 
>>> The only tenable public line will be that "more research is required’’ <<<
 
>>> possibility on a transmissible prion remains open<<<
 
O.K., so it’s about 23 years later, so somebody please tell me, when is "more research is required’’ enough time for evaluation ?
 
Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease
 
Received July 24, 2014; Accepted September 16, 2014; Published November 3, 2014
 
 
*** Singeltary comment PLoS ***
 
*** Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
 
Posted by flounder on 05 Nov 2014 at 21:27 GMT
 
 
please see ;
 
O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations
 
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France
 
Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.
 
*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,
 
***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),
 
***is the third potentially zoonotic PD (with BSE and L-type BSE),
 
***thus questioning the origin of human sporadic cases. We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.
 
===============
 
***thus questioning the origin of human sporadic cases***
 
===============
 
 
snip...see ;
 
Monday, November 16, 2015
 
*** Docket No. APHIS-2007-0127 Scrapie in Sheep and Goats Terry Singeltary Sr. Submission ***
 
 
 
==========================================
 
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
 
==========================================
 
PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS
 
*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***
 
O18
 
Zoonotic Potential of CWD Prions
 
Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1, Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western Reserve University, Cleveland, Ohio, USA, 2Second University of Naples, Naples, Italy, 3Encore Health Resources, Houston, Texas, USA
 
*** These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.
 
==================
 
***These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.***
 
==================
 
P.105: RT-QuIC models trans-species prion transmission
 
Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward Hoover Prion Research Center; Colorado State University; Fort Collins, CO USA
 
Conversely, FSE maintained sufficient BSE characteristics to more efficiently convert bovine rPrP than feline rPrP. Additionally, human rPrP was competent for conversion by CWD and fCWD.
 
***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.
 
================
 
***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.***
 
================
 
 
CWD TSE Prion in cervids to hTGmice, Heidenhain Variant Creutzfeldt-Jacob Disease MM1 genotype, and iatrogenic CJD ???
 
P07 Behavioral Neurology: Aging and Dementia MRI More Useful Than PET for Diagnosis of Heidenhain Variant Creutzfeldt-Jacob Disease (P07.163)
 
Jonathan Beary1 and Edward Manno2 1 General Neurology, Neurological Institute Cleveland Clinic Cleveland OH 2 Cerebrovascular Neurology, Neurological Institute Cleveland Clinic Cleveland OH
 
OBJECTIVE: To demonstrate that MRI detection of subtle focal cortical abnormalities can prove more useful than positron emission tomography (PET) in the diagnosis of Heidenhain variant Creutzfeldt-Jakob Disease (hvCJD).
 
BACKGROUND: hvCJD is a rare neurodegenerative, spongiform encephalopathy with an aggressive clinical course. PET brain imaging has been reported to detect focal cortical abnormalities in hvCJD with greater sensitivity than MRI. However, because PET is both more costly and less accessable than MRI, early diagnosis of this disease and subsequent prognostication may be unnecessarily delayed. The reliability of MRI over PET in detecting isolated occipital cortical changes suggestive of hvCJD has not been well studied.
 
DESIGN/METHODS: This is a case report with relevent neuroimaging review.
 
RESULTS: A 70 year-old right-handed male experienced visual hallucinations and visuospatial disorientation with worsening ataxia followed by progressive anterograde amnesia and cortical blindness. Six weeks later he was comatose with startle myoclonus. A sharply-contoured periodic pattern was evident posteriorly on continuous EEG monitoring with brain MRI revealing subtle bilateral occipital cortical diffusion restriction. PET brain imaging showed diffuse non-focal cortical hypometabolism. Both cerebrospinal fluid (CSF) 14-3-3 and tau protein studies were positive. EEG progressed to refractory status epilepticus and the patient died four days later. ***The presence of abnormal brain protease-resistant prion protein and MM1 genotype at autopsy supported the diagnosis of hvCJD.
 
CONCLUSIONS: hvCJD should be considered in patients with rapid-onset idiopathic visual disturbance and dementia. When combined with EEG and CSF analysis, isolated MRI visual cortex diffusion restriction is suggestive of this ultra-aggressive prion variant. MRI is able to efficiently facilitate valuable prognostication early in hvCJD and can be more useful than costly PET imaging.
 
Disclosure: Dr. Beary has nothing to disclose. Dr. Manno has nothing to disclose.
 
 
> The presence of abnormal brain protease-resistant prion protein and MM1 genotype at autopsy supported the diagnosis of hvCJD.
 
Wednesday, January 01, 2014
 
Molecular Barriers to Zoonotic Transmission of Prions
 
*** chronic wasting disease, there was no absolute barrier to conversion of the human prion protein.
 
*** Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype.
 
 
 
Subtype 1: (sCJDMM1 and sCJDMV1)
 
This subtype is observed in patients who are MM homozygous or MV heterozygous at codon 129 of the PrP gene (PRNP) and carry PrPSc Type 1. Clinical duration is short, 3‑4 months.32 The most common presentation in sCJDMM1 patients is cognitive impairment leading to frank dementia, gait or limb ataxia, myoclonic jerks and visual signs leading to cortical blindness (Heidenhain’s syndrome)...
 
 
Animals injected with iatrogenic Creutzfeldt–Jakob disease MM1 and genetic Creutzfeldt–Jakob disease MM1 linked to the E200K mutation showed the same phenotypic features as those infected with sporadic Creutzfeldt–Jakob disease MM1 prions...
 
 
*** our results raise the possibility that CJD cases classified as VV1 may include cases caused by iatrogenic transmission of sCJD-MM1 prions or food-borne infection by type 1 prions from animals, e.g., chronic wasting disease prions in cervid. In fact, two CJD-VV1 patients who hunted deer or consumed venison have been reported (40, 41). The results of the present study emphasize the need for traceback studies and careful re-examination of the biochemical properties of sCJD-VV1 prions. ***
 
 
snip...see full text ;
 
 
Wednesday, June 16, 2010
 
Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties
 
The epidemiological findings in sCJD demonstrate that approximately 80% of patients are diagnosed with “classic CJD” types MM1 and MV1, which might intriguingly suggest an infectious rather than genetic origin for the majority of sCJD cases.
 
snip...
 
Therefore if sCJD(MV2) and sCJD(VV2) were to become iatrogenic sources of human infection, the host response may be indistinguishable from sCJD(MM1) and more transmissible with respect to further infection.
 
END...TSS
 
 
*** Needless conflict ***
 
Nature 485, 279–280 (17 May 2012) doi:10.1038/485279b
 
Published online 16 May 2012
 
Terry S. Singeltary Sr. said:
 
I kindly wish to submit the following please ;
 
 
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
 
Title: Transmission of scrapie prions to primate after an extended silent incubation period
 
Authors
 
item Comoy, Emmanuel - item Mikol, Jacqueline - item Luccantoni-Freire, Sophie - item Correia, Evelyne - item Lescoutra-Etchegaray, Nathalie - item Durand, Valérie - item Dehen, Capucine - item Andreoletti, Olivier - item Casalone, Cristina - item Richt, Juergen item Greenlee, Justin item Baron, Thierry - item Benestad, Sylvie - item Hills, Bob - item Brown, Paul - item Deslys, Jean-Philippe -
 
Submitted to: Scientific Reports Publication Type: Peer Reviewed Journal Publication Acceptance Date: May 28, 2015 Publication Date: June 30, 2015 Citation: Comoy, E.E., Mikol, J., Luccantoni-Freire, S., Correia, E., Lescoutra-Etchegaray, N., Durand, V., Dehen, C., Andreoletti, O., Casalone, C., Richt, J.A., Greenlee, J.J., Baron, T., Benestad, S., Brown, P., Deslys, J. 2015. Transmission of scrapie prions to primate after an extended silent incubation period. Scientific Reports. 5:11573.
 
Interpretive Summary:
 
The transmissible spongiform encephalopathies (also called prion diseases) are fatal neurodegenerative diseases that affect animals and humans. The agent of prion diseases is a misfolded form of the prion protein that is resistant to breakdown by the host cells. Since all mammals express prion protein on the surface of various cells such as neurons, all mammals are, in theory, capable of replicating prion diseases. One example of a prion disease, bovine spongiform encephalopathy (BSE; also called mad cow disease), has been shown to infect cattle, sheep, exotic undulates, cats, non-human primates, and humans when the new host is exposed to feeds or foods contaminated with the disease agent. The purpose of this study was to test whether non-human primates (cynomologous macaque) are susceptible to the agent of sheep scrapie. After an incubation period of approximately 10 years a macaque developed progressive clinical signs suggestive of neurologic disease. Upon postmortem examination and microscopic examination of tissues, there was a widespread distribution of lesions consistent with a transmissible spongiform encephalopathy. This information will have a scientific impact since it is the first study that demonstrates the transmission of scrapie to a non-human primate with a close genetic relationship to humans. This information is especially useful to regulatory officials and those involved with risk assessment of the potential transmission of animal prion diseases to humans.
 
Technical Abstract:
 
Classical bovine spongiform encephalopathy (c-BSE) is an animal prion disease that also causes variant Creutzfeldt-Jakob disease in humans. Over the past decades, c-BSE's zoonotic potential has been the driving force in establishing extensive protective measures for animal and human health. In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.
 
***This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated. Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.
 
 
*** Docket No. APHIS-2007-0127 Scrapie in Sheep and Goats Terry Singeltary Sr. Submission ***
 
Monday, November 16, 2015
 
*** Docket No. APHIS-2007-0127 Scrapie in Sheep and Goats Terry Singeltary Sr. Submission ***
 
 
 
98 | Veterinary Record | January 24, 2015
 
EDITORIAL
 
Scrapie: a particularly persistent pathogen
 
Cristina Acín
 
Resistant prions in the environment have been the sword of Damocles for scrapie control and eradication. Attempts to establish which physical and chemical agents could be applied to inactivate or moderate scrapie infectivity were initiated in the 1960s and 1970s,with the first study of this type focusing on the effect of heat treatment in reducing prion infectivity (Hunter and Millson 1964). Nowadays, most of the chemical procedures that aim to inactivate the prion protein are based on the method developed by Kimberlin and collaborators (1983). This procedure consists of treatment with 20,000 parts per million free chlorine solution, for a minimum of one hour, of all surfaces that need to be sterilised (in laboratories, lambing pens, slaughterhouses, and so on). Despite this, veterinarians and farmers may still ask a range of questions, such as ‘Is there an official procedure published somewhere?’ and ‘Is there an international organisation which recommends and defines the exact method of scrapie decontamination that must be applied?’
 
From a European perspective, it is difficult to find a treatment that could be applied, especially in relation to the disinfection of surfaces in lambing pens of affected flocks. A 999/2001 EU regulation on controlling spongiform encephalopathies (European Parliament and Council 2001) did not specify a particular decontamination measure to be used when an outbreak of scrapie is diagnosed. There is only a brief recommendation in Annex VII concerning the control and eradication of transmissible spongiform encephalopathies (TSE s).
 
Chapter B of the regulation explains the measures that must be applied if new caprine animals are to be introduced to a holding where a scrapie outbreak has previously been diagnosed. In that case, the statement indicates that caprine animals can be introduced ‘provided that a cleaning and disinfection of all animal housing on the premises has been carried out following destocking’.
 
Issues around cleaning and disinfection are common in prion prevention recommendations, but relevant authorities, veterinarians and farmers may have difficulties in finding the specific protocol which applies. The European Food and Safety Authority (EFSA ) published a detailed report about the efficacy of certain biocides, such as sodium hydroxide, sodium hypochlorite, guanidine and even a formulation of copper or iron metal ions in combination with hydrogen peroxide, against prions (EFSA 2009). The report was based on scientific evidence (Fichet and others 2004, Lemmer and others 2004, Gao and others 2006, Solassol and others 2006) but unfortunately the decontamination measures were not assessed under outbreak conditions.
 
The EFSA Panel on Biological Hazards recently published its conclusions on the scrapie situation in the EU after 10 years of monitoring and control of the disease in sheep and goats (EFSA 2014), and one of the most interesting findings was the Icelandic experience regarding the effect of disinfection in scrapie control. The Icelandic plan consisted of: culling scrapie-affected sheep or the whole flock in newly diagnosed outbreaks; deep cleaning and disinfection of stables, sheds, barns and equipment with high pressure washing followed by cleaning with 500 parts per million of hypochlorite; drying and treatment with 300 ppm of iodophor; and restocking was not permitted for at least two years. Even when all of these measures were implemented, scrapie recurred on several farms, indicating that the infectious agent survived for years in the environment, even as many as 16 years after restocking (Georgsson and others 2006).
 
In the rest of the countries considered in the EFSA (2014) report, recommendations for disinfection measures were not specifically defined at the government level. In the report, the only recommendation that is made for sheep is repopulation with sheep with scrapie-resistant genotypes. This reduces the risk of scrapie recurrence but it is difficult to know its effect on the infection.
 
Until the EFSA was established (in May 2003), scientific opinions about TSE s were provided by the Scientific Steering Committee (SSC) of the EC, whose advice regarding inactivation procedures focused on treating animal waste at high temperatures (150°C for three hours) and high pressure alkaline hydrolysis (SSC 2003). At the same time, the TSE Risk Management Subgroup of the Advisory Committee on Dangerous Pathogens (ACDP) in the UK published guidance on safe working and the prevention of TSE infection. Annex C of the ACDP report established that sodium hypochlorite was considered to be effective, but only if 20,000 ppm of available chlorine was present for at least one hour, which has practical limitations such as the release of chlorine gas, corrosion, incompatibility with formaldehyde, alcohols and acids, rapid inactivation of its active chemicals and the stability of dilutions (ACDP 2009).
 
In an international context, the World Organisation for Animal Health (OIE) does not recommend a specific disinfection protocol for prion agents in its Terrestrial Code or Manual. Chapter 4.13 of the Terrestrial Code, General recommendations on disinfection and disinsection (OIE 2014), focuses on foot-and-mouth disease virus, mycobacteria and Bacillus anthracis, but not on prion disinfection. Nevertheless, the last update published by the OIE on bovine spongiform encephalopathy (OIE 2012) indicates that few effective decontamination techniques are available to inactivate the agent on surfaces, and recommends the removal of all organic material and the use of sodium hydroxide, or a sodium hypochlorite solution containing 2 per cent available chlorine, for more than one hour at 20ºC.
 
The World Health Organization outlines guidelines for the control of TSE s, and also emphasises the importance of mechanically cleaning surfaces before disinfection with sodium hydroxide or sodium hypochlorite for one hour (WHO 1999).
 
Finally, the relevant agencies in both Canada and the USA suggest that the best treatments for surfaces potentially contaminated with prions are sodium hydroxide or sodium hypochlorite at 20,000 ppm. This is a 2 per cent solution, while most commercial household bleaches contain 5.25 per cent sodium hypochlorite. It is therefore recommended to dilute one part 5.25 per cent bleach with 1.5 parts water (CDC 2009, Canadian Food Inspection Agency 2013).
 
So what should we do about disinfection against prions? First, it is suggested that a single protocol be created by international authorities to homogenise inactivation procedures and enable their application in all scrapie-affected countries. Sodium hypochlorite with 20,000 ppm of available chlorine seems to be the procedure used in most countries, as noted in a paper summarised on p 99 of this issue of Veterinary Record (Hawkins and others 2015). But are we totally sure of its effectiveness as a preventive measure in a scrapie outbreak? Would an in-depth study of the recurrence of scrapie disease be needed?
 
What we can conclude is that, if we want to fight prion diseases, and specifically classical scrapie, we must focus on the accuracy of diagnosis, monitoring and surveillance; appropriate animal identification and control of movements; and, in the end, have homogeneous and suitable protocols to decontaminate and disinfect lambing barns, sheds and equipment available to veterinarians and farmers. Finally, further investigations into the resistance of prion proteins in the diversity of environmental surfaces are required.
 
References
 
snip...
 
98 | Veterinary Record | January 24, 2015
 
 
*** These results suggest that AA fibrils are relatively heat stable and that similar to prions, autoclaving at 135 °C is required to destroy the pathogenicity of AA fibrils.
 
*** These findings may contribute to the prevention of AA fibril transmission through food materials to different animals and especially to humans.
 
New studies on the heat resistance of hamster-adapted scrapie agent: Threshold survival after ashing at 600°C suggests an inorganic template of replication
 
The infectious agents responsible for transmissible spongiform encephalopathy (TSE) are notoriously resistant to most physical and chemical methods used for inactivating pathogens, including heat. It has long been recognized, for example, that boiling is ineffective and that higher temperatures are most efficient when combined with steam under pressure (i.e., autoclaving). As a means of decontamination, dry heat is used only at the extremely high temperatures achieved during incineration, usually in excess of 600°C. It has been assumed, without proof, that incineration totally inactivates the agents of TSE, whether of human or animal origin.
 
 
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production
 
Histochemical analysis of hamster brains inoculated with the solid residue showed typical spongiform degeneration and vacuolation. Re-inoculation of these brains into a new cohort of hamsters led to onset of clinical scrapie symptoms within 75 days, suggesting that the specific infectivity of the prion protein was not changed during the biodiesel process. The biodiesel reaction cannot be considered a viable prion decontamination method for MBM, although we observed increased survival time of hamsters and reduced infectivity greater than 6 log orders in the solid MBM residue. Furthermore, results from our study compare for the first time prion detection by Western Blot versus an infectivity bioassay for analysis of biodiesel reaction products. We could show that biochemical analysis alone is insufficient for detection of prion infectivity after a biodiesel process.
 
 
Detection of protease-resistant cervid prion protein in water from a CWD-endemic area
 
The data presented here demonstrate that sPMCA can detect low levels of PrPCWD in the environment, corroborate previous biological and experimental data suggesting long term persistence of prions in the environment2,3 and imply that PrPCWD accumulation over time may contribute to transmission of CWD in areas where it has been endemic for decades. This work demonstrates the utility of sPMCA to evaluate other environmental water sources for PrPCWD, including smaller bodies of water such as vernal pools and wallows, where large numbers of cervids congregate and into which prions from infected animals may be shed and concentrated to infectious levels.
 
 
A Quantitative Assessment of the Amount of Prion Diverted to Category 1 Materials and Wastewater During Processing
 
Keywords:Abattoir;bovine spongiform encephalopathy;QRA;scrapie;TSE
 
In this article the development and parameterization of a quantitative assessment is described that estimates the amount of TSE infectivity that is present in a whole animal carcass (bovine spongiform encephalopathy [BSE] for cattle and classical/atypical scrapie for sheep and lambs) and the amounts that subsequently fall to the floor during processing at facilities that handle specified risk material (SRM). BSE in cattle was found to contain the most oral doses, with a mean of 9864 BO ID50s (310, 38840) in a whole carcass compared to a mean of 1851 OO ID50s (600, 4070) and 614 OO ID50s (155, 1509) for a sheep infected with classical and atypical scrapie, respectively. Lambs contained the least infectivity with a mean of 251 OO ID50s (83, 548) for classical scrapie and 1 OO ID50s (0.2, 2) for atypical scrapie. The highest amounts of infectivity falling to the floor and entering the drains from slaughtering a whole carcass at SRM facilities were found to be from cattle infected with BSE at rendering and large incineration facilities with 7.4 BO ID50s (0.1, 29), intermediate plants and small incinerators with a mean of 4.5 BO ID50s (0.1, 18), and collection centers, 3.6 BO ID50s (0.1, 14). The lowest amounts entering drains are from lambs infected with classical and atypical scrapie at intermediate plants and atypical scrapie at collection centers with a mean of 3 × 10−7 OO ID50s (2 × 10−8, 1 × 10−6) per carcass. The results of this model provide key inputs for the model in the companion paper published here.
 
 
*** Infectious agent of sheep scrapie may persist in the environment for at least 16 years ***
 
Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3
 
 
PL1
 
Using in vitro prion replication for high sensitive detection of prions and prionlike proteins and for understanding mechanisms of transmission.
 
Claudio Soto
 
Mitchell Center for Alzheimer's diseases and related Brain disorders, Department of Neurology, University of Texas Medical School at Houston.
 
Prion and prion-like proteins are misfolded protein aggregates with the ability to selfpropagate to spread disease between cells, organs and in some cases across individuals. I n T r a n s m i s s i b l e s p o n g i f o r m encephalopathies (TSEs), prions are mostly composed by a misfolded form of the prion protein (PrPSc), which propagates by transmitting its misfolding to the normal prion protein (PrPC). The availability of a procedure to replicate prions in the laboratory may be important to study the mechanism of prion and prion-like spreading and to develop high sensitive detection of small quantities of misfolded proteins in biological fluids, tissues and environmental samples. Protein Misfolding Cyclic Amplification (PMCA) is a simple, fast and efficient methodology to mimic prion replication in the test tube. PMCA is a platform technology that may enable amplification of any prion-like misfolded protein aggregating through a seeding/nucleation process. In TSEs, PMCA is able to detect the equivalent of one single molecule of infectious PrPSc and propagate prions that maintain high infectivity, strain properties and species specificity. Using PMCA we have been able to detect PrPSc in blood and urine of experimentally infected animals and humans affected by vCJD with high sensitivity and specificity. Recently, we have expanded the principles of PMCA to amplify amyloid-beta (Aβ) and alphasynuclein (α-syn) aggregates implicated in Alzheimer's and Parkinson's diseases, respectively. Experiments are ongoing to study the utility of this technology to detect Aβ and α-syn aggregates in samples of CSF and blood from patients affected by these diseases.
 
=========================
 
***Recently, we have been using PMCA to study the role of environmental prion contamination on the horizontal spreading of TSEs. These experiments have focused on the study of the interaction of prions with plants and environmentally relevant surfaces. Our results show that plants (both leaves and roots) bind tightly to prions present in brain extracts and excreta (urine and feces) and retain even small quantities of PrPSc for long periods of time. Strikingly, ingestion of prioncontaminated leaves and roots produced disease with a 100% attack rate and an incubation period not substantially longer than feeding animals directly with scrapie brain homogenate. Furthermore, plants can uptake prions from contaminated soil and transport them to different parts of the plant tissue (stem and leaves). Similarly, prions bind tightly to a variety of environmentally relevant surfaces, including stones, wood, metals, plastic, glass, cement, etc. Prion contaminated surfaces efficiently transmit prion disease when these materials were directly injected into the brain of animals and strikingly when the contaminated surfaces were just placed in the animal cage. These findings demonstrate that environmental materials can efficiently bind infectious prions and act as carriers of infectivity, suggesting that they may play an important role in the horizontal transmission of the disease.
 
========================
 
Since its invention 13 years ago, PMCA has helped to answer fundamental questions of prion propagation and has broad applications in research areas including the food industry, blood bank safety and human and veterinary disease diagnosis.
 
 
Wednesday, December 16, 2015
 
Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission
 
Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission
 
Timm Konold1*, Stephen A. C. Hawkins2, Lisa C. Thurston3, Ben C. Maddison4, Kevin C. Gough5, Anthony Duarte1 and Hugh A. Simmons1
 
1 Animal Sciences Unit, Animal and Plant Health Agency Weybridge, Addlestone, UK, 2 Pathology Department, Animal and Plant Health Agency Weybridge, Addlestone, UK, 3 Surveillance and Laboratory Services, Animal and Plant Health Agency Penrith, Penrith, UK, 4 ADAS UK, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK, 5 School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK
 
Classical scrapie is an environmentally transmissible prion disease of sheep and goats. Prions can persist and remain potentially infectious in the environment for many years and thus pose a risk of infecting animals after re-stocking. In vitro studies using serial protein misfolding cyclic amplification (sPMCA) have suggested that objects on a scrapie affected sheep farm could contribute to disease transmission. This in vivo study aimed to determine the role of field furniture (water troughs, feeding troughs, fencing, and other objects that sheep may rub against) used by a scrapie-infected sheep flock as a vector for disease transmission to scrapie-free lambs with the prion protein genotype VRQ/VRQ, which is associated with high susceptibility to classical scrapie. When the field furniture was placed in clean accommodation, sheep became infected when exposed to either a water trough (four out of five) or to objects used for rubbing (four out of seven). This field furniture had been used by the scrapie-infected flock 8 weeks earlier and had previously been shown to harbor scrapie prions by sPMCA. Sheep also became infected (20 out of 23) through exposure to contaminated field furniture placed within pasture not used by scrapie-infected sheep for 40 months, even though swabs from this furniture tested negative by PMCA. This infection rate decreased (1 out of 12) on the same paddock after replacement with clean field furniture. Twelve grazing sheep exposed to field furniture not in contact with scrapie-infected sheep for 18 months remained scrapie free. The findings of this study highlight the role of field furniture used by scrapie-infected sheep to act as a reservoir for disease re-introduction although infectivity declines considerably if the field furniture has not been in contact with scrapie-infected sheep for several months. PMCA may not be as sensitive as VRQ/VRQ sheep to test for environmental contamination.
 
snip...
 
Discussion
 
Classical scrapie is an environmentally transmissible disease because it has been reported in naïve, supposedly previously unexposed sheep placed in pastures formerly occupied by scrapie-infected sheep (4, 19, 20). Although the vector for disease transmission is not known, soil is likely to be an important reservoir for prions (2) where – based on studies in rodents – prions can adhere to minerals as a biologically active form (21) and remain infectious for more than 2 years (22). Similarly, chronic wasting disease (CWD) has re-occurred in mule deer housed in paddocks used by infected deer 2 years earlier, which was assumed to be through foraging and soil consumption (23).
 
Our study suggested that the risk of acquiring scrapie infection was greater through exposure to contaminated wooden, plastic, and metal surfaces via water or food troughs, fencing, and hurdles than through grazing. Drinking from a water trough used by the scrapie flock was sufficient to cause infection in sheep in a clean building. Exposure to fences and other objects used for rubbing also led to infection, which supported the hypothesis that skin may be a vector for disease transmission (9). The risk of these objects to cause infection was further demonstrated when 87% of 23 sheep presented with PrPSc in lymphoid tissue after grazing on one of the paddocks, which contained metal hurdles, a metal lamb creep and a water trough in contact with the scrapie flock up to 8 weeks earlier, whereas no infection had been demonstrated previously in sheep grazing on this paddock, when equipped with new fencing and field furniture. When the contaminated furniture and fencing were removed, the infection rate dropped significantly to 8% of 12 sheep, with soil of the paddock as the most likely source of infection caused by shedding of prions from the scrapie-infected sheep in this paddock up to a week earlier.
 
This study also indicated that the level of contamination of field furniture sufficient to cause infection was dependent on two factors: stage of incubation period and time of last use by scrapie-infected sheep. Drinking from a water trough that had been used by scrapie sheep in the predominantly pre-clinical phase did not appear to cause infection, whereas infection was shown in sheep drinking from the water trough used by scrapie sheep in the later stage of the disease. It is possible that contamination occurred through shedding of prions in saliva, which may have contaminated the surface of the water trough and subsequently the water when it was refilled. Contamination appeared to be sufficient to cause infection only if the trough was in contact with sheep that included clinical cases. Indeed, there is an increased risk of bodily fluid infectivity with disease progression in scrapie (24) and CWD (25) based on PrPSc detection by sPMCA. Although ultraviolet light and heat under natural conditions do not inactivate prions (26), furniture in contact with the scrapie flock, which was assumed to be sufficiently contaminated to cause infection, did not act as vector for disease if not used for 18 months, which suggest that the weathering process alone was sufficient to inactivate prions.
 
PrPSc detection by sPMCA is increasingly used as a surrogate for infectivity measurements by bioassay in sheep or mice. In this reported study, however, the levels of PrPSc present in the environment were below the limit of detection of the sPMCA method, yet were still sufficient to cause infection of in-contact animals. In the present study, the outdoor objects were removed from the infected flock 8 weeks prior to sampling and were positive by sPMCA at very low levels (2 out of 37 reactions). As this sPMCA assay also yielded 2 positive reactions out of 139 in samples from the scrapie-free farm, the sPMCA assay could not detect PrPSc on any of the objects above the background of the assay. False positive reactions with sPMCA at a low frequency associated with de novo formation of infectious prions have been reported (27, 28). This is in contrast to our previous study where we demonstrated that outdoor objects that had been in contact with the scrapie-infected flock up to 20 days prior to sampling harbored PrPSc that was detectable by sPMCA analysis [4 out of 15 reactions (12)] and was significantly more positive by the assay compared to analogous samples from the scrapie-free farm. This discrepancy could be due to the use of a different sPMCA substrate between the studies that may alter the efficiency of amplification of the environmental PrPSc. In addition, the present study had a longer timeframe between the objects being in contact with the infected flock and sampling, which may affect the levels of extractable PrPSc. Alternatively, there may be potentially patchy contamination of this furniture with PrPSc, which may have been missed by swabbing. The failure of sPMCA to detect CWD-associated PrP in saliva from clinically affected deer despite confirmation of infectivity in saliva-inoculated transgenic mice was associated with as yet unidentified inhibitors in saliva (29), and it is possible that the sensitivity of sPMCA is affected by other substances in the tested material. In addition, sampling of amplifiable PrPSc and subsequent detection by sPMCA may be more difficult from furniture exposed to weather, which is supported by the observation that PrPSc was detected by sPMCA more frequently in indoor than outdoor furniture (12). A recent experimental study has demonstrated that repeated cycles of drying and wetting of prion-contaminated soil, equivalent to what is expected under natural weathering conditions, could reduce PMCA amplification efficiency and extend the incubation period in hamsters inoculated with soil samples (30). This seems to apply also to this study even though the reduction in infectivity was more dramatic in the sPMCA assays than in the sheep model. Sheep were not kept until clinical end-point, which would have enabled us to compare incubation periods, but the lack of infection in sheep exposed to furniture that had not been in contact with scrapie sheep for a longer time period supports the hypothesis that prion degradation and subsequent loss of infectivity occurs even under natural conditions.
 
In conclusion, the results in the current study indicate that removal of furniture that had been in contact with scrapie-infected animals should be recommended, particularly since cleaning and decontamination may not effectively remove scrapie infectivity (31), even though infectivity declines considerably if the pasture and the field furniture have not been in contact with scrapie-infected sheep for several months. As sPMCA failed to detect PrPSc in furniture that was subjected to weathering, even though exposure led to infection in sheep, this method may not always be reliable in predicting the risk of scrapie infection through environmental contamination. These results suggest that the VRQ/VRQ sheep model may be more sensitive than sPMCA for the detection of environmentally associated scrapie, and suggest that extremely low levels of scrapie contamination are able to cause infection in susceptible sheep genotypes.
 
Keywords: classical scrapie, prion, transmissible spongiform encephalopathy, sheep, field furniture, reservoir, serial protein misfolding cyclic amplification
 
 
Wednesday, December 16, 2015
 
*** Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission
 
 
Monday, January 4, 2016
 
Long live the OIE, or time to close the doors on a failed entity?
 
 
Saturday, December 12, 2015
 
CHRONIC WASTING DISEASE CWD TSE PRION REPORT DECEMBER 14, 2015
 
 
Sunday, January 17, 2016
 
Wisconsin Captive CWD Lotto Pays Out Again indemnity payment of $298,770 for 228 white-tailed deer killed on farm
 
 
TEXAS MONTHLY CHRONIC WASTING DISEASE CWD JANUARY 2016 DEER BREEDERS STILL DON'T GET IT $
 
Chronic Wasting Unease
 
The emergence of a deadly disease has wildlife officials and deer breeders eyeing each other suspiciously.
 
 
Sunday, January 17, 2016
 
Texas 10,000 deer in Texas tested for deadly disease CWD TSE, but not tested much in the most logical place, the five-mile radius around the Medina County captive-deer facility where it was discovered
 
 
December 28, 2015 at 2:21am
 
Australian government assessing risk of importing beef from US, Japan and the Netherlands
 
 
Thursday, September 10, 2015
 
25th Meeting of the Transmissible Spongiform Encephalopathies Advisory Committee Food and Drug Administration Silver Spring, Maryland June 1, 2015
 
 
Sunday, January 17, 2016
 
Of Grave Concern Heidenhain Variant Creutzfeldt Jakob Disease
 
 
 kind regards, terry

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