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CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE

Implications for Creutzfeldt-Jakob Disease (CJD) in Dentistry: a Review of Current Knowledge

J.T. Walker1,*, J. Dickinson1, J.M. Sutton1, P.D. Marsh1,2 and N.D.H. Raven1

1 TSE Research Group, Centre for Emergency Preparedness and Response, HPA, Porton Down, Salisbury SP4 0JG, UK; and
2 Leeds Dental Institute, Leeds, LS2 9LU, UK

Correspondence: * corresponding author, jimmy.walker{at}hpa.org.uk


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 TYPES OF HUMAN TSE...
 INACTIVATION OF PRION AGENTS
 CONCLUSIONS
 REFERENCES
 
This review explores our current understanding of the risks of (variant) Creutzfeldt-Jakob disease transmission via dental practice, and whether they merit the rigorous enforcement of improved standards of instrument cleaning and decontamination. The recognition of prions as novel infectious agents in humans has caused significant concern among the public and medical professionals alike. Creutzfeldt-Jakob disease (CJD) in humans has been shown to be transmissible via several routes, including transplantation, contaminated medical products, and via neurosurgery. While the likelihood of transmission via dentistry is undoubtedly very low, this may be amplified considerably by unknown risk factors, such as disease prevalence (particularly in the UK), altered tissue distribution of vCJD, and the failure of decontamination processes to address the inactivation of prions adequately. Since current diagnostic techniques are unable to detect PrPSc in human dental tissues, there is limited evidence for the presence of infectivity. Given these uncertainties, the control of risk by reinforced and improved decontamination practices seems the most appropriate response.

Key Words: cross-infection • infection control • vCJD • dentistry • decontamination • prion • TSE • dental instruments


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
TYPES OF HUMAN TSE...
 INACTIVATION OF PRION AGENTS
 CONCLUSIONS
 REFERENCES
 
Human transmissible spongiform encephalopathies (TSEs) present several significant challenges to those working in health care, including neurology, surgery, and dentistry. Despite many years of research, there is still no treatment or prophylaxis for this invariably fatal disease, and no diagnostic test to identify individuals with this disease. Additionally, the agent of the disease is a protein that is remarkably resistant to inactivation by conventional methods, raising concerns about transmission among healthcare professionals (Sutton et al., 2006). TSEs are neurodegenerative diseases characterized by the presence of microscopic vacuoles in the brain’s gray matter (Kordek, 2000). The infectious entity is hypothesized to be a proteinaceous infectious agent, termed ’prion’, although this view is not universally accepted (Chesebro, 2003). Prions have resulted in several diseases, including Creutzfeldt–Jakob disease (CJD), variant CJD (vCJD) (Will et al., 1996; Bruce et al., 1997), kuru (Gajdusek et al., 1977), Gerstmann-Sträussler-Scheinker (GSS) syndrome and fatal familial insomnia in humans, chronic wasting disease in elk and mule deer (Williams and Young, 1980), scrapie in sheep and goats, and bovine spongiform encephalopathy (BSE) in cattle (Wilesmith et al., 1988). All TSEs have prolonged incubation periods, from 1.5 to more than 50 years (Collinge et al., 2006), with a gradual increase in severity of symptoms and accumulation of prion protein in the CNS. In vCJD, this leads to ataxia, cognitive impairment, involuntary movements (which may be dystonic, choreiform, or myoclonic), and neuropathological changes, including formation of amyloid plaques, spongiform vacuolation (Ironside et al., 1996), and neuronal loss, (Ironside et al., 2000), resulting in death (Ironside et al., 2002). vCJD in the UK population was almost certainly acquired by the consumption of meat products contaminated with BSE (Bruce et al., 1997; Hill et al., 1997; Will, 1999). The only specific marker associated with these pathological diseases is the prion protein isoform termed ’PrP scrapie’ (PrPSc), or, alternatively, ’PrP-resistant’ (PrPres), due to its enhanced resistance to proteolysis. The normal form of the cellular prion protein PrPc is a glycophosphatidylinositol (GPI) anchored protein that is highly expressed in neurons. It has been suggested that PrPc influences synaptic functions in neurons (Mouillet-Richard et al., 2000), possibly by regulating copper concentration in the synaptic region of the neuron, or it may play a major role in cell survival (Hornshaw et al., 1995; Brown, 1997; Kuwahara et al., 1999; Lasmezas, 2003). Prion (PrPSc) accumulation occurs in a range of tissues; with vCJD, for example, the amount of disease-associated prion protein is higher in peripheral lymphoreticular tissues than in sporadic CJD (Hill et al., 1999). In vCJD, this accumulation occurs at different concentrations in the brain (considered the highest-risk tissue), tonsil (medium risk), dental pulp, and gingival tissue and blood (low risk) (Table 1Go) (WHO, 2006).


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  		Table 1. Potential Infectivity of Tissues by Risk Category (WHO, 2006)
 

   TYPES OF HUMAN TSE DISEASE
TOP
 ABSTRACT
 INTRODUCTION
 TYPES OF HUMAN TSE...
INACTIVATION OF PRION AGENTS
 CONCLUSIONS
 REFERENCES
 
The human TSE diseases present as inherited (familial), acquired, or sporadic forms (Table 2Go) and are often categorized as follows:


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  		Table 2. The Different Types of Transmissible Spongiform Encephalopathies and Their Causes
 
Sporadic Forms of CJD (sCJD)
These affect approximately one per million of the population per year, worldwide, and account for about 85% of all cases of CJD. This particular form of the disease arises in middle to late life (Cousens et al., 1997), with a peak age of onset between 60 and 65 years of age. Although there are spongiform changes, neuronal loss, and astrocytosis, there are no PrP-immunopositive amyloid plaques in the affected brain (unlike vCJD), and PrPSc has not been detected in lymphoid tissue (Collinge et al., 1990; Lantos et al., 1992). While the underlying cause of sCJD is unknown, there is neither an infective basis nor an identified geographical clustering (Will and Matthews, 1982). However, there have been indications of a significant association with (i) previous surgery and (ii) with more than 10 years’ residence or employment on a farm or market garden (Collins et al., 1999).

Inherited or Familial Forms of CJD (fCJD)
These are caused by many insertion and point mutations, account for approximately 10–15% of cases, and are all autosomal-dominantly inherited. Rare disorders, such as Gerstmann-Sträussler-Scheinker (GSS) syndrome, do not manifest until early-to-middle adult life and typically have an earlier age of onset and a more prolonged course (5–11 yrs) than sCJD (Collinge et al., 1989; Collins et al., 2001).

Acquired Forms of CJD
These include kuru, iatrogenic CJD (iCJD), and vCJD. Transmission from human to human was first recognized in the form of kuru. This fatal disease, which results in cerebellar degeneration, was endemic among the Fore ethnic group in the eastern highlands of Papua New Guinea and was spread by ritualistic cannibalism. While this ritualistic practice ceased over 40 years ago, occasional new cases are indicative of the lengthy incubation periods (Gajdusek and Gibbs, 1971; Collins et al., 2001; Collinge et al., 2006).

Iatrogenic (iCJD)
This was first recognised in 1974 and describes transmission from human to human through the exposure to cadaver-derived growth hormone, pituitary gonadotropins (Brown et al., 2000), dura mater homografting (Brown et al., 2000), corneal grafts (Duffy et al., 1974), blood (Llewelyn et al., 2004; Peden et al., 2004), or inadequately sterilized neurosurgical instruments (Bernoulli et al., 1977). The pattern of illness from iCJD differs according to the route of transmission. In general, peripherally acquired CJD has a long incubation period, a more protracted illness, and is observed in the early stages as a disorder of coordination and imbalance. Centrally transmitted CJD has a shorter incubation period, with a more rapid illness where the early stages are usually associated with problems of memory and cognition (dementia), and the clinical pattern is often similar to that seen in sporadic CJD. All these transmissions have involved cross-contamination with materials in, or adjacent to, the brain (except corneal graft and blood), which has been shown to have the highest concentrations of infectivity (Table 1Go).

Variant CJD (vCJD)
Ten cases of vCJD were identified in 1996 by the CJD Surveillance Unit in individuals with a previously unrecognized but consistent disease pattern, with a median age at death of 29 years and an unusual clinical and pathological phenotype (Will et al., 1996). There is convincing evidence that vCJD is a new disease (Bruce et al., 1997; Hill et al., 1997), and that the PrPSc deposited in the brain in vCJD is similar to experimentally transmitted BSE, as shown by several laboratory transmission studies in primates (Herzog et al., 2004, 2005). Although the evidence is currently weak, the most likely hypothesis is that transmission of BSE to the human population in the UK was through the dietary route, possibly due to high-titer (CNS) bovine tissues (Will, 1999). vCJD is most common in the UK, and although there is an overlap between vCJD and sCJD in the age of death, there is a higher incidence of sCJD in the age group 40–44 years at death, compared with the younger age of death for vCJD (median age of death of 29 yrs) (Will et al., 1996). The clinical course of the variant disease is much longer than that of sCJD, with a median duration of illness in vCJD of 13 months, compared with 4 months in sCJD. To date, vCJD has been confined to a limited number of countries, with 166 definite or probable cases in the UK to the end of November 2007 (CJD Surveillance Unit, 2007b), with France (25 cases), Ireland (5), Italy (1), The Netherlands (2), Portugal (3), and Spain (1) having indigenous cases, plus further cases from Canada, Japan, Ireland, the USA, and Saudi Arabia, where the disease is believed to have been acquired either in the UK or from meat imported from the UK.

Initial early data anticipated that there may be thousands of cases of vCJD in the UK; however, more recent estimates suggest fewer than 500 cases in total (Clarke and Ghani, 2005). This decline in the estimated numbers must be qualified by the observation that the risk factors for vCJD include a young age and homozygosity for methionine at codon-129 of the prion protein gene (PRNP).

More recent animal studies have indicated that all 3 genotypes (PRNP-Val/Val, PRNP-Met/Val, and PRNP-Met/Met) are susceptible to disease (Bishop et al., 2006). A recent study has identified a human female with atypical sporadic CJD and valine homozygous at PRNP codon 129 (Mead et al., 2007), which could represent the first case of clinical disease in this genogroup. This could feasibly change the analysis of risk within the population as a whole, although the single case to date makes interpretation difficult.

A retrospective study in tonsils and appendix detected 3 appendix samples with lymphoreticular accumulation of PrPSc out of 12,674 samples, equating to 237 cases per million population in the UK (± 49–692, 95% confidence limits) (Hilton et al., 2004). The number of positive samples was greater than would be predicted from the numbers of persons diagnosed with vCJD in the UK, and the histology has revealed a different pattern of PrPSc staining in two of the three positive appendix cases. These two specimens have now been shown to be homozygous for valine at codon 129 in the PRNP, and this was the first indication that this valine-homozygous subgroup is susceptible to vCJD infection (Ironside et al., 2006). From animal studies, it seems unlikely that these individuals would go on to develop the disease in the course of their normal lifespan (Bishop et al., 2006), although if the recent case observed in a Val/Val individual proves to be vCJD in origin (Mead et al., 2007), then this may need to be re-evaluated.

Pre- or sub-clinical incubation of the disease may pose a cross-infection risk to individuals with more susceptible PRNP-genotypes, such as PRNP-Met/Met, than PRNP-Met/Val or PRNP-Val/Val genotypes via transplant, transfusion, and surgery. However, in transgenic animals with a human PRNP-Val/Val-129 genotype, there is evidence that the BSE/vCJD agent generates a phenotype resembling sCJD (Wadsworth et al., 2004). The manifestation of future cases of BSE-derived human TSE disease may, therefore, be more difficult to identify, even if presenting clinically.

As previously mentioned, it is likely that the majority of vCJD transmission cases have involved high-titer tissues from the CNS or with neuronal lineage (Will, 1999). However, there have now been four probable cases of vCJD derived from transfusion of whole blood, three of which developed clinical vCJD (Llewelyn et al., 2004; Health Protection Agency, 2006; Wroe et al., 2006). In the remaining case, a person with the PRNP-Met/Val genotype, the individual failed to exhibit symptoms of vCJD and died of other causes 5 yrs post-transfusion; however, PrPSc was detected in the spleen and cervical lymph node, but not in the brain (Peden et al., 2004; Wroe et al., 2006). In such transfusion cases, the assumed low titer of infectivity in the blood product is compensated for by the quantity of blood product transferred from donor to patient. Measures have been implemented since 1980, to protect the blood supply from vCJD contamination, including leucoreduction and restrictions on blood and tissue donations from "at-risk patients" and transfusion recipients (Health Protection Agency, 2006). In the absence of effective prion disinfection, all procedures involving coming into contact with vCJD-infected blood potentially carry a small risk of vCJD transmission. This is in direct contrast to sCJD, where no evidence of transmission by blood transfusion has yet been identified (Hewitt et al., 2006). The extended tissue distribution of vCJD infectivity—to include the retina and optic nerve (Wadsworth et al., 2001), distal ileum and rectum (Joiner et al., 2005)—may mean that other potential routes of infection, e.g., dentistry, also need to be considered (Porter, 2003; Scully et al., 2003).

Animal Model Studies with Tissues of Relevance to Dentistry
Salivary glands have also been shown to harbor infectivity in scrapie-affected goats (Pattison and Millson, 1962), mice (Eklund et al., 1967; Sakaguchi et al., 1993), and sheep (Vascellari et al., 2007). Levels of PrPSc immunoreactivity in the major and minor salivary glands of both naturally and experimentally infected sheep were estimated, by Western blot, to be from 0.02 to 0.005% of that in the brain (Vascellari et al., 2007). Staining of ductal and acinar epithelium, and occasionally the lumen, of the salivary ducts suggests the possible role of saliva in the transmission of natural scrapie (Vascellari et al., 2007). Studies with chronic wasting disease (CWD) have shown that saliva from infected elk can be used to transmit disease by the oral route to other elk, which provides further evidence for saliva having a role in the natural transmission of disease (Mathiason et al., 2006). Alternative models of transmissible mink encephalopathy (TME) in hamsters have shown the submandibular lymph node to be PrPSc-positive, by Western blot and immunohistochemistry (Bartz et al., 2003). One of 3 hamsters challenged intra-nasally had positive submandibular lymph nodes just 4 wks post-inoculation (p.i.), with all 3 animals positive at 6 wks (Kincaid and Bartz, 2007).

The TME model has also been used to investigate infectivity via the oral cavity and has demonstrated that transmission of the TME agent through the tongue is 100,000-fold more efficient than by oral ingestion (Bartz et al., 2003). This intra-tongue (i.t.) model has indicated that TME can replicate in the tongue (1–2 wks p.i.) and submandibular lymph nodes, and that brain invasion is via retrograde axonal transport to the hypoglossal nucleus. Following intracranial (i.c.) inoculation, PrPSc has also been detected in the tongue, demonstrating centrifugal spread of prions from the brain to the tongue in the anterograde direction along the tongue-associated cranial nerves and the mandibular division of the trigeminal ganglion (Bartz et al., 2005). This centrifugal spread of the prion from the brain to the tongue demonstrates that neuro-invasion does not require agent replication in the lymphoreticular systems (LRS) (Bartz et al., 2005). In addition, while the majority of the PrPSc in the tongue has been found in the lamina propria, where it is associated with sensory nerve fibers in the lingual papillae, the PrPSc has also been found to be located in the taste buds and stratified squamous epithelium of the lingual mucosa (Mulcahy et al., 2004; DeJoia et al., 2006). These types of epithelial cells (neuro-epithelial cells at chemosensory mucosal surfaces that undergo normal turnover infected with a prion agent) could therefore potentially shed prions into the mouth and play a role in the horizontal transmission of prion disease (DeJoia et al., 2006), e.g., through innervation or damage to the tongue of an asymptomatic individual. Such studies demonstrating the presence of PrPSc in tongue tissue also suggest that food products containing ruminant or cervid tongue may be potential sources of prion infection for humans (Bartz et al., 2003).

Several studies have demonstrated the distribution of abnormal prion proteins in oral tissues with immunoreactivity to PrPSc in the trigeminal ganglia, salivary gland, and tongue in a variety of animal models, signifying the relevance of prion transmission to procedures in dentistry (Table 3Go). Infectivity has been observed in the trigeminal ganglion during pre-clinical disease in both experimentally and naturally infected animals. Immunoreactivity to PrPSc has been shown in the trigeminal ganglia of cattle orally fed BSE agent (Wells et al., 1998), hamsters infected with scrapie (Groschup et al., 1999), and naturally infected sheep (van Keulen et al., 2000). Following intraperitoneal challenge in Syrian hamsters with the 263K scrapie agent, infectivity was detected in the trigeminal ganglion (titer 8.1 log LD50 i.d. per g), dental pulpal tissue (titer 5.6 log LD50 i.c. units per g of tissue), and gingival tissue (titer 7.2 log LD50 i.c. units per g of tissue) (Ingrosso et al., 1999).


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  		Table 3. Investigation of TSE Infectivity in a Range of Oral Tissues from Human and Animal Studies (updated from Smith et al., 2003)
 
Infectivity of Human Dental Tissues
To date, there have been no proven cases of association of CJD with dentistry, which would indicate that levels of PrPSc in dental tissues through either sCJD, fCJD, or iCJD are likely to be low. However, as discussed above, animal studies have detected PrPSc in a range of oral tissues (Table 3Go), indicating that transmission is feasible (Mulcahy et al., 2004; Bartz et al., 2005). There have been several clusters of cases of CJD where a potential connection through dentistry has been suggested, with one such case involving two patients and their dentist, all of whom died from sCJD (Will and Matthews, 1982). However, as yet, there has been no proven epidemiological evidence that the dental treatment in such cases was the cause of prion transmission, and other causes are also being investigated (Arakawa et al., 1991). While other case-control studies have identified significant association with physical injuries and surgical operations, there has been no proven significant risk associated with a history of major dental treatment or dental extractions (Collins et al., 1999).

Studies of human dental tissues for the presence of PrPSc have resulted in a limited number of positive human oral tissues (Table 3Go). Western blot, paraffin-embedded tissue (PET) blot, and immunohistochemistry (IHC) have been used to examine human vCJD dental tissue, including tonsil, tongue (full thickness, anterior, and posterior regions), submandibular and parotid salivary glands (without lymph nodes), trigeminal ganglia, alveolar nerve (maxillary division) and inferior alveolar nerve, and dental pulp and gingiva from numerous different post mortem cases (Head et al., 2003). While PrPSc was detected in the tonsils in all cases, the majority of the oral tissues were negative, with the exception of the trigeminal ganglia. The sensitivity of the assay used indicated that PrPSc must have been at a level of less than 1% of that found in the brain. Further, in the case of the gingiva and salivary gland, the upper limit of infectivity can be reduced to 1/1000 of the level found in the brain. In follow-up studies, PrPSc was detected in the trigeminal ganglia in variant, sporadic, and iatrogenic CJD, in some instances at higher levels than in any tissue other than the brain (Head et al., 2004; Lee et al., 2005). Since the trigeminal ganglion innervates the oral and nasal cavities and the anterior of the eye, this may raise concerns about the extent of deposition along the cranial nerves. Further research is ongoing to investigate the extent of the deposition of PrPSc in oral tissues, to provide evidence for updating the UK Health Department (DoH) risk assessment for dentistry (Bennett et al., 2007).

A study of dental pulp from sCJD patients did not identify any PrPSc immunoreactivity by enhanced Western blot (Blanquet-Grossard et al., 2000), and there is as yet no evidence of significant levels of PrPSc in oral-related vCJD tissues. However, it must be taken into consideration that no in vitro assay for PrPSc has yet achieved the sensitivity of animal transmission studies in detection of the agent (Sutton et al., 2006), and sensitive bioassay studies are currently under way to investigate human vCJD dental tissue further (HPA, unpublished observations).


   INACTIVATION OF PRION AGENTS
TOP
 ABSTRACT
 INTRODUCTION
 TYPES OF HUMAN TSE...
 INACTIVATION OF PRION AGENTS
CONCLUSIONS
 REFERENCES
 
Routine cleaning and sterilization processes are ineffective at rendering prions non-infectious, since prion agents are heat-resistant and show extraordinarily tight binding to surgical steel (Zobeley et al., 1999). The prion also becomes more resistant to inactivation processes when dried onto such surfaces (Taylor, 1996; Peretz et al., 2006), and has been shown to transmit disease experimentally (Zobeley et al., 1999) and clinically, even after disinfection (Bernoulli et al., 1977). TSE agents are at best only partially inactivated by the sterilization techniques currently available in primary dental care, since they are far more resistant to physical and chemical inactivation than are conventional pathogens (Gill et al., 2001).

There is a recommended hierarchical system for managing human TSE risks from surgical and dental instruments (Table 4Go). Instrument management forms a key component, with dental instruments that come into contact with "high infectivity" tissues from suspected or confirmed CJD patients being classed as single-use, and hence are incinerated immediately after use.


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  		Table 4. Current Recommendations from the CDC (USA), ACDP (UK), and WHO for Disinfection/Sterilization Approaches for Preventing Nosocomial/Iatrogenic Transmission of CJD (Sutton et al., 2006)
 
Endodontic files are used in dental procedures involved in the maintenance of dental pulp and the treatment of the pulp cavity, which includes blood (Wroe et al., 2006) and peripheral nerve tissue known to carry vCJD. Since endodontic files have an intricate surface topography with a high ’surface area to volume’ ratio, their intricate surfaces are able to trap protein, which is tenaciously attached to the surface through subsequent autoclaving cycles (Smith et al., 2005; Walker et al., 2007). A recent communication, entitled "Advice for dentists on re-use of endodontic instruments and variant Creutzfeldt-Jakob Disease (vCJD)", issued by the UK Department of Health, has advised dentists to ensure that endodontic reamers and files are treated as single-use as a precaution, to reduce any potential risk of vCJD transmission (English Department of Health, 2007; Irish Department of Health, 2007; Welsh Department of Health, 2007). In addition, recent studies have identified that there is a high variability of protein residues found on a range of dental instruments that have been cleaned by different methods (manual, manual/ultrasonic, and washer disinfector) (Bennett et al., 2007). Due to the experimental results available (Table 3Go), risk assessments are now indicating that current decontamination technologies used in dental practices should be rigorously enforced (Bennett et al., 2007; Bourvis et al., 2007).

Other than this mandatory guidance—that endodontic files and reamers must be treated as single-use—no other special precautions are necessary over the routine universal precautions adopted for a person undergoing dental treatment. Removal from service and storage in a secure facility are recommended for surgical instruments from suspected CJD individuals or persons with neurological symptoms awaiting diagnosis (Murdoch et al., 2007). Where dental instruments need to be reprocessed, they can be decontaminated according to the WHO guidelines: 20,000 ppm active chlorine is effective, while 1 N NaOH provides a significant reduction in titer, either alone or when instruments are autoclaved under these conditions (WHO, 2000, 2006). Such treatments can be damaging to instruments, potentially hazardous to operators, and clearly are not practical for the routine decontamination of the vast majority of surgical instruments (Sehulster, 2004).

Several alternative solutions to CJD decontamination have been proposed for use in healthcare facilities to supplement existing measures and provide a practical solution (Table 5Go). Currently, however, according to SEAC guidelines (http://www.seac.gov.uk/statements/statement310806.htm), none of the methods offers sufficient safeguards to advocate their use in place of the front-line instrument management systems used to reduce risks associated with known or suspected vCJD cases (WHO, 2000, 2006). While some products independently certified for use by a European Community Notified Body (CE Marked) [e.g., HamoTM 100 Prion Inactivating Detergent – www.steris.com (Fichet et al., 2004, 2007b), Prionzyme-MTM – www.genencor.com (McLeod et al., 2004), Rely-OnTM – wwww.dupont.com (Jackson et al., 2005), neodisher Septoclean www.drweigert.com (Lemmer et al., 2004)] have been shown to reduce the levels of prion infectivity, their use remains at the discretion of individual users, subject to local or national restrictions. The products HamoTM 100, Neodisher SeptocleanTM, and Prionzyme-MTM operate under relatively mild alkaline conditions, while Rely-OnTM operates at neutral pH, which clearly represents an improvement in terms of instrument damage and user/environmental safety over existing recommended conditions. Other agents have also been shown to exert potential prion-decontaminating activities, based on either alkaline cleaning, peracetic acid treatment, or enzymic procedures (Baier et al., 2004; Rosenberg, 2005; Peretz et al., 2006). Further research is required to assess the suitability of these developing techniques for their routine application in general dental practice.


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  		Table 5. Experimental Studies of Decontamination Processes and Their Effectiveness as Demonstrated in in vivo Studies
 

   CONCLUSIONS
TOP
 ABSTRACT
 INTRODUCTION
 TYPES OF HUMAN TSE...
 INACTIVATION OF PRION AGENTS
 CONCLUSIONS
REFERENCES
 
While the risk of cross-infection due to the presence of bacteria, viruses, and fungi on dental instruments can be safely reduced through standard autoclaving procedures, the resistance of prions to thermal inactivation poses a particularly interesting challenge to cross-infection control. Although studies are currently being undertaken to assess the prevalence of vCJD, there is still no sensitive diagnostic assay to assist diagnosis. PrPSc has been detected, by Western blot assays, in only a limited number of dental tissues at relatively low levels, and further work is in progress that will help inform risk assessments for dental surgery in terms of iatrogenic transmission of vCJD. Hence, where infectivity might yet be present in tissues where current diagnostic techniques are unable to detect PrPSc, it may be prudent [as the UK Departments of Health have recently proposed (English Department of Health, 2007; Irish Department of Health, 2007; Welsh Department of Health, 2007)], to reinforce standards of cleaning and decontamination of re-sterilizible surgical instruments.


   ACKNOWLEDGMENTS
 
The authors are currently undertaking research funded by the English Department of Health. The views expressed in the publication are those of the authors and not necessarily those of the Department of Health or any other funding body.

Received for publication October 19, 2007. Revision received January 16, 2008. Accepted for publication February 11, 2008.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 TYPES OF HUMAN TSE...
 INACTIVATION OF PRION AGENTS
 CONCLUSIONS
 REFERENCES
 

  • ACDP/SEAC Guidelines: Advisory Committee on Dangerous Pathogens and the Spongiform Encephalopathy Advisory Committee (2003). Transmissible spongiform encephalopathy agents: safe working and the prevention of infection. http://www.advisorybodies.doh.gov.uk/acdp/tseguidance/ (accessed 3/3/08).
  • Arakawa K, Nagara H, Itoyama Y, Dohura K, Tomokane N, Tateishi J, et al. (1991). Clustering of three cases of Creutzfeldt-Jakob disease near Fukuoka City, Japan. Acta Neurol Scand 84:445–447.[Medline] [Order article via Infotrieve]
  • Baier M, Schwarz A, Mielke M (2004). Activity of an alkaline ’cleaner’ in the inactivation of the scrapie agent. J Hosp Infect 57:80–84.[CrossRef][Medline] [Order article via Infotrieve]
  • Bartz JC, Kincaid AE, Bessen RA (2003). Rapid prion neuroinvasion following tongue infection. J Virol 77:583–591.[CrossRef][Medline] [Order article via Infotrieve]
  • Bartz JC, Aiken JM, Bessen RA (2004). Delay in onset of prion disease for the HY strain of transmissible mink encephalopathy as a result of prior peripheral inoculation with the replication-deficient DY strain. J Gen Virol 85(Pt 1):265–273.[Abstract/Free Full Text]
  • Bartz JC, DeJoia C, Tucker T, Kincaid AE, Bessen RA (2005). Extraneural prion neuroinvasion without lymphoreticular system infection. J Virol 79:11858–11863.[Abstract/Free Full Text]
  • Baxter HC, Campbell GA, Whittaker AG, Jones AC, Aitken A, Simpson AH, et al. (2005). Elimination of transmissible spongiform encephalopathy infectivity and decontamination of surgical instruments by using radio-frequency gas-plasma treatment. J Gen Virol 86(Pt 8):2393–2399.[Abstract/Free Full Text]
  • Bennett P, Grove P, Perera L, McLean I (2007). Potential vCJD transmission risks via dentistry: an interim review. http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_081170 (accessed 3/3/08).
  • Bernoulli C, Siegfried J, Baumgartner G, Regli F, Rabinowicz T, Gajdusek DC, et al. (1977). Danger of accidental person-to-person transmission of Creutzfeldt-Jakob disease by surgery. Lancet 1:478–479.[Medline] [Order article via Infotrieve]
  • Bishop MT, Hart P, Aitchison L, Baybutt HN, Plinston C, Thomson V, et al. (2006). Predicting susceptibility and incubation time of human-to-human transmission of vCJD. Lancet Neurol 5:393–398.[CrossRef][Medline] [Order article via Infotrieve]
  • Blanquet-Grossard F, Sazdovitch V, Jean A, Deslys JP, Dormont D, Hauw JJ, et al. (2000). Prion protein is not detectable in dental pulp from patients with Creutzfeldt-Jakob disease [letter]. J Dent Res 79:700.[Free Full Text]
  • Bourvis N, Boelle PY, Cesbron JY, Valleron AJ (2007). Risk assessment of transmission of sporadic Creutzfeldt-Jakob disease in endodontic practice in absence of adequate prion inactivation. PLoS ONE 2(12):e1330.[Medline] [Order article via Infotrieve]
  • Brown P, Preece M, Brandel JP, Sato T, McShane L, Zerr I, et al. (2000). Iatrogenic Creutzfeldt-Jakob disease at the millennium. Neurology 55:1075–1081.[Abstract/Free Full Text]
  • Brown SL (1997). Atmospheric and potable water exposures to methyl tert-butyl ether (MTBE). Regul Toxicol Pharmacol 25:256–276.[CrossRef][Medline] [Order article via Infotrieve]
  • Bruce ME, Will RG, Ironside JW, McConnell I, Drummond D, Suttie A, et al. (1997). Transmissions to mice indicate that ’new variant’ CJD is caused by the BSE agent. Nature 389:498–501.[CrossRef][Medline] [Order article via Infotrieve]
  • Carp RI (1982). Transmission of scrapie by oral route: effect of gingival scarification. Lancet 1:170–171.[Medline] [Order article via Infotrieve]
  • Casalone C, Corona C, Crescio MI, Martucci F, Mazza M, Ru G, et al. (2005). Pathological prion protein in the tongues of sheep infected with naturally occurring scrapie. J Virol 79:5847–5849.[Abstract/Free Full Text]
  • Centers for Disease Control and Prevention (2007). Centers for Disease Control and Prevention (CDC) Creutzfeldt-Jakob Disease Infection-Control Practices. http://www.cdc.gov/ncidod/dvrd/cjd/qa_cjd_infection_control.htm (accessed 3/3/08).
  • Chesebro B (2003). Introduction to the transmissible spongiform encephalopathies or prion diseases. Br Med Bull 66:1–20.[Abstract/Free Full Text]
  • CJD Surveillance Unit (2007a). CJD statistics (world wide). Edinburgh. http://www.cjd.ed.ac.uk/vcjdworld.htm (accessed 3/3/08).
  • CJD Surveillance Unit (2007b). CJD statistics (UK). Edinburgh. http://www.cjd.ed.ac.uk/figures.htm (accessed 3/3/08).
  • Clarke P, Ghani AC (2005). Projections of the future course of the primary vCJD epidemic in the UK: inclusion of subclinical infection and the possibility of wider genetic susceptibility. J R Soc Interface 2:19–31.[Abstract/Free Full Text]
  • Collinge J, Harding AE, Owen F, Poulter M, Lofthouse R, Boughey AM, et al. (1989). Diagnosis of Gerstmann-Straussler syndrome in familial dementia with prion protein gene analysis. Lancet 2:15–17.[Medline] [Order article via Infotrieve]
  • Collinge J, Owen F, Poulter M, Leach M, Crow TJ, Rossor MN, et al. (1990). Prion dementia without characteristic pathology. Lancet 336:7–9.[CrossRef][Medline] [Order article via Infotrieve]
  • Collinge J, Whitfield J, McKintosh E, Beck J, Mead S, Thomas DJ, et al. (2006). Kuru in the 21st century—an acquired human prion disease with very long incubation periods. Lancet 367:2068–2074.[CrossRef][Medline] [Order article via Infotrieve]
  • Collins S, Law MG, Fletcher A, Boyd A, Kaldor J, Masters CL (1999). Surgical treatment and risk of sporadic Creutzfeldt-Jakob disease: a case-control study. Lancet 353:693–697.[CrossRef][Medline] [Order article via Infotrieve]
  • Collins S, McLean CA, Masters CL (2001). Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, and kuru: a review of these less common human transmissible spongiform encephalopathies. J Clin Neurosci 8:387–397.[CrossRef][Medline] [Order article via Infotrieve]
  • Cousens SN, Zeidler M, Esmonde TF, De Silva R, Wilesmith JW, Smith PG, et al. (1997). Sporadic Creutzfeldt-Jakob disease in the United Kingdom: analysis of epidemiological surveillance data for 1970–96. BMJ 315:389–395.[Abstract/Free Full Text]
  • DeJoia C, Moreaux B, O’Connell K, Bessen RA (2006). Prion infection of oral and nasal mucosa. J Virol 80:4546–4556.[Abstract/Free Full Text]
  • Duffy P, Wolf J, Collins G, DeVoe AG, Streeten B, Cowen D (1974). Possible person-to-person transmission of Creutzfeldt-Jakob disease [letter]. N Engl J Med 290:692–693.[Medline] [Order article via Infotrieve]
  • Eklund CM, Kennedy RC, Hadlow WJ (1967). Pathogenesis of scrapie virus infection in the mouse. J Infect Dis 117:15–22.[Medline] [Order article via Infotrieve]
  • English Department of Health (2007). Advice for dentists on re-use of endodontic instruments and variant Creutzfeldt-Jakob Disease (vCJD). http://www.dh.gov.uk/en/Publicationsandstatistics/Lettersandcirculars/Dearcolleagueletters/DH_074001 (accessed 3/3/08).
  • Fichet G, Comoy E, Duval C, Antloga K, Dehen C, Charbonnier A, et al. (2004). Novel methods for disinfection of prion-contaminated medical devices. Lancet 364:521–526.[CrossRef][Medline] [Order article via Infotrieve]
  • Fichet G, Antloga K, Comoy E, Deslys JP, McDonnell G (2007a). Prion inactivation using a new gaseous hydrogen peroxide sterilisation process. J Hosp Infect 67:278–286.[Medline] [Order article via Infotrieve]
  • Fichet G, Comoy E, Dehen C, Challier L, Antloga K, Deslys JP, et al. (2007b). Investigations of a prion infectivity assay to evaluate methods of decontamination. J Microbiol Methods 70:511–518.[CrossRef][Medline] [Order article via Infotrieve]
  • Gajdusek DC, Gibbs CJ Jr (1971). Transmission of two subacute spongiform encephalopathies of man (Kuru and Creutzfeldt-Jakob disease) to new world monkeys. Nature 230:588–591.[CrossRef][Medline] [Order article via Infotrieve]
  • Gajdusek DC, Gibbs CJ Jr, Asher DM, Brown P, Diwan A, Hoffman P, et al. (1977). Precautions in medical care of, and in handling materials from, patients with transmissible virus dementia (Creutzfeldt-Jakob disease). N Engl J Med 297:1253–1258.[Abstract]
  • Genencor (2006). Genencor International launches revolutionary enzyme technology for prion decontamination. http://www.biospace.com/news_story.aspx?NewsEntityID:13485 (accessed 3/3/08).
  • Gill DS, Tredwin CJ, Gill SK, Ironside JW (2001). The transmissible spongiform encephalopathies (prion diseases): a review for dental surgeons. Internat Dent J 51:439–446.
  • Groschup M, Beekes M, McBride P, Hardt M, Hainfellner J, Budka H (1999). Deposition of disease associated prion protein involves the peripheral nervous system in experimental scrapie. Acta Neuropathol 98:453–457.[CrossRef][Medline] [Order article via Infotrieve]
  • Head MW, Ritchie D, McLoughlin V, Ironside JW (2003). Investigation of PrPres in dental tissues in variant CJD. Br Dent J 195:339–443.[Medline] [Order article via Infotrieve]
  • Head MW, Ritchie D, Smith N, McLoughlin V, Nailon W, Samad S, et al. (2004). Peripheral tissue involvement in sporadic, iatrogenic, and variant Creutzfeldt-Jakob disease: an immunohistochemical, quantitative, and biochemical study. Am J Pathol 164:143–153.[Abstract/Free Full Text]
  • Health Protection Agency (2006). New case of variant CJD associated with blood transfusion. http://www.hpa.org.uk/hpa/news/articles/press_releases/2006/060209_cjd.htm (accessed 3/3/08).
  • Herzog C, Salès N, Etchegaray N, Charbonnier A, Freire S, Dormont D, et al. (2004). Tissue distribution of bovine spongiform encephalopathy agent in primates after intravenous or oral infection. Lancet 363:422–428.[CrossRef][Medline] [Order article via Infotrieve]
  • Herzog C, Riviere J, Lescoutra-Etchegaray N, Charbonnier A, Leblanc V, Sales N, et al. (2005). PrPTSE distribution in a primate model of variant, sporadic, and iatrogenic Creutzfeldt-Jakob disease. J Virol 79:14339–14345.[Abstract/Free Full Text]
  • Hewitt PE, Llewelyn CA, Mackenzie J, Will RG (2006). Creutzfeldt-Jakob disease and blood transfusion: results of the UK Transfusion Medicine Epidemiological Review study. Vox Sang 91:221–230.[CrossRef][Medline] [Order article via Infotrieve]
  • Hill AF, Desbruslais M, Joiner S, Sidle KC, Gowland I, Collinge J, et al. (1997). The same prion strain causes vCJD and BSE. Nature 389:448–450, 526.[CrossRef][Medline] [Order article via Infotrieve]
  • Hill AF, Butterworth RJ, Joiner S, Jackson G, Rossor MN, Thomas DJ, et al. (1999). Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 353:183–189.[CrossRef][Medline] [Order article via Infotrieve]
  • Hilton DA, Ghani AC, Conyers L, Edwards P, McCardle L, Ritchie D, et al. (2004). Prevalence of lymphoreticular prion protein accumulation in UK tissue samples. J Pathol 203:733–739.[CrossRef][Medline] [Order article via Infotrieve]
  • Hornshaw MP, McDermott JR, Candy JM (1995). Copper binding to the N-terminal tandem repeat regions of mammalian and avian prion protein. Biochem Biophys Res Commun 207:621–629.[CrossRef][Medline] [Order article via Infotrieve]
  • Ingrosso L, Pisani F, Pocchiari M (1999). Transmission of the 263K scrapie strain by the dental route. J Gen Virol 80(Pt 11):3043–3047.[Abstract/Free Full Text]
  • Irish Department of Health (2007). Advice for dentists on re-use of endodontic instruments and variant Creutzfeldt-Jakob Disease (vCJD). http://www.dhsspsni.gov.uk/cjd_endo_april_2007.pdf (accessed 3/3/08).
  • Ironside JW, Sutherland K, Bell JE, McCardle L, Barrie C, Estebeiro K, et al. (1996). A new variant of Creutzfeldt-Jakob disease: neuro -pathological and clinical features. Cold Spring Harb Symp Quant Biol 61:523–530.[Abstract/Free Full Text]
  • Ironside JW, Head MW, Bell JE, McCardle L, Will RG (2000). Laboratory diagnosis of variant Creutzfeldt-Jakob disease. Histopathology 37:1–9.[CrossRef][Medline] [Order article via Infotrieve]
  • Ironside JW, McCardle L, Horsburgh A, Lim Z, Head MW (2002). Pathological diagnosis of variant Creutzfeldt-Jakob disease. APMIS 110:79–87.[CrossRef][Medline] [Order article via Infotrieve]
  • Ironside JW, Bishop MT, Connolly K, Hegazy D, Lowrie S, Le Grice M, et al. (2006). Variant Creutzfeldt-Jakob disease: prion protein genotype analysis of positive appendix tissue samples from a retrospective prevalence study. BMJ 332:1186–1188; erratum in BMJ 333:416, 2006.[Abstract/Free Full Text]
  • Jackson GS, McKintosh E, Flechsig E, Prodromidou K, Hirsch P, Linehan J, et al. (2005). An enzyme-detergent method for effective prion decontamination of surgical steel. J Gen Virol 86:869–878.[Abstract/Free Full Text]
  • Joiner S, Linehan JM, Brandner S, Wadsworth JD, Collinge J (2005). High levels of disease related prion protein in the ileum in variant Creutzfeldt-Jakob disease. Gut 54:1506–1508.[Free Full Text]
  • Kincaid AE, Bartz JC (2007). The nasal cavity is a route for prion infection in hamsters. J Virol 81:4482–4491.[Abstract/Free Full Text]
  • Kordek R (2000). The diagnosis of human prion diseases. Folia Neuropathol 38(4):151–160.[Medline] [Order article via Infotrieve]
  • Kuwahara C, Takeuchi AM, Nishimura T, Haraguchi K, Kubosaki A, Matsumoto Y, et al. (1999). Prions prevent neuronal cell-line death. Nature 400:225–226.[CrossRef][Medline] [Order article via Infotrieve]
  • Lantos PL, McGill IS, Janota I, Doey LJ, Collinge J, Bruce MT, et al. (1992). Prion protein immunocytochemistry helps to establish the true incidence of prion diseases. Neurosci Lett 147:67–71.[CrossRef][Medline] [Order article via Infotrieve]
  • Lasmezas CI (2003). Putative functions of PrP(C). Br Med Bull 66:61–70.[Abstract/Free Full Text]
  • Lee CC, Kuo LT, Wang CH, Scaravilli F, An SF (2005). Accumulation of prion protein in the peripheral nervous system in human prion diseases. J Neuropathol Exp Neurol 64:716–721.[Medline] [Order article via Infotrieve]
  • Lemmer K, Mielke M, Pauli G, Beekes M (2004). Decontamination of surgical instruments from prion proteins: in vitro studies on the detachment, destabilization and degradation of PrPSc bound to steel surfaces. J Gen Virol 85(Pt 12):3805–3816.[Abstract/Free Full Text]
  • Llewelyn CA, Hewitt PE, Knight RS, Amar K, Cousens S, Mackenzie J, et al. (2004). Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Lancet 363:417–421.[CrossRef][Medline] [Order article via Infotrieve]
  • Masters CL, Harris JO, Gajdusek DC, Gibbs CJ Jr, Bernoulli C, Asher DM (1979). Creutzfeldt-Jakob disease: patterns of worldwide occurrence and the significance of familial and sporadic clustering. Ann Neurol 5:177–188.[CrossRef][Medline] [Order article via Infotrieve]
  • Mathiason CK, Powers JG, Dahmes SJ, Osborn DA, Miller KV, Warren RJ, et al. (2006). Infectious prions in the saliva and blood of deer with chronic wasting disease. Science 314:133–136.[Abstract/Free Full Text]
  • McLeod AH, Murdoch H, Dickinson J, Dennis MJ, Hall GA, Buswell CM, et al. (2004). Proteolytic inactivation of the bovine spongiform encephalopathy agent. Biochem Biophys Res Commun 317:1165–1170.[CrossRef][Medline] [Order article via Infotrieve]
  • Mead S, Joiner S, Desbruslais M, Beck JA, O’Donoghue M, Lantos P, et al. (2007). Creutzfeldt-Jakob disease, prion protein gene codon 129VV, and a novel PrPSc type in a young British woman. Arch Neurol 64:1780–1784.[Abstract/Free Full Text]
  • Moudjou M, Frobert Y, Grassi J, La Bonnardière C (2001). Cellular prion protein status in sheep: tissue-specific biochemical signatures. J Gen Virol 82(Pt 8):2017–2024.[Abstract/Free Full Text]
  • Mouillet-Richard S, Ermonval M, Chebassier C, Laplanche JL, Lehmann S, Launay JM, et al. (2000). Signal transduction through prion protein. Science 289:1925–1928.[Abstract/Free Full Text]
  • Mulcahy ER, Bartz JC, Kincaid AE, Bessen RA (2004). Prion infection of skeletal muscle cells and papillae in the tongue. J Virol 78:6792–6798.[Abstract/Free Full Text]
  • Murdoch H, Walker J, Sutton J, Raven N (2007). Transmission of vCJD by surgery; perception, risks and research. J Instit Decon Sci 11:36–39.
  • Pattison IH, Millson GC (1962). Distribution of the scrapie agent in the tissues of experimentally inoculated goats. J Comp Pathol 72:233–244.[Medline] [Order article via Infotrieve]
  • Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW (2004). Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 364:527–529.[CrossRef][Medline] [Order article via Infotrieve]
  • Peretz D, Supattapone S, Giles K, Vergara J, Freyman Y, Lessard P, et al. (2006). Inactivation of prions by acidic sodium dodecyl sulfate. J Virol 80:322–331.[Abstract/Free Full Text]
  • Porter SR (2003). Prion disease: possible implications for oral health care. J Am Dent Assoc 134:1486–1491.[Abstract/Free Full Text]
  • Rosenberg U (2005). Effective cleaning processes and efficacy against prions. Zentr Steril 13:258–270.
  • Sakaguchi S, Katamine S, Yamanouchi K, Kishikawa M, Moriuchi R, Yasukawa N, et al. (1993). Kinetics of infectivity are dissociated from PrP accumulation in salivary glands of Creutzfeldt-Jakob disease agent-inoculated mice. J Gen Virol 74(Pt 10):2117–2123.[Abstract/Free Full Text]
  • Scully C, Smith AJ, Bagg J (2003). Prions and the human transmissible spongiform encephalopathies. Dent Clin North Am 47:493–516.[Medline] [Order article via Infotrieve]
  • Sehulster LM (2004). Prion inactivation and medical instrument reprocessing: challenges facing healthcare facilities. Infect Control Hosp Epidemiol 25:276–279.[CrossRef][Medline] [Order article via Infotrieve]
  • Smith A, Letters S, Lange A, Perrett D, McHugh S, Bagg J (2005). Residual protein levels on reprocessed dental instruments. J Hosp Infect 61:237–241.[CrossRef][Medline] [Order article via Infotrieve]
  • Smith AJ, Bagg J, Ironside JW, Will RG, Scully C (2003). Prions and the oral cavity. J Dent Res 82:769–775.[Abstract/Free Full Text]
  • Sutton JM, Dickinson J, Walker JT, Raven ND (2006). Methods to minimize the risks of Creutzfeldt-Jakob disease transmission by surgical procedures: where to set the standard? Clin Infect Dis 43:757–764.[Medline] [Order article via Infotrieve]
  • Taylor D (1996). Exposure to, and inactivation of the unconventional agents that cause transmissible degenerative encephalopathies. In: Prion diseases. Baker H, Ridley R, editors. Totowa, NJ: Humana Press, pp. 105–118.
  • Thomzig A, Kratzel C, Lenz G, Kruger D, Beekes M (2003). Widespread PrPsc accumulation in muscles of hamsters orally infected with scrapie. EMBO Rep 4:530–533.[CrossRef][Medline] [Order article via Infotrieve]
  • van Keulen LJ, Schreuder BE, Vromans ME, Langeveld JP, Smits MA (2000). Pathogenesis of natural scrapie in sheep. Arch Virol Suppl 16:57–71.[Medline] [Order article via Infotrieve]
  • Vascellari M, Nonno R, Mutinelli F, Bigolaro M, Di Bari MA, Melchiotti E, et al. (2007). PrPSc in salivary glands of scrapie-affected sheep. J Virol 81:4872–4876.[Abstract/Free Full Text]
  • Wadsworth JD, Joiner S, Hill AF, Campbell TA, Desbruslais M, Luthert PJ, et al. (2001). Tissue distribution of protease resistant prion protein in variant Creutzfeldt-Jakob disease using a highly sensitive immunoblotting assay. Lancet 358:171–180.[CrossRef][Medline] [Order article via Infotrieve]
  • Wadsworth JD, Asante EA, Desbruslais M, Linehan JM, Joiner S, Gowland I, et al. (2004). Human prion protein with valine 129 prevents expression of variant CJD phenotype. Science 306:1793–1796.[Abstract/Free Full Text]
  • Walker JT, Dickinson J, Sutton JM, Raven ND, Marsh PD (2007). Cleanability of dental instruments—implications of residual protein and risks from Creutzfeldt-Jakob disease. Br Dent J 203:395–401.[Medline] [Order article via Infotrieve]
  • Wells GA, Hawkins S, Green RB, Austin AR, Dexter I, Spencer YJ, et al. (1998). Preliminary observations on the pathogenesis of experimental bovine spongiform encephalopathy (BSE): an update. Vet Rec 142:103–106.[Abstract/Free Full Text]
  • Welsh Department of Health (2007). Advice for dentists on re-use of endodontic instruments and variant Creutzfeldt-Jakob Disease (vCJD). http://wales.gov.uk/topics/health/professionals/dental/guidance/cdo-letters/cjd?lang=en (accessed 3/3/08). Welsh Assembly Government.
  • WHO (2000). WHO infection control guidelines for transmissible spongiform encephalopathies. http://whqlibdoc.who.int/hq/2000/WHO_CDS_CSR_APH_2000.3.pdf (accessed 3/3/08).
  • WHO (2006). WHO guidelines on tissue infectivity distribution in TSEs. http://www.who.int/bloodproducts/cs/TSEPUBLISHEDREPORT.pdf (accessed 3/3/08). Geneva: WHO.
  • Wilesmith JW, Wells GA, Cranwell MP, Ryan JB (1988). Bovine spongiform encephalopathy: epidemiological studies. Vet Rec 123:638–644.[Abstract]
  • Will RG (1999). The transmission of prions to humans. Acta Paediatr Suppl 433:28–32.[CrossRef]
  • Will RG (2003). Acquired prion disease: iatrogenic CJD, variant CJD, kuru. Br Med Bull 66:255–265.[Abstract/Free Full Text]
  • Will RG, Matthews W (1982). Evidence for case-to-case transmission of Creutzfeldt-Jakob disease. J Neurol Neurosci Psychiatry 45:235–238.
  • Will RG, Ironside JW, Zeidler M, Cousens SN, Estibeiro K, Alperovitch A, et al. (1996). A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 347:921–925.[CrossRef][Medline] [Order article via Infotrieve]
  • Williams ES, Young S (1980). Chronic wasting disease of captive mule deer: a spongiform encephalopathy. J Wildl Dis 16:89–98.[Abstract]
  • Wroe SJ, Pal S, Siddique D, Hyare H, Macfarlane R, Joiner S, et al. (2006). Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt-Jakob disease associated with blood transfusion: a case report. Lancet 368:2061–2067.[CrossRef][Medline] [Order article via Infotrieve]
  • Yan ZX, Stitz L, Heeg P, Pfaff E, Roth K (2004). Infectivity of prion protein bound to stainless steel wires: a model for testing decontamination procedures for transmissible spongiform encephalopathies. Infect Control Hosp Epidemiol 25:280–283.[CrossRef][Medline] [Order article via Infotrieve]
  • Zobeley E, Flechsig E, Cozzio A, Enari M, Weissmann C (1999). Infectivity of scrapie prions bound to a stainless steel surface. Mol Med 5:240–243.[Medline] [Order article via Infotrieve]

Journal of Dental Research, Vol. 87, No. 6, 511-519 (2008)
DOI: 10.1177/154405910808700613
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