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.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract
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
http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/all-clinically-relevant-blood.html
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
Website: http://www.bse.org.uk
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;
http://web.archive.org/web/20040622230927/http://www.bseinquiry.gov.uk/files/yb/1989/09/06013001.pdf
sutures
http://web.archive.org/web/20060225051622/http://www.bseinquiry.gov.uk/files/yb/1989/07/27002001.pdf
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
http://web.archive.org/web/20090718143231/http://www.bseinquiry.gov.uk/files/yb/1989/09/06011001.pdf
http://web.archive.org/web/20091024173355/http://www.bseinquiry.gov.uk/files/yb/1989/09/06010001.pdf
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
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.