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Summaries abstract -------------------------------------------------------------------------------- British Dental Journal 202, 470 - 471 (2007) Dental treatment and risk of vCJD Abstract 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 There was no 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. Top of page Professor of Oral Medicine, UCL Eastman Dental Institute http://www.nature.com/bdj/journal/v202/n8/abs/bdj.2007.356.html RESEARCH SUMMARY 470 BRITISH DENTAL JOURNAL VOLUME 202 NO. 8 APR 28 2007 ABSTRACT 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 There was no statistically signifi cant 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. EDITOR'S SUMMARY Variant Creutzfeldt-Jakob disease (vCJD) has caused considerable public concern due to its link with BSE-contaminated beef products and evidence that it can be transmitted by blood transfusions. The fact that the prion protein responsible for vCJD can be found and transmitted in blood raises the question of cross infection during routine healthcare procedures such as dental treatment. Previous studies have not shown dental treatment to be a risk factor for the sporadic form of CJD. This paper by Everington et al. is the first study to date to look at whether dental treatment is a risk factor for variant CJD. The paper’s findings are encouraging: the analysis of interviews with the relatives of 130 vCJD patients and 66 community and 53 hospital controls showed no significant increase in risk of vCJD associated with dental treatment. The authors acknowledge that the study is limited by its reliance on reported data from relatives and by the number of vCJD cases to date, and more detailed research is being investigated. However, it is important to note that the study assumes that infection control procedures are in place, fully complied with and not significantly less effective than they are expected to be. The authors state that the results do not preclude the possibility that some cases of vCJD have arisen because of secondary transmission through dental treatment. If anything, this work emphasises the need for infection control procedures in dentistry to be carefully considered and strictly adhered to. While more detailed studies are required in order to confirm that dental treatment is not a risk factor for vCJD, this work is an important first step and goes some way towards reassuring patients and practitioners that as long as infection control measures are in place and fully complied with, the risk of a patient contracting vCJD as a result of dental treatment is extremely small. The full paper can be accessed from the BDJ website (www.bdj.co.uk), under ‘Research’ in the table of contents for Volume 202 issue 8. Rowena Milan, Journal Editor DOI: 10.1038/bdj.2007.356 Dental treatment and risk of vCJD 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 VERIFIABLE CPD PAPER ONLINE • This manuscript is the fi rst attempt to investigate potential links between dental treatment and the development of vCJD using case control methodology. • The results highlight diffi culties in collecting retrospective data from relatives of CJD cases regarding dental treatment history. • Access to case and control dental records in the future may provide more useful information. I N B R I E F © 2007 Nature Publishing Group BRITISH DENTAL JOURNAL VOLUME 202 NO. 8 APR 28 2007 471 AUTHOR QUESTIONS AND ANSWERS 1. Why did you undertake this research? The research was undertaken to determine if there was a link between previous dental treatment and development of vCJD. It has been postulated that although dental treatment involves contact with tissues that have low levels of infectious prion proteins, the large numbers of dental interventions may represent a risk factor at population levels either through cross contamination and/or trauma to the oral cavity resulting in an increased susceptibility by an as yet undetermined aetiology. It is important to exclude dental treatment as a risk factor for development of vCJD. 2. What would you like to do next in this area to follow on from this work? In order to obtain more robust data (as opposed to data obtained from interview of relatives) we wish to review the dental records of CJD cases and controls. This exercise is currently underway as a pilot study to assess the logistics of recovering dental records from a small cohort of CJD patients and appropriate control. RESEARCH SUMMARY COMMENT Four types of human prion disease are presently recognised, of which sporadic Creutzfeldt-Jakob disease (CJD) is probably the most common. Variant CJD (vCJD) has attracted particular attention in view of its arising principally in young adults, variable clinical features, geographic clustering of affected individuals (eg in the UK), wide distribution of prion protein outside the neural system and probable transmission via blood transfusions.1,2 Published data suggest that dentistry is a very unlikely route of transmission of prion disease and this case control study indicates that there is unlikely to be an association between previous dental health care and potential acquisition of prions causing vCJD. Although prions have been detected in oral tissue of appropriate experimental animals and/or individuals with vCJD, there is no evidence that prions can be spread as a consequence of exposure3 to oral fluids, nor via social or sexual contact. Hence despite the self acknowledged limitations of their study, the findings of Everington and coworkers are perhaps unsurprising and potentially reassuring to both patients and oral health care staff. While it is not known if a further wave of vCJD infections will emerge, the present epidemiological data do not support the notion that prion transmission is likely to occur during dental care. For now, the risks of prion transmission during dental care should be considered to be extremely low – as detailed in the Department of Health’s risk assessment4 – provided of course that currently advised infection control measures are adhered to. S. R. Porter, Professor of Oral Medicine, UCL Eastman Dental Institute 1. Collinge J. Molecular neurology of prion disease. J Neurol Neurosurg Psychiatry 2005; 76: 906-919. 2. Health Protection Agency. Variant CJD and blood products. http://www.hpa.org.uk/infections/topics_az/cjd/blood_products.htm (accessed 28th January 2007). 3. Carp R I. Transmission of scrapie via oral route: effect of gingival scarifi cation. Lancet 1982; 1: 170-171. 4. Department of Health. Risk assessment for vCJD and dentistry. www.dh.gov.uk/assetRoot/04/07/83/02/04078302.pdf (accessed 16 January 2007). http://www.nature.com/bdj/journal/v202/n8/pdf/bdj.2007.356.pdf please note, sporadic CJD i.e. iCJD, has been documented to transmit from different routes and sources in the medical and surgical arena; 6. CJD IN FARMERS The second annual report on CJD surveillance in the UK, which is about to be published, gives occupational history details of 29 definite and probable CJD cases recorded in people who had a history of employment at any time in particular occupational groups of potential significance for the occurrence of the disease. The 29 cases were amongst 95 diagnosed over a 3 year period: the other 66 cases did not fall into such occupational groups. MEDICAL/PARAMEDICAL/DENTISTRY 7 ANIMAL LABORATORY 1 PHARMACEUTICAL LABORATORY 0 RESEARCH LABORATORY 0 FARMERS/VETERINARY SURGEONS 7 BUTCHERS/ABATTOIR WORKERS/OCCUPATION OCCUPATION INVOLVING ANIMAL PRODUCTS 9 http://www.bseinquiry.gov.uk/files/yb/1993/07/19001001.pdf PLEASE SEE DENTAL RISK FROM HUMAN AND ANIMAL TSE Subject: MASTER DENTIST FALLS VICTIM TO CJD Iatrogenic CJD infection is inadvertently transmitted usually from a case with sCJD in the course of medical/surgical treatment, e.g. human pituitary hormone therapy, human dura mater grafts, corneal grafts or neurological instruments. Specific precautions should be taken in the management of persons with confirmed or suspected transmissible spongiform encephalopathy (TSEs) and their tissues. http://www.eurosurveillance.org/ew/2001/010705.asp Iatrogenic cases (about 260 cases world wide) result from the accidental transmission of the causative agent by contaminated surgical equipment or as a result of cornea or dura mater transplants or the administration of human-derived pituitary growth hormones. The incubation period between the exposure and onset of illness in iatrogenic cases varies from 15 months to 30 years. Eva Mitrová1 and Girma Belay1 (1) Institute of Preventive and Clinical Medicine, Limbová 14, 833 01 Bratislava, Slovakia http://www.springerlink.com/content/v2361482271k2371/ Creutzfeldt-Jakob Disease (CJD) Policy the management of patients with definite, probable and possible CJD or variant CJD Author: Johanna Hill Department: Infection Control Date of issue: June 2006 Date of review: June 2008 Policy number: ICC 18 http://www.westminster-pct.nhs.uk/pdfs/ICC18WCJD.pdf PRIONS AND THE ORAL CAVITY snip... Case Reports There have been two reports of clusters of CJD cases with a possible connection through dentistry, but there is no strong epidemiological evidence to link the dental treatment in these cases with transmission of prions (Will and Matthews, 1982; Arakawa et al., 1991). Case Control Studies in sCJD Many series and case control studies have searched for risk factors such as diet, exposure to animals, surgical treatment including dentistry, and occupational exposures. A retrospective case-controlled study (Kondo and Kuroiwa, 1982) of 60 definite cases of sporadic CJD, occurring in Japan between 1975 and 1977, found no association with dental extractions. However, the authors did report a significant association with physical injuries, including surgical operations, but not including dental treatment, blood transfusions, or lumbar punctures. More recently, an Australian study has reported that surgical procedures were significantly associated with the development of sCJD, although they found no significant risk associated with a history of major dental treatment (Collins et al., 1999). An analysis of 26 CJD cases and 40 matched controls from the United States (Davanipour et al., 1985) failed to discover a significant odds ratio for endodontic surgery, though these workers did note statistically significant odds ratios for intra-ocular pressure testing, injury to or surgery on the head, face, or neck, and trauma to other parts of the body. Infectivity in Human Trigeminal Nerve and Oral Tissues PrPsc has been detected by polyclonal antibodies to scrapieassociated fibril/prion protein in the trigeminal ganglion of one patient with fCJD and one patient with sCJD (Table 3) (Guiroy et al., 1989). These workers also noted the presence of specific immunostaining of dystrophic axons in the nerve roots and around the degenerating ganglion cells of the trigeminal ganglion, suggesting centripetal or centrifugal extension of the disease process along the axons. Positive immunochemistry for PrP has been reported for the trigeminal ganglion in vCJD (Ironside et al., 2002) but was not detected in cranial nerves or salivary gland tissue. One study has investigated the levels of prion protein in pulpal tissue from eight patients with sCJD (Blanquet-Grossard et al., 2000). By Western blotting, using a specific monoclonal antibody, this group was unable to detect any prion protein in pulpal tissue. However, the authors suggested that since the method used was relatively insensitive, the potential for transmission of CJD via dental procedures, although low, could not be dismissed. These workers calculated that 1 g of sCJDinfected pulp would be expected to contain 40 log10 LD50/g of infectivity, compared with 108-9 LD50/g of infectivity in brain tissue. Implications for Dental Treatment There are few experimental data on which to base risk assessments for potential transmission of CJD via dental procedures. Animal models provide useful data, but, by virtue of differing genetic susceptibilities and the varied properties of the different strains of prions used, this information cannot be directly extrapolated to the clinical setting. However, there is a general consensus that all instruments, including dental handpieces, used for treatment 774 Smith et al. J Dent Res 82(10) 2003 on known or suspected cases of CJD of any type should not be re-used on other patients (WHO, 2000), but rather should be incinerated. The situation is less clear-cut for treatment of healthy patients deemed to be "at risk" of developing CJD. These include recipients of contaminated dura mater grafts or relatives of patients with fCJD, for which there is significant variation between different sets of official recommendations, from stringent decontamination protocols for instruments, including extended periods of autoclaving in a vacuum autoclave (ACDP/SEAC, 1998), to no special precautions at all (WHO, 2000). There is no evidence that TSEs can be transmitted by aerosol routes or contaminated surfaces; therefore, the only components of infection control procedures that merit special consideration are those relating to re-usable instruments. Routine surgery protocols for surgery surface and environmental cleaning, which are used to limit transmission of blood-borne viruses, are sufficient for treatment of known, suspected, or "at-risk" cases. At the time of writing, there is no evidence in humans to suggest that oral tissues carry high levels of PrPsc (see note below). Since it is not possible to identify patients who may be asymptomatic carriers of PrPsc, particularly vCJD, the most important recommendation is to ensure that the quality of pre-sterilization cleaning of instruments used on all patients is of the highest standard, and that instruments which cannot be reliably cleaned are treated as single-use. CONCLUSION The last five years have seen the emergence of a new human TSE termed "variant CJD", which results from exposure to the BSE agent. This has been accompanied by a wealth of scientific data on the responsible infectious agents called prions. However, data concerning the distribution of PrPsc and infectivity in the oral cavity are sparse. The available animal model evidence illustrates a potential for transmission via the dental route, but differences in patterns of disease and in strains of the agent make it difficult to extrapolate these findings directly to humans. Data concerning the distribution of PrPsc and infectivity in the human oral cavity are urgently required to determine the risk, if any, of cross-infection during common dental procedures. http://jdr.iadrjournals.org/cgi/reprint/82/10/769.pdf TOPICAL DENTAL PRODUCTS WOULD ALSO BE OF CONCERN, since there was a suggestion that kuru had been transmitted through the gums and/or gum abrasions. http://www.bseinquiry.gov.uk/files/yb/1989/04/17005001.pdf http://www.bseinquiry.gov.uk/files/yb/1989/03/21015001.pdf NOT FOR PUBLICATION COMMITTE ON DENTAL AND SURGICAL MATERIALS http://www.bseinquiry.gov.uk/files/yb/1991/11/20006001.pdf NOT FOR PUBLICATION (and they meant it...tss) COMMITTEE ON DENTAL AND SURGICAL MATERIALS http://www.bseinquiry.gov.uk/files/yb/1988/11/16006001.pdf http://www.bseinquiry.gov.uk/files/yb/1993/11/01005001.pdf 18 January 2007 - Draft minutes of the SEAC 95 meeting (426 KB) held on 7 64. A member noted that at the recent Neuroprion meeting, a study was Other work presented suggested that BSE and bovine amyloidotic spongiform http://www.seac.gov.uk/minutes/95.pdf Models Qingzhong Kong, Ph.D., Assistant Professor, Pathology, Case Western Reserve Bovine Amyloid Spongiform Encephalopathy (BASE) is an atypical BSE strain ***These results indicate that BASE is transmissible to humans and suggest that BASE is more virulent than There is a growing number of human CJD cases, and they were presented last He estimates that it may be up to 14 or 15 persons which display selectively Singeltary, Sr et al. JAMA.2001; 285: 733-734. http://jama.ama-assn.org/http://www.neurology.org/cgi/eletters/60/2/176#535 MARCH 26, 2003 RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States Email Terry S. Singeltary: flounder@wt.net I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc? http://www.neurology.org/cgi/eletters/60/2/176#535
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