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Health protection experts have said they are investigating whether the human form of mad cow disease can be passed on through dental procedures. Government scientists will use mice to discover whether they can catch variant Creutzfeldt-Jakob disease (vCJD) from contaminated dental instruments. They will also see whether mice who have been purposely infected with BSE - as if they had eaten contaminated meat - show signs of the disease in the tissue in their mouths. The three-year experiment, which has just started, was outlined at the Health Protection Agency's (HPA) annual conference at the University of Warwick today. The aim is to give the Department of Health more guidance on the risks posed by vCJD in dentistry and to determine whether stricter advice on the best cleaning methods needs to be issued. At the moment experts believe the risk is very small, but want to carry out controlled tests to confirm this. Millions of people in the UK were potentially exposed to BSE from contaminated beef in the 1980s. Since then it has also emerged that donated blood and tissue may also cause vCJD to spread. It is believed that at least two people have been infected after having a blood transfusion in the UK. The Government has since taken measures to protect the blood supply by banning donations from certain groups, including those who have had blood transfusions since 1980. There have also been concerns about whether the prions that carry vCJD can be spread by surgical instruments, especially when used during brain surgery. Joanne Dickinson, who is one of those carrying out the research, said: "This is really an information gathering exercise. "The Department of Health will have the information to decide what the level of risk is and what measures need to be put in place." An estimated 75 million dental procedures are conducted in the UK each year and that two million of these are invasive root canal treatments. The study will involved around 30 dental practices in the South West of England. http://www.telegraph.co.uk/news/main.jhtml?xml=/news/2005/09/12/umadcow.xml&sSheet=/portal/2005/09/12/ixportaltop.html Variant CJD - dying down or lying low? The number of deaths due to variant Creutzfeldt-Jakob Disease (vCJD) is currently in decline. Has the UK population had a lucky escape from the human form of BSE, and can preventative measures be relaxed now? A precautionary approach combined with better disease detection and effective decontamination is still vital, says Neil Raven. Estimates of the scale of the vCJD epidemic have oscillated hugely since the first case was identified by the Edinburgh-based National CJD Surveillance Unit in 1996. Fortunately the most extreme scenarios, in which the human epidemic mirrored the BSE epidemic itself, have not been realised. There is still significant uncertainty, however, about the eventual toll of human disease directly due to dietary BSE exposure. There has been a marked decline in the number of vCJD deaths in the past two years, suggesting a final running total of perhaps no more than 200 cases if this trend continues. However, screening of extracted tonsil and appendix tissue from the general population has revealed a potentially radically different situation. Here the detection of abnormal prion protein in approximately 1 in 4000 samples indicates the possibility of an as yet silent future vCJD epidemic based on a broad estimate centred on 3,800 potential cases. A lively debate continues as to whether these represent sub-clinical or pre-clinical individuals, and if they will ever go on to develop vCJD, or a pathologically similar disease, and no one currently knows the answer. Health protection measures must, therefore, continue to follow an active precautionary path and will evolve as new information emerges. Transmission by transfusion The wisdom of this precautionary approach has been demonstrated by two recent likely instances of vCJD transmission via blood transfusion. Both cases were known recipients of blood from individuals who subsequently went on to develop vCJD. One developed vCJD while the second died of other causes but showed evidence of the presence of abnormal prion protein at autopsy. This second case was especially significant since the individual had a different prion genotype from all of the previously recorded cases of vCJD, suggesting that susceptibility to vCJD infection is not confined to the one-third of the UK population that has the Met/Met codon 129 genotype. Statistically the chances of both these cases being of primary origin, i.e. from dietary BSE exposure, appear remote. The presumption must therefore now be that vCJD is transmissible via blood transfusion. Fortunately back in 1998, less than three years after the disease was first identified, a wide range of precautionary blood protective measures were introduced just in case of such an eventuality. These will undoubtedly already have prevented some additional exposures to vCJD infectivity from occurring and they continue to be updated regularly and revised on the basis of new knowledge. At the time, questions were raised as to whether such measures were really necessary, however they appear to have been very prudent. Health protection focus The risk of contracting vCJD by eating BSE infectious meat now looks to be minimal. The highest health protection priority must therefore be the prevention of any potential second wave of disease associated with person-to-person transmission. Although the number of known vCJD cases is very small, we also know that CJD can lie hidden, possibly for decades, from any current means we have of detecting it. There may be a significant number of individuals in the population unknowingly and silently incubating vCJD, and their presence cannot Page 8 The risk of contracting vCJD by eating BSE infectious meat now looks to be minimal. be ignored. Even if they do not go on to develop the disease themselves, they may be effective carriers able to transmit the disease to susceptible individuals under certain circumstances. Fortunately vCJD, like CJD, cannot be casually acquired. All evidence to date indicates that there must be appreciable transdermal exposure of an individual to infectious tissue from an infected individual. So, how could this occur? Blood transfusion and blood products clearly represent one potential source; surgery in all its forms and particularly neurosurgery another. Dentistry is frequently overlooked as being less invasive, but this is counterbalanced by the sheer number of dental procedures that take place. Add to this the possibility that some individuals in the general population may be particularly susceptible to the disease, then the risk must be given considerable weight. Blood transfusion In blood transfusion, exposure of one individual to a tissue from another is unavoidable. The need for blood transfusion is also frequently in response to an emergency situation, and the risk of acquiring vCJD is then greatly outweighed by the immediate and known risk to the recipient of not receiving a transfusion. This has to be borne in mind when considering methods for detecting or eliminating vCJD infectivity in blood. If these are too wasteful, too complex or overwhelmingly expensive then they will not be viable. Assuming vCJD is lying low in the population, however, there is still scope to improve our levels of health protection. If CJD infectivity in blood can be clearly and unequivocally detected, or if all blood can be treated in such a way as to remove any infectivity present, then this route of transmission can be effectively blocked. Leucodepletion has already been introduced as a physical measure that may significantly reduce the level of vCJD infectivity, and other methods of this nature are being developed. Rapid and reliable detection of vCJD infectivity in blood donations, so as to eliminate their use, appears however to be a much more difficult proposition. A number of post-mortem diagnostic tests for BSE in cattle are now available, but none of these has the characteristics required to detect vCJD in human blood. Crude estimates suggest that there may well be no more than one or two vCJD infectious units in a millilitre of blood, though precisely what constitutes an infectious unit of vCJD is not at present known. Our best current measure of it is to seek to detect the abnormal form of the prion protein. This molecule is intimately associated with both the development of the disease and the presence of infectivity, and its detection in a blood sample would be sufficient indication of the potential for disease transmission for a blood donation not to be used. Detection methods that rely on concentrating the abnormal prion molecule from a large initial sample volume are unsuitable for blood screening because too much of the blood collected needs to be diverted to the testing procedure itself. The only feasible alternatives, therefore, appear to be amplifying production of the abnormal prion molecule in some way so that there is more to detect, or increasing the sensitivity of the detection assay. The former approach is being pursued by the development of a "Conformation Dependent Immunoassay" in Prusiner's laboratory in San Francisco. It remains to be seen, however, whether signal amplification of this kind will produce few enough false positives to be usable. Research within the Health Protection Agency has concentrated on increasing the inherent sensitivity of prion detection itself. We have developed an extremely sensitive enzyme-linked immunoassay (ELISA) capable of detecting signal molecules at the low concentrations necessary. This novel ELISA uses a temperature stable adenylate kinase enzyme to generate ATP, which can in turn be detected extremely sensitively by bioluminescence. The key to developing this as a viable method for screening blood is to couple the enzyme to the best antibodies to the abnormal prion protein available, and to ensure that the complex environment that blood constitutes does not interfere with the assay. A principle obstacle to the development of any detection method, however, remains the availability of propriate positive test materials from preclinical or even clinical cases of vCJD. Surgery and dentistry With the rare exceptions of blood transfusion and organ transplantation, there is no requirement in either surgery or dentistry for potentially infectious material to be transferred from one patient to another. The solution here is to prevent secondary transmission of vCJD by achieving prion decontamination as we long have for other infectious agents. Decontamination Current research at the Agency has developed an enzymatic process compatible with surgical and dental instruments that is able to give the levels of prion inactivation needed to ensure that this potential route for vCJD transmission can be effectively blocked. We have chosen to collaborate with a major industrial enzyme manufacturer, Genencor International, to guarantee that the enzyme developed can be mass produced in the quantities required. This scale-up has now been achieved and a new specifically engineered protease, tentatively called "Prionzyme", will be available for field testing later in the year. Meanwhile, with our health protection remit firmly in mind, we are concentrating on ensuring that whatever methods are put forward for instrument decontamination, they will deliver the levels of inactivation necessary - all this, just in case vCJD is still lying low rather than dying down. The visible incidence of vCJD has now fallen to a point at which an optimistic assessment would be that the epidemic in humans is subsiding. It is the nature of health protection, however, that the worst as well as the best scenarios should be guarded against. The Agency will continue to develop the precautionary approaches described above and, as necessary, seek new ones. Neil Raven is General Project Manager of Technology Development & Biological Investigations at HPA Porton Down, Wiltshire. Page 9 The magazine of the Health Protection Agency Issue Two Summer 2005 Dentistry - keeping infections at bay. Photo HPA snip... Mad Cow Disease Transmissible spongiform encephalopathies (TSEs) are an unusual group of neurological disorders affecting man and animals. Examples are kuru of man, bovine pongiform encephalopathy (BSE) of cattle, scrapie (sheep), chronic wasting disease (mule deer), transmissible mink encephalopathy and Creutzfeld-Jacob Disease (CJD) of man. They are all associated with the presence of an abnormal protein in the central nervous system. This is a protease-resistant form (PrPres) of a normal cellular protein (PrPc) which is devoid of nucleic acid. BSE was first diagnosed in a cow in England in 1986 and, by October 2001, over 179,000 cows had developed the disease. At the same time, over 100 people had developed Lord Soulsby of Swaffham Prior qualified as a Veterinary Surgeon from the University of Edinburgh. After general practice he completed a PhD in 1952 and entered an academic career in the Universities of Bristol, Cambridge and Pennsylvania, USA. He was ennobled in 1990. He has been or is President of the Royal College of Veterinary Surgeons, The Royal Society of Medicine, the Royal Institute of Public Health, and the Parliamentary and Scientific Committee a new disease designated variant Creutzfeld- Jacob Disease (vCJD). BSE was traced to the use of animal meat carcase waste in the food chain. This followed a change in the rendering process allowing recycling of material from BSE affected cattle. The origin of the BSE agent, whether from scrapieinfected sheep or a spontaneous mutation in cattle, is open to debate. The transmission of the BSE agent to man is something of an enigma. The rapidly progressive disease, vCJD, has predominantly occurred in the UK where the majority of BSE cases have occurred, and about 150 cases of vCJD have now been reported. It is assumed that the infective agent (whatever exactly that is) entered the human food chain from infected animals. Affected persons are frequently in their twenties in contrast to classical CJD which affects much older patients. Despite the absence of direct evidence for transmission from cattle to man, the food chain remains the most likely route of infection leading to vCJD. The control policy is to eradicate BSE from the UK. It is illegal to feed ruminant derived protein to food producing animals, and to avoid human exposure to BSE brain, spinal cord and other specified materials are excluded from the human food chain. It should be noted that vCJD occurs in other countries but the number of cases is very low, as has been the number of cases of BSE in cattle. Whether other TSEs such as scrapie can cause disease in man remains to be seen, but it seems unlikely on present evidence. snip...end http://www.hpa.org.uk/hpa/publications/HPM/summer_2005.pdf Programme at a glance Sunday 11 September 2005 http://hpaconference.org.uk/glance.asp Research Project: Transmission, Differentiation, and Pathobiology of Transmissible Spongiform Encephalopathies Title: Prion Infection of Mucosal Tissue Bessen, Richard - MONTANA STATE UNIVERSITY Technical Abstract: To investigate the site(s) of prion agent shedding in chronic wasting disease (CWD), we examined the distribution of the prion agent in mucosal tissue from ruminants and rodents with experimental prion disease. We chose the tongue as a peripheral target of prion infection since is a densely innervated tissue at the oral mucosa that we postulate can be a site of CWD agent shedding. The prion agent, PrP**Sc, was present in tongues from elk infected with the CWD agent and sheep infected with the scrapie agent. In hamsters infected with the prion agent, PrP**Sc was found in nerve fibers and skeletal muscle cells as well as in taste cells. In fungiform papillae on the tongue, the distribution of PrP**Sc was consistent with deposition in the taste bud and the surrounding stratified squamous epithelium. These findings suggest that the prion agent can spread from the brain to the tongue along sensory and motor fibers. The presence of the prion agent in the tongue of ruminants and rodents indicates that 1) ingestion of tongue or tongue derived food products can pose a risk to human and animal health, and 2) the localization of the prion agent at the mucosal surface of the tongue could provide a site for prion agent shedding and subsequent transmission to naive hosts. http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=183606 STATEMENT ON BSE RISK FROM BOVINE TONSIL AND CONSUMPTION OF OX TONGUE Summary SEAC were asked to advise on the possible BSE risk to the UK population from the consumption of tonsil present on ox tongue. Although the scientific evidence does not conclusively prove that tonsil tissue on ox tongue could be infective, SEAC agreed it was prudent to assume this was the case. SEAC considered that in view of the level of scientific uncertainty in this area it was not possible to advise precisely on the magnitude of that risk. However, the committee agreed that any BSE risk from eating tongue was likely to be very small. Background The Committee published a statement in October 2002 when it considered new research showing BSE infectivity had been found in bovine palatine tonsil. The Committee recommended that an assessment of BSE risk from bovine tonsil be conducted. This work was commissioned by the Food Standards Agency, and presented to SEAC at the June 2003 meeting. The Committee was asked to advise on two reports • A Veterinary Laboratories Agency (VLA) report on the presence of tonsil tissue on ox tongue. • An assessment of BSE risk from bovine tonsil carried out by DNV consulting © SEAC 2003 2 Distribution of tonsil tissue in Ox tongue Bovine tonsil is not a single organ but comprises tissue that is discrete (palatine tonsil) and tissue organised more diffusely, such as lingual tonsil present on ox tongue. Bovine tonsil is Specified Risk Material (SRM) from 6 months of age in cattle from the UK and Portugal, and from 12 months of age in cattle from other EU countries. Ox tongue is not classified as SRM and is sold for human consumption. The location of palatine tonsil means that it is unlikely to be removed with ox tongue, but there is a possibility that some lingual tonsil might be present in tongue prepared for human consumption. In October 2002, the Committee recommended that it would be prudent to carry out further examination of the amount and distribution of tonsillar tissue present in ox tongue prepared for human consumption. Subsequently, an examination of current practices showed that the majority of tongues prepared for human consumption contained some lingual tonsil. Twenty four percent (24%) of tongues examined were free of macroscopically visible lingual tonsil. In 26% of tongues examined, the majority of lingual tonsil was removed but identifiable tonsillar tissue was still present. However, a significant amount of tonsillar tissue was present on about 50% of tongues examined. It was also shown that even when all macroscopically visible tonsil tissue had been removed from ox tongue, microscopic tonsil tissue could still be present. The Committee noted the implications of these findings with respect to new EU legislation due for introduction in October 2003. The research showed that the EU proposed method of harvesting ox tongue would not exclude all tonsillar tissue from tongues intended for human consumption. Infectivity in tonsil tissue Cattle were experimentally infected with BSE, and pooled palatine tonsil tissue was taken from animals culled 10 months post inoculation (m.p.i.). Samples of this tissue were inoculated (intracerebrally) into five calves. The Committee was notified in September 2002 when one animal from this group developed BSE at 45 m.p.i. These assays are still ongoing and to date the other four animals in this group remain healthy with no clinical evidence of BSE at 58 m.p.i. Additional groups that received pooled palatine tonsil taken from animals at different time points after inoculation with BSE (6,18 & 26 m.p.i.) are also still healthy at 51 to 55 m.p.i. © SEAC 2003 3 The Committee acknowledged that a single finding supports the evidence for infectivity of palatine tonsil. They agreed that there was no direct evidence to suggest that lingual tonsil on ox tongue was infective. However, the positive finding in palatine tonsil meant that infectivity in the lingual tonsil, which has not been specifically assayed for infectivity, could not be ruled out. No infectivity was detected in ox tongue in the mouse bioassay but ox tongue has not been tested in the more sensitive cattle bioassay. The Committee reiterated their previous opinion that, although the possibility of experimental artefact could not be excluded, it was prudent to assume that this research suggested evidence of infectivity in all bovine tonsil tissue. The Committee recommended that tongue from experimentally challenged animals should be examined for the presence of prion protein (PrPSc). A positive result would indicate the potential for infectivity although a negative result would not necessarily exclude this possibility. A positive result would also help to ascertain if PrPSc was associated with discrete follicular, diffuse lymphoid tissue or with other structures in lingual tonsil as this could influence the final evaluation of risk. Members highlighted the scientific uncertainty over the postulated route of infection for tonsil. To date, no infectivity has been detected by the mouse bioassay in material from the tongue, cranial cervical ganglion and lymph nodes of the head from preclinical or clinical cases of BSE, whether experimental or naturally infected. Pooled lymph nodes and spleen taken from naturally infected BSE cases did not show evidence of infectivity in the cattle bioassay. Also, infectivity has not been detected in mesenteric, prescapular and popliteal lymph nodes (some pooled) in the cattle pathogenesis experiment following intracerebral inoculation of tissues collected at 6, 18 and 26 month post exposure. The Committee noted that this assay is ongoing and currently at 52 to 55 m.p.i. Members noted that if infectivity is detected in bovine tongue it may not necessarily derive from lymphoid tissue but could reside in the associated nerves. This suggestion was based on experimental research on scrapie pathogenesis in hamsters, which showed that the hypoglossal nerve in the tongue could act as a reservoir of prion infection after direct inoculation into the tongue as well as intracerebral inoculation. © SEAC 2003 4 Assessment of potential public health implications The risk assessment considered the possible range of human exposure to BSE infectivity from the consumption of bovine tonsil present on ox tongue. As the amount of tonsil that might be consumed with tongue was not defined, one exposure estimate in the risk assessment was based on the assumption that 100% of the tonsil tissue, estimated to be 50g, is present on every tongue consumed. The Committee agreed this was a precautionary estimate. It was likely that tongue would be peeled before consumption. This would remove the superficial layer, reducing the amount of any adherent tonsil tissue and thus the exposure. Also, tongue meat is usually served sliced making it unlikely that one person would consume all the lymphoid tissue remaining on any one tongue. The risk assessment also considered a more plausible scenario in which 10% of tonsil tissue was present on the tongue when consumed. Estimates of infectivity of tonsil tissue For the purposes of the risk assessment, the total infectivity of a tonsil was estimated as 0.25 bovine oral ID50 units in an infected animal. It was assumed that infectivity was present in the tonsil tissue at a similar level over the entire incubation period of the disease. The quantitative estimate of worst-case exposure to infectivity for a population (assuming all tonsil was included with the tongue) was calculated as 90 bovine oral ID50 units per year, distributed over the tongue-eating population. The Committee identified a number of key scientific uncertainties in this estimate. The main area of uncertainty was the level of infectivity in tonsil tissue. This was estimated by extrapolation of the BSE incubation period for palatine tonsil (45 m.p.i.) from a dose response curve based on BSE-infected brain tissue. Members agreed it would have been preferable to base the estimate of infectivity of tonsil on a dose response curve derived from lymphoid tissue, but this information was not currently available. The Committee noted that inter-animal variations in incubation period could also increase the uncertainty in estimates of tonsil infectivity. © SEAC 2003 5 Conclusions This research does not conclusively show that tongue is infective. However, the Committee agreed that in view of the paucity of data, it was prudent to assume that a risk existed for those who consumed bovine tongue. The Committee agreed the risk of human infection was likely to be very small but concluded that it was not possible to advise the FSA precisely on the magnitude of the risk due to the uncertainty inherent in the data used for the risk assessment. The long incubation period of BSE in the animal that developed disease after challenge with palatine tonsil and the fact that only a single animal has to date developed disease suggests that the infectivity of this tissue was low. The Committee reiterated its previous advice that any potential BSE risk was likely to be low given the decline of the BSE epidemic in the UK and the existing feed controls. Recommendations The Committee identified further scientific work that would help refine the risk estimates and reiterated previous recommendations that further study on lymphoid tissues and tongue from cattle should be carried out, using the most sensitive assays, as these become available. http://www.seac.gov.uk/statements/Bovine_Tonsil.pdf Page 1 of 4 STATEMENT ON INFECTIVITY IN BOVINE TONSIL Background 1. The views of the Committee were sought on unpublished results from an ongoing long-term study of the pathogenesis of BSE in cattle. This study is being carried out by the Veterinary Laboratory Agency and is funded by the Food Standards Agency (FSA). 2. In this study, cattle were orally dosed with 100g of BSE-infected bovine brain material. At various times after oral dosing, cattle were killed and different tissues tested for infectivity. In the first instance, the presence of infectivity was assessed by injection of various tissues into inbred mice ("mouse bioassay "). In this research infectivity was detected in: • distal ileum (the earliest infectivity was detected at 6 months after inoculation.) • brain and spinal cord and closely associated nervous tissue (infectivity was detected in the months just prior to the clinical onset of BSE in cattle) • at a single time point (around the time of clinical onset) bone marrow was also found to contain infectivity. However, no infectivity was detected in the other tissues tested by the mouse bioassay. 3. It was recognised that assay of bovine material in mice involves crossing a species barrier, which may reduce the sensitivity of the assay to detect infectivity. Subsequent research showed that intracerebral injection in calves ("cattle bioassay") was several hundred-fold more sensitive than the mouse bioassay with respect to the detection of putative infectivity in bovine tissues. Therefore, starting about 6 years ago, a study was initiated to test a range of cattle tissues that had been tested in the mouse bioassay using the more sensitive cattle bioassay. The Committee was presented with recent results from this ongoing cattle bioassay. Page 2 of 4 Research Findings 4. Early results from the cattle bioassay study confirmed infectivity in the distal ileum, brain and spinal cord at certain times in the incubation period to those previously reported in the mouse bioassay. However, new findings show that one of five cattle that received pooled palatine tonsil tissue, taken 10 months after experimental inoculation with BSE, had shown clinical evidence of the onset of BSE at 45 months post-inoculation. At present, the 4 remaining animals are still alive (48 months after inoculation), without confirmed evidence of clinical onset of BSE. The equivalent result in the original mouse bioassay was negative. 5. The Committee considered that although at present only one of the five animals has shown evidence of transmission of BSE, the finding was significant and was unlikely to result from experimental artefact. The Committee noted that the significance of this finding would be strengthened if any of the other four animals in the experimental group developed BSE or if tonsil tissue sampled at 6, 18 or 26 months after inoculation also showed evidence of infectivity in this study. The Committee noted that these studies are ongoing. Assessment of potential public health implications 6. The Committee noted that tonsils from cattle are Specified Risk Material (SRM) from 6 months of age in cattle from the UK and Portugal, and SRM from 12 months of age for other EU countries. Bovine tongue is not classified as SRM and therefore can be sold for human consumption. Although the location of palatine tonsil is such that it is unlikely to be removed with tongue, there is a possibility that some lingual tonsil, which is close to the root of the tongue, might be present in that part of the tongue removed and intended for human food consumption. examination of current practices of cutting and removal of the tongue indicated no visible lingual tonsil was present on tongue as removed. The Committee was informed that such tissue was not detectable if tongue was cut in a particular area. The Committee considered, nevertheless, that it would be prudent to conduct further examination of current practices of preparing bovine tongue and of the amount and distribution of any tonsil tissue in tongues prepared for human consumption. Page 3 of 4 8. Despite the paucity of data on current practices, the Committee considered that any potential risk was likely to be low as the long incubation period of the one animal that had developed BSE (45 months post-inoculation) in this experiment suggested that the level of infectivity was low. Additionally the Committee considered that the potential for exposure is limited given: The number of BSE infected cattle entering the food chain is likely to be very small because of the decline of the BSE epidemic in the UK, existing feed controls and the over thirty month (OTM) rule. Tonsil is SRM from the age of 6 months in the UK and Portugal and 12 months in other EU states. Although the quantity of tonsil tissue attached to tongues is unknown, it is likely, at most, to be small. 9. On the question of whether tonsil should be made SRM from any age, the Committee acknowledged this was a risk management issue and thus is beyond their remit. However they considered that this option should be examined as part of the overall risk assessment. 10. With respect to bovine lymphatic tissue other than tonsil, the Committee noted that a previous study on pooled lymph nodes or spleen taken from naturally infected animals with clinical BSE had not shown evidence of infectivity by cattle bioassay. The Committee was informed that assay of specific lymph nodes were included in the ongoing experiment and at present have not shown evidence of infectivity, but the assay is incomplete. Conclusions 11. The Committee concluded that although only one of the five animals inoculated with tonsil tissue has so far succumbed to BSE, this finding is significant and unlikely to be an experimental artefact. However, the significance of this finding would be strengthened by: • the pending results from the other four animals in the experimental group; which are currently not showing definite clinical signs of BSE • the results from other experimental groups of animals which received tonsil tissues sampled at 6, 18 or 26 months after inoculation. . 12. The Committee was not able to assess the magnitude of the potential risk, as insufficient information on current practices was available at the time of assessment. In view of this, the Committee made a number of recommendations. Page 4 of 4 Recommendations 13. The Committee recommended that a risk assessment be carried out to establish the potential level of exposure to BSE infectivity that the human population might be exposed to as a consequence of the possibility of infectivity in tonsil tissue. The Committee considered that further work was needed to establish the distribution of tonsillar tissue in tongues prepared for human consumption. The assessment should include risks associated with both UK and imported meats. The Committee recommended that it is also necessary to investigate the food uses of tongues and of tonsils from young animals that are not classified as SRM. 14. The Committee recommended that, in addition to cattle bioassay, further studies on lymphoid tissues from cattle should be carried out, using the most sensitive assays, as these become available. These should include validation of this interim finding by exploring all available techniques to detect PrPsc on both the original tonsil tissue material collected, as well as any lymphoreticular tissue tested in the mouse bioassay that had not been included in the cattle bioassay. SEAC Statement 2002/1 http://www.seac.gov.uk/statements/tonsil211002.pdf 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] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12144804&dopt=Abstract 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 http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10580068&dopt=Abstract 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: http://www.pnas.org/cgi/content/full/97/7/3418 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 http://jama.ama-assn.org/issues/v285n6/ffull/jlt0214-2.html 1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8 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. PMID: 8006664 [PubMed - indexed for MEDLINE] TSS
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