England Creutzfeldt-Jakob disease (CJD) biannual update (February 2020) Health Protection Report Volume 14 Number 3 11 February 2020
England Creutzfeldt-Jakob disease (CJD) biannual update (February 2020) Health Protection Report Volume 14 Number 3 11 February 2020
Public Health England
Creutzfeldt-Jakob disease (CJD) biannual update (February 2020) Health Protection Report Volume 14 Number 3 11 February 2020
Creutzfeldt-Jakob disease (CJD) biannual update (February 2020) Health Protection Report Volume 14 Number 3 Creutzfeldt-Jakob disease (CJD) biannual update (February 2020)
This six-monthly report provides an update on the enhanced surveillance of potential iatrogenic (healthcare-acquired) exposures to Creutzfeldt-Jakob Disease (CJD). The data is correct as of 31 December 2019. For numbers of CJD case reports, readers should consult data provided by the National CJD Research and Surveillance Unit (NCJDRSU, http://www.cjd.ed.ac.uk/surveillance/data-and-reports).
Monitoring of patients 'at increased risk' of CJD
Individuals who have been identified as ‘at increased risk’ of CJD as a consequence of their medical care are informed of their exposure and asked to follow public health precautions to avoid potentially transmitting the infection to others. They are also followed up to help determine the risks of CJD transmission to patients through different routes and to ascertain whether any people who may have been exposed to increased CJD risks go on to develop CJD.
Public Health follow up activities include clinical monitoring, General Practitioner (GP) updates, and post mortem investigations to determine whether asymptomatic individuals in these groups have been infected with the CJD agent.. A number of different organisations are involved in these activities: Public Health England (PHE), Health Protection Scotland (HPS), UCL Institute of Child Health/Great Ormond Street Hospital (ICH), NHS Blood and Transplant (NHSBT), National CJD Research and Surveillance Unit (NCJDRSU), National Prion Clinic (NPC), and the UK Haemophilia Centre Doctors' Organisation (UKHCDO). The PHE CJD Section coordinates the collation of data on individuals identified as ‘at increased risk’ of CJD, and who have been informed of this. These individuals are followed up through public health monitoring and research activities by different organisations.
Creutzfeldt-Jakob disease (CJD) biannual update (February 2020)
Health Protection Report Volume 14 Number 3
The PHE CJD Section currently holds data on the following groups of patients who have been identified as ‘at increased risk’ of CJD:
• recipients of blood components from donors who subsequently developed vCJD
• blood donors to individuals who later developed vCJD
• other recipients of blood components from these blood donors
• recipients of certain plasma products between 1990 and 2001 (non-bleeding disorder patients)
• certain surgical contacts of patients diagnosed with CJD
• highly transfused recipients.
Data on the following risk groups are not held by PHE, but are held by other organisations:
• bleeding disorder patients who received plasma products between 1990 and 2001 (UKHCDO)
• recipients of human derived growth hormone before 1985 (ICH)
• patients who could have received a dura mater graft before August 1992 (data not currently collected)
• individuals treated with gonadotrophin sourced from humans before 1973 (data not currently collected)
• family risk of genetic prion disease (NPC).
Patients with bleeding disorders who received UK sourced plasma products (UKHCDO): The definition of those considered at increased risk of CJD within this group was revised in 2012, following a re-assessment of the risk for vCJD transmission through blood. The change concerned the date from which the UK blood (and plasma) donor population was considered to have been significantly infectious for vCJD. The risk period was narrowed from 1980-2001 to 1990-2001. Individuals who were treated with UK sourced plasma products during the 1980s, but not between 1990 and 2001, have been informed of this change, where possible.
Creutzfeldt-Jakob disease (CJD) biannual update (February 2020)
Health Protection Report Volume 14 Number 3
The data from the UKHCDO are likely to be a slight underestimate of the true number of patients with bleeding disorders who received UK-sourced clotting factors (1990 to 2001), as there was incomplete reporting of identified patients by haemophilia centres to the UKHCDO database. Notified patients are given the option of removing their details from the UKHCDO database, and are then removed from the ‘at increased risk' totals. The data on patients who received human-derived growth hormone held by the ICH is also a slight underestimate of the total as a small number of these patients are not included in the ICH follow-up.
Creutzfeldt-Jakob disease (CJD) biannual update (February 2020)
Health Protection Report Volume 14 Number 3
Summary of all ‘at increased risk’ groups on which data are collected (Data correct as of 31 December 2019)
‘At increased risk’ Group Identified as ‘at increased risk’ Number notified All Alive Cases Asymptomatic infections a
Recipients of blood from donors who later developed vCJD
67 27 14 3 1
Blood donors to individuals who later developed vCJD 112 108 100 0 0
Other recipients of blood components from these donors 34 32 13 0 0
Plasma product recipients (non-bleeding disorders) who received UK sourced plasma products 1990-2001 2 2 2 0 0
Certain surgical contacts of patients diagnosed with CJD 327 272 219 0 0
Highly transfused recipients 3 3 1 0 0
Total for ‘at increased risk’ groups where PHE holds data 545 444 349 3 1
Patients with bleeding disorders who received UK sourced plasma products 1980-2001b,e 3,600 3,251c 2,686 0 1
Recipients of human derived growth hormoneb 1,883 1,883 1,451d 81 0
Total for all ‘at increased risk’ groups 6,028 5,578 4,486 84 2
a. An asymptomatic infection is when an individual does not exhibit any of the signs and symptoms of CJD in life but abnormal prion protein indicative of CJD infection has been found in tissue obtained at post mortem.
b. These are minimum figures. Central reporting for bleeding disorder patients is incomplete, and a small number of patients have opted out of the central UKHCDO database. A small number of ‘at increased risk’ growth hormone recipients are not included in the Institute of Child Health study. Not all of the ‘at increased risk’ growth hormone recipients have been notified. There is no central record of who has been informed.
c. These are the minimum number of people notified based on those patients who were seen for care after the notification exercise. It is likely that many more of the ‘at increased risk’ patients received their notification letter but as they were not subsequently recorded as being seen for care this cannot be confirmed.
d. Data is correct as of 31 December 2016. Information on non-CJD related deaths is currently not available.
e. Including a small proportion of individuals known to have been treated with UK plasma products 1980-2001, and presumed to have been treated 1990-2001
Creutzfeldt-Jakob disease (CJD) biannual update (February 2020) Health Protection Report Volume 14 Number 3
Current status of ‘at increased risk’ groups (Data correct as of 31 December 2019)
snip (go to link to see chart)
About Public Health England
Public Health England exists to protect and improve the nation’s health and wellbeing, and reduce health inequalities. We do this through world-class science, research, knowledge and intelligence, advocacy, partnerships and the delivery of specialist public health services. We are an executive agency of the Department of Health Social Care, and are a distinct delivery organisation with operational autonomy to advise and support government, local authorities and the NHS in a professionally independent manner.
About Health Protection Report
Health Protection Report is a national public health bulletin for England and Wales, published by Public Health England. It is PHE’s principal channel for the dissemination of laboratory data relating to pathogens and infections/communicable diseases of public health significance and of reports on outbreaks, incidents and ongoing investigations. Public Health England, Wellington House, 133-155 Waterloo Road, London SE1 8UG. Tel: 020 7654 8000 www.gov.uk/phe Twitter: @PHE_uk Facebook: www.facebook.com/PublicHealthEngland Queries relating to this document should be directed to: CJD Section, National Infection Service, PHE Colindale, 61 Colindale Avenue, London NW9 5EQ. hcai.amrdepartment@phe.gov.uk.
© Crown copyright 2020 You may re-use this information (excluding logos) free of charge in any format or medium, under the terms of the Open Government Licence v3.0. To view this licence, visit OGL. Where we have identified any third party copyright information you will need to obtain permission from the copyright holders concerned. Published: February 2020 PHE publications PHE supports the UN gateway number: GW-1100 Sustainable Development Goals
FRIDAY, JANUARY 31, 2020
CJD TSE Prion Blood Products, iatrogenic transmission, Confucius is confused again, WHAT IF? Docket Number: FDA-2012-D-0307
THURSDAY, JANUARY 30, 2020
Docket Number: FDA-2012-D-0307 Recommendations to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Components; Draft Guidance for Industry Draft Guidance for Industry Singeltary Submission
Monday, February 3, 2020
Informing Patient Contacts About Iatrogenic Creutzfeldt Jakob Disease
mSphere. 2020 Jan-Feb; 5(1): e00649-19. Published online 2020 Jan 29. doi: 10.1128/mSphere.00649-19 PMCID: PMC6992370 PMID: 31996421
Correlation between Bioassay and Protein Misfolding Cyclic Amplification for Variant Creutzfeldt-Jakob Disease Decontamination Studies
Maxime Bélondrade,#a Christelle Jas-Duval,#a,b Simon Nicot,#a Lilian Bruyère-Ostells,a Charly Mayran,a Laetitia Herzog,b Fabienne Reine,b Juan Maria Torres,c Chantal Fournier-Wirth,a Vincent Béringue,b Sylvain Lehmann,d and Daisy Bougardcorresponding authora Mark D. Zabel, Editor Mark D. Zabel, Colorado State University; Author information Article notes Copyright and License information Disclaimer Associated Data Supplementary Materials Go to:
ABSTRACT
To date, approximately 500 iatrogenic Creutzfeldt-Jakob disease cases have been reported worldwide, most of them resulting from cadaveric dura mater graft and from the administration of prion-contaminated human growth hormone. The unusual resistance of prions to decontamination processes, their large tissue distribution, and the uncertainty about the prevalence of variant Creutzfeldt-Jakob disease (vCJD) in the general population lead to specific recommendations regarding identification of tissue at risk and reprocessing of reusable medical devices, including the use of dedicated treatment for prion inactivation. We previously described an in vitro assay, called Surf-PMCA, which allowed us to classify prion decontamination treatments according to their efficacy on vCJD prions by monitoring residual seeding activity (RSA). Here, we used a transgenic mouse line permissive to vCJD prions to study the correlation between the RSA measured in vitro and the in vivo infectivity. Implantation in mouse brains of prion-contaminated steel wires subjected to different decontamination procedures allows us to demonstrate a good concordance between RSA measured by Surf-PMCA (in vitro) and residual infectivity (in vivo). These experiments emphasize the strength of the Surf-PMCA method as a rapid and sensitive assay for the evaluation of prion decontamination procedures and also confirm the lack of efficacy of several marketed reagents on vCJD prion decontamination.
IMPORTANCE Creutzfeldt-Jakob diseases are neurodegenerative disorders for which transmission linked to medical procedures have been reported in hundreds of patients. As prion diseases, they are characterized by an unusual resistance to conventional decontamination processes. Moreover, their large tissue distribution and the ability of prions to attach to many surfaces raised the risk of transmission in health care facilities. It is therefore of major importance that decontamination procedures applied to medical devices before their reprocessing are thoroughly validated for prion inactivation. We previously described an in vitro assay, which allowed us to classify accurately prion decontamination treatments according to their efficacy on variant Creutzfeldt-Jakob disease. The significance of this study is in demonstrating the concordance between previous in vitro results and infectivity studies in transgenic mice. Furthermore, commercial reagents currently used in hospitals were tested by both protocols, and we observed that most of them were ineffective on human prions.
KEYWORDS: PMCA, bioassay, decontamination, prion, variant Creutzfeldt-Jakob disease
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DISCUSSION We demonstrated in this study that our previous results obtained by monitoring the RSA by Surf-PMCA for the evaluation of decontamination procedures against vCJD prions were concordant with the measure of residual infectivity in tgBov mice.
The choice of the transgenic model for the in vivo assay was driven by literature review. Although vCJD PrPTSE and bovine PrPC differ with regard to their primary sequence, the capacity of vCJD prions to transmit in transgenic mice overexpressing bovine PrP without species barrier has been comprehensively described (39). Due to the absence of this species barrier, it has been reported previously that tgBov line 110 mice were highly susceptible to vCJD prions (38, 40,–42). vCJD represents human infection with bovine spongiform encephalopathy (BSE) from cattle. This phenomenon has been designated “traceback,” and traceback studies have been proven to be a useful tool to identify the origin of prions (39, 43, 44). These results suggest that BSE prions retain their host preference after repeated passages through human PrP (42), as in other species, including sheep, cat, and mouse. It must also be noted that bovine PrP mice succumb quicker with vCJD prions but are intrinsically not more susceptible than tgHu line 650 mice to vCJD prions (45). Although homogenate substrate used for Surf-PMCA originated from tgHu mice (overexpressing 6 times the physiological level of human PrP) (46), survival time bioassays based on this transgenic line are limited by the long incubation period of vCJD (exceeding 500 d.p.inoc when undiluted) (45). tgBov mice (overexpressing 6 times the physiological level of bovine PrP) (47) were previously used and showed a good dynamic range with one animal dying with up to a 10−6 dilution of a vCJD brain homogenate in 500 d.p.inoc (38). Our results are concordant with these data, as 10−2 and 10−3 dilution vCJD-contaminated steel wires implanted in tgHu mice gave an attack rate of 100%; however, the incubation time exceeded 700 d.p.imp—almost the life span of the animals—which precludes their use to monitor a reduction factor. On the other hand, tgBov mice showed a better dynamic range with one animal dying after exposure with a 10−5 dilution vCJD-contaminated steel wires. Surprisingly, whereas attack rates and incubation times obtained with the 10−3 vCJD dilution indicated an expected lower infectivity of steel wire-bound prions than with the diluted prions, very similar results were obtained at the 10−5 dilution limit for the two groups (wires or dilution). One explanation could be that in the case of very low quantity of prions, the process used for wire contamination with IBH (one single wire per well and air drying overnight) may have potentiated vCJD transmission. A second hypothesis would rely on the longer total brain local exposure of mice with wires that remain in the brain for a long time, in contrast to injected brain homogenates that circulate immediately. Despite the relevance of the tgBov model as a vCJD bioassay, the limited dynamic of steel wire endpoint titration (50% attack rate for animals implanted with 10−4 dilution vCJD-contaminated steel wires) and its nonlinear decrease did not allow the calculation of an accurate 50% endpoint titer. Furthermore, although there were initially 10 mice per implantation condition, some animals were lost, which limited statistical significance. However, compared with the 263K hamster model, in which the dilution limit is 10−6 diluted contaminated steel wires (22% transmission rate) (19), the 10−5 dilution limit we obtained with tgBov inoculated with vCJD prions is only 1 log unit less sensitive and allows the comparison of the residual infectivity with the RSA measured by Surf-PMCA. Therefore, when vCJD-contaminated steel wires were treated by either standard or commercial treatments, the tgBov model was sensitive enough for results to be interpreted. Fully effective standard treatments showed no transmission of vCJD in the tgBov mice model. Except for sodium hypochlorite at 2,000 ppm, the other partially effective treatments led to few animals developing TSE. As inferred from the Surf-PMCA results, out of six commercial treatments, four poorly decreased the infectious load adsorbed on steel wires, with treatment A seeming to shorten the survival time compared with the water-only control. Despite PMCA being demonstrated as more sensitive than bioassays by several log units of magnitude for the detection of prions (34, 35, 48, 49), and that, to our knowledge, this is the first time the steel wire assay has been used with vCJD prions, we showed a high concordance between the Surf-PMCA results and the use of steel wires as vCJD carrier in transgenic mice.
We demonstrated using Surf-PMCA and tgBov infectivity studies that some of the commercial chemicals tested were not fully effective for decontaminating vCJD prions on surfaces. However, all these treatments were approved regarding their efficacy on the 263K prion strain. Our results confirm the inaccuracy of 263K prions regarding the validation of decontamination procedures used in health care facilities for the inactivation of vCJD prions. Nevertheless, our results regarding the effectiveness of vCJD prion decontamination by marketed reagents should be mitigated owing to the specific experimental set up whereby wires were air dried after contamination. Although all reagents evaluated in this study were previously validated using similar prion-dried conditions (using 263K prion-contaminated steel wires in hamsters), it is important to note that in health care facilities, it is recommended that MDs are kept continuously moist before prion decontamination. Whether vCJD-bound prions would behave differently if steel wires are kept moist after contamination remains to be established. Our Surf-PMCA method should be able to provide complementary data to help manufacturers of products to evaluate and improve their effectiveness in more real conditions. In addition, although TSE agents have notable extreme resistance to most decontamination processes, iatrogenic transmission of CJD via neurosurgical instruments has been reported in only four cases worldwide, and two cases have occurred because of contaminated stereotactic electroencephalography (EEG) depth electrodes in Switzerland (12). No new cases of iatrogenic transmission of CJD have been reported for several decades, underlining the poor transmission efficiency and the probable effectiveness of risk management procedures currently in place in health care facilities.
Recently, vCJD diagnosis has been possible in plasma samples from clinical and preclinical patients using the PMCA amplification technique (7) and in cerebrospinal fluid samples from clinical vCJD patients, including the first heterozygous methionine/valine patient (29), who might be the first case of a feared second wave of vCJD cases (50, 51). The capacity of PMCA to regenerate infectivity has already been demonstrated on nonhuman prions such as with scrapie prions, for which Moudjou et al. showed that infectivity of a 10−9 dilution of infected brain amplified by one round of PMCA was similar to that of the initial brain (34). Although sometimes debated (52, 53), the infectivity of vCJD PMCA amplicons, as well as the capacities of PMCA amplicons to faithfully maintain the pathological features of the original inoculum, led us to challenge tgBov mice with PMCA amplicons obtained from 10−7 vCJD-contaminated steel wires. By comparing the results with those obtained with a 10−3 vCJD-IBH dilution, we observed an equivalent survival time, demonstrating the ability of PMCA to regenerate at least 4 log units of vCJD infectivity. We also obtained a similar profile on Western blots for the PrPTSE present in the mouse brains. Altogether, these results confirmed that an RSA detected by the Surf-PMCA assay can be linked to residual infectivity in mice.
To extend the use of Surf-PMCA for the evaluation of prion decontamination treatments, it could be of interest to adapt it to other human prions, in particular sporadic CJD prions which represent 85% of TSE cases. Considering the differences of the biochemical properties of PrPTSE among the different sporadic CJD (sCJD) subtypes, such as solubility in detergents, heat stability, or sensitivity to protease digestion (54,–56), the behavior of non-vCJD human prions should be considered with regard to decontamination procedures. Similarly, other protein misfolding diseases such as Alzheimer’s and Parkinson diseases should also be considered on a precautionary basis in the development of decontamination procedures adapted to MDs (57). Adaptation and automation of Surf-PMCA would be of significant interest for a rapid and low-cost evaluation of new decontamination processes regarding misfolding diseases.
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MONDAY, FEBRUARY 10, 2020
Correlation between Bioassay and Protein Misfolding Cyclic Amplification for Variant Creutzfeldt-Jakob Disease Decontamination Studies
ALL iatrogenic CJD is, is sporadic CJD, until the iatrogenic event is discovered, traced back, proven, documented in the academic domain, and finally the public domain, which very seldom happens due to lack of trace back efforts, thus, all iatrogeic events stay as sporadic cjd.
cwd tse prion and steel wires
''Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice.''
*** 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.
FRIDAY, OCTOBER 04, 2019
Inactivation of chronic wasting disease prions using sodium hypochlorite
i think some hunters that don't read this carefully are going to think this is a cure all for cwd tse contamination. IT'S NOT!
first off, it would take a strong bleach type sodium hypochlorite, that is NOT your moms bleach she uses in her clothes, and store bought stuff.
Concentrated bleach is an 8.25 percent solution of sodium hypochlorite, up from the “regular bleach” concentration of 5.25 percent.Nov 1, 2013 https://waterandhealth.org/disinfect/high-strength-bleach-2/
second off, the study states plainly;
''We found that a five-minute treatment with a 40% dilution of household bleach was effective at inactivating CWD seeding activity from stainless-steel wires and CWD-infected brain homogenates. However, bleach was not able to inactivate CWD seeding activity from solid tissues in our studies.''
''We initially tested brains from two CWD-infected mice and one uninfected mouse using 40% bleach for 5 minutes. The results from these experiments showed almost no elimination of prion seeding activity (Table 4). We then increased the treatment time to 30 minutes and tested 40% and 100% bleach treatments. Again, the results were disappointing and showed less than a 10-fold decrease in CWD-seeding activity (Table 4). Clearly, bleach is not able to inactivate prions effectively from small brain pieces under the conditions tested here.''
''We found that both the concentration of bleach and the time of treatment are critical for inactivation of CWD prions. A 40% bleach treatment for 5 minutes successfully eliminated detectable prion seeding activity from both CWD-positive brain homogenate and stainless-steel wires bound with CWD. However, even small solid pieces of CWD-infected brain were not successfully decontaminated with the use of bleach.''
i think with all the fear from recent studies, and there are many, of potential, or likelihood of zoonosis, if it has not already happened as scjd, i think this study came out to help out on some of that fear, that maybe something will help, but the study plainly states it's for sure not a cure all for exposure and contamination of the cwd tse prion on surface materials. imo...terry
However, in a US study conducted in 1996 [34], only 53% of dentists used autoclaves to decontaminate root-canal files. In a survey conducted in France in 2004, only 79% of dentists used an autoclave [35]. The problem of correct use of the autoclaves and regular checking of their efficacy has also been raised by many authors in several countries [34]. A recent survey on dental practice also showed that other elementary precautionary measures against CJD transmission were not widely respected. For example, the vast majority of dentists did not actively seek out patients at-risk for any form of CJD (sporadic, iatrogenic or familial) [36]. Therefore, in the current situation and despite recommended decontamination procedures, the risk of sCJD transmission during dental care might still not be zero. In any case, our findings constitute a strong argument for the strict respect of the official recommendations on decontamination procedures in dentistry, and even suggest that the cost-benefit of single-use endodontic instruments should be re-evaluated.
PLoS One. 2020; 15(1): e0227487.
Published online 2020 Jan 7. doi: 10.1371/journal.pone.0227487
PMCID: PMC6946595
PMID: 31910440
Role of donor genotype in RT-QuIC seeding activity of chronic wasting disease prions using human and bank vole substrates
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Utilizing the same set of samples we also demonstrated that CWD prions sourced from WTD, elk or mule deer can seed human rPrP with high efficiency. To date, we are aware of only one report on the seeding activity of human substrate with CWD prions using RT-QuIC. This report showed that CWD prions from white-tailed deer could be used to seed human substrate (129M) and that the CWD conversion was more efficient than conversion with classical BSE prions [30]. Our study reconfirms that CWD is an efficient seed for human rPrP substrate. The relatively high efficiency of RT-QuIC amplification of CWD prions using human rPrP substrate may seem counter to the status of the broader understanding of CWD not being associated with human disease. This understanding is based on the published body of work on CWD and human transmission from either PMCA based amplification, transgenic mouse studies and non-human primates [31–37]. Collectively this work indicates that the species barrier is strong between humans and cervid CWD, and the efficient converstion of CWD prions using human rPrP by RT-QuIC does not challenge this because RT-QuIC exclusively assess the primary structure compatibility of the substrate with that of the secondary and tertiary structure of the seed. However, RT-QuIC does offer us a means to rapidly assess large numbers of amino acid substitutions between and within species associated with CWD to determine whether.
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sporadic CJD, along with new TSE prion disease in humans, of which the young are dying, of which long duration of illness from onset of symptoms to death have been documented, only to have a new name added to the pot of prion disease i.e. sporadic GSS, sporadic FFI, and or VPSPR. I only ponder how a familial type disease could be sporadic with no genetic link to any family member? when the USA is the only documented Country in the world to have documented two different cases of atypical H-type BSE, with one case being called atypical H-G BSE with the G meaning Genetic, with new science now showing that indeed atypical H-type BSE is very possible transmitted to cattle via oral transmission (Prion2014). sporadic CJD and VPSPR have been rising in Canada, USA, and the UK, with the same old excuse, better surveillance. You can only use that excuse for so many years, for so many decades, until one must conclude that CJD TSE prion cases are rising. a 48% incease in CJD in Canada is not just a blip or a reason of better surveillance, it is a mathematical rise in numbers. More and more we are seeing more humans exposed in various circumstance in the Hospital, Medical, Surgical arenas to the TSE Prion disease, and at the same time in North America, more and more humans are becoming exposed to the TSE prion disease via consumption of the TSE prion via deer and elk, cattle, sheep and goats, and for those that are exposed via or consumption, go on to further expose many others via the iatrogenic modes of transmission of the TSE prion disease i.e. friendly fire. I pondered this mode of transmission via the victims of sporadic FFI, sporadic GSS, could this be a iatrogenic event from someone sub-clinical with sFFI or sGSS ? what if?
Thursday, March 8, 2018
Familial human prion diseases associated with prion protein mutations Y226X and G131V are transmissible to transgenic mice expressing human prion protein
Furthermore, GSS A117V infected vole brains were able to induce the same disease phenotype in recipient voles within 3–4 months after challenge, proving that a prion agent propagated in the brains of infected animals. These findings imply that brains of GSS patients harbor infectious prions with transmissibility features similar to those found in other human and animal TSEs.
THURSDAY, DECEMBER 12, 2019
Heidenhain Variant Creutzfeldt Jakob Disease hvCJD, sporadic spontaneous CJD and the TSE Prion December 14, 2019
SUNDAY, DECEMBER 29, 2019
Variant CJD 18 years of research and surveillance
WEDNESDAY, DECEMBER 04, 2019
Three Cases of Creutzfeldt-Jakob Disease with Visual Disturbances as Initial Manifestation
Friday, September 27, 2019
Prion disease and recommended procedures for flexible endoscope reprocessing – a review of policies worldwide and proposal for a simplified approach Singeltary, GUT journal and Bramble et al
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i tried to tell GUT journal, and Bramble et al this way back, decades ago...terry
were not all CJDs, even nvCJD, just sporadic, until proven otherwise?
Terry S. Singeltary Sr., P.O. BOX, Bacliff, Texas 77518 USA
########### http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############
Professor Michael Farthing wrote:
Louise Send this to Bramble (author) for a comment before we post. Michael
-----Original Message-----
From: Terry S. Singeltary Sr. [mailto:flounder@wt.net] ;
Sent: 03 June 2002 17:14
Subject: gutjnl_el;21 Terry S. Singeltary Sr. (3 Jun 2002) "CJDs (all human TSEs) and Endoscopy Equipment"
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Date submitted: 3 Jun 2002 eLetter ID: gutjnl_el;21
Gut eLetter for Bramble and Ironside 50 (6): 888
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Name: Terry S. Singeltary Sr. Email: flounder@wt.net Title/position: disabled {neck injury} Place of work: CJD WATCH IP address: 216.119.162.85 Hostname: 216-119-162-85.ipset44.wt.net Browser: Mozilla/5.0 (Windows; U; Win98; en-US; rv:0.9.4) Gecko/20011019 Netscape6/6.2
Parent ID: 50/6/888
Citation: Creutzfeldt-Jakob disease: implications for gastroenterology
M G Bramble and J W Ironside Gut 2002; 50: 888-890 (Occasional viewpoint)
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"CJDs (all human TSEs) and Endoscopy Equipment"
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regarding your article;
Creutzfeldt-Jakob disease: implications for gastroenterology
i belong to several support groups for victims and relatives of CJDs. several years ago i did a survey regarding endoscopy equipment and how many victims of CJDs have had any type of this procedure done. to my surprise, many victims had some kind of endoscopy work done on them. as this may not be a smoking gun, i think it should warrant a 'red flag' of sorts, especially since data now suggests a substantial TSE infectivity in the gut wall of species infected with TSEs. If such transmissions occur, the ramifications of spreading TSEs from endoscopy equipment to the general public would be horrible, and could potential amplify the transmission of TSEs through other surgical procedures in that persons life, due to long incubation and sub-clinical infection. Science to date, has well established transmission of sporadic CJDs with medical/surgical procedures.
Terry S. Singeltary Sr. CJD WATCH
Subject: Re: gutjnl_el;21 Terry S. Singeltary Sr. (3 Jun 2002) "CJDs (all human TSEs) and Endoscopy Equipment" Date: Thu, 20 Jun 2002 16:19:51 -0700 From: "Terry S. Singeltary Sr." To: Professor Michael Farthing CC: lcamp@BMJgroup.com References: <001501c21099$5c8bc620$7c58d182@mfacdean1.cent.gla.ac.uk>
Greetings again Professor Farthing and BMJ,
I was curious why my small rebuttal of the article described below was not listed in this month's journal of GUT? I had thought it was going to be published, but I do not have full text access. Will it be published in the future? Regardless, I thought would pass on a more lengthy rebuttal of mine on this topic, vCJD vs sCJDs and endoscopy equipment. I don't expect it to be published, but thought you might find it interesting, i hope you don't mind and hope to hear back from someone on the questions I posed...
Here is my short submission I speak of, lengthy one to follow below that:
Date submitted: 3 Jun 2002
snip...see full text;
Friday, September 27, 2019
Prion disease and recommended procedures for flexible endoscope reprocessing – a review of policies worldwide and proposal for a simplified approach Singeltary, GUT journal and Bramble et al
FRIDAY, JANUARY 24, 2020
Man died of CJD 30 years after brain surgery 36 years old DOD
SATURDAY, SEPTEMBER 21, 2019
National Variability in Prion Disease–Related Safety Policies for Neurologic Procedures
Wednesday, September 11, 2019
Is the re-use of sterilized implant abutments safe enough? (Implant abutment safety) iatrogenic TSE Prion
FRIDAY, SEPTEMBER 06, 2019
Disinfection of Multi-Use Ocular Equipment for Ophthalmological Procedures: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines
***> In conclusion, sensory symptoms and loss of reflexes in Gerstmann-Sträussler-Scheinker syndrome can be explained by neuropathological changes in the spinal cord. We conclude that the sensory symptoms and loss of lower limb reflexes in Gerstmann-Sträussler-Scheinker syndrome is due to pathology in the caudal spinal cord. <***
***> The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.<***
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***
***> All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals.<***
***> In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids.'' Scientific opinion on chronic wasting disease (II) <***
RESEARCH ARTICLE
Enhanced detection of prion infectivity from blood by preanalytical enrichment with peptoid-conjugated beads
Simone HornemannID1 *, Petra Schwarz1 , Elisabeth J. Rushing1 , Michael D. Connolly3 , Ronald N. Zuckermann3 , Alice Y. Yam2¤ , Adriano AguzziID1 * 1 Institute of Neuropathology, University of Zurich, Zurich, Switzerland, 2 Novartis Vaccines and Diagnostics Inc., Emeryville, California, United States of America, 3 Biological Nanostructures Facility, The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America ¤ Current address: Sutro Biopharma, San Francisco, California, United States of America * Adriano.Aguzzi@usz.ch (AA); Simone.Hornemann@usz.ch (SH)
Abstract
Prions cause transmissible infectious diseases in humans and animals and have been found to be transmissible by blood transfusion even in the presymptomatic stage. However, the concentration of prions in body fluids such as blood and urine is extremely low; therefore, direct diagnostic tests on such specimens often yield false-negative results. Quantitative preanalytical prion enrichment may significantly improve the sensitivity of prion assays by concentrating trace amounts of prions from large volumes of body fluids. Here, we show that beads conjugated to positively charged peptoids not only captured PrP aggregates from plasma of prion-infected hamsters, but also adsorbed prion infectivity in both the symptomatic and preclinical stages of the disease. Bead absorbed prion infectivity efficiently transmitted disease to transgenic indicator mice. We found that the readout of the peptoidbased misfolded protein assay (MPA) correlates closely with prion infectivity in vivo, thereby validating the MPA as a simple, quantitative, and sensitive surrogate indicator of the presence of prions. The reliable and sensitive detection of prions in plasma will enable a wide variety of applications in basic prion research and diagnostics.
Tables of Cases Examined
National Prion Disease Pathology Surveillance Center Cases Examined¹ Updated December 9, 2019
Year Total Referrals² Prion Disease Sporadic Familial Iatrogenic vCJD
1999 & earlier 380 230 200 27 3 0
2000 145 102 90 12 0 0
2001 209 118 110 8 0 0
2002 241 144 124 18 2 0
2003 259 160 137 21 2 0
2004 316 181 164 16 0 1³
2005 327 178 156 21 1 0
2006 365 179 159 17 1 2⁴
2007 374 210 191 19 0 0
2008 384 221 205 16 0 0
2009 398 232 210 21 1 0
2010 401 246 218 28 0 0
2011 392 238 214 24 0 0
2012 413 244 221 23 0 0
2013 416 258 223 34 1 0
2014 355 208 185 21 1 1⁵
2015 402 264 244 20 0 0
2016 396 277 248 29 0 0
2017 375 266 247 19 0 0
2018 309 223 204 18 1 0
2019 351 220 183 16 0 0
TOTAL 72086 4399⁷ 3933⁸ 428⁹ 13 4
1Listed based on the year of death or, if not available, on year of referral;
2Cases with suspected prion disease for which brain tissue was submitted;
3Disease acquired in the United Kingdom;
4Disease acquired in the United Kingdom in one case and in Saudi Arabia in the other;
5Disease possibly acquired in a Middle Eastern or Eastern European country;
6Includes 20 cases in which the diagnosis is pending, and 19 inconclusive cases;
7Includes 21 (21 from 2019) cases with type determination pending in which the diagnosis of vCJD has been excluded.
8The sporadic cases include 3831 cases of sporadic Creutzfeldt-Jakob disease (sCJD), 67 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 35 cases of sporadic Fatal Insomnia (sFI).
9Total does not include 264 Familial cases diagnosed by blood test only.
''In the 2016 guidance, we recommended that prospective blood donors should be indefinitely deferred if they report having a blood relative with CJD. However, almost all cases reported are sCJD, not a genetic form of CJD. Blood relatives of individuals with sCJD are not at increased risk of developing the disease. The rare genetic forms of CJD (e.g., fCJD, GSS, FFI) share pathophysiological features with sCJD, and the transmission risk by blood components remains theoretical. Consequently, we recommend that establishments may stop asking prospective donors about having blood relatives with CJD.''
Greetings FDA et al,
I would again kindly like to comment on Docket Number: FDA-2012-D-0307, Docket Number: FDA-2012-D-0307 Recommendations to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Components; Draft Guidance for Industry Draft Guidance for Industry.
I still believe, that it is extremely dangerous to continue to base the safety of blood from the TSE Prion, by only believing the nvcjd only theory.
TSE Prion disease have expanded to other species i.e. the camel, and we now know that cwd and scrapie will transmit to pigs by oral routes.
Chronic Wasting Disease CWD TSE Prion in cervid has exploded across the USA, Canada, Mexico has now clue, Norway, Sweden, Finland, S. Korea, and we know that cwd is detected in the blood of cervid. CWD TSE Prion is highly infectious, and the risk factors from blood there from are very real.
we also know that all iatrogenic CJD is, is sporadic CJD, until the iatrogenic event is discovered, traced back, proven, documented in the academic domain, and finally the public domain, which very seldom happens due to lack of trace back efforts, thus, all iatrogeic events stay as sporadic cjd.
with the blood of cervid and cwd tse prion being detected there from, the science showing that cwd zoonotic potential is now real, the many different strains of cwd to date, with no real factor of how many different strains there are, with science now showing that indeed BSE, Scrapie, and CWD, both typical and atypical strains, showing scientific links to sporadic cjd, and that cwd in humans would would NOT look like nvcjd, but science shows that it would look like sporadic cjd, therefore, iatrogenic cjd from human cwd exposure is very real threat, i find these weakening of rules for blood risk factors from all the different strains of sporadic cjd very worrisome, especially now that officials are classifying vpspr, sgss, sffi, as sporadic cjd cases. we have no clue whether or not these are from iatrogenic events or not. this will be a foolish move if we put once again, corporate interest over human and animal health, but does not surprise me.
THIS will be very dangerous, and a foolish move for people who need blood, and for the medical and surgical theaters, and humans there from, and simply are not based on sound science imo, but are based on corporate greed.
WE KNOW now that the real statistics on human TSE Prion IS NOT one in a million, but data now shows that sporadic CJD, 85%+ of all human TSE Prion, the read statistics now show that those figures are one in 5,000. and sporadic cjd is NOT a single strain, but many, many, different strains, and the routes and sources are simply unknown.
NO WHERE IN SCIENCE LITERATURE HAS THE SPONTANEOUS CJD EVER BEEN PROVEN, without route and source, a happenstance of bad luck, this is simply wishful thinking$
TO weaken, instead of enhance and strengthen the risk of sporadic CJD tse prion from blood products by this Docket Number FDA-2012-D-0307 Recommendations, will only enhance the risk of TSE Prion to hemophiliacs, the medical and surgical arenas around the globe
yes, human tse prion are now 1 in 5,000. let that sink in.
MONDAY, JANUARY 20, 2020
sporadic CJD one in a million, FAKE NEWS PEOPLE!
this myth has been incorrect for decades, and had been stated as such by a few, but again, the media is too lazy to do it's job and print the facts.
human tse prion, including 85%+ of all human tse i.e. sporadic cjd, is now one in 5,000!
MONDAY, AUGUST 26, 2019
Creutzfeldt Jakob Disease CJD, TSE, Prion, Surveillance Update August 2019
SUNDAY, MARCH 10, 2019
National Prion Disease Pathology Surveillance Center Cases Examined¹ Updated Feb 1, 2019 Variably protease-sensitive prionopathy VPSPr
U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
THURSDAY, SEPTEMBER 26, 2019
Veterinary Biologics Guideline 3.32E: Guideline for minimising the risk of introducing transmissible spongiform encephalopathy prions and other infectious agents through veterinary biologics
SATURDAY, JANUARY 18, 2020
United States wildlife and wildlife product imports from 2000–2014 and TSE PRION aka Mad Cow Type Disease
***> HUMAN TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION DISEASE 1 IN 5,000 NOT ONE IN A MILLION!
***> I urge every Country around the Globe to Declare an Extraordinary Emergency Due To A Foreign Animal Disease Chronic Wasting Disease CWD TSE Prion from the USA, Canada, and Mexico (they have no clue), all of North America should have this Declaration of Emergency against them, just like the one called way back when the shoe was on the other foot with the mad sheep of mad river valley, except this time, it's not a wag the dog false flag, this is for real...terry
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. at
4:33 PM
