Post by Terry S. Singeltary Sr. on Feb 7, 2023 15:05:03 GMT -6
National Prion Disease Pathology Surveillance Center Cases Examined1 (September 20, 2022)
Year Total Neuropath Referrals2 Prion Disease Sporadic Familial iCJD vCJD
1999 & earlier 383 232 202 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 315 180 163 16 0 13
2005 328 179 157 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 397 231 210 20 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 401 263 243 20 0 0
2016 395 277 248 29 0 0
2017 375 266 247 19 0 0
2018 308 221 202 18 1 0
2019 434 281 259 22 0 0
2020 365 252 227 24 1 0
2021 343 248 223 22 0 0
2022 213 124 98 9 0 0
TOTAL 82116 50827 45568 4889 14 4
Year CSF Only & RT-QuIC Positive10
2015 140
2016 183
2017 227
2018 266
2019 311
2020 310
2021 341
2022 262
TOTAL 2040
1 Listed based on the year of death or, if not available, on year of referral;
2 Cases with suspected prion disease for which brain tissue and/or blood (in familial cases) were submitted;
3 Disease acquired in the United Kingdom;
4 Disease acquired in the United Kingdom in one case and in Saudi Arabia in the other;
5 Disease possibly acquired in a Middle Eastern or Eastern European country;
6 Includes 28 cases in which the diagnosis is pending (1 from 2020, 3 from 2021 and 24 from 2022), and 20 inconclusive cases;
7 Includes 20 (3 from 2021 and 17 from 2022) cases with type determination pending in which the diagnosis of vCJD has been excluded.
8 The sporadic cases include 4437 cases of sporadic Creutzfeldt-Jakob disease (sCJD), 82 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 37 cases of sporadic Fatal Insomnia (sFI).
9 Total does not include 300 Familial cases diagnosed by blood only. 10 Lists number of patients (deceased and alive) who have had a positive RT-QuIC and no neuropath examination.
case.edu/medicine/pathology/sites/case.edu.pathology/files/2022-10/WebTable%20NPDPSC.pdf
FRIDAY, DECEMBER 02, 2022
Creutzfeldt Jacob Disease CJD TSE Prion December 2022 Annual Update
creutzfeldt-jakob-disease.blogspot.com/2022/12/creutzfeldt-jacob-disease-cjd-tse-prion.html
SUNDAY, MAY 08, 2022
USA National Prion Disease Pathology Surveillance Center Surveillance Update April 11th, 2022
creutzfeldt-jakob-disease.blogspot.com/2022/05/usa-national-prion-disease-pathology.html
Tuesday APRIL 05, 2022
Incidence of Creutzfeldt-Jakob Disease in the United States 1993-2014
creutzfeldt-jakob-disease.blogspot.com/2022/04/incidence-of-creutzfeldt-jakob-disease_5.html
TUESDAY, MAY 24, 2022
Texas Creutzfeldt Jakob Disease CJD TSE Prion Update Singeltary FOIA Request Received May 23, 2022
cjdtexas.blogspot.com/2022/05/texas-creutzfeldt-jakob-disease-cjd-tse.html
TUESDAY, MAY 10, 2022
Concordance of CSF RT-QuIC across the European Creutzfeldt-Jakob Disease surveillance network
creutzfeldt-jakob-disease.blogspot.com/2022/05/concordance-of-csf-rt-quic-across.html
Canada Definite and probable CJD, 1998-2022 As of October 31, 2022
Year Sporadic Iatrogenic CJD Genetic vCJD Total
1998 22 1 1 0 24
1999 27 2 3 0 32
2000 32 0 3 0 35
2001 27 0 3 0 30
2002 30 0 5 1 36
2003 27 1 1 0 29
2004 42 0 4 0 44
2005 42 0 2 0 44
2006 39 0 5 0 44
2007 35 0 4 0 39
2008 48 0 1 0 49
2009 48 0 5 0 53
2010 35 0 3 0 38
2011 46 0 4 1 51
2012 62 0 1 0 63
2013 50 0 1 0 51
2014 51 0 5 0 56
2015 44 0 8 0 52
2016 57 1 6 0 64
2017 82 0 5 0 87
2018 75 1 5 0 81
2019 76 0 2 0 78
2020 65 0 4 0 69
2021 56 0 3 0 59
2022 64 0 1 0 65
Total 1183 6 83 2 1274
Cases with definite and probable diagnosis to date
www.canada.ca/en/public-health/services/surveillance/blood-safety-contribution-program/creutzfeldt-jakob-disease/cjd-surveillance-system.html#ref
United Kingdom
CREUTZFELDT-JAKOB DISEASE IN THE UK (By Calendar Year)
Source: NCJDRSU website www.cjd.ed.ac.uk - updated 07/11/2022
REFERRALS OF SUSPECT CJD DEATHS OF DEFINITE AND PROBABLE CJD
Year Referrals Year Sporadic1 Iatrogenic Genetic2 vCJD Total Deaths
1990 [53]† 1990 28 5 0 - 33
1991 75 1991 31 1 4 - 36
1992 96 1992 45 2 6 - 53
1993 79 1993 36 4 7 - 47
1994 119 1994 53 1 9 - 63
1995 87 1995 35 4 5 3 47
1996 132 1996 40 4 6 10 60
1997 163 1997 59 6 7 10 82
1998 155 1998 64 3 5 18 90
1999 170 1999 62 6 2 15 85
2000 178 2000 48 1 3 28 80
2001 179 2001 58 4 6 20 88
2002 164 2002 73 0 5 17 95
2003 163 2003 79 5 7 18 109
2004 114 2004 50 2 6 9 67
2005 124 2005 67 4 13 5 89
2006 112 2006 68 1 9 5 83
2007 119 2007 63 2 11 5 81
2008 150 2008 84 5 6 2 97
2009 153 2009 78 2 8 3 91
2010 150 2010 85 3 6 3 97
2011 158 2011 91 4 14 5 114
2012 127 2012 92 5 12 0 109
2013 152 2013 108 2 10 1 121
2014 130 2014 100 3 13 0 116
2015 140 2015 105 0 4 0 109
2016 148 2016 118 1 6 1 126
2017 159 2017 122 0 12 0 134
2018 167 2018 137 2 12 0 151
2019 147 2019 128 1 7 0 136
2020 172 2020 135 1 8 0 144
2021 179 2021 132 0 6 0 138
2022 148 2022 113 0 3 0 116
Total Referrals 4562 Total Deaths 2587 84 238 178 3087
† Referral figure for 1990 is from 1 May onwards *As at 7 th November 2022
Summary of vCJD cases
Deaths from definite vCJD (confirmed): 123
Deaths from probable vCJD (without neuropathological confirmation): 55
Number of deaths from definite or probable vCJD (as above): 178
Number of definite/probable vCJD cases still alive: 0
Total number of definite or probable vCJD (dead and alive): 178
1 There are, in addition, a total of 20 cases of vPSPr (death in 1997(1 case), 2004(1), 2006(1), 2008(3), 2010(1), 2012(4), 2013(1), 2016(3), 2017(1), 2018(1), 2019(1), 2020(2)) not included in the above figures.
2 includes all genetic prion disease, including GSS.
Source: NCJDRSU website www.cjd.ed.ac.uk - updated 07/11/2022
www.cjd.ed.ac.uk/sites/default/files/figs.pdf
Latest NCJDRSU annual report, covering the period 1990-2021
www.cjd.ed.ac.uk/sites/default/files/report30.pdf
Safe laboratory management of prions and proteopathic seeds
CORRESPONDENCE| VOLUME 20, ISSUE 12, P981, DECEMBER 01, 2021
Safe laboratory management of prions and proteopathic seeds
Simon Mead Thomas Evans
on behalf of the Advisory Committee for Dangerous Pathogens Transmissible Spongiform Encephalopathy Subgroup Published:December, 2021DOI: doi.org/10.1016/S1474-4422(21)00379-3
Prions, the infectious agents of fatal and transmissible neurodegenerative disorders in humans and animals, are comprised of assemblies of misfolded forms of prion protein (PrP). The death of a 33-year-old researcher of prion diseases from variant Creutzfeldt-Jakob disease (ie, the strain of disease that is derived from bovine spongiform encephalopathy) 9 years after a percutaneous exposure to prion-contaminated material, and the death from or diagnosis of prion disease in two other people in Europe after working in prion research, emphasises the importance of statutory guidance for laboratory safety when working with dangerous pathogens.1 People in numerous laboratories handling diagnostic blood, CSF, and other low-risk biofluid samples from patients with or suspected to have Creutzfeldt-Jakob disease have contacted us to suggest that the existing guidance was not sufficiently clear or proportionate.
Evidence has accrued for the potential for proteins that are linked to neurodegenerative diseases, other than PrP, to adopt abnormal conformations, self-propagate, and cause transmissible pathologies and diseases in humans and laboratory animals.2, 3 These proteins share a range of pathological properties but are also distinct from prions in important ways, including that there are no known animal or human epidemics or established occupational risks. Experiments that involve inoculating, concentrating, or synthesising these so-called proteopathic seeds have become routine in the past decade, but no statutory guidance is available for safety. Human–human transmission of amyloid β proteopathic seeds has been observed in some specific circumstances that were also shown to transmit prion infection (eg, use of cadaver-derived human pituitary hormones or dura mater in neurosurgery) and can cause iatrogenic cerebral amyloid angiopathy and fatal brain haemorrhage after long latencies.4 The popularity of this field of research, and the long latencies that are to be expected for diseases that are caused by these proteopathic seeds, mean that occupational exposures might not yet have resulted in any clinical consequences. It is prudent, therefore, to consider potential risks from laboratory work involving these agents.
The UK's Advisory Committee for Dangerous Pathogens convened a subgroup to revise guidance for safe working with prions and to consider whether any measures were needed for work with proteopathic seeds, involving experts from research laboratories for prion and other neurodegenerative diseases, infectious disease specialists, pathologists, veterinarians, and health and safety experts. In the new guidance, we emphasise a distinction between high-risk CNS tissues and research samples that contain high concentrations of prions, which need to be managed in specialised laboratories with strict policies, and low-risk biofluids, such as blood and CSF, from patients who are suspected to have Creutzfeldt-Jakob disease with no or low concentrations of prions, which can be managed in a high-throughput diagnostic laboratory setting through adherence to appropriate general laboratory practices. We also concluded that the poorly defined pathogenicity in humans of proteopathic seeds when prepared in concentrated forms for biochemical, structural, or transmission studies means that they should now be considered as hazard group 2 pathogens, necessitating work in a containment level 2 facility. We recommend a range of safety measures,5 including special attention to risk assessment and staff training; recording of accidental exposures; special caution with the use of any sharp tools to avoid percutaneous injury; work inside a microbiological safety cabinet; and the use of spill trays, absorbent material, and defined procedures to decontaminate equipment and spills to avoid contamination of the laboratory environment.
Importantly, we do not recommend any changes to existing procedures for the routine handling of tissues and biofluids from patients with non-prion neurodegenerative conditions for diagnostic or research purposes. We hope that this new guidance will be seen as proportionate and precautionary and help organisations to have increased confidence about the safety of their employees.5
We declare no competing interests. Members of the Advisory Committee for Dangerous Pathogens Transmissible Spongiform Encephalopathy Subgroup are listed in the appendix.
www.thelancet.com/journals/laneur/article/PIIS1474-4422(21)00379-3/fulltext
www.thelancet.com/cms/10.1016/S1474-4422(21)00379-3/attachment/3f032b9d-8532-4292-bd54-e23c2f50fbf3/mmc1.pdf
www.thelancet.com/journals/laneur/article/PIIS1474-4422(21)00379-3/fulltext
www.thelancet.com/action/showPdf?pii=S1474-4422%2821%2900379-3
The importance of ongoing international surveillance for Creutzfeldt–Jakob disease
Neil Watson1, Jean-Philippe Brandel2, Alison Green1, Peter Hermann3, Anna Ladogana 4, Terri Lindsay1, Janet Mackenzie1, Maurizio Pocchiari 4, Colin Smith1, Inga Zerr3 and Suvankar Pal 1 ✉
Abstract | Creutzfeldt–Jakob disease (CJD) is a rapidly progressive, fatal and transmissible neurodegenerative disease associated with the accumulation of misfolded prion protein in the CNS. International CJD surveillance programmes have been active since the emergence, in the mid-1990s, of variant CJD (vCJD), a disease linked to bovine spongiform encephalopathy. Control measures have now successfully contained bovine spongiform encephalopathy and the incidence of vCJD has declined, leading to questions about the requirement for ongoing surveillance. However, several lines of evidence have raised concerns that further cases of vCJD could emerge as a result of prolonged incubation and/or secondary transmission. Emerging evidence from peripheral tissue distribution studies employing high-sensitivity assays suggests that all forms of human prion disease carry a theoretical risk of iatrogenic transmission. Finally, emerging diseases, such as chronic wasting disease and camel prion disease, pose further risks to public health. In this Review, we provide an up-to-date overview of the transmission of prion diseases in human populations and argue that CJD surveillance remains vital both from a public health perspective and to support essential research into disease pathophysiology, enhanced diagnostic tests and much-needed treatments.
www.nature.com/articles/s41582-021-00488-7.pdf
see also;
thedaily.case.edu/researchers-find-infectious-prions-creutzfeldt-jakob-disease-patient-skin/
www.ncbi.nlm.nih.gov/pmc/articles/PMC7187701/
www.nih.gov/news-events/nih-research-matters/prions-found-skin-people-creutzfeldt-jakob-disease
ACDP TSE subgroup minutes, agendas and papers, history
app.box.com/s/hhhhg857fjpu2bnxhv6e/folder/2936396377
TUESDAY, NOVEMBER 1, 2022
SEAC Scientific Steering Committee on TSE Prion
bovineprp.blogspot.com/2022/11/seac-scientific-steering-committee-on.html
iatrogenic TSE PrP
itseprion.blogspot.com/
NOW LET'S LOOK AT THE LATEST ON TSE PRION ZOONOSIS RISK FACTORS
O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France
Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases).
Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.
*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,
***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),
***is the third potentially zoonotic PD (with BSE and L-type BSE),
***thus questioning the origin of human sporadic cases.
We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.
===============
***thus questioning the origin of human sporadic cases***
===============
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
==============
PRION 2015 CONFERENCE
www.ncbi.nlm.nih.gov/pmc/articles/PMC5019500/
***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.
***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
PRION 2016 TOKYO
Saturday, April 23, 2016
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
Title: Transmission of scrapie prions to primate after an extended silent incubation period)
*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.
*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.
*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.
www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160
PRION CONFERENCE 2022 ABSTRACTS CWD TSE PrP ZOONOSIS
Transmission of prion infectivity from CWD-infected macaque tissues to rodent models demonstrates the zoonotic potential of chronic wasting disease.
Samia Hannaouia, Ginny Chenga, Wiebke Wemheuerb, Walter J. Schulz-Schaefferb, Sabine Gilcha, and Hermann M. Schätzla
Aims: Chronic wasting disease (CWD) is a prion disease of cervids. Its rapid geographic expansion, shedding of infectivity and persistence in the environment for many years are of concern for humans. Here, we provide the first evidence by transmission experiments to different transgenic mouse models and bank voles that Cynomolgus macaques inoculated via different routes with CWD-positive cervid tissues harbor infectious prions that elicit clinical disease in rodents.
Material and Methods: We used tissue materials from macaques inoculated with CWD to inoculate transgenic mice overexpressing cervid PrPCfollowed by transmission into bank voles. We used RT-QuIC, immunoblot and PET blot analysis to assess brains, spinal cords, and tissues of the gastrointestinal tract (GIT) for the presence of prions.
Results: Our results show that of the macaque materials that induced clinical disease in transgenic mice,73% were from the CNS (46% spinal cord and 27% brain), and 27% were from the spleen, although attack rates were low around 20%. Clinical mice did not display PK-resistant PrPSc(PrPres) in immunoblot, but showed low-levels of prion seeding activity. Transmission into bank voles from clinical transgenic mice led to a 100% attack rate with typical PrPressignature in immunoblot, which was different from that of voles inoculated directly with CWD or scrapie prions. High-level prion seeding activity in brain and spinal cord and PrPresdeposition in the brain were present. Remarkably, we also found prion seeding activity in GIT tissues of inoculated voles. Second passage in bank voles led to a 100% attack rate in voles inoculated with brain, spinal cord and small intestine material from first round animals, with PrPresin immunoblot, prion seeding activity, and PrPresdeposition in the brain. Shortened survival times indicate adaptation in the new host. This also shows that prions detected in GIT tissues are infectious and transmissible. Transmission of brain material from sick voles back to cervidized mice revealed transmission in these mice with a 100% attack rate, and interestingly, with different biochemical signature and distribution in the brain.
Conclusions: Our findings demonstrate that macaques, considered the best model for the zoonotic potential of prions, were infected upon CWD challenge, including oral one. The disease manifested as atypical in macaques and transgenic mice, but with infectivity present at all times, as unveiled in the bank vole model with an unusual tissue tropism.
Transmission of Cervid Prions to Humanized Mice Demonstrates the Zoonotic Potential of CWD
Samia Hannaouia, Irina Zemlyankinaa, Sheng Chun Changa, Maria Immaculata Arifina, Vincent Béringueb, Debbie McKenziec, Hermann M. Schatzla, and Sabine Gilcha
Aims: Chronic wasting disease (CWD), a prion disease of cervids, spreads efficiently among wild and farmed animals. Potential transmission to humans of CWD is a growing concern due to its increasing prevalence. Here, we aimed to determine the zoonotic potential of CWD using a mouse model for human prion diseases.
Material and Methods: Transgenic mice overexpressing human PrPChomozygous for methionine at codon 129 (tg650) were inoculated intracerebrally with brain homogenates of white-tailed deer infected with Wisc-1/CWD1 or 116AG CWD strains. Mice were monitored for clinical signs and were euthanized at terminal disease. Brains were tested by RT-QuIC, western blot upon PK digestion, and immunohistochemistry; fecal homogenates were analyzed by RT-QuIC. Brain/spinal cord and fecal homogenates of CWD-inoculated tg650 mice were inoculated into tg650 mice or bank voles. Brain homogenates of bank voles inoculated with fecal homogenates of CWD-infected tg650 mice were used for second passage in bank voles.
Results: Here, we provide the strongest evidence supporting the zoonotic potential of CWD prions, and their possible phenotype in humans. Inoculation of mice expressing human PrPCwith deer CWD isolates (strains Wisc-1 and 116AG) resulted in atypical clinical manifestations in > 75% of the mice, with myoclonus as leading clinical sign. Most of tg650 brain homogenates were positive for seeding activity in RT-QuIC. Clinical disease and presentation was transmissible to tg650 mice and bank voles. Intriguingly, protease-resistant PrP in the brain of tg650 mice resembled that found in a familial human prion disease and was transmissible upon passage. Abnormal PrP aggregates upon infection with Wisc-1 were detectable in thalamus, hypothalamus, and midbrain/pons regions.
Unprecedented in human prion disease, feces of CWD-inoculated tg650 mice harbored prion seeding activity and infectious prions, as shown by inoculation of bank voles and tg650 with fecal homogenates.
Conclusions: This is the first evidence that CWD can infect humans and cause disease with a distinctive clinical presentation, signature, and tropism, which might be transmissible between humans while current diagnostic assays might fail to detect it. These findings have major implications for public health and CWD-management.
www.tandfonline.com/doi/full/10.1080/19336896.2022.2091286
Year Total Neuropath Referrals2 Prion Disease Sporadic Familial iCJD vCJD
1999 & earlier 383 232 202 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 315 180 163 16 0 13
2005 328 179 157 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 397 231 210 20 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 401 263 243 20 0 0
2016 395 277 248 29 0 0
2017 375 266 247 19 0 0
2018 308 221 202 18 1 0
2019 434 281 259 22 0 0
2020 365 252 227 24 1 0
2021 343 248 223 22 0 0
2022 213 124 98 9 0 0
TOTAL 82116 50827 45568 4889 14 4
Year CSF Only & RT-QuIC Positive10
2015 140
2016 183
2017 227
2018 266
2019 311
2020 310
2021 341
2022 262
TOTAL 2040
1 Listed based on the year of death or, if not available, on year of referral;
2 Cases with suspected prion disease for which brain tissue and/or blood (in familial cases) were submitted;
3 Disease acquired in the United Kingdom;
4 Disease acquired in the United Kingdom in one case and in Saudi Arabia in the other;
5 Disease possibly acquired in a Middle Eastern or Eastern European country;
6 Includes 28 cases in which the diagnosis is pending (1 from 2020, 3 from 2021 and 24 from 2022), and 20 inconclusive cases;
7 Includes 20 (3 from 2021 and 17 from 2022) cases with type determination pending in which the diagnosis of vCJD has been excluded.
8 The sporadic cases include 4437 cases of sporadic Creutzfeldt-Jakob disease (sCJD), 82 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 37 cases of sporadic Fatal Insomnia (sFI).
9 Total does not include 300 Familial cases diagnosed by blood only. 10 Lists number of patients (deceased and alive) who have had a positive RT-QuIC and no neuropath examination.
case.edu/medicine/pathology/sites/case.edu.pathology/files/2022-10/WebTable%20NPDPSC.pdf
FRIDAY, DECEMBER 02, 2022
Creutzfeldt Jacob Disease CJD TSE Prion December 2022 Annual Update
creutzfeldt-jakob-disease.blogspot.com/2022/12/creutzfeldt-jacob-disease-cjd-tse-prion.html
SUNDAY, MAY 08, 2022
USA National Prion Disease Pathology Surveillance Center Surveillance Update April 11th, 2022
creutzfeldt-jakob-disease.blogspot.com/2022/05/usa-national-prion-disease-pathology.html
Tuesday APRIL 05, 2022
Incidence of Creutzfeldt-Jakob Disease in the United States 1993-2014
creutzfeldt-jakob-disease.blogspot.com/2022/04/incidence-of-creutzfeldt-jakob-disease_5.html
TUESDAY, MAY 24, 2022
Texas Creutzfeldt Jakob Disease CJD TSE Prion Update Singeltary FOIA Request Received May 23, 2022
cjdtexas.blogspot.com/2022/05/texas-creutzfeldt-jakob-disease-cjd-tse.html
TUESDAY, MAY 10, 2022
Concordance of CSF RT-QuIC across the European Creutzfeldt-Jakob Disease surveillance network
creutzfeldt-jakob-disease.blogspot.com/2022/05/concordance-of-csf-rt-quic-across.html
Canada Definite and probable CJD, 1998-2022 As of October 31, 2022
Year Sporadic Iatrogenic CJD Genetic vCJD Total
1998 22 1 1 0 24
1999 27 2 3 0 32
2000 32 0 3 0 35
2001 27 0 3 0 30
2002 30 0 5 1 36
2003 27 1 1 0 29
2004 42 0 4 0 44
2005 42 0 2 0 44
2006 39 0 5 0 44
2007 35 0 4 0 39
2008 48 0 1 0 49
2009 48 0 5 0 53
2010 35 0 3 0 38
2011 46 0 4 1 51
2012 62 0 1 0 63
2013 50 0 1 0 51
2014 51 0 5 0 56
2015 44 0 8 0 52
2016 57 1 6 0 64
2017 82 0 5 0 87
2018 75 1 5 0 81
2019 76 0 2 0 78
2020 65 0 4 0 69
2021 56 0 3 0 59
2022 64 0 1 0 65
Total 1183 6 83 2 1274
Cases with definite and probable diagnosis to date
www.canada.ca/en/public-health/services/surveillance/blood-safety-contribution-program/creutzfeldt-jakob-disease/cjd-surveillance-system.html#ref
United Kingdom
CREUTZFELDT-JAKOB DISEASE IN THE UK (By Calendar Year)
Source: NCJDRSU website www.cjd.ed.ac.uk - updated 07/11/2022
REFERRALS OF SUSPECT CJD DEATHS OF DEFINITE AND PROBABLE CJD
Year Referrals Year Sporadic1 Iatrogenic Genetic2 vCJD Total Deaths
1990 [53]† 1990 28 5 0 - 33
1991 75 1991 31 1 4 - 36
1992 96 1992 45 2 6 - 53
1993 79 1993 36 4 7 - 47
1994 119 1994 53 1 9 - 63
1995 87 1995 35 4 5 3 47
1996 132 1996 40 4 6 10 60
1997 163 1997 59 6 7 10 82
1998 155 1998 64 3 5 18 90
1999 170 1999 62 6 2 15 85
2000 178 2000 48 1 3 28 80
2001 179 2001 58 4 6 20 88
2002 164 2002 73 0 5 17 95
2003 163 2003 79 5 7 18 109
2004 114 2004 50 2 6 9 67
2005 124 2005 67 4 13 5 89
2006 112 2006 68 1 9 5 83
2007 119 2007 63 2 11 5 81
2008 150 2008 84 5 6 2 97
2009 153 2009 78 2 8 3 91
2010 150 2010 85 3 6 3 97
2011 158 2011 91 4 14 5 114
2012 127 2012 92 5 12 0 109
2013 152 2013 108 2 10 1 121
2014 130 2014 100 3 13 0 116
2015 140 2015 105 0 4 0 109
2016 148 2016 118 1 6 1 126
2017 159 2017 122 0 12 0 134
2018 167 2018 137 2 12 0 151
2019 147 2019 128 1 7 0 136
2020 172 2020 135 1 8 0 144
2021 179 2021 132 0 6 0 138
2022 148 2022 113 0 3 0 116
Total Referrals 4562 Total Deaths 2587 84 238 178 3087
† Referral figure for 1990 is from 1 May onwards *As at 7 th November 2022
Summary of vCJD cases
Deaths from definite vCJD (confirmed): 123
Deaths from probable vCJD (without neuropathological confirmation): 55
Number of deaths from definite or probable vCJD (as above): 178
Number of definite/probable vCJD cases still alive: 0
Total number of definite or probable vCJD (dead and alive): 178
1 There are, in addition, a total of 20 cases of vPSPr (death in 1997(1 case), 2004(1), 2006(1), 2008(3), 2010(1), 2012(4), 2013(1), 2016(3), 2017(1), 2018(1), 2019(1), 2020(2)) not included in the above figures.
2 includes all genetic prion disease, including GSS.
Source: NCJDRSU website www.cjd.ed.ac.uk - updated 07/11/2022
www.cjd.ed.ac.uk/sites/default/files/figs.pdf
Latest NCJDRSU annual report, covering the period 1990-2021
www.cjd.ed.ac.uk/sites/default/files/report30.pdf
Safe laboratory management of prions and proteopathic seeds
CORRESPONDENCE| VOLUME 20, ISSUE 12, P981, DECEMBER 01, 2021
Safe laboratory management of prions and proteopathic seeds
Simon Mead Thomas Evans
on behalf of the Advisory Committee for Dangerous Pathogens Transmissible Spongiform Encephalopathy Subgroup Published:December, 2021DOI: doi.org/10.1016/S1474-4422(21)00379-3
Prions, the infectious agents of fatal and transmissible neurodegenerative disorders in humans and animals, are comprised of assemblies of misfolded forms of prion protein (PrP). The death of a 33-year-old researcher of prion diseases from variant Creutzfeldt-Jakob disease (ie, the strain of disease that is derived from bovine spongiform encephalopathy) 9 years after a percutaneous exposure to prion-contaminated material, and the death from or diagnosis of prion disease in two other people in Europe after working in prion research, emphasises the importance of statutory guidance for laboratory safety when working with dangerous pathogens.1 People in numerous laboratories handling diagnostic blood, CSF, and other low-risk biofluid samples from patients with or suspected to have Creutzfeldt-Jakob disease have contacted us to suggest that the existing guidance was not sufficiently clear or proportionate.
Evidence has accrued for the potential for proteins that are linked to neurodegenerative diseases, other than PrP, to adopt abnormal conformations, self-propagate, and cause transmissible pathologies and diseases in humans and laboratory animals.2, 3 These proteins share a range of pathological properties but are also distinct from prions in important ways, including that there are no known animal or human epidemics or established occupational risks. Experiments that involve inoculating, concentrating, or synthesising these so-called proteopathic seeds have become routine in the past decade, but no statutory guidance is available for safety. Human–human transmission of amyloid β proteopathic seeds has been observed in some specific circumstances that were also shown to transmit prion infection (eg, use of cadaver-derived human pituitary hormones or dura mater in neurosurgery) and can cause iatrogenic cerebral amyloid angiopathy and fatal brain haemorrhage after long latencies.4 The popularity of this field of research, and the long latencies that are to be expected for diseases that are caused by these proteopathic seeds, mean that occupational exposures might not yet have resulted in any clinical consequences. It is prudent, therefore, to consider potential risks from laboratory work involving these agents.
The UK's Advisory Committee for Dangerous Pathogens convened a subgroup to revise guidance for safe working with prions and to consider whether any measures were needed for work with proteopathic seeds, involving experts from research laboratories for prion and other neurodegenerative diseases, infectious disease specialists, pathologists, veterinarians, and health and safety experts. In the new guidance, we emphasise a distinction between high-risk CNS tissues and research samples that contain high concentrations of prions, which need to be managed in specialised laboratories with strict policies, and low-risk biofluids, such as blood and CSF, from patients who are suspected to have Creutzfeldt-Jakob disease with no or low concentrations of prions, which can be managed in a high-throughput diagnostic laboratory setting through adherence to appropriate general laboratory practices. We also concluded that the poorly defined pathogenicity in humans of proteopathic seeds when prepared in concentrated forms for biochemical, structural, or transmission studies means that they should now be considered as hazard group 2 pathogens, necessitating work in a containment level 2 facility. We recommend a range of safety measures,5 including special attention to risk assessment and staff training; recording of accidental exposures; special caution with the use of any sharp tools to avoid percutaneous injury; work inside a microbiological safety cabinet; and the use of spill trays, absorbent material, and defined procedures to decontaminate equipment and spills to avoid contamination of the laboratory environment.
Importantly, we do not recommend any changes to existing procedures for the routine handling of tissues and biofluids from patients with non-prion neurodegenerative conditions for diagnostic or research purposes. We hope that this new guidance will be seen as proportionate and precautionary and help organisations to have increased confidence about the safety of their employees.5
We declare no competing interests. Members of the Advisory Committee for Dangerous Pathogens Transmissible Spongiform Encephalopathy Subgroup are listed in the appendix.
www.thelancet.com/journals/laneur/article/PIIS1474-4422(21)00379-3/fulltext
www.thelancet.com/cms/10.1016/S1474-4422(21)00379-3/attachment/3f032b9d-8532-4292-bd54-e23c2f50fbf3/mmc1.pdf
www.thelancet.com/journals/laneur/article/PIIS1474-4422(21)00379-3/fulltext
www.thelancet.com/action/showPdf?pii=S1474-4422%2821%2900379-3
The importance of ongoing international surveillance for Creutzfeldt–Jakob disease
Neil Watson1, Jean-Philippe Brandel2, Alison Green1, Peter Hermann3, Anna Ladogana 4, Terri Lindsay1, Janet Mackenzie1, Maurizio Pocchiari 4, Colin Smith1, Inga Zerr3 and Suvankar Pal 1 ✉
Abstract | Creutzfeldt–Jakob disease (CJD) is a rapidly progressive, fatal and transmissible neurodegenerative disease associated with the accumulation of misfolded prion protein in the CNS. International CJD surveillance programmes have been active since the emergence, in the mid-1990s, of variant CJD (vCJD), a disease linked to bovine spongiform encephalopathy. Control measures have now successfully contained bovine spongiform encephalopathy and the incidence of vCJD has declined, leading to questions about the requirement for ongoing surveillance. However, several lines of evidence have raised concerns that further cases of vCJD could emerge as a result of prolonged incubation and/or secondary transmission. Emerging evidence from peripheral tissue distribution studies employing high-sensitivity assays suggests that all forms of human prion disease carry a theoretical risk of iatrogenic transmission. Finally, emerging diseases, such as chronic wasting disease and camel prion disease, pose further risks to public health. In this Review, we provide an up-to-date overview of the transmission of prion diseases in human populations and argue that CJD surveillance remains vital both from a public health perspective and to support essential research into disease pathophysiology, enhanced diagnostic tests and much-needed treatments.
www.nature.com/articles/s41582-021-00488-7.pdf
see also;
thedaily.case.edu/researchers-find-infectious-prions-creutzfeldt-jakob-disease-patient-skin/
www.ncbi.nlm.nih.gov/pmc/articles/PMC7187701/
www.nih.gov/news-events/nih-research-matters/prions-found-skin-people-creutzfeldt-jakob-disease
ACDP TSE subgroup minutes, agendas and papers, history
app.box.com/s/hhhhg857fjpu2bnxhv6e/folder/2936396377
TUESDAY, NOVEMBER 1, 2022
SEAC Scientific Steering Committee on TSE Prion
bovineprp.blogspot.com/2022/11/seac-scientific-steering-committee-on.html
iatrogenic TSE PrP
itseprion.blogspot.com/
NOW LET'S LOOK AT THE LATEST ON TSE PRION ZOONOSIS RISK FACTORS
O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France
Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases).
Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.
*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,
***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),
***is the third potentially zoonotic PD (with BSE and L-type BSE),
***thus questioning the origin of human sporadic cases.
We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.
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***thus questioning the origin of human sporadic cases***
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***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
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PRION 2015 CONFERENCE
www.ncbi.nlm.nih.gov/pmc/articles/PMC5019500/
***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.
***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
PRION 2016 TOKYO
Saturday, April 23, 2016
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
Title: Transmission of scrapie prions to primate after an extended silent incubation period)
*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.
*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.
*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.
www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160
PRION CONFERENCE 2022 ABSTRACTS CWD TSE PrP ZOONOSIS
Transmission of prion infectivity from CWD-infected macaque tissues to rodent models demonstrates the zoonotic potential of chronic wasting disease.
Samia Hannaouia, Ginny Chenga, Wiebke Wemheuerb, Walter J. Schulz-Schaefferb, Sabine Gilcha, and Hermann M. Schätzla
Aims: Chronic wasting disease (CWD) is a prion disease of cervids. Its rapid geographic expansion, shedding of infectivity and persistence in the environment for many years are of concern for humans. Here, we provide the first evidence by transmission experiments to different transgenic mouse models and bank voles that Cynomolgus macaques inoculated via different routes with CWD-positive cervid tissues harbor infectious prions that elicit clinical disease in rodents.
Material and Methods: We used tissue materials from macaques inoculated with CWD to inoculate transgenic mice overexpressing cervid PrPCfollowed by transmission into bank voles. We used RT-QuIC, immunoblot and PET blot analysis to assess brains, spinal cords, and tissues of the gastrointestinal tract (GIT) for the presence of prions.
Results: Our results show that of the macaque materials that induced clinical disease in transgenic mice,73% were from the CNS (46% spinal cord and 27% brain), and 27% were from the spleen, although attack rates were low around 20%. Clinical mice did not display PK-resistant PrPSc(PrPres) in immunoblot, but showed low-levels of prion seeding activity. Transmission into bank voles from clinical transgenic mice led to a 100% attack rate with typical PrPressignature in immunoblot, which was different from that of voles inoculated directly with CWD or scrapie prions. High-level prion seeding activity in brain and spinal cord and PrPresdeposition in the brain were present. Remarkably, we also found prion seeding activity in GIT tissues of inoculated voles. Second passage in bank voles led to a 100% attack rate in voles inoculated with brain, spinal cord and small intestine material from first round animals, with PrPresin immunoblot, prion seeding activity, and PrPresdeposition in the brain. Shortened survival times indicate adaptation in the new host. This also shows that prions detected in GIT tissues are infectious and transmissible. Transmission of brain material from sick voles back to cervidized mice revealed transmission in these mice with a 100% attack rate, and interestingly, with different biochemical signature and distribution in the brain.
Conclusions: Our findings demonstrate that macaques, considered the best model for the zoonotic potential of prions, were infected upon CWD challenge, including oral one. The disease manifested as atypical in macaques and transgenic mice, but with infectivity present at all times, as unveiled in the bank vole model with an unusual tissue tropism.
Transmission of Cervid Prions to Humanized Mice Demonstrates the Zoonotic Potential of CWD
Samia Hannaouia, Irina Zemlyankinaa, Sheng Chun Changa, Maria Immaculata Arifina, Vincent Béringueb, Debbie McKenziec, Hermann M. Schatzla, and Sabine Gilcha
Aims: Chronic wasting disease (CWD), a prion disease of cervids, spreads efficiently among wild and farmed animals. Potential transmission to humans of CWD is a growing concern due to its increasing prevalence. Here, we aimed to determine the zoonotic potential of CWD using a mouse model for human prion diseases.
Material and Methods: Transgenic mice overexpressing human PrPChomozygous for methionine at codon 129 (tg650) were inoculated intracerebrally with brain homogenates of white-tailed deer infected with Wisc-1/CWD1 or 116AG CWD strains. Mice were monitored for clinical signs and were euthanized at terminal disease. Brains were tested by RT-QuIC, western blot upon PK digestion, and immunohistochemistry; fecal homogenates were analyzed by RT-QuIC. Brain/spinal cord and fecal homogenates of CWD-inoculated tg650 mice were inoculated into tg650 mice or bank voles. Brain homogenates of bank voles inoculated with fecal homogenates of CWD-infected tg650 mice were used for second passage in bank voles.
Results: Here, we provide the strongest evidence supporting the zoonotic potential of CWD prions, and their possible phenotype in humans. Inoculation of mice expressing human PrPCwith deer CWD isolates (strains Wisc-1 and 116AG) resulted in atypical clinical manifestations in > 75% of the mice, with myoclonus as leading clinical sign. Most of tg650 brain homogenates were positive for seeding activity in RT-QuIC. Clinical disease and presentation was transmissible to tg650 mice and bank voles. Intriguingly, protease-resistant PrP in the brain of tg650 mice resembled that found in a familial human prion disease and was transmissible upon passage. Abnormal PrP aggregates upon infection with Wisc-1 were detectable in thalamus, hypothalamus, and midbrain/pons regions.
Unprecedented in human prion disease, feces of CWD-inoculated tg650 mice harbored prion seeding activity and infectious prions, as shown by inoculation of bank voles and tg650 with fecal homogenates.
Conclusions: This is the first evidence that CWD can infect humans and cause disease with a distinctive clinical presentation, signature, and tropism, which might be transmissible between humans while current diagnostic assays might fail to detect it. These findings have major implications for public health and CWD-management.
www.tandfonline.com/doi/full/10.1080/19336896.2022.2091286