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Iatrogenic Creutzfeldt-Jakob disease via surgical instruments and decontamination possibilities for the TSE prion

Posted Sep 08 2013 12:47pm
Subject: Iatrogenic Creutzfeldt-Jakob disease via surgical instruments and decontamination possibilities for the TSE prion
 
 
please note, all Iatrogenic Creutzfeldt Jakob Disease iCJD is, is sporadic Creutzfeldt Jakob Disease sCJD, until route and source of iatrogenic event took place, and documented. until then, it’s all sporadic CJD.
 
I have put together a few cases from the past, of folks and hospitals that were exposed to the TSE prion disease...also, some science on the extent of decontamination of the TSE prion disease. ...
 
 
kind regards, terry
 
 
 
 >>>Prions, the causative agents of the transmissible spongiform encephalopathies, are notoriously difficult to inactivate. Current decontamination recommendations by the World Health Organization include prolonged exposure to 1 N sodium hydroxide or > 20,000 ppm sodium hypochlorite, or autoclaving. For decontamination of large stainless steel surfaces and equipment as in abattoirs, for example, these methods are harsh or unsuitable. The current study was designed to evaluate the effectiveness of a commercial product containing sodium percarbonate to inactivate prions. Samples of mouse brain infected with a mouse-adapted strain of the scrapie agent (RML) were exposed to a sodium percarbonate-based product (SPC-P). Treated samples were evaluated for abnormal prion protein (PrPSc)- immunoreactivity by western blot analysis, and residual infectivity by mouse bioassay.<<<
 
 >>This study demonstrates that exposure of the RML scrapie agent to an SPC-containing product alone or in combination with SDS does not eliminate prion infectivity, but does render PrPSc sensitive to proteinase K. Because of this, it is interesting to consider the potential viability of a combination of SPC and SDS, even at relatively low concentrations and mild temperatures, concomitant with or followed by a protease for prion decontamination. Also, because the SPC product we used contains additional proprietary ingredients, we cannot rule-out contributions to increased PK-sensitivity or increased survival by other components of the product. Studies in our laboratory are currently underway examining exposure of prions to chemical grade SPC with or without SDS followed by exposure to a protease. <<<
 
 
SNIP...another study below ;
 
 
 >>>Conventional sterilization and disinfection methods are inadequate in reducing prion infectivity of contaminated instruments, and World Health Organization recommendations for disinfection using bleach or sodium hydroxide are often impractical for routine decontamination.<<<
 
 
======================
 
 
Iatrogenic Creutzfeldt-Jakob disease via surgical instruments
 
Jonathan G. Thomas Affiliations Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA , Carol E. Chenoweth Affiliations Department of Infection Control and Epidemiology, and Department of Internal Medicine-Infectious Diseases, University of Michigan, Ann Arbor, MI, USA , Stephen E. Sullivan Affiliations Department of Neurosurgery, University of Michigan, 1500 E. Medical Center Drive, Room 3552 Taubman Center, Ann Arbor, MI 48109-5338, USA Corresponding Author InformationCorresponding author. Tel.: +1 734 936 9579; fax: +1 734 936 9294. email address Received 1 August 2012; accepted 24 January 2013.
 
Abstract
 
Creutzfeldt-Jakob disease (CJD) is a neurodegenerative prion disease that can spread via contaminated neurosurgical instruments previously used on an infected patient. We examine current guidelines on how to recognize, handle, and prevent instrument-related iatrogenic CJD. Despite only four reported patients worldwide implicating contaminated neurosurgical instruments, and none in the past 30 years, the public health consequences of potential instrument-related iatrogenic CJD can be far-reaching. Conventional sterilization and disinfection methods are inadequate in reducing prion infectivity of contaminated instruments, and World Health Organization recommendations for disinfection using bleach or sodium hydroxide are often impractical for routine decontamination. Recently, possible CJD exposure via infected surgical instruments was suspected at a large teaching hospital. Although CJD was later disproven, the intervening investigation exposed the difficulty in tracking infected surgical instruments and in protecting subsequent surgical patients from prion infection. To identify patients at risk for iatrogenic CJD, infectivity of instruments after this index patient is estimated using simple scenario modeling, assuming a certain log reduction of infectivity for each cleansing cycle. Scenario modeling predicts that after six cycles of instrument use with conventional cleansing following an index patient, other patients are highly unlikely to be at risk for iatrogenic CJD. Despite its rarity, the threat of iatrogenic CJD transmission via contaminated instruments poses tremendous challenges to neurosurgeons. Basic prevention strategies should be employed for patients with suspected CJD, including use of disposable instruments where possible and quarantining non-disposable instruments until the diagnosis is ascertained, or using special instrument reprocessing methods if CJD is suspected.
 
Keywords: Creutzfeld-Jakob disease, Iatrogenic, Sterilization, Transmission
 
 
 
 
Appendix 2: Scrapie Disinfection Guidelines
 
*** The following suggested procedures do not guarantee total and complete disinfection and inactivation of the infectious agent.
 
Nonetheless, current information regarding the efficiency of following these disinfection procedures under laboratory conditions suggests these procedures will reduce infectivity in the environment. Until more specific information is available, good sanitary practices are recommended following each lambing. The following methods below should be applied to lambing areas where infected or exposed animals have lambed. Pastures
 
1. If practical, till soil under or do not use the area to graze susceptible animals.
 
2. If this is impractical, do not use the pasture until the animal waste has decomposed and the weather has had an opportunity to dilute any infectivity.
 
Drylots
 
1. Remove the manure and bedding and, when practical, the top 1 to 2 inches of soil to reduce contamination.
 
2. Bury or till under the removed material; or, compost the removed material in areas not accessed by domestic or wild ruminants until it can be buried or tilled under. Earth Surfaces Inside Structures or Used for Confined Lambing Pens
 
1. Remove the organic material and, when practical, the top 1 to 2 inches of soil to reduce contamination.
 
2. Bury or till under the removed material; or, compost the removed material in areas not accessed by domestic or wild ruminants until it can be buried or tilled under. Non-earth Surfaces (These include cement, wood, metal, tools, equipment, instruments, feed, hay, bedding, and other materials.)
 
1. Remove all organic material. Bury, incinerate, or compost the removed material in areas not accessed by domestic or wild ruminants and then till under, bury or incinerate.
 
2. When practical for other items bury or incinerate by high-temperature incineration methods.
 
3. Clean and wash surfaces and remaining items using hot water and detergent. Allow all surfaces, tools, and equipment to dry completely before disinfecting and sanitizing using the following suggested methods.
 
a. Autoclave instruments, small tools, and other items at 277 °F for 1 hour. This method is more effective when preceded by the treatment described in b or c below.
 
For General Distribution 67
 
Scrapie Program Standards Volume 2 June 2013
 
b. To clean dry surfaces, apply a 2 percent available chlorine solution1 (equivalent to about 20,000 p/m available chlorine: 50 ounces [6-1/4 cups] bleach to 78 ounces [9 ¾ cups] water to give 1 gallon of solution) at room temperature (at least 65 °F) for at least 1 hour. Note: Bleach is caustic and can be hazardous if swallowed, gets in the eyes, is breathed in, or is left on the skin. Further, care must be taken to prevent contamination of water from run off and to comply with any environmental regulations for use of this product. Read the material safety data sheet prior to use and use appropriate personal protective equipment or hire trained personnel to do the work.
 
*** c. To clean dry surfaces, apply 1-molar solution of sodium hydroxide1 (approximately 4-percent solution [5 ounces sodium hydroxide dissolved in l gallon water]) at room temperature (at least 65 °F) for at least 1 hour. Synonyms for sodium hydroxide are caustic soda, soda lye, and sodium hydrate. Note: Sodium hydroxide is caustic and can be hazardous if swallowed, gets in the eyes, is breathed in, or is left on the skin. Further, care must be taken to prevent contamination of water from run off and to comply with any environmental regulations for use of this product. Read the material safety data sheet prior to use and use appropriate personal protective equipment or hire trained personnel to do the work.
 
1 40 CFR § 152 declares prions a pest under the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA). Accordingly, only products registered with the Environmental Protection Agency (EPA) specifically for the reduction of prion infectivity can be used at these sites. Currently there are no EPA registered products available; EPA has therefore granted APHIS an exemption for the use of chlorine and sodium hydroxide for use in its prion control and eradication programs. The instructions above conform to those on the exemption labels.
 
For General Distribution 68
 
Scrapie Program Standards Volume 2 June 2013
 
 
 
 
 
Exposure of RML scrapie agent to a sodium percarbonate-based product and sodium dodecyl sulfate renders PrPSc protease sensitive but does not eliminate infectivity
 
BMC Veterinary Research 2013, 9:8 doi:10.1186/1746-6148-9-8 Jodi D Smith (jodi.smith@ars.usda.gov) Eric M Nicholson (eric.nicholson@ars.usda.gov) Gregory H Foster (ghfoster@mac.com) Justin J Greenlee (justin.greenlee@ars.usda.gov) ISSN 1746-6148
 
Article type Research article Submission date 18 September 2012 Acceptance date 8 January 2013 Publication date 11 January 2013 Article URL http://www.biomedcentral.com/1746-6148/9/8
 
BMC Veterinary Research
 
© 2013 Smith et al.
 
Exposure of RML scrapie agent to a sodium percarbonate-based product and sodium dodecyl sulfate renders PrPSc protease sensitive but does not eliminate infectivity
 
Jodi D Smith1 Email: jodi.smith@ars.usda.gov Eric M Nicholson1 Email: eric.nicholson@ars.usda.gov Gregory H Foster1 Email: ghfoster@mac.com Justin J Greenlee1* * Corresponding author Email: justin.greenlee@ars.usda.gov
 
1 Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, 1920 Dayton Ave, Ames, IA 50010, USA
 
Abstract
 
Background
 
Prions, the causative agents of the transmissible spongiform encephalopathies, are notoriously difficult to inactivate. Current decontamination recommendations by the World Health Organization include prolonged exposure to 1 N sodium hydroxide or > 20,000 ppm sodium hypochlorite, or autoclaving. For decontamination of large stainless steel surfaces and equipment as in abattoirs, for example, these methods are harsh or unsuitable. The current study was designed to evaluate the effectiveness of a commercial product containing sodium percarbonate to inactivate prions. Samples of mouse brain infected with a mouse-adapted strain of the scrapie agent (RML) were exposed to a sodium percarbonate-based product (SPC-P). Treated samples were evaluated for abnormal prion protein (PrPSc)- immunoreactivity by western blot analysis, and residual infectivity by mouse bioassay.
 
Results
 
Exposure to a 21% solution of SPC-P or a solution containing either 2.1% or 21% SPC-P in combination with sodium dodecyl sulfate (SDS) resulted in increased proteinase K sensitivity of PrPSc. Limited reductions in infectivity were observed depending on treatment condition. A marginal effect on infectivity was observed with SPC-P alone, but an approximate 2–3 log10 reduction was observed with the addition of SDS, though exposure to SDS alone resulted in an approximate 2 log10 reduction.
 
Conclusions
 
This study demonstrates that exposure of a mouse-adapted scrapie strain to SPC-P does not eliminate infectivity, but does render PrPSc protease sensitive.
 
Keywords Inactivation, Prion, Scrapie, Sodium dodecyl sulfate, Sodium percarbonate
 
SNIP...
 
A major finding of this study was the increased sensitivity of PrPSc to PK by the SPC-based product without (SPC-PH only) or with SDS at room temperature, as judged by immunoblotting after exposure of the samples to limited proteolysis. Based on the loss of detectable PrPSc immunoreactivity after incubation at pH 11, it appears this effect may be largely pH-dependent. It is well established that prion infectivity is reduced under extremely basic conditions, such as exposure to NaOH (pH 12–14) [19-21]. While the pH generated by SPC-P is lower at 11, it appears to be a favorable characteristic of the compound with regard to PrPSc protease sensitivity. However, a solely pH-dependent effect does not explain why SPC-PL treatment alone (pH 11) did not yield similar WB results. One possible explanation is that a lower concentration of the product may have contained diminished buffering capacity resulting in a drop in pH as treatment proceeded, but serial pH evaluation of treated brain homogenate at 30, 90, and 180 min revealed that the pH remained above 10.7. Although treatment with the SPC product did render PrPSc sensitive to digestion by proteinase K, it did not eliminate infectivity. Recent studies examining prion infectivity in infected tissue and cell cultures have also demonstrated loss of detectable PrPSc on western blot, but residual infectivity [22,23]. Our results support the inference that biochemical analysis alone is insufficient for determination of prion infectivity. The observed PrPSc/infectivity mismatch in this study and in others warrants a number of considerations including WB sensitivity, epitope disruption by inactivation treatments, and alternative infectious agents to PrPSc, such as PK-sensitive forms of PrP or viruses. It is possible the amount of residual PrPSc in our treated samples was below the detection limit of our WB (0.025 mg equivalents of brain tissue for this particular inoculum [24]), or it may be that a true dissociation of PrPSc and TSE infectivity exists supporting the actuality of alternative infectious agents to PrPSc [25]. A recent study has demonstrated poor correlation between infectivity and WB results for sheep scrapie and sheep BSE [26] in line with observations that PK-sensitive PrP particles are associated with disease [27,28].
 
The bioassay results we present indicate that exposure to the selected SPC-based product alone or in combination with 2.5% SDS is not a viable option for the inactivation of prions. No decrease in infectivity was observed using the SPC-PL solution alone, and a modest 1 log10 reduction was achieved with the SPC-PH solution. However, recent investigations have demonstrated differential susceptibility of distinct prion strains to the same inactivation procedure [29]; therefore, we are currently investigating the efficacy of these treatment conditions in an ovine scrapie model. It should also be acknowledged that chemical treatment of the scrapie agent has been shown to delay the dose–response relationship [30,31] resulting in prolonged incubation times without a change in calculable titer. It is possible our results could be reflecting this phenomenon, but without bioassay data from serial dilutions of treated brain homogenate this cannot be definitively determined. Some caution may therefore be warranted when interpreting these results. The addition of 2.5% SDS to the SPC-P solutions resulted in a 2–3 log10 reduction in infectivity, but exposure to SDS alone resulted in an approximate 2 log10 reduction. This suggests much of the observed combinatorial effect was due to SDS. Prior studies using SDS have demonstrated minimal effects on CJD infectivity [16], but up to a 3 log10 reduction on scrapie infectivity [17]. Exposure of hamster-adapted Sc237 scrapie to room temperature SDS at pH values of ≤4.5 or ≥10 resulted in increased PK sensitivity of PrPSc, and exposure to acidic SDS resulted in decreased infectivity [11]. Since SDS at room temperature is an effective denaturant at a pH ≥10, this could have contributed to the loss of detectable PrPScimmunoreactivity we observed after proteolysis in samples treated with SPC-P and SDS. There was also enhanced reduction in infectivity with the combination of SPC-PL and SDS. This may be indicative of an enhanced effect of SDS under basic conditions or a two-step mechanism whereby denaturation of PrPSc by the relatively high pH of the solution and/or SDS is followed by exposure of sites sensitive to oxidative damage. Alternatively, the two treatment components could be acting on different PrPSc fractions in the inoculum resulting in an additive effect since the combination of SPC-PL and SDS was roughly equivalent to slightly greater than the sum of the effects of each individual component. The combination of SPC-PH and SDS did not provide an equivalent or better increase in survival time than the combination of SPC-PL and SDS. While we are confident in this result, we cannot definitively explain this observation. Perhaps disease in this group was exacerbated by oxidative damage induced by the introduction of treated brain samples containing a greater concentration of sodium percarbonate. Oxidative stress, whether a cause or consequence of disease progression, is considered an important contributor to prion neuropathology [32-34]. It is also possible that the SPC-P solution at higher concentration may somehow be interfering with the denaturing action of SDS. SDS action may be enhanced when combined with lower concentrations of SPC-P for longer exposure times, but restricted by higher concentrations, perhaps via chemical modification of SDS binding sites on the protein.
 
Oxidizing agents have been used with variable success in prion inactivation studies. Exposure of prions to halogens such as sodium hypochlorite at ≥ 20,000 ppm is an accepted means of decontamination [8], but chlorine dioxide is much less effective at inactivating hamster-adapted 263 K scrapie [35]. Peroxygens such as liquid hydrogen peroxide [13,35,36] and peracetic acid [37] also promote limited inactivation. However, recent studies using vaporized hydrogen peroxide to decontaminate stainless steel surfaces have demonstrated significant reductions in infectivity for hamster-adapted 263 K scrapie and mouse-adapted BSE [13,15]. A protective effect from oxidation by peracetic acid has been demonstrated with the ME7 scrapie agent and attributed to prion aggregation [37]. Peracetic acid at 2% was effective at inactivating the ME7 scrapie agent in intact brain tissue, but not homogenized tissue. Samples in the current study were homogenized, which may have imparted a degree of protection from oxidation and contributed to the ineffectiveness of SPC-P alone at decreasing infectivity. We propose that the addition of SDS would have decreased aggregation of cell membranes to which infectivity is bound, thus enhancing the activity of SPC-P and perhaps contributing to the increased survival observed with the combination.
 
Conclusions
 
This study demonstrates that exposure of the RML scrapie agent to an SPC-containing product alone or in combination with SDS does not eliminate prion infectivity, but does render PrPSc sensitive to proteinase K. Because of this, it is interesting to consider the potential viability of a combination of SPC and SDS, even at relatively low concentrations and mild temperatures, concomitant with or followed by a protease for prion decontamination. Also, because the SPC product we used contains additional proprietary ingredients, we cannot rule-out contributions to increased PK-sensitivity or increased survival by other components of the product. Studies in our laboratory are currently underway examining exposure of prions to chemical grade SPC with or without SDS followed by exposure to a protease.
 
 
 
 
 
 
Saturday, January 12, 2013
 
Exposure of RML scrapie agent to a sodium percarbonate-based product and sodium dodecyl sulfate renders PrPSc protease sensitive but does not eliminate infectivity
 
 
 
 
Research Article Resistance of Bovine Spongiform Encephalopathy (BSE) Prions to Inactivation Kurt Giles, Affiliations: Institute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, California, United States of America, Department of Neurology, University of California San Francisco, San Francisco, California, United States of America
 
X David V. Glidden, Affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America
 
X Robyn Beckwith, Affiliation: Institute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, California, United States of America
 
X Rose Seoanes, Affiliation: Institute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, California, United States of America
 
X David Peretz, Affiliations: Institute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, California, United States of America, Department of Neurology, University of California San Francisco, San Francisco, California, United States of America
 
Current address: Novartis Vaccines and Diagnostics, Emeryville, California, United States of America
 
X Stephen J. DeArmond, Affiliations: Institute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, California, United States of America, Department of Pathology, University of California San Francisco, San Francisco, California, United States of America
 
X Stanley B. Prusiner mail * E-mail: stanley@ind.ucsf.edu
 
Affiliations: Institute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, California, United States of America, Department of Neurology, University of California San Francisco, San Francisco, California, United States of America, Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, United States of America
 
X
 
Abstract Distinct prion strains often exhibit different incubation periods and patterns of neuropathological lesions. Strain characteristics are generally retained upon intraspecies transmission, but may change on transmission to another species. We investigated the inactivation of two related prions strains: BSE prions from cattle and mouse-passaged BSE prions, termed 301V. Inactivation was manipulated by exposure to sodium dodecyl sulfate (SDS), variations in pH, and different temperatures. Infectivity was measured using transgenic mouse lines that are highly susceptible to either BSE or 301V prions. Bioassays demonstrated that BSE prions are up to 1,000-fold more resistant to inactivation than 301V prions while Western immunoblotting showed that short acidic SDS treatments reduced protease-resistant PrPSc from BSE prions and 301V prions at similar rates. Our findings argue that despite being derived from BSE prions, mouse 301V prions are not necessarily a reliable model for cattle BSE prions. Extending these comparisons to human sporadic Creutzfeldt-Jakob disease and hamster Sc237 prions, we found that BSE prions were 10- and 106-fold more resistant to inactivation, respectively. Our studies contend that any prion inactivation procedures must be validated by bioassay against the prion strain for which they are intended to be used.
 
Author Summary “Mad cow” disease, formally known as bovine spongiform encephalopathy (BSE), belongs to a family of diseases affecting humans and a number of commercially important animal species. These diseases are not spread by bacteria or viruses, but by infectious proteins, termed “prions.” Prions are known to be very difficult to inactivate, but little is known about the relative difficulty of inactivation for prions from different species. Here, we studied the inactivation of BSE prions and compared it to the inactivation of prions from humans, mice, and hamsters. We used highly sensitive, genetically engineered mouse models to detect low levels of infectivity. We then quantified the levels of inactivation for a range of treatments and calculated differences between prions from different species. We found that naturally occurring BSE prions can be up to 1 million times more difficult to inactivate than the most commonly used hamster prions. BSE prions were also 1,000 times more difficult to inactivate than a mouse prion that was thought to be a surrogate for BSE prions. This study demonstrates that prion inactivation procedures need to be validated directly against the prion strains for which they are intended to be used.
 
Citation: Giles K, Glidden DV, Beckwith R, Seoanes R, Peretz D, et al. (2008) Resistance of Bovine Spongiform Encephalopathy (BSE) Prions to Inactivation. PLoS Pathog 4(11): e1000206. doi:10.1371/journal.ppat.1000206
 
Editor: David Westaway, University of Alberta, Canada
 
Received: March 7, 2008; Accepted: October 15, 2008; Published: November 14, 2008
 
Copyright: © 2008 Giles et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
 
Funding: This work was supported by grants from the National Institutes of Health (R01AI064709, AG02132, AG10770, and AG021601) as well as by a gift from the G. Harold and Leila Y. Mathers Charitable Foundation.
 
Competing interests: The authors have declared that no competing interests exist.
 
 
snip...
 
 
Discussion The application of survival analysis techniques to prion incubation periods provides a more accurate representation of the data. The distribution of animals succumbing to disease is rarely symmetrical, and not all animals become sick at low levels of infectivity. These factors are reflected by reporting median incubation periods and asymmetric 95% ci, which are by definition wider than standard deviation or standard error of the mean. These techniques also allow us to quantify inactivation using different Tg model systems, in an unbiased way.
 
We previously demonstrated that human CJD prions were significantly more resistant to inactivation than hamster Sc237 prions [23]. This differential inactivation of prion strains has also been observed by others. The phenolic detergent Environ LpH was shown to inactivate all detectable infectivity of hamster Sc237 prions [44],[45], but only modestly reduced infectivity of mouse RML prions [46].
 
Rodent-passaged prion strains are widely used in prion research. While these have been invaluable for understanding prion biology, great care must be taken in extrapolating any characteristics of these prions back to the original species and strain from which they were derived. Recommendations for the inactivation of human CJD prions were partly based on experiments on adapted strains of CJD passaged in mice [47], hamsters [48], and guinea pigs [49]. However, since the sequence of PrPSc is encoded by the host in which the prions were last passaged, these “CJD” strains are actually mouse, hamster and guinea pig prions, respectively, which may exhibit different resistances to inactivation compared to the human CJD prions from which they were originally derived.
 
Gel electrophoresis can be used to identify the PK-resistant core of PrPSc, which can differ between strains. This technique was used to classify human prion strains based on the size of the unglycosylated, protease-resistant PrPSc fragments: type 1 results from cleavage at residue 82 and has a fragment size of 21 kDa and type 2 results from cleavage at residue 97 and has a fragment size of 19 kDa [50]. Despite the assumption that 301V is representative of the BSE strain from which it was derived, we observed a difference in the sizes of the unglycosylated bands between the two strains (Figure 1), which is consistent with previously published results. A mixture of N-terminal sequences was obtained from the 301V strain, starting with residue 81 [51]. In contrast, BSE was not recognized by an antibody directed against residues 89–104, suggesting the major cleavage point is within this region [52]. Furthermore, cattle BSE and mouse 301V PrPSc have different susceptibilities to acidic SDS (Figure 1B, Tables 1 and 2), suggesting that they are different strains.
 
We observed differences in the relative effectiveness of treatments on the two strains, as measured by Western blots and infectivity bioassay. In all cases, increasing the time and temperature of acidic SDS treatments led to reduced PrPSc levels and increased inactivation. For acidic SDS treatments of <8 18="" 1="" 1b="" 1c="" 301v="" 4="" 65="" 8="" a="" acidic="" acoh="" alone="" and="" approaching="" as="" at="" background="" bioassay.="" blots="" both="" bse="" by="" cattle="" compared="" contrast="" demonstrated="" detected="" div="" exposure="" fold="" for="" h="" igure="" immunoblots="" implies="" in="" inactivation="" incubation="" infectivity="" levels="" logs="" longer="" min="" more="" mouse="" of="" or="" prions.="" prions="" prpsc="" reduced="" reduction="" relatively="" residual="" resistant="" sds="" showed="" signal="" significantly="" similar="" that="" the="" to="" treated="" treatments="" unchanged="" up="" water="" were="" western="" which="" with="">
 
Western blotting is a rapid and convenient way of determining the level of PrPSc, but it is limited by a dynamic range of ~100-fold. It has long been known that the PrPSc level correlates with infectivity [53], but the precise relationship between the two remains to be determined. While PrPSc was originally defined as resistance to PK, we have since shown that there are both protease-resistant (r) and protease-sensitive (s) forms of PrPSc [54]. Western blotting only detects rPrPSc, while the conformation-dependent immunoassay [8] and the amyloid seeding assay [55] are able to detect both rPrPSc and sPrPSc.
 
The apparent discrepancies we observed between PrPSc level and infectivity for 301V and BSE prions may be due to several factors. First, the sPrPSc fraction, and its associated infectivity, may be variable between 301V and BSE. If 301V and BSE have differing amounts of rPrPSc and sPrPSc, and at least some infectivity is associated with sPrPSc, then Western blot results would not necessarily correlate with infectivity. Second, structural differences between the strains may result in different levels of inactivation. Presumably, the quaternary structure would be broken down first when inactivating prions, whereas the tertiary structure would have to be unfolded to diminish higher levels of infectivity. In such a case, mouse 301V prions may have an equally stable quaternary structure but less stable tertiary structure compared to cattle BSE prions.
 
Cattle or human prions passaged in rodents give rise to rodent prions. Mouse 301V prions are very resistant to inactivation [56]. Additionally, a human prion strain causing Gerstmann-Sträussler-Scheinker disease was passaged in mice; the resulting strain, termed M1000, was reported to be highly resistant to inactivation [57]. However, for both 301V and M1000, the relative susceptibilities to inactivation were not directly compared to their respective parent strains. We demonstrate here that mouse 301V and its parent strain, BSE, have different resistances to inactivation. Therefore, any extrapolation from a rodent-passaged prion strain to the original parent strain must be interpreted cautiously. A more suitable model for BSE prions may be BSE passaged in Tg(BoPrP) mice, which produce PrPSc with the BoPrP sequence as well as with the same electrophoretic mobility and glycosylation pattern as cattle BSE prions [58]. Infected brains from this line were recently shown to be suitable for evaluation of BSE tests [59]. However, these bovine prions are in the milieu of mouse brain homogenate rather than cattle brain homogenate, and it remains to be determined whether this has an effect on the inactivation characteristics.
 
As with the results reported previously for hamster Sc237 and human sCJD prions [23], the inactivation of cattle BSE and mouse 301V prions from stainless-steel surfaces is more difficult than inactivating similar levels of infectivity in brain homogenates. Stainless-steel wire as a model for surface contamination [60] provides a useful tool to study prion inactivation from surgical instruments or machinery used in slaughterhouses. After 4-mm wires were incubated in 10% brain homogenate, then washed extensively, we were able to elute PrP equivalent to ~250 ng of brain tissue from each wire. Other investigators were able to elute substantially higher PrP levels from wires soaked in brain homogenate [61], but their wires were not exhaustively washed, as ours were. Previous studies, using very similar washing strategies, reported the inability to detect eluted PrP or other proteins from stainless-steel wires [62]. However, 2 M NaOH used in those studies may have hydrolyzed many of the proteins, including PrP.
 
In conclusion, we have quantified the relative resistance to inactivation of four prion strains from different species. Cattle BSE prions appear to be the most resistant strain studied. In comparison, human sCJD prions are approximately 10-fold less resistant to inactivation by SDS at neutral or acidic pH, or by heat alone. Mouse 301V prions are 100- to 1,000-fold less resistant, and hamster Sc237 prions are up to 1,000,000-fold less resistant to inactivation. As shown by our findings, prion inactivation based on rodent-passaged prion strains may not be effective against the naturally occurring strains for which they were developed.
 
 
 
 
 
HOSPITAL EPIDEMIOLOGY AND INFECTION CONTROL
 
POLICIES AND PROCEDURES FOR PATIENTS WITH SUSPECTED OR CONFIRMED HUMAN PRION DISEASE (E.G., CREUTZFELDT-JAKOB DISEASE [CJD])*
 
POLICY 4.2
 
Issued: 4/89
 
Last Reviewed: 05/12
 
 
 
 
Bovine Spongiform Encephalopathy Mad Cow Disease, BSE
 
Last Updated: May 2012
 
Even the harshest combination of chemical and physical disinfection is not guaranteed to destroy all prions. In experiments, a stainless-steel wire remained infectious after cleaning with sodium hydroxide and autoclaving. Surgical instruments that have undergone repeated cycles of cleaning and disinfection have transmitted the sporadic (genetic) form of CJD iatrogenically. For this reason, disposable equipment and instruments may be recommended instead of disinfection during some medical procedures.
 
 
 
 
The emergence of vCJD in humans has been causally linked to ingestion of BSE (Bruce et al., 1997). Recommended safety precautions for handling the agent are based on the assumption that BSE is zoonotic. Biocontainment for necropsies and tissue handling should be risk-based and compliant with relevant national regulations; any procedure creating aerosols must be conducted under containment level 3 (see Chapter 1.1.2 Biosafety and biosecurity in the veterinary microbiology laboratory and animal facilities), and the laboratory must comply with national biocontainment and biosafety regulations to protect staff from exposure to the pathogen. Recommended decontamination procedures may not be completely effective when dealing with high-titre material or when the agent is protected within dried organic matter. Recommended physical inactivation is by porous load autoclaving at 134°C–138°C for 18 minutes at 30 lb/in2 (208 kPa or 2.2 bar). However, temperatures at the higher end of the range may be less effective than those at the lower end and total inactivation may not be achieved under certain conditions, such as when the test material is in the form of a macerate. Recommended decontamination procedures may not be completely effective under some circumstances. Disinfection of potential fomites is carried out using sodium hypochlorite containing 2% available chlorine, or 2 N sodium hydroxide, applied for more than 1 hour at 20°C for surfaces, or overnight for equipment.
 
 
 
 
The safest and most unambiguous method for ensuring that there is no risk of residual infectivity on contaminated instruments and other materials is to discard and destroy them by incineration.6 Current recommendations for inactivation of prions on instruments and other materials are based on the use of sodium hypochlorite, NaOH, Environ LpH and the moist heat of autoclaving with combinations of heat and chemical being most effective (Table 9).5,6 Surgical Procedures Precautions for surgical procedures on patients diagnosed with prion disease are outlined in an infection control guideline for transmissible spongiform encephalopathies developed by a consultation convened by the WHO in 1999.6 Sterilization of reusable surgical instruments and decontamination of surfaces should be performed in accordance with recommendations described by the CDC (www.cdc.gov) and the WHO infection control guidelines.6 Table 9 summarizes the key recommendations for decontamination of reusable instruments and surfaces. Contaminated disposable instruments or materials should be incinerated at 1000° C or greater.7
 
 
 
 
WHO Tables on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies Updated 2010
 
 
 
 
Dissociation between Transmissible Spongiform Encephalopathy (TSE) Infectivity and Proteinase K-Resistant PrPSc Levels in Peripheral Tissue from a Murine Transgenic Model of TSE Disease Karen Dobie and Rona Barron + Author Affiliations
 
Neurobiology Division, The Roslin Institute & R(D)SVS, Easter Bush, Midlothian, United Kingdom ABSTRACT Most current diagnostic tests for transmissible spongiform encephalopathies (TSE) rely on the presence of proteinase K (PK)-resistant PrPSc (PrP-res) in postmortem tissues as an indication of TSE disease. However, a number of studies have highlighted a discrepancy between TSE infectivity and PrP-res levels in both natural and experimental cases of TSE disease. Previously, we have shown high TSE infectivity levels in the brain tissue of mice that have a clinical TSE disease with associated vacuolar pathology but little or no detectable PrP-res. Here, the levels of TSE infectivity and PrP-res within a peripheral tissue of this mouse model were investigated. Biochemical analysis showed that low levels of PrP-res were present in the spleen tissue in comparison to the levels observed in the spleen of mice infected with ME7 or 79A. However, upon subpassage of brain and spleen tissue from clinically ill mice with little or no PrP-res detectable, similar short incubation periods to disease were observed, indicating that infectivity levels were similarly high in both tissues. Thus, the discrepancy between PrP-res and TSE infectivity was also present in the peripheral tissues of this disease model. This result indicates that peripheral tissues can contain higher levels of infectivity given the correct combination of host species, PrP genotype, and TSE agent. Therefore, the assumption that the levels of peripheral infectivity are lower than those in the central nervous system is not always correct, and this could have implications for current food safety regulations.
 
FOOTNOTES Received 19 December 2012. Accepted 7 March 2013. Address correspondence to Rona Barron, rona.barron@roslin.ed.ac.uk. Published ahead of print 13 March 2013
 
Copyright © 2013, American Society for Microbiology. All Rights Reserved.
 
 
 
 
 
 
 
2012
 
 
***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.
 
Second threat
 
snip...
 
 
 
MAD COW USDA ATYPICAL L-TYPE BASE BSE, the rest of the story...
 
***Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate Model
 
 
 
***Infectivity in skeletal muscle of BASE-infected cattle
 
 
 
***feedstuffs- It also suggests a similar cause or source for atypical BSE in these countries.
 
 
 
***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans.
 
 
 
The present study demonstrated successful intraspecies transmission of H-type BSE to cattle and the distribution and immunolabeling patterns of PrPSc in the brain of the H-type BSE-challenged cattle. TSE agent virulence can be minimally defined by oral transmission of different TSE agents (C-type, L-type, and H-type BSE agents) [59]. Oral transmission studies with H-type BSEinfected cattle have been initiated and are underway to provide information regarding the extent of similarity in the immunohistochemical and molecular features before and after transmission.
 
In addition, the present data will support risk assessments in some peripheral tissues derived from cattle affected with H-type BSE.
 
 
 
Sunday, August 26, 2012
 
Detection of PrPSc in peripheral tissues of clinically affected cattle after oral challenge with BSE
 
 
 
Monday, September 3, 2012
 
Sale of misbranded and/or non-inspected meat and meat products to Omaha Public Schools indicted
 
 
 
Thursday, September 05, 2013
 
Possible Patient Exposure to Creutzfeldt-Jakob Disease Announced New Hampshire DHHS
 
Press Release
 
 
 
Friday, July 19, 2013
 
Beaumont Hospital in Dublin assessing patients for CJD
 
 
 
Monday, April 15, 2013
 
Dr. Stephen B. Thacker Director Centers for Disease Control and Prevention′s Office of Science, Epidemiology and Laboratory Services (OSELS) dies from Creutzfeldt Jakob Disease CJD
 
 
 
Tuesday, July 31, 2012
 
11 patients may have been exposed to fatal disease Creutzfeldt-Jakob Disease CJD Greenville Memorial Hospital
 
 
 
Thursday, August 02, 2012
 
CJD case in Saint John prompts letter to patients Canada CJD case in Saint John prompts letter to patients
 
 
 
Wednesday, November 30, 2011
 
First iCJD Death Confirmed in Korea
 
 
 
Thursday, December 08, 2011
 
A case of Iatrogenic Creutzfeldt Jakob Disease (iCJD) in a patient who had received a German-manufactured human dura mater graft 23 years ago
 
 
 
Thursday, December 8, 2011
 
S. Korea confirms second case of iatrogenic Creutzfeldt-Jakob disease 48-year-old man
 
2011/12/08 11:08 KST
 
 
 
Monday, December 12, 2011
 
Second iatrogenic CJD case confirmed Korea
 
 
 
 
 
Saturday, February 12, 2011
 
Another Pathologists dies from CJD, another potential occupational death ?
 
another happenstance of bad luck, a spontaneous event from nothing, or friendly fire ??
 
 
 
 
Tuesday, March 29, 2011
 
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY EXPOSURE SPREADING VIA HOSPITALS AND SURGICAL PROCEDURES AROUND THE GLOBE
 
 Mad cow disease warning to 38 patients in Wales
 
 Section Health | Published on 29 Mar 2011
 
 Public Health Wales has contacted 38 patients who may have been put at risk of contracting Creutzfeldt-Jakob Disease (CJD) during surgery.
 
 CJD, an incurable brain disease, is commonly known as a human form of mad cow disease because bovine spongiform encephalopathy is the cause of variant Creutzfeldt-Jakob disease in humans.
 
 Letters were sent to those at risk after it became apparent that a patient who underwent surgery in a hospital in the Abertawe Bro Morgannwg Health Board area in 2007 was at high risk of the disease.
 
 All surgical instruments used on the patient were removed from use when the patient’s history became known, and all patients operated on with the same instruments in the interim have now been informed.
 
 Public Health Wales says that the risk of transmission of CJD from one patient to another via surgical instruments is extremely low. There have only ever been six cases worldwide of any form of CJD being transmitted in this way.
 
 Dr Jörg Hoffmann, Consultant in Communicable Disease Control for Public Health Wales, said: “In this incident, we do not have a single confirmed case of CJD. However, we do have one patient who was at high risk and 38 people at extremely low risk.
 
“We know that all the surgical instruments used on this group of patients were cleaned, disinfected and sterilised normally. However, it is possible that the proteins that cause CJD, known as prions, survived these routine sterilisation procedures so an extremely small risk of transmission remains.
 
“We have identified and written to all patients concerned to make them aware of the extremely low risk. They have been offered information and support and a helpline has been set up for anyone who has received a letter and has further questions.
 
“All patients at risk have been contacted and there is no risk to anybody else. People who have had any type of surgery in the Abertawe Bo Morgannwg Health Board area since 2007 but who have not been contacted by us have no reason at all to worry.”
 
CJD is a rare disease that affects the structures of the brain and causes incurable neurological symptoms. There is currently no treatment or cure for CJD.
 
 Anyone who is aware they are at increased risk of CJD should not donate blood or organs and should always inform their surgeon or other health care professional before undergoing any health procedure.
 
 More information on CJD is available from the Public Health Wales website at: http://www.wales.nhs.uk/sitesplus/888/page/43948
 
 
 
 
cjd and surgical instruments
 
 
 
 
 
Tulane Medical Center alerts patients after medical gear improperly sterilized
 
Published: Thursday, March 10, 2011, 9:30 PM
 
Tulane Medical Center has notified 360 patients that it failed to properly sanitize gastrointestinal scoping equipment used during seven weeks last fall, potentially exposing the group to various infectious diseases.
 
Dr. Robert Lynch, the hospital’s CEO, acknowledged the error in a Jan. 3 letter that invited affected patients to obtain free screening for hepatitis B, hepatitis C and HIV. The letter, however, characterized the chances of infection as “minimal to non-existent.”
 
Lynch cited a mistake in one of five steps in its sanitizing protocol and framed the tests as a way “to reassure patients whose procedures were impacted.”
 
State epidemiologist Dr. Raoult Ratard, who has conferred with Tulane officials about the case, said the chances of the equipment transmitting an infection “would be extremely, extremely small. I think Tulane just wants to be careful.”
 
That has not satisfied at least one patient, identified as “John Doe” in the lawsuit he filed Feb. 22 in Orleans Parish Civil District Court. The suit, which seeks class-action status, accuses the hospital of negligence and alleges a long list of harmful effects ranging from “mental anguish” to “loss of enjoyment of life.”
 
According to Lynch’s letter and a follow-up written statement released Thursday, a routine maintenance inspection confirmed that part of the disinfecting procedure for endoscopes and bronchoscopes did not occur at a sufficient temperature. The error persisted from Oct. 7 to Dec. 1 on equipment used for colonoscopies, sigmoidoscopies and upper-endoscopies of the stomach. “Once this was discovered, it was remediated immediately,” Lynch wrote, explaining that the hospital immediately contacted infection control experts, including the Ratard’s unit at the Louisiana Department of Health and Hospitals.
 
According to the Centers for Disease Control and Prevention, infection associated with the use of endoscopes occurs in about 1 in 1.8 million procedures, low odds but enough to make endoscopes the most likely medical device to yield outbreaks associated with health-care institutions.
 
 Neither the letter nor Tulane’s statement detailed its sanitizing procedure.
 
According to Ratard, the scopes in question cannot be sanitized using steam because of the likelihood of heat damage. Instead, the key step of the cleaning process calls for application of a chemical disinfectant or sterilant for a specified period of time at an elevated temperature. Ratard said the settings on the sanitizer were elevated, but still too low, though he could not recall specifics. He attributed the mistake to human error.
 
 Ratard characterized Tulane’s mistake as “fairly common” in American health care and said the hospital “has handled this by the book” by notifying patients and offering them several rounds of testing, along with follow-up counseling.
 
 Harvey attorney Ron Austin, lead counsel on John Doe’s class-action petition, said the hospital’s admission of error does not mitigate the risk involved for the affected patients.
 
“This is extremely serious, and it’s unfortunate,” he said. “They are petrified. They are extremely angry. How do you have that conversation with your partner that you may have HIV, and what of the social fallout for anyone who discovers that?”
 
The suit also names John Doe’s wife, Jane Doe, as a plaintiff, because of her potential exposure through the couple’s sexual relations.
 
 Austin said both Does have been tested for infectious diseases and both have been negative, though follow-up testing will be ordered because of the incubation periods of some viruses.
 
 The case has been assigned to Judge Paulette Irons, who will decide whether to certify the matter as a class action.
 
 Tulane Medical Center is jointly owned by the for-profit Health Care Corporation of America and Tulane University.
 
 A decade ago, the hospital suffered a black eye and a subsequent legal tussle when it announced that eight surgery patients had been exposed to a rare, incurable brain disorder because they all underwent operations using some of the same instruments used on a patient with Creutzfeldt-Jakob disease.
 
 Those incidents were not a clear-cut matter of errant sanitizing, however. With a similar pathology to mad-cow disease, Creutzfeldt-Jakob disease is spread through protein agents that, at least at the time, were resistant to standard sterilizing procedures. The condition was diagnosed with certainty in an initial Tulane surgery patient only after death.
 
 The hospital settled a negligence claim by one of the subsequently exposed patients. The financial terms were never disclosed. None of the eight is known to have developed the disease.
 
 Bill Barrow can be reached at bbarrow@timespicayune.com or 504.826.3452.
 
 Related topics: tulane medical center, tulane university
 
 
 
 
Saturday, September 11, 2010
 
 Brisbane hospital workers feared mad cow
 
 
 
 
snip...see full text ;
 
 
 
Tuesday, March 29, 2011
 
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY EXPOSURE SPREADING VIA HOSPITALS AND SURGICAL PROCEDURES AROUND THE GLOBE
 
 
 
 
Pathologist dies of suspected Creutzfeldt-Jakob (Mad cow) disease
 
29 March, 2009 03:33:00
 
Creutzfeldt-Jakob disease (mad cow) research pathologist Antonio Ruiz Villaescusa died Sat., March 28, from the disease. Colleagues suspect he may have contracted the disease from exposure to infected human tissue, according to the Barcelona Reporter newspaper.
 
Ruiz headed the department of pathology at the University Hospital in Madrid and was studying whether the disease is passed on to people who have been exposed to infected tissue.
 
The head of the pathology department at the Fundación Alcorcón, Dr. Radish, will perform an autopsy to clarify the cause of death and the final results will be announced in about a month, according to the Spanish news site.
 
Ruiz was recognized internationally for his study in the fields of neuropathology and anatomopatología, and devoted much of his professional life to the study of human transmissible spongiform encephalopathy.
 
Creutzfeldt-Jakob disease is a rare and invariably fatal brain disorder, according to the National Institute of Neurological Disorders and Stroke. There is currently no single diagnostic test for the disease. The only way to confirm a Creutzfeldt-Jakob disease diagnosis is by brain biopsy or autopsy.
 
 
 
 
 
 
 
e-mail: fpinedo@fhalcorcon.es e-mail: mpdominguez@fhalcorcon.es
 
 
Dr. Alberto Rábano Gutiérrez. Fundación Hospital Alcorcón. Madrid
 
 
 
 
 
 
Thursday, April 12, 2012
 
Health professions and risk of sporadic Creutzfeldt–Jakob disease, 1965 to 2010
 
Eurosurveillance, Volume 17, Issue 15, 12 April 2012
 
Research articles
 
 
 
 
Eurosurveillance, Volume 17, Issue 15, 12 April 2012
 
Research articles
 
Health professions and risk of sporadic Creutzfeldt–Jakob disease, 1965 to 2010
 
E Alcalde-Cabero1, J Almazán-Isla1, J P Brandel2, M Breithaupt3, J Catarino4, S Collins5, J Haybäck6, R Höftberger7, E Kahana8, G G Kovacs7,9, A Ladogana10, E Mitrova11, A Molesworth12, Y Nakamura13, M Pocchiari10, M Popovic14, M Ruiz-Tovar1, A L Taratuto15, C van Duijn16, M Yamada17, R G Will12, I Zerr3, J de Pedro Cuesta ()1 1.National Centre of Epidemiology - Consortium for Biomedical Research in Neurodegenerative Diseases (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas – CIBERNED), Carlos III Institute of Health, Madrid, Spain 2.Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS 975, National CJD Surveillance Network, Assistance publique - Hôpitaux de Paris (APHP), National Reference Centre for CJD, Pitié-Salpêtrière Hospital Group, Paris, France 3.Department of Neurology, National Reference Centre for TSE, Georg-August University, Göttingen, Germany 4.Alameda Epidemiology and Health Statistics Department, Lisbon, Portugal 5.Department of Pathology, University of Melbourne, Melbourne, Australia 6.Institute of Neuropathology, Zurich University Hospital, Zurich, Switzerland 7.Institute of Neurology, Vienna Medical University, Vienna, Austria 8.Department of Neurology, Barzilai Medical Centre, Ashkelon, Israel 9.National Reference Centre for Human Prion Diseases, Semmelweis University, Budapest, Hungary 10.Department of Cell Biology and Neurosciences, Health Institute, Rome, Italy 11.Department of Prion Diseases, Slovak Medical University Research Base, Bratislava, Slovakia 12.National CJD Research and Surveillance Unit, Western General Hospital, Edinburgh, United Kingdom 13.Department of Public Health, Jichi Medical University, Shimotsuke, Japan 14.Institute of Pathology, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia 15.Department of Neuropathology/FLENI, Referral Centre for CJD and other TSEs, Institute for Neurological Research, Buenos Aires, Argentina 16.National Surveillance of CJD, Erasmus MC, Rotterdam, The Netherlands 17.Neurology Department, Kanazawa University Hospital, Kanazawa, Japan
 
--------------------------------------------------------------------------------
 
 Citation style for this article: Alcalde-Cabero E, Almazán-Isla J, Brandel JP, Breithaupt M, Catarino J, Collins S, Haybäck J, Höftberger R, Kahana E, Kovacs GG, Ladogana A, Mitrova E, Molesworth A, Nakamura Y, Pocchiari M, Popovic M, Ruiz-Tovar M, Taratuto AL, van Duijn C, Yamada M, Will RG, Zerr I, de Pedro Cuesta J. Health professions and risk of sporadic Creutzfeldt–Jakob disease, 1965 to 2010 . Euro Surveill. 2012;17(15):pii=20144. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20144 Date of submission: 04 November 2011
 
--------------------------------------------------------------------------------
 
 
In 2009, a pathologist with sporadic Creutzfeldt–Jakob Disease (sCJD) was reported to the Spanish registry. This case prompted a request for information on health-related occupation in sCJD cases from countries participating in the European Creutzfeldt Jakob Disease Surveillance network (EuroCJD). Responses from registries in 21 countries revealed that of 8,321 registered cases, 65 physicians or dentists, two of whom were pathologists, and another 137 healthcare workers had been identified with sCJD. Five countries reported 15 physicians and 68 other health professionals among 2,968 controls or non-cases, suggesting no relative excess of sCJD among healthcare professionals. A literature review revealed: (i) 12 case or small case-series reports of 66 health professionals with sCJD, and (ii) five analytical studies on health-related occupation and sCJD, where statistically significant findings were solely observed for persons working at physicians' offices (odds ratio: 4.6 (95 CI: 1.2–17.6)). We conclude that a wide spectrum of medical specialities and health professions are represented in sCJD cases and that the data analysed do not support any overall increased occupational risk for health professionals. Nevertheless, there may be a specific risk in some professions associated with direct contact with high human-infectivity tissue.
 
 
snip...
 
 
Discussion
 
Despite a number of case reports of sCJD in physicians and technicians, the findings of this EuroCJD survey do not suggest an increased risk of sCJD in health professionals, nor do analytical studies show a clear excess risk for health-related professions. Methodological limitations of analytical studies in which occupational data were frequently provided by informants who were probably aware of the sCJD diagnosis [3-7,26] argue in favour of a cautious interpretation of the positive association reported for persons working at physicians’ offices [19]. Consequently, the main finding of this literature review and complementary EuroCJD observation is that health professionals, including medical staff, are not at greater risk of developing sCJD. However, this cannot exclude the possibility that there may be an occupational risk in specific circumstances, for example, for people in contact with high-risk central nervous system tissue, and appropriate precautions, as recommended by national authorities, should therefore be followed, particularly regarding laboratory work.
 
Although in some studies occupation was specifically analysed [19,25] and occupation may be the subject of specific inquiry in some surveillance systems, a limitation of some registries and scientific studies is that occupation may not have been systematically recorded. When occupation was recorded, it is unlikely that a framework for consistent occupational data collection was used, so that neither registries nor case–control studies have incorporated the classic epidemiological double approach. Recording of occupation may not identify specific chemical or biological exposures, which would require data for professions (job titles, medical specialisations) being cross-referenced with branches of activity (laboratory, administrative or clinical patient-contact work). The lack of registered surveillance data that combine profession with activity (e.g. contact with human tissue), when compared with the descriptions from previous case reports and the incident in Spain, illustrates the limits of the validity of available data for analytical purposes and precludes formal use of statistical testing. Although our study does not provide evidence of an excess risk of sCJD in health professionals, the fact that the data collected were mainly linked to medical speciality rather than actual activity might have concealed an excess risk of sCJD for some specific health professionals.
 
A case–control study seeking to examine the putative occupational risk posed by surgical injuries should have a biologically clear working hypothesis and a custom-tailored methodology. Matrices designed by linking medical speciality and surgical/forensic-anatomical/pathological activity, in which the health professional can come into direct contact with high human-infectivity tissue by accident might not provide a sufficient background for analysis, without appropriate control being made for the influence of PRNP genotype, surgical or laboratory work history and long latency. Assuming that among non-cases or controls the proportion of medical specialities with potential exposure (surgeons, forensic surgeons and other surgical specialists, pathologists) may be low, i.e. approximately 1 per 1,000 (based on the figures of 3/2,968 in Table 2), the study size that would afford the necessary statistical power for a proper examination of the specific practices of health professions is higher than that provided by existing CJD registries in any one country. Since complementary analyses would be needed for professional and activity categories defined in terms of temporal references that have not been explored to date, such as ‘ever employed’ or ‘currently employed’, as well as duration of employment, requirements for study size and collaboration would be even higher.
 
In conclusion, a wide spectrum of medical specialities and health professions are represented in sCJD registries. Although selection due to higher ascertainment may lie behind the case reports of certain professions involved in clinical management or care of patients with sCJD, the biological significance of these observations remains uncertain and available data do not indicate an increased risk of sCJD in health professionals. However, the methodological issues mentioned above indicate the need for caution in drawing conclusions from the data and large-scale studies with specific causal hypotheses are needed in order for further research to be undertaken into the potential link between health professions and sCJD.
 
 
 
 
 
 
Wednesday, December 28, 2011
 
FDA Targets Risks From Reused Devices
 
 
 
 
From: TSS
 
Subject: Investigation of a Possible Iatrogenic Case of Creutzfeldt-Jakob Disease After a Neurosurgical Procedure
 
Date: December 10, 2006 at 12:10 pm PST
 
 
Investigation of a Possible Iatrogenic Case of Creutzfeldt-Jakob Disease After a Neurosurgical Procedure
 
 
Natalie Keeler, DVM, Lawrence B. Schonberger, MD, Ermias D. Belay, MD, Lynne Sehulster, PhD, George Turabelidze, MD, and James J. Sejvar, MD
 
Volume 27(2006), pages 1352 - 1357 DOI: 10.1086/509844
 
Abstract Objective. To investigate a case of Creutzfeldt-Jakob disease (CJD) possibly acquired from contaminated neurosurgical instruments.
 
Design. Retrospective review of medical records, hospital databases, service log books, and state vital statistics.
 
Setting. A tertiary care hospital (hospital A) in Missouri.
 
Patients. The case patient was a 38-year-old African American woman with a 9-month history of progressive memory loss, visual disturbances, and dementia. She underwent neurosurgery in November 1996. CJD was confirmed in April 2004 by immunodiagnostic testing of brain biopsy samples. All patients who underwent neurosurgery at the same hospital within 6 months before or after the case patient's procedure were identified and investigated for preoperative or postoperative evidence of CJD.
 
Results. We reviewed data on 268 neurosurgical procedures, 84 pathology log entries, and 60 death certificates for neurosurgical patients at hospital A and identified 2 suspected cases of CJD. Clinical features and definitive prion testing of stored brain biopsy samples excluded a diagnosis of CJD. Standard operating room procedures were in place, but specific protocols for handling instruments potentially contaminated with prions were not used.
 
Conclusions. Neurosurgical instruments were not implicated as the source exposure for CJD in the case patient. The 2 patients with suspected CJD were identified from different data sources, suggesting good internal consistency in data collection. The key elements of this investigation are suggested for use in future investigations into potential cases of iatrogenic CJD.
 
 
 
 
 
Diseases and Conditions Reportable In Missouri (19 CSR 20-20.020)
 
Numbers in parenthesis represent ICD-9 and ICD-10 Codes
 
Report Diseases and Conditions to your local health agency or to:
 
Missouri Department of Health and Senior Services during business hours 573-751-9071, after hours
 
and on weekends 800-392-0272 or by fax 573-751-6417
 
2. Category II diseases or findings and their
 
reporting requirements are –
 
(A) Category IIA diseases or finding shall be
 
reported to the local health authority or the
 
Department of Health and Senior Services within
 
three (3) days of first knowledge or suspicion.
 
Category IIA diseases or findings are—
 
snip...
 
* Creutzfeldt-Jakob disease (046.1, A81.0)
 
snip...end...TSS
 
 
 
 
-------- Original Message --------
 
Subject: Re: A NEW BRUNSWICKER REPORTED DEAD OF CJD AFTER BRAIN SURGERY (7 CJD cases possible in N.B., officials say)
 
Date: Fri, 26 Sep 2003 17:11:39 –0500
 
From: "Terry S. Singeltary Sr."
 
Reply-To: Bovine Spongiform Encephalopathy
 
To: BSE-L@uni-karlsruhe.de
 
References: <3f71d32b .5000506="" wt.net=""> <3f72fb5f .5030205="" wt.net=""> <3f743ce8 .8070804="" wt.net="">
 
European Journal of Epidemiology 16 (4) p.353-355 April 2000 Kluwer
 
Creutzfeldt–Jakob Disease in health professionals in Slovakia Mitrová Eva1 and Belay Girma1
 
1.Institute of Preventive and Clinical Medicine, Limbová 14, 833 01 Bratislava, Slovakia
 
 
Creutzfeldt–Jakob disease (CJD) is the most important human transmissible spongiform encephalopathy (prion disease), recognised in sporadic, genetic but also iatrogenic forms. The identification of 8 health care workers in a group of 114 definitive CJD patients in Slovakia suggested the possibility of professionaly acquired CJD and induced the investigation of potential endo- and exogenous risk factors. In CJD-affected health professionals special attention was paid to a detailed occupational history, including a possible professional contact with CJD patient and to the findings characteristic for iatrogenic CJD: early cerebellar symptomatology, long duration of the disease, absence of typical EEG finding and homozygosity of PRNP gene at codon 129. Analysis of epidemiological, clinical and molecular biological data in investigated group of CJD-affected health professionals gave no evidence of an occupational risk for CJD.
 
??? Creutzfeldt–Jakob disease, Health professionals, Iatrogenic
 
PDF(63K)
 
BibTex
 
EndNode
 
 Copyright© 2000 Kluwer Academic Publishers All rights reserved
 
 
 
 
comments from Tom about these cases;
 
 
Comment (webmaster): 7% of sporadic CJD in health professionals is way too high to occur by chance, despite the tone of the abstract. Now the first thing Dr. Mitrova would have done is rule out familial CJD of the form E200K, which has a very extensive cluster in Slovakia, though the abstract does not really say what was sequenced besides codon 129 of the prion gene. Little credence can be given to the idea that a characteristic pattern exists for iatrogenic CJD, which is a total hodge-podge after the dominant forms, growth hormone and dura mater, are subtracted.
 
 
One very real possibility in Slovakia is that the high numbers of E200K cases, prior to diagnosis, has led to a secondary epidemic in health care workers. This source would be missed by epidemiology because only exposure to clinical E200K (hospice workers) would be considered.
 
 
One clear-cut case of a health worker at occupational risk is the orthopedic surgeon who removed dura mater from sheep brain for the company in Germany selling dura mater for human transplants.
 
 
Until Germany conducts a Prionics-type survey of its sheep, we will have no real idea of the prevalence of scrapie there. The whole dura mater tragedy unfolding in Japan may have resulted from sheep dura mater being used instead of human cadaver. If so, this unfortunate 'experiment' would prove transmissibility of scrapie to humans (though who would doubt this in a scrapie dura mater brain transplant?).
 
 
Spinal dura contains elastin and collagen gene products, which would allow the species origin of the transplant to be determined even decades later (if it is not resorbed). Thus it is still possible to determine is causing the Japanese dura mater outbreak.
 
 
The other related case of a possibly affected caregiver is a husband-and-wife pair who contracted sporadic CJD within a few years of each other:
 
 
 
 
i'd say this doctor has seemingly misrepresented medical information that was readily available to him from official Health Canada web sites and prominent previous alerts that he and his hospital would have previously received.
 
 
Tutogen Medical, Inc. was formerly known as Pfrimmer-Viggo GmbH+Co, Erlangen, Germany). Their Canadian distributor is listed as Centerpulse Dental Canada (hmmm) where in the US it is Tutogen Medical Inc.[Product lines: Dental, Spine, Membrans, Sports Medicine, Bone (more hmmm) ]
 
 
 
 
what would you call this Health Canada statement ...
 
 
"The April 2001, edition of "Neurology" published details of the first case of classical Creutzfeldt-Jakob Disease (CJD) associated with the use of Tutoplast Dura. Following the publication of this news, Health Canada took action to obtain further information on the current surgical need for the use of Tutoplast Dura in Canada. It wrote to orthopaedic, neurosurgical and otolaryngological professional associations seeking advice on the importance to their members of the continued availability of Tutoplast dura mater. The Canadian Neurosurgical Society (CNSS) responded by conducting a survey of their members. Of those who replied, 61% supported discontinuing the use of donor dura mater.
 
 
On April 10, 2002, Health Canada suspended the medical device licence for Tutoplast Dura. The suspension means that the importation and sale of this medical device is no longer permitted in Canada. Tutoplast Dura manufactured before 1992 was processed with a less concentrated disinfectant solution than material manufactured after October 1992. The disinfectant used initially, which was in accordance with what was known regarding prion diseases at the time, was a ten times weaker solution of sodium hydroxide than was used starting in 1992. Tutoplast Dura (manufactured by Tutogen Medical GmbH of Germany) was first sold in Canada in January, 1982."
 
 
On the company's website in Germany, it seems they have now gone over to Tutomesh ... from bovine pericardium " that is prepared using the TUTOPLAST® procedure thus eliminating antigenic properties"
 
 
 
 
Some previous experiences in Japan:
 
 
"The most recent recipient of a dura mater graft among the 43 graft-associated CJD patients was a woman aged 65 years at the time of onset of CJD. She had two neurosurgical procedures in 1991 to repair a cerebral arterial aneurysm (one in September and one in October); dura mater grafts were used during both operations. In February 1994, 28 months after the second operation, she developed progressive dysphagia, dysarthria, and unsteady gait, followed within a few weeks by dementia. In April 1995, she developed generalized myoclonic jerks and akinetic mutism. An electroencephalograph showed a 6- to 10-Hz background rhythm with the periodic synchronized slow activity complexes typical of CJD. Examination of the cerebrospinal fluid revealed a normal protein level and cell count. A magnetic resonance imaging scan showed marked cerebral and cerebellar atrophy. The patient died in October 1995, and no autopsy was performed.
 
 
Neither the brand nor year of processing of the dura mater grafts used in this patient in 1991 could be determined. However, the hospital in which both neurosurgical procedures were performed opened in 1989 and reported using only two brands of dura mater grafts in 1991, LYODURA{Registered} and Tutoplast (Pfrimmer-Viggo GmbH+Co, Erlangen, Germany). The investigation suggested that in this pa tient, the use of LYODURA{Registered} processed before May 1987 was unlikely but could not be ruled out.
 
 
 
... Even stringent donor screening and processing of each dura separately to avoid possible cross-contamination may not completely eliminate the potential for an infectious graft. In addition, the treatment of dura with NaOH may not inactivate all of the infectious agent that may be present (6). Therefore, surgeons should be aware of the possibly inherent risk for CJD transmission by dura mater grafts and may want to consider the alternative use of autologous fascia lata, fascia temporalis, or synthetic substitutes (4). "
 
 
 
 
 
September 2003
 
Information
 
Tutoplast Dura mater
 
Health Canada is the national authority that regulates the safety, efficacy and quality of therapeutic products (such as medical devices) used in Canada. It derives its statutory authority over therapeutic products from the Food and Drugs Act and Regulations.
 
Tutoplast Dura mater is a medical device that was available in Canada between January 1982 and April 2002 for use in various surgical treatments, including neurosurgery.
 
The term "medical device" covers a wide range of products used in the treatment, mitigation, diagnosis or prevention of a disease or abnormal physical condition. Some examples include pacemakers, artificial heart valves, hip implants, synthetic skin, medical laboratory diagnostic instruments, test kits for diagnosis and contraceptive devices.
 
The Medical Devices Bureau of the Therapeutic Products Directorate (TPD) at Health Canada is the national authority that monitors and evaluates the safety, effectiveness and quality of diagnostic and therapeutic medical devices in Canada. The Medical Devices Bureau enforces the Medical Devices Regulations, which aim to ensure to the extent possible, the safety, effectiveness and quality of medical devices in Canada. This is done through a combination of pre-market review, post-approval surveillance and quality systems in the manufacturing process.
 
In Canada, certain medical devices must have a Medical Device Licence before they can be sold. To determine which ones need a Licence, all medical devices have been categorized based on the risk associated with their use. This approach means that all medical devices are grouped into four classes with Class I devices presenting the lowest potential risk (e.g. a thermometer) and Class IV devices presenting the greatest potential risk (e.g. pacemakers).
 
Prior to selling a medical device in Canada, manufacturers of Class II, III and IV devices must obtain a Medical Device Licence. Although Class I devices do not require a Licence, they are monitored through Establishment Licences.
 
What is Tutoplast dura mater?
 
Dura mater is a tissue that covers and protects the brain and spinal cord. Commercially processed dura mater, obtained from human donors, has been used in the surgical treatment of many conditions in Canada since the 1970s.
 
Tutoplast Dura manufactured before 1992 was processed with a less concentrated disinfectant solution than material manufactured after October 1992. The disinfectant used initially, which was in accordance with what was known regarding prion diseases at the time, was a ten times weaker solution of sodium hydroxide than was used starting in 1992.
 
Processed dura mater is regulated as a class IV medical device. Tutoplast Dura (manufactured by Tutogen Medical GmbH of Germany) was first sold in Canada in January, 1982.
 
The April 2001, edition of "Neurology" published details of the first case of classical Creutzfeldt-Jakob Disease (CJD) associated with the use of Tutoplast Dura.
 
Following the publication of this news, Health Canada took action to obtain further information on the current surgical need for the use of Tutoplast Dura in Canada. It wrote to orthopaedic, neurosurgical and otolaryngological professional associations seeking advice on the importance to their members of the continued availability of Tutoplast dura mater. The Canadian Neurosurgical Society (CNSS) responded by conducting a survey of their members. Of those who replied, 61% supported discontinuing the use of donor dura mater.
 
On April 10, 2002, Health Canada suspended the medical device licence for Tutoplast Dura. The suspension means that the importation and sale of this medical device is no longer permitted in Canada.
 
Physicians were advised at the time to place any existing Tutoplast product in a secure location and immediately inform the manufacturer or distributor.
 
This action was based on the following considerations:
 
Advice received through Health Canada's consultation with the Canadian Neurosurgical Society The recommendations of a leading Canadian expert on prion illness (Dr. Neil Cashman). The availability of adequate alternative materials that can be used instead of commercially-processed dura mater obtained from human donors.
 
The Canadian distributor of Tutoplast Dura conducted the recall of the product as per Health Canada's request.
 
The day following the suspension of the licence (April 11, 2002), Health Canada initiated an Import Alert with Canadian Customs.
 
Health Canada informed international partners of the suspension and recall action through the National Competent Authority Report system. Health Canada forwarded copies of the medical device suspension letter and of the Safety Advisory to the German authorities for information pertaining to the manufacturer Tutogen Medical GmbH in their jurisdiction.
 
Health Canada sent a letter to health care professionals on April 11, 2002, advising them:
 
Not to use Tutoplast Dura manufactured by Tutogen Medical GmbH in any surgical procedure, as it is no longer licensed for sale in Canada. To place any remaining stocks of Tutoplast Dura in a secure location so that it can no longer be used and immediately inform the manufacturer or distributor who sold the product.
 
Individuals who want more information on the recall may leave a message on the Medical Devices Hotline at 1-800-267-9675. A Health Canada official will return the call.
 
Last Updated: 2003-09-24
 
TSS
 
 
Terry S. Singeltary Sr. wrote:
 
 
> I was amazed at the comment the doctor made about this in an
> article yesterday. i had to send a note to him.....tss
>
> snip...
>
> Dr. Dow said he doubted that the woman had died of an infected brain
> patch. And while there is a theoretical risk that the disease could be
> spread through instruments contaminated with prion proteins from a
> patient with CJD, he added to my knowledge there has been no proven
> case of a neurosurgical instrument contaminated with protein from a
> patient with CJD causing infection in another patient.
>
> snip...
>
> end
>
>
>
> what do you call this;
>
> 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]
>
>
>
>
> 7 CJD cases possible in N.B., officials say
> Brain-wasting ailment confirmed in woman who died in July, after she had
> neurosurgery
>
> RICHARD FOOT
> CanWest News Service
>
>
> Thursday, September 25, 2003
> ADVERTISEMENT
>
> Click here to find out more!
>
>
>
>
>
>
> New Brunswick health officials have warned seven former hospital
> patients they may have contracted Creutzfeldt-Jakob disease during
> neurosurgery in Moncton, N.B., following the death of a woman this
> summer from the rare but fatal brain-wasting illness.
>
> The woman died on July 31, about six weeks after undergoing neurosurgery
> at Moncton Hospital, where doctors noticed she was showing symptoms of
> the disease.
>
> On Monday, autopsy results of her brain tissue confirmed she died of
> classical Creutzfeldt-Jakob disease, or CJD.
>
> Only about 30 Canadians are diagnosed each year with classical CJD,
> which is a related but separate illness from the human form of mad cow
> disease, called variant-CJD.
>
> "I want to make it very clear that this is not a case of mad cow
> disease,'' Gordon Dow, the hospital's chief of infectious diseases, said
> yesterday in Moncton.
>
> How the woman contracted classical CJD remains a mystery. It's also
> unclear what specific type of infection she had.
>
> If she died of sporadic CJD, her death poses no risk to the seven other
> patients. However, officials cannot rule out the chance she died of a
> less common form called iatrogenic CJD.
>
> This is contracted when the disease is mistakenly passed from one person
> to another, through shared surgical instruments or through brain tissue
> transplants. The woman may have been infected during a brain tissue
> transplant on her spinal cord in 1992, when doctors implanted a tissue
> graft taken from the brains of human cadavers.
>
> The type of implant used in 1992, known as Tutoplast dura mater, was
> banned by Health Canada last year because of concerns that it could
> transmit CJD.
>
> The woman returned to hospital for a second operation in June this year,
> and died shortly afterwards. The instruments used in her operation have
> since been incinerated, but of the seven patients warned in the wake of
> the woman's death, two may have been exposed to those instruments before
> they were destroyed. Five others received similar brain tissue
> transplants in the early 1990s.
>
> © Copyright 2003 Montreal Gazette
>
>
>
> Terry S. Singeltary Sr. wrote:
>
>>
>>
>> Brain-wasting disease confirmed in N.B. woman
>>
>>
>> By LUMA MUHTADIE
>> Globe and Mail Update
>>
>>
>>
>>
>>
>>
>> A New Brunswick woman died in hospital from Creutzfeldt-Jakob disease,
>> health officials in Moncton announced on Wednesday.
>>
>> Officials stressed that the case of so-called “classical” CJD cannot
>> spread from person to person, and is not connected to the variant of the
>> disease, which has been linked to mad cow or bovine spongiform
>> encephalopathy.
>>
>> “This is not a case of mad cow disease,” Gordon Dow, chief of infectious
>> diseases at Moncton Hospital, told the press conference.
>>
>> However, health officials said that tests were inconclusive as to
>> whether the disease developed spontaneously in the 55-year-old woman (as
>> it does in about 30 Canadians a year) or whether it was iatrogenic,
>> meaning it resulted from an infection acquired during a medical
>> procedure.
>>
>> In 1992, doctors in Moncton grafted a patch made from tissue taken from
>> a human corpse onto the woman's brain. She returned to the Moncton
>> Hospital in June for a secondary neurosurgical operation, and in a
>> follow-up consultation on June 18, possible CJD was diagnosed. She died
>> on July 31 and the diagnosis of CJD was confirmed through an autopsy on
>> Monday.
>>
>> Health Canada banned the use of brain-tissue patches taken from human
>> corpses last year due to CJD fears.
>>
>> Dr. Dow said he doubted that the woman had died of an infected brain
>> patch. And while there is a theoretical risk that the disease could be
>> spread through instruments contaminated with prion proteins from a
>> patient with CJD, he added “to my knowledge there has been no proven
>> case of a neurosurgical instrument contaminated with protein from a
>> patient with CJD causing infection in another patient.”
>>
>> He said it would be very useful to know if the patient represented a
>> sporadic form of CJD, in which case there would be “absolutely no risk
>> to anybody else” or if she acquired the disease from the graft she
>> received in 1992, “whereby potentially, other patients could have been
>> exposed to the same graft.”
>>
>> As a safety measure, the Moncton Hospital quarantined all neurosurgical
>> and spinal instruments in the region, later narrowing the quarantine to
>> only those instruments used in the woman's more recent operation.
>>
>> The hospital also searched the charts of all patients who received graft
>> surgery within one year on either side of the woman's original surgery
>> -– or from 1991 to 1993 -– to identity all potential recipients of the
>> same graft. Seven individuals were found and informed that they were at
>> a small risk of infection.
>>
>> CJD is a degenerative disease of the central nervous system that
>> initially alters the personality or makes social interaction difficult,
>> but quickly progresses into problems with speech, memory and vision. It
>> eventually leads to motor problems such as stiffness, paralysis and
>> twitching.
>>
>> “During this rapid deterioration, patients quickly become confined to
>> bed in a mute, paralyzed state -- probably in a semi-comatose state --
>> with very little insight or understanding ... or sensation of their
>> illness and subsequently die,” Dr. Dow said.
>>
>> It generally takes six months from the onset of symptoms until death.
>> There is currently no treatment available for CJD.
>>
>>
>>
>>
>> spontaneous my @ss..... how can these people continue to believe that
>> 85%+ of all CJDs happen from nothing (a spontaneous happening without
>> route and source). this is total BSeee and they cannot prove this. it is
>> only
>> wishful thinking by scientist and there politicians that advocate this
>> myth $$$
>>
>> TSS
>>
>> Terry S. Singeltary Sr. wrote:
>>
>>> ######## Bovine Spongiform Encephalopathy
>>> #########
>>>
>>> New Brunswicker reported dead of Creutzfeldt-Jakob
>>> Last Updated Wed, 24 Sep 2003 12:25:17
>>>
>>> MONCTON - A New Brunswick resident has died of Creutzfeldt-Jakob
>>> disease
>>> after brain surgery, CBC has learned.
>>>
>>> Sources tell CBC News that this case was not the CJD variant caused by
>>> eating tainted beef and is not related to bovine spongiform
>>> encephalopathy, or mad cow disease.
>>>
>>> Diagnosis of the disease cannot be confirmed until after death.
>>>
>>> Public health authorities are expected to hold a news conference later
>>> Wednesday to release more details.
>>>
>>> * FROM APRIL 13, 2002: Health Canada bans 'brain patch' linked to
>>> brain disease
>>>
>>> <%20%0Ahttp://www.cbc.ca/storyview/CBC/2002/04/12/Consumers/brainpatch_020412>
>>>
>>>
>>>
>>> * FROM MAY 9, 2001: Possible Creutzfeldt-Jakob case reported in
>>> Windsor
>>>
>>> Classical CJD, which occurs naturally in a small number of people, can
>>> be transmitted by transplants of human tissue.
>>>
>>> The disease affects the central nervous system.
>>>
>>> It occurs in the world population at a rate of about one case per
>>> million people per year – about 30 cases are diagnosed each year in
>>> Canada. Most cases die within months.
>>>
>>> Written by CBC News Online staff
>>>
>>>
>>> it would be most interesting how this hospital has handled the
>>> quarantining
>>> of the surgical instruments and the operating/surgical arena after this
>>> surgery
>>> and the finding of CJD in the patient. were the instruments used on
>>> this
>>> victim used on any other persons and can they trace all tools ??
>>>
>>> TSS
>>>
>>> ############
>>>
>>
>>
>
>
 
 
 
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]
 
 
 
 
 
 
Thursday, July 08, 2010
 
Nosocomial transmission of sporadic Creutzfeldt–Jakob disease: results from a risk-based assessment of surgical interventions Public release date: 8-Jul-2010
 
 
 
 
Thursday, July 08, 2010
 
GLOBAL CLUSTERS OF CREUTZFELDT JAKOB DISEASE - A REVIEW 2010
 
 
 
Tuesday, May 28, 2013
 
Late-in-life surgery associated with Creutzfeldt-Jakob disease: a methodological outline for evidence-based guidance
 
 
 
Wednesday, June 02, 2010
 
CJD Annex H UPDATE AFTER DEATH PRECAUTIONS Published: 2 June 2003 Updated: May 2010
 
 
 
 
 Tuesday, May 11, 2010
 
 Current risk of iatrogenic Creutzfeld–Jakob disease in the UK: efficacy of available cleaning chemistries and reusability of neurosurgical instruments
 
 
 
 
Tuesday, May 04, 2010
 
 Review of the Human Pituitary Trust Account and CJD Issue 20 January 2010
 
 
 
 
Tuesday, March 16, 2010
 
Transmissible Spongiform Encephalopathy Agents: Safe Working and the Prevention of Infection: Part 4 REVISED FEB. 2010
 
 
 
 
Monday, August 17, 2009
 
 Transmissible Spongiform Encephalopathy Agents: Safe Working and the Prevention of Infection: Annex J,K, AND D Published: 2009
 
 
 
 
 Monday, July 20, 2009
 
Pre-surgical risk assessment for variant Creutzfeldt-Jakob disease (vCJD) risk in neurosurgery and eye surgery units
 
 
 
 
 Friday, July 17, 2009
 
Revision to pre-surgical assessment of risk for vCJD in neurosurgery and eye surgery units Volume 3 No 28; 17 July 2009
 
 
 
 
Sunday, May 10, 2009
 
 Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (Singeltary submission)
 
 
 
 
Thursday, January 29, 2009
 
Medical Procedures and Risk for Sporadic Creutzfeldt-Jakob Disease, Japan, 1999-2008 (WARNING TO Neurosurgeons and Ophthalmologists) Volume 15, Number 2-February 2009 Research
 
 
 
 
Wednesday, August 20, 2008
 
 Tonometer disinfection practice in the United Kingdom: A national survey
 
 
 
 
Tuesday, August 12, 2008
 
 Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007 (occupational exposure to prion diseases)
 
 
 
 
Monday, December 31, 2007
 
 Risk Assessment of Transmission of Sporadic Creutzfeldt-Jakob Disease in Endodontic Practice in Absence of Adequate Prion Inactivation
 
 
 
 
Subject: CJD: update for dental staff
 
 Date: November 12, 2006 at 3:25 pm PST
 
1: Dent Update. 2006 Oct;33(8):454-6, 458-60.
 
 CJD: update for dental staff.
 
 
 
Tuesday, December 18, 2012
 
Bioassay Studies Support the Potential for Iatrogenic Transmission of Variant Creutzfeldt Jakob Disease through Dental Procedures
 
 
 
Thursday, January 17, 2013
 
TSE guidance, surgical, dental, blood risk factors, Part 4 Infection control of CJD, vCJD and other human prion diseases in healthcare and community settings (updated January 2013)
 
 
 
Tuesday, May 28, 2013
 
Late-in-life surgery associated with Creutzfeldt-Jakob disease: a methodological outline for evidence-based guidance
 
 
 
Sunday, June 9, 2013
 
TSEAC March 14, 2013: Transmissible Spongiform Encephalopathies Advisory Committee Meeting Webcast
 
 
 
Friday, August 16, 2013
 
*** Creutzfeldt-Jakob disease (CJD) biannual update August 2013 U.K. and Contaminated blood products induce a highly atypical prion disease devoid of PrPres in primates
 
 
 
Sunday, August 11, 2013
 
Creutzfeldt-Jakob Disease CJD cases rising North America updated report August 2013
 
*** Creutzfeldt-Jakob Disease CJD cases rising North America with Canada seeing an extreme increase of 48% between 2008 and 2010
 
 
 
From: Terry S. Singeltary Sr.
 
Sent: Saturday, September 07, 2013 12:33 PM
 
To: jon.burns@house.ga.gov
 
Cc: stephen.allison@house.ga.gov ; jimmy.pruett@house.ga.gov ; sharon.beasley-teague@house.ga.gov ; rbruce5347@aol.com ; pam.dickerson@house.ga.gov ; emory.dunahoo@house.ga.gov ; earl@ehrhart.4emm.com ; david.knight@house.ga.gov ; tommccall@bellsouth.net ; john.meadows@house.ga.gov ; jay.roberts@house.ga.gov ; jason.shaw@house.ga.gov ; jason.spencer@house.ga.gov ; al.williams@house.ga.gov
 
Subject: Georgia House Bill 1043 and Chronic Wasting Disease CWD
 
Greetings Honorable Representatives of the House, Game, Fish, & Parks,
 
I wish to submit some recent science about chronic wasting disease cwd from the Prion2013 congressional abstracts.
 
I lost my mother to hvCJD ‘confirmed’, and have been following the mad cow follies for almost 16 years daily. sadly, cwd is just another part of those follies.
 
I have studied and kept up with these follies daily for almost 16 years, as a layperson.
 
I believe that when officials are making decisions, they need all the scientific information available to make sound decisions. many times this does not happen due to the industries involved and politics and greed there from.
 
So, I send this science on the cwd tse prion disease in good faith.
 
TO date, with the limited CWD testing in Georgia, CWD has not been detected. does not mean it is not already there. BUT, if you approve Bill 1043, the chances of CWD being introduced into your state goes up greatly.
 
Inactivation of the TSE Prion disease
 
Chronic Wasting Disease CWD, and other TSE prion disease, these TSE prions know no borders.
 
these TSE prions know no age restrictions.
 
The TSE prion disease survives ashing to 600 degrees celsius, that’s around 1112 degrees farenheit.
 
you cannot cook the TSE prion disease out of meat.
 
you can take the ash and mix it with saline and inject that ash into a mouse, and the mouse will go down with TSE.
 
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production as well.
 
the TSE prion agent also survives Simulated Wastewater Treatment Processes.
 
IN fact, you should also know that the TSE Prion agent will survive in the environment for years, if not decades.
 
you can bury it and it will not go away.
 
The TSE agent is capable of infected your water table i.e. Detection of protease-resistant cervid prion protein in water from a CWD-endemic area.
 
it’s not your ordinary pathogen you can just cook it out and be done with. that’s what’s so worrisome about Iatrogenic mode of transmission, a simple autoclave will not kill this TSE prion agent.
 
New studies on the heat resistance of hamster-adapted scrapie agent: Threshold survival after ashing at 600°C suggests an inorganic template of replication
 
The infectious agents responsible for transmissible spongiform encephalopathy (TSE) are notoriously resistant to most physical and chemical methods used for inactivating pathogens, including heat. It has long been recognized, for example, that boiling is ineffective and that higher temperatures are most efficient when combined with steam under pressure (i.e., autoclaving). As a means of decontamination, dry heat is used only at the extremely high temperatures achieved during incineration, usually in excess of 600°C. It has been assumed, without proof, that incineration totally inactivates the agents of TSE, whether of human or animal origin.
 
 
 
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production
 
Histochemical analysis of hamster brains inoculated with the solid residue showed typical spongiform degeneration and vacuolation. Re-inoculation of these brains into a new cohort of hamsters led to onset of clinical scrapie symptoms within 75 days, suggesting that the specific infectivity of the prion protein was not changed during the biodiesel process. The biodiesel reaction cannot be considered a viable prion decontamination method for MBM, although we observed increased survival time of hamsters and reduced infectivity greater than 6 log orders in the solid MBM residue. Furthermore, results from our study compare for the first time prion detection by Western Blot versus an infectivity bioassay for analysis of biodiesel reaction products. We could show that biochemical analysis alone is insufficient for detection of prion infectivity after a biodiesel process.
 
 
 
Detection of protease-resistant cervid prion protein in water from a CWD-endemic area
 
The data presented here demonstrate that sPMCA can detect low levels of PrPCWD in the environment, corroborate previous biological and experimental data suggesting long term persistence of prions in the environment2,3 and imply that PrPCWD accumulation over time may contribute to transmission of CWD in areas where it has been endemic for decades. This work demonstrates the utility of sPMCA to evaluate other environmental water sources for PrPCWD, including smaller bodies of water such as vernal pools and wallows, where large numbers of cervids congregate and into which prions from infected animals may be shed and concentrated to infectious levels.
 
 
 
A Quantitative Assessment of the Amount of Prion Diverted to Category 1 Materials and Wastewater During Processing
 
Keywords:Abattoir;bovine spongiform encephalopathy;QRA;scrapie;TSE
 
In this article the development and parameterization of a quantitative assessment is described that estimates the amount of TSE infectivity that is present in a whole animal carcass (bovine spongiform encephalopathy [BSE] for cattle and classical/atypical scrapie for sheep and lambs) and the amounts that subsequently fall to the floor during processing at facilities that handle specified risk material (SRM). BSE in cattle was found to contain the most oral doses, with a mean of 9864 BO ID50s (310, 38840) in a whole carcass compared to a mean of 1851 OO ID50s (600, 4070) and 614 OO ID50s (155, 1509) for a sheep infected with classical and atypical scrapie, respectively. Lambs contained the least infectivity with a mean of 251 OO ID50s (83, 548) for classical scrapie and 1 OO ID50s (0.2, 2) for atypical scrapie. The highest amounts of infectivity falling to the floor and entering the drains from slaughtering a whole carcass at SRM facilities were found to be from cattle infected with BSE at rendering and large incineration facilities with 7.4 BO ID50s (0.1, 29), intermediate plants and small incinerators with a mean of 4.5 BO ID50s (0.1, 18), and collection centers, 3.6 BO ID50s (0.1, 14). The lowest amounts entering drains are from lambs infected with classical and atypical scrapie at intermediate plants and atypical scrapie at collection centers with a mean of 3 × 10−7 OO ID50s (2 × 10−8, 1 × 10−6) per carcass. The results of this model provide key inputs for the model in the companion paper published here.
 
 
 
PPo4-4:
 
Survival and Limited Spread of TSE Infectivity after Burial
 
Karen Fernie, Allister Smith and Robert A. Somerville The Roslin Institute and R(D)SVS; University of Edinburgh; Roslin, Scotland UK
 
Scrapie and chronic wasting disease probably spread via environmental routes, and there are also concerns about BSE infection remaining in the environment after carcass burial or waste 3disposal. In two demonstration experiments we are determining survival and migration of TSE infectivity when buried for up to five years, as an uncontained point source or within bovine heads. Firstly boluses of TSE infected mouse brain were buried in lysimeters containing either sandy or clay soil. Migration from the boluses is being assessed from soil cores taken over time. With the exception of a very small amount of infectivity found 25 cm from the bolus in sandy soil after 12 months, no other infectivity has been detected up to three years. Secondly, ten bovine heads were spiked with TSE infected mouse brain and buried in the two soil types. Pairs of heads have been exhumed annually and assessed for infectivity within and around them. After one year and after two years, infectivity was detected in most intracranial samples and in some of the soil samples taken from immediately surrounding the heads. The infectivity assays for the samples in and around the heads exhumed at years three and four are underway. These data show that TSE infectivity can survive burial for long periods but migrates slowly. Risk assessments should take into account the likely long survival rate when infected material has been buried.
 
The authors gratefully acknowledge funding from DEFRA.
 
 
 
PPo3-22:
 
Detection of Environmentally Associated PrPSc on a Farm with Endemic Scrapie
 
Ben C. Maddison,1 Claire A. Baker,1 Helen C. Rees,1 Linda A. Terry,2 Leigh Thorne,2 Susan J. Belworthy2 and Kevin C. Gough3 1ADAS-UK LTD; Department of Biology; University of Leicester; Leicester, UK; 2Veterinary Laboratories Agency; Surry, KT UK; 3Department of Veterinary Medicine and Science; University of Nottingham; Sutton Bonington, Loughborough UK
 
Key words: scrapie, evironmental persistence, sPMCA
 
Ovine scrapie shows considerable horizontal transmission, yet the routes of transmission and specifically the role of fomites in transmission remain poorly defined. Here we present biochemical data demonstrating that on a scrapie-affected sheep farm, scrapie prion contamination is widespread. It was anticipated at the outset that if prions contaminate the environment that they would be there at extremely low levels, as such the most sensitive method available for the detection of PrPSc, serial Protein Misfolding Cyclic Amplification (sPMCA), was used in this study. We investigated the distribution of environmental scrapie prions by applying ovine sPMCA to samples taken from a range of surfaces that were accessible to animals and could be collected by use of a wetted foam swab. Prion was amplified by sPMCA from a number of these environmental swab samples including those taken from metal, plastic and wooden surfaces, both in the indoor and outdoor environment. At the time of sampling there had been no sheep contact with these areas for at least 20 days prior to sampling indicating that prions persist for at least this duration in the environment. These data implicate inanimate objects as environmental reservoirs of prion infectivity which are likely to contribute to disease transmission.
 
 
 
Wednesday, July 10, 2013
 
Rapid assessment of bovine spongiform encephalopathy prion inactivation by heat treatment in yellow grease produced in the industrial manufacturing process of meat and bone meals
 
BMC Veterinary Research 2013, 9:134 doi:10.1186/1746-6148-9-134
 
 
 
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Subject: Georgia House Bill 1043 and Chronic Wasting Disease CWD
 
Greetings Honorable Representatives of the House, Game, Fish, & Parks,
 
 
 
 
*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies.
 
 
 
 
Sunday, August 11, 2013
 
Creutzfeldt-Jakob Disease CJD cases rising North America updated report August 2013
 
Creutzfeldt-Jakob Disease CJD cases rising North America with Canada seeing an extreme increase of 48% between 2008 and 2010 (Prion2013)
 
 
 
Sunday, August 11, 2013
 
Creutzfeldt-Jakob Disease CJD cases rising North America updated report August 2013
 
Creutzfeldt-Jakob Disease CJD cases rising North America with Canada seeing an extreme increase of 48% between 2008 and 2010
 
 
 
Tuesday, March 5, 2013
 
Use of Materials Derived From Cattle in Human Food and Cosmetics; Reopening of the Comment Period FDA-2004-N-0188-0051 (TSS SUBMISSION)
 
FDA believes current regulation protects the public from BSE but reopens comment period due to new studies
 
 
 
Friday, June 29, 2012
 
Highly Efficient Prion Transmission by Blood Transfusion
 
 
 
Thursday, October 25, 2012
 
Current limitations about the cleaning of luminal endoscopes and TSE prion risk factors there from
 
Article in Press
 
 
 
Saturday, January 16, 2010
 
Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to Bramble et al
 
Evidence For CJD/TSE Transmission Via Endoscopes
 
From Terry S. Singletary, Sr flounder@wt.net 1-24-3
 
 
 
Monday, May 6, 2013
 
Warning of mad cow disease threat to blood transfusions
 
 
 
Thursday, January 17, 2013
 
TSE guidance, surgical, dental, blood risk factors, Part 4 Infection control of CJD, vCJD and other human prion diseases in healthcare and community settings (updated January 2013)
 
 
 
Tuesday, May 21, 2013
 
CJD, TSE, PRION, BLOOD Abstracts of the 23rd Regional Congress of the International Society of Blood Transfusion, Amsterdam, The Netherlands, June 2-5, 2013
 
 
 
4th CASE VCJD VIA BLOOD TRANSFUSION, BSE, BASE, AND SPORADIC CJD
 
By Terry S Singeltary
 
Bacliff, Texas USA Jan 24, 07
 
4th CASE VCJD VIA BLOOD TRANSFUSION, BSE, BASE, AND SPORADIC CJD
 
 
 
 
 
FC5.1.1
 
 
Transmission Results in Squirrel Monkeys Inoculated with Human sCJD, vCJD, and GSS Blood Specimens: the Baxter Study
 
Brown, P1; Gibson, S2; Williams, L3; Ironside, J4; Will, R4; Kreil, T5; Abee, C3 1Fondation Alliance BioSecure, France; 2University of South Alabama, USA; 3University of Texas MD Anderson Cancer Center, USA; 4Western General Hospital, UK; 5Baxter BioSience, Austria
 
Background: Rodent and sheep models of Transmissible Spongiform Encephalopathy (TSE) have documented blood infectivity in both the pre-clinical and clinical phases of disease. Results in a (presumably more appropriate) non-human primate model have not been reported.
 
Objective: To determine if blood components (red cells, white cells, platelets, and plasma) from various forms of human TSE are infectious.
 
Methods: Blood components were inoculated intra-cerebrally (0.1 ml) and intravenously (0.5 ml) into squirrel monkeys from 2 patients with sporadic Creutzfeldt- Jakob disease (sCJD) and 3 patients with variant Creutzfeldt-Jakob disease (vCJD). Additional monkeys were inoculated with buffy coat or plasma samples from chimpanzees infected with either sCJD or Gerstmann-Sträussler-Scheinker disease (GSS). Animals were monitored for a period of 5 years, and all dying or sacrificed animals had post-mortem neuropathological examinations and Western blots to determine the presence or absence of the misfolded prion protein (PrPTSE).
 
Results: No transmissions occurred in any of the animals inoculated with blood components from patients with sporadic or variant CJD. All donor chimpanzees (sCJD and GSS) became symptomatic within 6 weeks of their pre-clinical phase plasmapheresis, several months earlier than the expected onset of illness. One monkey inoculated with purified leukocytes from a pre-clinical GSS chimpanzee developed disease after 36 months.
 
Conclusion: No infectivity was found in small volumes of blood components from 4 patients with sporadic CJD and 3 patients with variant CJD. ***However, a single transmission from a chimpanzee-passaged strain of GSS shows that infectivity may be present in leukocytes, and the shock of general anaesthesia and plasmspheresis appears to have triggered the onset of illness in pre-clinical donor chimpanzees.
 
 
 
Saturday, September 5, 2009
 
TSEAC MEETING FEBRUARY 12, 2004 THE BAXTER STUDY GSS
 
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Prion2013
 
 
 
Oral.05: Contaminated blood products induce a highly atypical prion disease devoid of PrPres in primates
 
 
Emmanuel Corney,1 Nina Jaffre,1 Jacqueline Mikol,1 Valerie Durand,1 Christelle Jas-Duval,1,2 Sophie Luccantoni-Freire,1 Evelyne Correia,1 Nathalie Lescoutra-Etcheqaray,3 Nathalie Streichenberqer,4 Stephane Haik,5 Chryslain Sumian,3 Paul Brown1 and Jean-Philippe Deslys1
 
 
1Commissariat a l'Energie Atomique; Institute of Emerging Diseases and Innovative Therapies (iMETI); Division of Prions and Related Diseases (SEPIA); Fontenay-aux- Roses, France; 2EFS·Nord de France; Lille, France; 3MacoPharm; Tourcoing, France; 4Hospices Civils de Lyon; Prion Unit; Neurobiology Department; Bron, France; 5Inserm; U 975·CNRS; UMR 7225 - Universite Pierre et Marie Curie; Paris, France
 
 
Background, Concerns about the blood-borne risk of prion infection have been confirmed by the occurrence in the UK of four transfusion-related infections of vCJD and an apparently silent infection in an hemophiliac patient. Asymptomatic incubation periods in prion diseases can extend over decades in humans. We present here unexpected results of experiments evaluating blood transmission risk in a non-human primate model.
 
 
Material and Methods, Cynomolgus macaques were inoculated with brain or blood specimens from vCJD infected humans or monkeys. Neuropathological and biochemical findings were obtained using current methods used for human patients.
 
 
Results, Thirteen out of 23 primates exposed to various human or macaque blood products exhibited a previously undescribed myelopathic syndrome, devoid of the classical features of prion disease, notably abnormal prion protein (PrPres) deposition, whereas the 14 corresponding brain-inoculated donor animals and 1 transfused animal exhibited the classical vCJD pattern. In passage experiments, plasma transfusion induced the same atypical phenotype after two years (again, with no detectable PrPres), whereas the intracerebral inoculation of spinal cord led to a typical prion disease with cerebral spongiosis and PrPres accumulation in the brain of the primate recipient. Interestingly, passage experiments in transgenic mice were largely unsuccessful.
 
 
In another experiment designed to test the efficacy of antiprion filters, three recipients of filtered red blood cells suspended in plasma are still healthy 4.5 y after transfusion whereas the recipients of unfiltered inocula died after 2.5 y with the atypical neurological profile.
 
 
Conclusion. We describe a new fatal neurological myelopathic syndrome in monkeys exposed to various vCJD/BSE-infected blood components.
 
 
Secondary transmission in primates confirms
 
 
(I) the transmissibility of this myelopathy, and
 
 
(2) its prion origin which could not be diagnosed as such in the first recipients.
 
 
This myelopathy might be compared in some respects to certain forms of human lower motor neuron disease, including neuromyelitis optica, the flail arm syndrome of amyotrophic lateral sclerosis (ALS), and the recently described FOSMN (facial onset sensory and motor neuronopathy) syndrome.
 
 
 
 
 
 
 
Sunday, September 1, 2013
 
Evaluation of the Zoonotic Potential of Transmissible Mink Encephalopathy
 
We previously described the biochemical similarities between PrPres derived from L-BSE infected macaque and cortical MM2 sporadic CJD: those observations suggest a link between these two uncommon prion phenotypes in a primate model (it is to note that such a link has not been observed in other models less relevant from the human situation as hamsters or transgenic mice overexpressing ovine PrP [28]). We speculate that a group of related animal prion strains (L-BSE, c-BSE and TME) would have a zoonotic potential and lead to prion diseases in humans with a type 2 PrPres molecular signature (and more specifically type 2B for vCJD)
 
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Together with previous experiments performed in ovinized and bovinized transgenic mice and hamsters [8,9] indicating similarities between TME and L-BSE, the data support the hypothesis that L-BSE could be the origin of the TME outbreaks in North America and Europe during the mid-1900s.
 
 
 
 
TSS
 
 
 
 
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