CREUTZFELDT JAKOB DISEASE: Sporadic Creutzfeldt Jakob Disease sCJD and Human TSE Prion Annual Report December 14, 2020

Sporadic Creutzfeldt Jakob Disease sCJD and Human TSE Prion Annual Report December 14, 2020

23 years to the day, December 14, 1997, Mom, DOD hvCJD confirmed, cjd and all human tse prion disease still NOT reportable in every state...so simple, yet, still not done, so damn wrong...terry

Prion disease is not one in a million

Dec 6, 2018 • ericminikel • Cambridge, MA

snip...

Ryan Maddox at the CDC has been doing this for the U.S., and he reported in 2016 that about 1 in every 6,000 deaths is due to prion disease. This figure probably captures some cases that were diagnosed only postmortem or never got referred to the surveillance center, although there might still be some underdiagnosis at work here.

Simon Mead has announced a figure of 1 in every 4,700 deaths in the U.K. Coming at it from several different angles and data sources, then, we converge on an answer that roughly 1 in every 5,000 people dies of prion disease, or in other words, the general population’s lifetime risk of prion disease is 1 in 5,000.

If you’re a researcher studying prion disease or a family affected by prion disease, people probably often ask you “oh, is that super rare?”. Next time this happens, give the best answer you can give: “it kills about 1 in 5,000 people.” Not super common, but not 1 in a million.

http://www.cureffi.org/2018/12/06/prion-disease-is-not-one-in-a-million/?fbclid=IwAR14xYqDVzbPLrEpagdUFgVYvdZaf6tNKI7Z4VDHR4jKDoy4nX_vLR-33sA

https://www.cureffi.org/2018/12/06/prion-disease-is-not-one-in-a-million/

MONDAY, JANUARY 20, 2020

sporadic CJD one in a million, FAKE NEWS PEOPLE!

***> HUMAN TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION DISEASE 1 IN 5,000 NOT ONE IN A MILLION IN 55 AND OLDER!

http://creutzfeldt-jakob-disease.blogspot.com/2020/01/sporadic-cjd-one-in-million-fake-news.html

USA Tables of Cases Examined National Prion Disease Pathology Surveillance Center Cases Examined¹ Updated quarterly.

Last updated on: October 8th, 2020

Year Total Referrals² Prion Disease Sporadic Familial Iatrogenic vCJD

1999 & earlier 382 231 200 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 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 396 277 248 29 0 0

2017 375 266 247 19 0 0

2018 309 223 204 18 1 0

2019 422 274 252 21 0 0

2020 252 159 125 11 1 0

TOTAL 75316 46117 41268 4439 14 4

1Listed based on the year of death or, if not available, on the 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 12 cases in which the diagnosis is pending, and 19 inconclusive cases;

7Includes 24 (1 from 1986, 1 from 2019, 22 from 2020) cases with type determination pending in which the diagnosis of vCJD has been excluded.

8The sporadic cases include 4020 cases of sporadic Creutzfeldt-Jakob disease (sCJD), 71 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 35 cases of sporadic Fatal Insomnia (sFI).

9Total does not include 277 Familial cases diagnosed by blood test only.

https://case.edu/medicine/pathology/divisions/national-prion-disease-pathology-surveillance-center/resources-professionals/tables-cases-examined

CJD FOUNDATION 2020 VIRTUAL CONFERENCE

Surveillance: Prion Diseases

 To estimate prion disease incidence in the US, we match death certificate data with data from the National Prion Disease Pathology Surveillance Center (NPDPSC).

 National multiple cause -of-death data (death certificate data) is compiled by CDC’s National Center for Health Statistics (NCHS).

• Routinely obtained and cost -effective

• Good source of information because of disease fatality rate (100%); diagnosis more accurate at late stages of disease

• If CJD, prion disease, GSS, etc. is listed anywhere on the death certificate, it is included in the NCHS data (misspellings, too).

 Results of specimen testing by NPDPSC may confirm or rule out suspected prion disease cases

• Cases are added to or subtracted from death certificate data based on NPDPSC information

Surveillance: Prion Diseases

 6781 decedents were identified as having prion disease during 2003-2018 for an average annual age-adjusted incidence of 1.2 cases per million population.

 The incidence among males was 1.3 per million, and among females, 1.1 per million.

 Incidence among white decedents (1.3 per million) was more than double the incidence among black decedents (0.6 per million).

 14 cases were <30 years of age: 7 cases per billion per year.

 Only 3 were sporadic forms of prion disease, 1 sporadic CJD and 2 sporadic fatal insomnia.

 The remaining 11 cases were familial (5 GSS, 2 FFI, 1 fCJD), variant CJD (2), and iatrogenic CJD (1, dura mater-associated).

 Incidence among those ≥65: 6 cases per million per year.

 1 CJD death for approximately every 6,000 deaths overall in the US each year

Surveillance: Prion Diseases

 Of the total cases each year during 2003 -2018, 6%-18% were the result of additions to the death certificate data based on positive neuropathologic and/or genetic findings.

 Out of all the death certificates with prion disease indicated, 2% - 6% were removed annually based on negative neuropathology results.

 NPDPSC’s now-regular use of the highly specific (few false positives), pre-mortem RT-QuICtest should lead to improvements in death certificate accuracy in the coming years.

 CDC case definition: Neuropsychiatric illness + positive RT-QuIC= probable CJD

Surveillance: Prion Diseases

 2017 data (542 cases):

 10 (2%) autopsy-negative cases excluded out of 511 cases identified through death certificate data

 23/121 (19%) death certificate cases with RT-QuICand no autopsy had a negative RT-QuIC

 42 autopsy -positive NPDPSC cases added (8% of total)

 2018 data (503 cases):

 8 (2%) autopsy-negative cases excluded out of 479 cases identified through death certificate data

 21/157 (13%) death certificate cases with RT-QuICand no autopsy had a negative RT-QuIC

 32 autopsy -positive NPDPSC cases added (6% of total)

Surveillance: Disease Confirmation

 Prion disease diagnoses still confirmed only by neuropathology

 Neuropathology can be a sentinel for unique and possibly emerging prion disease cases.

 RT-QuICcontinues to be assessed through comparison of results with the “gold standard” of brain tissue analysis.

 NPDPSC neuropathology results are used to adjust death certificate data, allowing for more accurate incidence calculations.

Surveillance: Mechanisms

 CDC may learn of a CJD case through a variety of different sources:

 NCHS (national multiple cause -of-death data)

 National Prion Disease Pathology Surveillance Center (NPDPSC)

 Public health departments and medical personnel

 Family members, the public, and the media

 Cause of death on death certificates can be amended; the process varies from state to state.

 Verified cases are included as part of our national prion disease surveillance.

 Surveillance does not capture every CJD case.

Surveillance: States

 CJD is now reportable to some degree in almost all states.

 State reporting requirements do not necessarily translate into more accurate surveillance.

 Misdiagnosed case will still be a misdiagnosed case.

 CDC helped co-author a Council of State and Territorial Epidemiologists (CSTE) position statement outlining specific CJD surveillance actions and goals.

 Making the disease reportable in a state may facilitate accomplishment of these goals.

 CDC provides funding to strategic states for enhanced surveillance activities.

Surveillance: Variant CJD

 Variant CJD is the human form of bovine spongiform encephalopathy (BSE, or “mad cow disease”).

 232 cases of variant CJD worldwide (178 in United Kingdom)

 4 cases in the United States, 2 in Canada

 None are believed to have been exposed to the infectious agent in North America.

Tissue Donation

 FDA Guidance for Industry: Human cells, tissue, and cellular and tissue -based products (corneas, skin, bone, heart valves, etc.) Ineligible:

 Persons who have been diagnosed with vCJD or any other form of CJD

 Persons who have a history of CJD in a blood relative

 Persons who spent three months or more cumulatively in the United Kingdom from the beginning of 1980 through the end of 1996

 Persons who spent 5 years or more cumulatively in Europe from 1980 until the present

SNIP...SEE FULL REPORT;

https://cjdfoundation.org/files/Conf2020/ryan-Maddox-virtual-conference.pdf

CJD FOUNDATION 2020 VIRTUAL CONFERENCE

https://www.youtube.com/watch?v=nQi_KUhrOb8&feature=youtu.be

https://cjdfoundation.org/2020-presentations

***> CANADA, I find it very odd that Canada has NO recorded or documented cases of Variably Protease-Sensitive Prionopathy (VPSPr)?

CANADA Creutzfeldt-Jakob disease surveillance system (CJDSS) report

Definite and probable CJD, 1998-2020

As of 31 October, 2020

Year Sporadic Iatrogenic Familial GSS FFI vCJD Total

1998 22 1 0 1 0 0 24

1999 27 2 2 1 0 0 32

2000 32 0 0 3 0 0 35

2001 27 0 2 1 0 0 30

2002 31 0 2 2 0 1 36

2003 27 1 1 0 0 0 29

2004 42 0 1 1 0 0 44

2005 42 0 1 1 0 0 44

2006 39 0 1 3 1 0 44

2007 35 0 0 4 0 0 39

2008 48 0 1 0 0 0 49

2009 48 0 3 2 0 0 53

2010 35 0 3 0 0 0 38

2011 46 0 3 1 0 1 51

2012 62 0 1 0 0 0 63

2013 50 0 0 0 1 0 51

2014 51 0 4 0 1 0 56

2015 44 0 5 1 2 0 52

2016 57 1 5 1 0 0 64

2017 82 0 2 1 1 0 86

2018 74 1 4 0 1 0 80

2019 76 0 2 0 0 0 78

2020 30 0 2 0 0 0 32

Total 1027 6 45 23 7 2 1110

Cases with definite and probable diagnosis to date.

Gerstmann-Sträussler-Scheinker disease (GSS)

Fatal familial insomnia (FFI)

Variant CJD (vCJD)

https://www.canada.ca/en/public-health/services/surveillance/blood-safety-contribution-program/creutzfeldt-jakob-disease/cjd-surveillance-system.html

Sporadic Creutzfeldt Jakob Disease sCJD and Human TSE Prion Annual Report December 2020

Application of telehealth for comprehensive Creutzfeldt-Jakob disease surveillance in the United Kingdom

Neil Watson Hatice Kurudzhu Alison Green David Summers Colin Smith Suvankar Pal Published:November 06, 2020DOI:https://doi.org/10.1016/j.jns.2020.117221 PlumX Metrics

Highlights • Creutzfeldt-Jakob disease (CJD) is fatal and transmissible. • National surveillance in the UK seeks to identify all cases, • The COVID-19 pandemic led to the complete adoption of telehealth for CJD surveillance. • Telehealth was associated with significantly shofter time to assessment than previous in-person assessments • Telehealth is an effective means of delivering rapid and comprehensive CJD surveillance

Abstract

Creutzfeldt-Jakob disease (CJD) is a fatal human prion disease. Surveillance systems operate globally with the goals of accurate in-life case ascertainment, appropriate public health interventions to minimise secondary transmission, and monitoring trends in disease epidemiology. The UK experienced the highest incidence of variant CJD (vCJD) in the world following widespread population exposure to bovine spongiform encephalopathy (BSE). 178 cases of vCJD have been identified in the UK by the National CJD Research & Surveillance Unit (NCJDRSU), including three cases of secondary transmission via blood transfusion. The NCJDRSU performs high-fidelity surveillance, assessing all cases of suspected CJD referred to the unit. COVID-19 has caused widespread disruption to healthcare and poses a threat to services.

The NCJDRSU converted to telehealth-based surveillance in March 2020.

We report the results of the application of telehealth for comprehensive CJD surveillance during the first four months of the pandemic.

59 cases were assessed for suspected CJD.

In 52 cases the relatives were interviewed for an informant history, by video conference or telephone call.

34 patients underwent video examination;

1 case was examined in-person.

MRI images were assessed in all cases and 46 underwent CSF testing.

Feedback was obtained from interviewees and the NCJDRSU team on their experiences.

50 cases were diagnosed with sporadic CJD;

5 received an alternative diagnosis, and the remaining 4 remained unresolved, with further investigations underway.

Telehealth significantly reduced time taken to assessment compared to in-person assessments in 2019. Telehealth is an effective way to provide comprehensive CJD surveillance at a national level.

To read this article in full you will need to make a payment

https://www.jns-journal.com/article/S0022-510X(20)30557-8/fulltext

THE NATIONAL CJD RESEARCH & SURVEILLANCE UNIT (NCJDRSU)

CREUTZFELDT-JAKOB DISEASE IN THE UK (By Calendar Year)

Source: NCJDRSU website www.cjd.ed.ac.uk - updated 02/11/2020

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 162 2003 79 5 6 18 108

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 93 5 11 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 145 2019 127 1 7 0 135

2020 142 2020 107 1 6 0 114

Total Referrals 4202 Total Deaths 2314 84 225 178 2801

† Referral figure for 1990 is from 1 May onwards * As at 2nd November 2020

Summary of vCJD cases Deaths

Deaths from definite vCJD (confirmed): 123

Deaths from probable vCJD (without neuropathological confirmation): 55

Deaths from probable vCJD (neuropathological confirmation pending): 0

Number of deaths from definite or probable vCJD (as above): 178

Alive

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 17 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)) not included in the above figures.

2 includes all genetic prion disease, including GSS.

Source: NCJDRSU website www.cjd.ed.ac.uk - updated 02/11/2020

http://www.cjd.ed.ac.uk/sites/default/files/figs.pdf

VARIANT CJD CASES WORLDWIDE

COUNTRY TOTAL NUMBER OF PRIMARY CASES (NUMBER ALIVE) TOTAL NUMBER OF SECONDARY CASES: BLOOD TRANSFUSION (NUMBER ALIVE) RESIDENCE IN UK > 6 MONTHS DURING PERIOD 1980-1996

UK 175 (0) 3 (0) 178§

France 28 (0) - 1

Republic of Ireland 4 (0) - 2

Italy 3 (0) - 0

USA 4† (0) - 2

Canada 2 (0) - 1

Saudi Arabia 1 (0) - 0

Japan 1* (0) - 0

Netherlands 3 (0) - 0

Portugal 2 (0) - 0

Spain 5 (0) - 0

Taiwan 1 (0) - 1

† The third US patient with vCJD was born and raised in Saudi Arabia and has lived permanently in the United States since late 2005. According to the US case-report, the patient was most likely infected as a child when living in Saudi Arabia.

The completed investigation of the fourth US patient did not support the patient’s having had extended travel to European countries, including the United Kingdom or travel to Saudi Arabia. It confirmed that the case was in a US citizen born outside the Americas and indicated that his infection occurred before he moved to the United States; the patient had resided in Kuwait, Russia and Lebanon (see http://wwwnc.cdc.gov/eid/article/21/5/pdfs/14-2017.pdf

* The case from Japan had resided in the UK for 24 days in the period 1980-1996. § Case 178 from the UK was heterozygous at codon129 of the PRNP gene

Source: www.cjd.ed.ac.uk – data correct as at 02/11/20

http://www.cjd.ed.ac.uk/sites/default/files/worldfigs.pdf

28t h ANNUAL REPORT 2019 CREUTZFELDT-JAKOB DISEASE SURVEILLANCE IN THE UK

The National CJD Research & Surveillance Unit Western General Hospital, Edinburgh, EH4 2XU & Chancellor’s Building, Royal Infirmary of Edinburgh, EH16 4SB www.cjd.ed.ac.uk

SNIP...

CLINICAL SURVEILLANCE

he national surveillance of CJD in the UK was initiated in May 1990. Surveillance is funded by the Department of Health and Social Care, UK and by the Scottish Government Health Department. The NCJDRSU aims to monitor characteristics of CJD, specifically sCJD and vCJD, to identify trends in incidence rates and to study risk factors for the development of disease. This report documents the findings in relation to UK cases of sCJD and vCJD as well as genetic and iatrogenic forms of disease referred up to 31st December 2019 (based on data ascertained up to 7 th July 2020). Mortality data from England and Wales include retrospective data from 1970; for Scotland and Northern Ireland, retrospective mortality data are available from 1985. Case definitions for the various types of CJD can be found at www.cjd.ed.ac.uk/sites/default/files/criteria.pdf. Cases classified as definite or probable are included in all analyses from Section 2.2 onwards.

snip...

2.2 Sporadic Creutzfeldt-Jakob Disease Between 1st January 1970 and 31st December 2019, 2626 cases of sCJD were identified (268 in England and Wales from 1970-1984 and 2358 in the UK from 1985-2019), of which 21 cases were alive on 31st December 2019. Two cases moved abroad after diagnosis and are therefore lost to follow-up. Of these 2626 cases, 1613 (61%) were classified as definite cases with the remainder classed as probable; 1328 (51%) were female and 1298 (49%) were male. Eight further cases have been identified: 3 in Jersey, 3 in the Isle of Man and 2 cases who were repatriated to the UK when they became ill but had been living abroad. These 8 cases are not included in the following UK analyses.

snip...

Geographical distribution of sCJD Over the period 1990-2019 the average crude annual mortality rates from sCJD per million population were 1.24 in England, 1.56 in Wales, 1.23 in Scotland and 0.91 in Northern Ireland (Tables 1a and 1b). When account is taken of age and sex, the variation in recorded mortality between the different countries is not statistically significant (p=0.23). Age- and sex- standardised mortality ratios (SMRs) for the 12 government office regions of the UK for the period 1st January 1990 to 31st December 2019 were calculated (Figure 5). An SMR of 100 equates to the national average mortality rate; an SMR above or below this value reflects relative high or low mortality, respectively. After adjusting for the age/sex distribution of the population, the variation in mortality rates between the different regions is not statistically significant (p=0.13).

snip...

2.3 Variant Creutzfeldt-Jakob Disease

Up to 31st December 2019, 178 cases of definite or probable vCJD had been identified in the UK (123 definite and 55 probable cases who did not undergo post mortem). Seventy-five (42%) of the 178 cases were female and 103 (58%) were male. The median age at onset of disease was 26½ years and the median age at death 28 years (compared with 67 years for the median age at onset and 68 years for the median age at death for sCJD). The youngest case was aged 12 years at onset while the oldest case was aged 74 years. The age- and sex-specific mortality rates for vCJD over the time period 1 May 1995 to 31 December 2019 are shown in Figure 6. The median duration of illness from the onset of first symptoms to death was 14 months (range 6-114) compared with a median duration of illness for cases of sCJD of 4 months (range 1 to 132) during the period 1990-2019. The last known UK case of vCJD was reported in 2016 with onset in 2014.

Of 161 vCJD cases tested, one case of definite vCJD was heterozygous (MV) at Codon 129 of the PRNP gene while the remaining 160 definite or probable vCJD cases were methionine homozygous (MM). A single case of possible vCJD with an MV genotype was described by Kaski et al. in 2009.1 To date, no case of vCJD has been identified in the UK in individuals born after 1989.

Geographical distribution of variant CJD

Tables 2a and 2b present data on the geographical distribution by residence at onset (for all 178 vCJD cases) and residence at death (for 175 vCJD cases who had died by 31st December 2019 and were resident in the UK at death), along with the crude mortality rate per million population per annum of each standard region.

Cases have been widely spread throughout the UK. Age- and sex- standardised incidence ratios (SIRs) based on cases' place of residence in 1991 (shortly after the time when exposure to the BSE agent is assumed to have peaked) are shown in Figure 7. There remains a relatively high incidence amongst those who lived in the north (Scotland, North East, North West, Yorkshire & Humberside; 16.9 million people, 74 vCJD cases) compared to the south (Wales, East Midlands, West Midlands, South West, South East, London, East of England; 31.7 million people, 100 vCJD cases) of Great Britain in 1991.2

The rate ratio controlling for age and sex is 1.39 (95% CI 1.03-1.88), ie individuals living in the “North” in 1991 are about one and a half times more likely to have developed vCJD than individuals who were living in the “South” in 1991.

2.4 Iatrogenic Creutzfeldt-Jakob disease

Since 1970, up to 31st December 2019, 88 cases of CJD attributable to iatrogenic exposure have been identified, 8 in individuals receiving dura mater implants, 79 in individuals who had received human-derived growth hormone (hGH) and one in a recipient of human gonadotrophin (hGN) who was treated in Australia. All of these individuals have died (Figure 8). The median age at death of the hGH/hGN group was 35 years (with a range of 20-51 years) and for the dura mater cases 46 years (range 27-78 years).

The first identified iatrogenic case was a dura mater recipient who died in 1979. The first hGH-related death occurred in 1985. Since 1985 in the UK, human pituitary-derived hormones have been replaced by synthetic preparations. Details of the UK human pituitary-derived hormone cases, with a discussion of the incubation periods, were published in 2003.3 A study of the accumulated UK experience with dura mater-related CJD, including incubation periods, was undertaken and the results published in 2006.4

Iatrogenic transmission of CJD/vCJD is also studied by the Unit through the identification and investigation of surgical or other links between cases. The Unit continues to collect risk factor information for all suspect cases of human prion diseases referred to the Unit as part of its core work.

2.5 Transfusion Medicine Epidemiology Review

The Transfusion Medicine Epidemiology Review (TMER) is a collaborative project between the UK NCJDRSU and UK Blood Services (UKBS). The main purpose is to investigate whether there is any evidence that CJD or vCJD may have been transmitted via the blood supply. Cases (definite and probable) are notified to the UKBS by NCJDRSU; a search establishes whether any have acted as donors or received blood transfusions. Donation/transfusion records are checked and all components traced through hospital records. Details of all identified recipients/donors are forwarded to NCJDRSU for subsequent checking to ensure none appear on the NCJDRSU database as a case of CJD.

Results from the vCJD arm of the project identified four instances of probable transfusion transmitted infection in 3 cases of vCJD and pre-clinical infection in a recipient with post-mortem confirmation of abnormal prion protein deposition in the spleen (all previously reported5678). There have been no new cases of transfusion-associated vCJD since 2007.

Results from all other types of CJD included in the project have not so far shown any evidence of transfusion transmission9 . This includes, to date, 312 blood component recipients identified from 40 sporadic CJD (sCJD) cases who were donors. None have been identified as CJD cases on the NCJDRSU database and death certificates from the 190 recipients who have subsequently died did not reveal CJD as a cause of death. Twenty-six sCJD cases with a history of blood component transfusion were traced by the blood services from which 262 donors were identified. None of these donors have been identified as CJD cases on the NCJDRSU database and death certificates from the 4 donors who have subsequently died did not reveal CJD as a cause of death.

(External collaborators on this project: Dr H Harvala Simmonds, Ms C Reynolds, Ms T Yawitch).

2.6 Study of Progressive Intellectual & Neurological Deterioration (PIND)

The aim of this project is to use the mechanism of the British Paediatric Surveillance Unit to identify all cases of progressive intellectual and neurological deterioration in children in the UK, particularly those with features suggestive of vCJD. All cases are discussed and allocated to a diagnostic category by an Expert Neurological Advisory Group made up of consultants who have specialised knowledge of paediatric neurology, neurogenetics and metabolic disease, together with representation from the National CJD Research & Surveillance Unit.10, 11, 12

As of 31st December 2019, after nearly 23 years of surveillance, 4633 patients with suspected PIND had been reported. There have been six cases of vCJD: four definite and two probable. Three were reported in 1999, one in 2000 and two in mid-2001. The youngest UK case of vCJD identified to date was aged 12 at onset. A total of 2032 cases had a confirmed underlying cause other than vCJD, being categorised into over 220 known neurodegenerative diseases.

(External collaborators on this project: Dr C Verity, Mrs E Baker, Ms AM Winstone, Ms P Maunder)

2.7 Surveillance of potential occupational exposure to CJD

Public Health England in collaboration with NCJDRSU have set up an occupational surveillance study with two parts: 1) a registry for the prospective long term monitoring of healthcare and laboratory workers who have incurred occupational exposures to prion diseases and 2) the retrospective review of possible occupational exposures of CJD cases who have been healthcare or laboratory workers. By the end of 2019, 2 healthcare workers and one laboratory worker had reported prion-disease exposures as a result of needle stick/sharps injuries. None have subsequently developed prion disease. Retrospective investigations of possible occupational exposures of CJD cases in the UK continues to be undertaken to determine if any exposure to prion disease occurred – there is no evidence to indicate the occurrence of occupational exposure to the prion agent. 13 14

(External collaborators on this project: K Sinka)

2.8 Prion surveillance in primary immunodeficiency patients

The study began in 2006 and aims to identify whether there is evidence of abnormal prion protein/vCJD in the blood and/or body tissues of primary immunodeficiency patients exposed to UK sourced immunoglobulin between 1996 and 2000.

By 22nd May 2020, a total of 80 patients registered in 17 immunology centres across Great Britain had participated in the study. Of these, 18 had died with a further 9 lost to follow up, leaving 53 participants registered over 12 sites. Participants have been followed up for approximately 1538 person-years following first exposure to UK-sourced immunoglobulin. In this time no participants have shown any clinical or pathological features suggestive of vCJD or evidence of abnormal prion protein in tissues tested.

(External collaborators on this project: M Turner, R McNairney, M Helbert, M Buckland, J Cooper, R Herriott, A Huissoon, M Gompels, S Jolles, C Chopra, G Hayman,

2.9 Enhanced surveillance of individuals identified as at increased risk of CJD

The potential for secondary transmission of CJD has led to collaborative studies undertaken between the UK Haemophilia Centre Doctors Organisation, Institute of Child Health (London), NHS Blood and Transplant, National Prion Clinic, Public Health England and Health Protection Scotland aimed at identifying whether there is evidence of clinical or sub-clinical infection in those judged to be at increased risk of CJD, such evidence is investigated through review of clinical records and medical histories, and through post-mortem investigations15.

As at 31st December 2019, three cases of vCJD and one asymptomatic infection had been identified in recipients of blood from donors who later developed vCJD (see section 2.5 TMER) and one asymptomatic infection in a bleeding-disorder patient who received UK sourced plasma products.

There have been no occurrences/diagnoses of CJD in individuals at risk through surgical exposures. Please see section 2.4 for figures relating to those at risk following treatment with pituitary derived hormones.

(External collaborators on this project: (H Ward, K Sinka, S Mead

LABORATORY ACTIVITIES

SNIP...SEE FULL REPORT;

http://www.cjd.ed.ac.uk/sites/default/files/Report28.pdf

Prion2019

https://www.tandfonline.com/doi/full/10.1080/19336896.2019.1615197

FRANCE CREUTZFELDT JAKOB DISEASE DOSSIER THÉMATIQUE 02 NOVEMBRE 2020 Maladie de Creutzfeldt-Jakob

Maladie de Creutzfeldt-Jakob : données

Le dispositif de surveillance de la Maladie de Creutzfeld-Jakob, basé sur les déclarations obligatoires et les notifications au RNS-MCJ permet de suivre l’évolution de cette pathologie

L’apparition du variant de la MCJ et son lien avec l’encéphalopathie spongiforme bovine (ESB)

Suite à la mise en évidence de la transmissibilité du prion par voie alimentaire à partir de produits animaux et responsable du variant de la maladie de Creutzfeldt Jakob (improprement appelée « crise de la vache folle »), 28 cas de vMCJ certains ou probables ont été identifiés en France et sont décédés entre 1992 et 2019 (tableau).

Il s'agissait de 12 hommes et 16 femmes. La médiane des âges lors de leur décès ou de leur diagnostic est de 36 ans (entre 19 et 58 ans). Parmi eux, 9 personnes résidaient en Ile-de-France et 19 dans d’autres régions.Tous les cas identifiés à ce jour étaient homozygotes Met-Met pour le codon 129 du gène de la protéine prion (PRNP) ; ils ne présentaient aucun facteur de risque identifié pour les autres formes reconnues de MCJ. Un cas avait séjourné très régulièrement au Royaume-Uni pendant une dizaine d'années à partir de 1987.

NOMBRE DE CAS DÉCÉDÉS CERTAINS OU PROBABLES DE MCJ EN FRANCE PAR ANNÉE DE SIGNALEMENT POUR LES SUSPICIONS, PAR ANNÉE DE DÉCÈS POUR LES CAS DE MCJ DÉCÉDÉS (MISE À JOUR DU 1ER OCTOBRE 2020) Année

Suspicions signalées MCJ sporadique MCJ iatrogène hormone de croissance Autre MCJ iatrogène MCJ génétique vMCJ certain ou probable décédé vMCJ probable non décédé Total MCJ

1992 71 38 7 2 4 0 0 51

1993 63 35 12 1 7 0 0 55

1994 90 45 5 3 7 0 0 60

1995 112 59 8 1 6 0 0 74

1996 200 68 10 0 10 1 0 89

1997 296 80 6 1 5 0 0 92

1998 457 81 8 1 13 0 0 103

1999 589 92 8 0 5 0 0 105

2000 823 88 9 0 8 1 0 106

2001 1100 109 5 0 15 1 0 130

2002 1044 107 2 2 13 3 0 127

2003 1084 108 8 1 10 0 0 127

2004 884 98 8 0 9 2 0 117

2005 925 82 4 1 10 6 0 103

2006 1314 124 5 0 8 6 0 143

2007 1372 138 1 0 15 3 0 157

2008 1475 105 5 0 12 0 0 122

2009 1485 114 4 0 14 2 0 134

2010 1614 151 0 0 10 0 0 161

2011 1609 115 0 0 6 0 0 121

2012 1693 131 0 1 11 0 0 143

2013 1744 123 0 0 6 1 0 130

2014 1721 150 0 0 16 1 0 167

2015 1959 130 1 0 8 0 0 139

2016 1952 136 0 0 12 0 0 148

2017 2091 124 1 0 20 0 0 145

2018 2025 102 0 0 9 0 0 111

2019 1974 91 1 0 3 1 0 96

2020 1520 38 0 0 0 0 0 38

4 décès de MCJ iatrogènes par hormone de croissance extractive sont survenus en 1991.

Une augmentation globale de l’incidence de la maladie de Creutzfeld-Jakob entre 1992 et 2002

La première explication de l’augmentation régulière de l’incidence de la Maladie de Creutzfeld-Jakob sporadique est la mise en place d’une surveillance active. Les deux crises "de la vache folle" (1996 et 2000) et la mise au point du test 14.3.3 (1997) ont vraisemblablement aussi contribué à une meilleure identification des cas, en particulier chez les personnes les plus âgées. Cette augmentation a d’ailleurs été observée dans tous les pays du réseau européen de surveillance active EuroCJD.

https://www.santepubliquefrance.fr/maladies-et-traumatismes/maladies-infectieuses-d-origine-alimentaire/maladie-de-creutzfeldt-jakob/donnees/#tabs

https://www.santepubliquefrance.fr/maladies-et-traumatismes/maladies-infectieuses-d-origine-alimentaire/maladie-de-creutzfeldt-jakob/documents/rapport-synthese/les-maladies-de-creutzfeldt-jakob-et-les-maladies-apparentees-en-france-en-2007

https://www.santepubliquefrance.fr/maladies-et-traumatismes/maladies-infectieuses-d-origine-alimentaire/maladie-de-creutzfeldt-jakob/documents/article/les-maladies-de-creutzfeldt-jakob-et-les-maladies-apparentees-en-france-en-2001

France Occupational Exposure vCJD

The epidemiological survey revealed that the patient had been employed from 2009 to 2012 in a laboratory involved in prion research. In particular, she has worked on transgenic animal models expressing human and bovine PrP and infected with strains of human or bovine prions. The patient had two work accidents. In May 2010, she stabbed her thumb with sharp ends curved forceps used to handle brain frozen sections of humanized transgenic mice infected with a sheep-adapted BSE agent. The mouse brain handled at the time of the accident was from a secondary intra-cerebral subpassage of sheep BSE in transgenic mice overexpressing a methionine 129-human PrP. To note transmission studies indicate a low or absent transmission barrier to sheep BSE in human M129-PrP mice. The neuropathological phenotype is similar to that observed in mice infected with cattle BSE or vCJD suggesting that sheep-BSE could act as a causal vCJD agent especially in codon 129-methionine homozygotes.

4,5 The patient immediately noticed a bleeding wound. After leaving the level 3 biosafety laboratory, the wounded finger was cleaned with water and immersed for more than ten minutes in a freshly diluted 2% sodium hypochlorite solution. The second accident occurred in September 2011 in a conventional laboratory with no contact with infectious prion material. No other risk factors were identified with the exception, as most French people in her age cohort, a dietary exposure from 1986 to 1996 to bovine products with a BSE risk.

Variant Creutzfeldt–Jakob Disease Diagnosed 7.5 Years after Occupational Exposure

Variant Creutzfeldt–Jakob disease was identified in a technician who had cut her thumb while handling brain sections of mice infected with adapted BSE 7.5 years earlier. The long incubation period was similar to that of the transfusion-transmitted form of the disease.

TO THE EDITOR:

We report a case of variant Creutzfeldt–Jakob disease (CJD) that was plausibly related to accidental occupational exposure in a technician who had handled murine samples contaminated with the agent that causes bovine spongiform encephalopathy (BSE) 7.5 years earlier.

In May 2010, when the patient was 24 years of age, she worked in a prion research laboratory, where she handled frozen sections of brain of transgenic mice that overexpressed the human prion protein with methionine at codon 129. The mice had been infected with a sheep-adapted form of BSE. During this process, she stabbed her thumb through a double pair of latex gloves with the sharp ends of a curved forceps used to handle the samples. Bleeding was noted at the puncture site.

In November 2017, she began having burning pain in the right shoulder and neck. The pain worsened and spread to the right half of her body during the following 6 months. In November 2018, an examination of a sample of cerebrospinal fluid (CSF) obtained from the patient was normal. Magnetic resonance imaging (MRI) of the brain showed a slight increase in the fluid-attenuated inversion recovery (FLAIR) signal in the caudates and thalami (Fig. S1A and S1B in the Supplementary Appendix, available with the full text of this letter at NEJM.org). In January 2019, she became depressed and anxious and had memory impairment and visual hallucinations. There was hypertonia on the right side of her body. At that time, an analysis of CSF for 14-3-3 protein was negative. In March 2019, MRI showed an increased FLAIR signal in pulvinar and dorsomedial nuclei of thalami (Fig. S1C through S1E).

The patient was found to be homozygous for methionine at codon 129 of the prion protein gene without mutation. An analysis of a sample of CSF on real-time quaking-induced conversion analysis was negative for a diagnosis of sporadic CJD. However, an analysis of plasma and CSF by means of protein misfolding cyclic amplification was positive for the diagnosis of variant CJD (Figure 1A and 1B). The patient died 19 months after the onset of symptoms. Neuropathological examination confirmed the diagnosis of variant CJD (Figure 1C and 1D). Western blot analysis showed the presence of type 2B protease-resistant prion protein in all sampled brain areas. The clinical characteristics of the patient and the postmortem neuropathological features were similar to those observed in 27 patients with variant CJD who had previously been reported in France.1 (Additional details are provided in the Supplementary Appendix.)

There are two potential explanations for this patient’s condition. Oral transmission from contaminated cattle products cannot be ruled out because the patient was born at the beginning of the French BSE outbreak in cattle. However, the last two patients who had confirmed variant CJD with methionine homozygosity at codon 129 in France and the United Kingdom died in 2014 and 2013, respectively, which makes oral transmission unlikely. In France, the risk of variant CJD in 2019 was negligible or nonexistent in the post-1969 birth cohort.2

Percutaneous exposure to prion-contaminated material is plausible in this patient, since the prion strain that she had handled was consistent with the development of variant CJD.3 The 7.5-year delay between the laboratory accident and her clinical symptoms is congruent with the incubation period in the transfusion-transmitted form of the disease. The ability of this strain to propagate through the peripheral route has been documented, and experimental studies with scrapie strains have shown that scarification and subcutaneous inoculation are effective routes.4,5 The last known Italian patient with variant CJD, who died in 2016, had had occupational contact with BSE-infected brain tissues, although subsequent investigation did not disclose a laboratory accident (Pocchiari M, Italian Registry of CJD: personal communication). Thus, the last two cases of variant CJD outside the United Kingdom have been associated with potential occupational exposure. Such cases highlight the need for improvements in the prevention of transmission of variant CJD and other prions that can affect humans in the laboratory and neurosurgery settings, as outlined in the Supplementary Appendix.

Jean-Philippe Brandel, M.D. Assistance Publique–Hôpitaux de Paris, Paris, France

M. Bustuchina Vlaicu, M.D. Groupe Hospitalier Nord-Essonne, Orsay, France

Audrey Culeux, B.Sc. INSERM Unité 1127, Paris, France

Maxime Belondrade, M.Sc. Daisy Bougard, Ph.D. Etablissement Français du Sang, Montpellier, France

Katarina Grznarova, Ph.D. Angeline Denouel, M.Sc. INSERM Unité 1127, Paris, France

Isabelle Plu, M.D. Elodie Bouaziz-Amar, Pharm.D., Ph.D. Danielle Seilhean, M.D., Ph.D. Assistance Publique–Hôpitaux de Paris, Paris, France

Michèle Levasseur, M.D. Groupe Hospitalier Nord-Essonne, Orsay, France

Stéphane Haïk, M.D., Ph.D. INSERM Unité 1127, Paris, France stephane.haik@upmc.fr

Supported by a grant (ANR-10-IAIHU-06) from Programme d’Investissements d’Avenir and Santé Publique France.

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

July 2, 2020 N Engl J Med 2020; 383:83-85 DOI: 10.1056/NEJMc2000687

https://www.nejm.org/doi/full/10.1056/NEJMc2000687

Supplementary Appendix

This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Brandel J-P, Vlaicu MB, Culeux A, et al. Variant Creutzfeldt–Jakob disease diagnosed 7.5 years after occupational exposure. N Engl J Med 2020;383:83-5. DOI: 10.1056/NEJMc2000687

Full case report

A woman, born in 1986, with only a medical history of dental avulsion and the removal of a nevus started to complain, in November 2017, of burning pain in the right shoulder and the right side of the neck. Over the next 6 months, the pain worsened and spread to the right half-body including the buttocks, the back of the thigh and the foot sole, and the face with ear pain. After several consultations, a first hospital assessment was carried out in November 2018. CSF examination was normal and brain MRI interpreted as normal despite slight high signals in the caudate nucleus and thalami (Supplementary figure 1). The diagnosis of Lyme disease was suspected and treatment with ceftriaxone was initiated. Pain persisted and the patient who was showing signs of depression was referred to a psychiatrist for antidepressant treatment. Memory impairment was noted by relatives in January 2019 and the patient was admitted to a neurology department in February 2019. Right extrapyramidal hypertonia, visual hallucinations and memory problems of recent events were observed. Neurological alterations were associated with severe anxiety. Inflammatory markers, biological and immunological assessments were normal. Serology for conventional agents was negative. Detection of anti-neuronal, anti-thyroid peroxidase, anti-thyroglobulin and anti-thyroidstimulating hormone receptor antibodies yielded negative results. Vitamin B1 and B6 levels were within normal limits. Standard CSF analysis was normal and 14-3-3 protein detection was negative. MRI from mid-March 2019 showed a high signal on the FLAIR sequences in the pulvinar and dorsomedian nuclei of the thalamus, bilaterally, more intense than those observed in the striatum (Supplementary figure 1). A generally slow activity was observed on EEGs. PRNP analysis revealed a homozygous methionine-methionine (MM) genotype at codon 129 without mutation. At this time, the patient fulfilled criteria of probable vCJD. Two different protein misfolding amplification methods were performed. As predicted in a suspected case of vCJD, RT-QuIC detection in the CSF gave a negative result.1 A PMCA test, recently validated for the diagnosis of vCJD in plasma and CSF was performed.2,3 PMCA detection was positive in plasma and CSF. Evolution was marked by the

worsening of cognitive impairment, a small step with balance disorders and an extrapyramidal syndrome.

The patient died 19 months after disease onset.

Neuropathological examination confirmed the diagnosis of vCJD by showing typical florid plaques in the cerebral cortex and cerebellum. Spongiform changes, gliosis and neuronal loss were predominantly observed in the subcortical gray matter. In addition, PrP immunohistochemistry showed multicentric plaques, clumpses, peri-cellular and peri-vascular PrP deposition (Supplementary figure 2). Western blot detection of PrPres was positive and type 2B PrPres was consistently detected in all studied brain areas.

Methods

Clinical and epidemiological data As with all other cases of French vCJD, a direct interview with the patient’s family was conducted. Clinical data were extracted from the medical records and further information was collected using the European network (EuroCJD) questionnaire. The data collected were gender, age at onset and death, clinical features, results of investigations, and specific medical risk factors. These included history of growth hormone therapy, transplantation, surgery, blood transfusion, blood products therapy (albumin, immunoglobulin, clotting factors), vaccinations, professional activity, and stays in UK. The reports of the two accidents at work were collected. Additional data were obtained from the authorities of the research institute. They explained precisely how the patient had been injured, the biological materials handled and how the wounds had been disinfected and treated. Genetic analysis The prion protein gene (PRNP) was analyzed as described previously to obtain the genotype at codon 129 and to exclude a pathogenic mutation.6 An informed consent for genetic analysis was obtained from the patient's husband.

Neuropathological analysis

Samples were taken from 1cm-thick coronal sections after two months of fixation in 10% formalin as described previously.7 After formic acid treatment, specimens were embedded in paraffin. Threemicrometer-thick sections were stained with hematoxylin and eosin and Periodic Acid–Schiff (PAS) methods. PrP immunohistochemistry was performed using the 12F10 mouse monoclonal antibody.8,9 Biochemical analysis PrPres analysis by Western blot was performed from frozen samples of the brain. Tissue homogenization, digestion with proteinase K, purification, electrophoresis and immunoblotting were

done as described previously.10 The biochemical classification according to Parchi and colleagues was used.11

Amplification methods

RT-QuIC analysis in the CSF was performed using hamster full-length (23–231) recombinant PrP as previously described.12 Thirty µl of CSF per well were added and analysis was performed in quadruplicate using a BMG-LABTECH Omega. PMCA amplification in plasma and CSF was performed as described by using brains from transgenic mice overexpressing human M129-PrP as substrate.2,3 For plasma samples, a capture of abnormal PrP using plasminogen-coated magnetic nanobeads was performed before serial amplification. Each round of PMCA comprised 80 cycles of 30 min incubation/20 s sonication. Implications If one considers our patient as a case of a documented accidental transmission of CJD in a research laboratory, several important points should be stressed:

- A single puncture without hollow needle containing infectious material is sufficient to transmit prions in human even with a short contact.

- The incubation period is similar to that seen in MM patients with transfusion-transmitted vCJD, suggesting that the level of accidentally delivered infectious dose is in the same range as that contained in a unit of non-leukodepleted red blood cells.

- Immersing this type of lesion in a freshly diluted 2% sodium hypochlorite solution was not sufficient to prevent contamination. Important consequences in terms of prevention of occupational risks and public health issue associated with prions should be underlined:

- Individual protection against accidental wounds should be reinforced in research laboratories, neuropathology department and autopsy rooms. Neurosurgery teams should take the risk into account, especially when a cortical biopsy is performed to explore patients with unexplained encephalopathy. This implies accurate information and training of exposed professionals.

- The efficacy of decontamination procedures to be applied in case of accidental exposure has not been demonstrated using adequate in vivo models of transmission. A more aggressive postexposure management is to be defined and validated experimentally.

- The mechanisms of prion neuro-invasion in this specific scenario are unknown and may involve prion propagation through (1) the peripheral innervation of digital pulp, (2) an up-take by phagocytes driving prion replication in the lymphoid system followed by propagation via the autonomous nervous system or (3) blood transport.

- No preventive treatment is available to date. While a few approaches that may limit peripheral prion propagation and neuro-invasion have been proposed (such as corticoids and pentosan polysulfate), their efficiency in such a transmission pattern and in the use of relevant prion strains has to be confirmed.

References

1. Zanusso G, Monaco S, Pocchiari M, Caughey B. Advanced tests for early and accurate diagnosis of Creutzfeldt-Jakob disease. Nat Rev Neurol 2016;12:325-33.

2. Bougard D, Brandel JP, Belondrade M, et al. Detection of prions in the plasma of presymptomatic and symptomatic patients with variant Creutzfeldt-Jakob disease. Science translational medicine 2016;8:370ra182.

3. Bougard D, Belondrade M, Mayran C, et al. Diagnosis of Methionine/Valine Variant Creutzfeldt-Jakob Disease by Protein Misfolding Cyclic Amplification. Emerging infectious diseases 2018;24:1364-6.

4. Plinston C, Hart P, Chong A, et al. Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy infection following passage in sheep. Journal of virology 2011;85:1174-81.

5. Joiner S, Asante EA, Linehan JM, et al. Experimental sheep BSE prions generate the vCJD phenotype when serially passaged in transgenic mice expressing human prion protein. J Neurol Sci 2018;386:4-11.

6. Laplanche JL, Delasnerie-Lauprêtre N, Brandel JP, et al. Molecular genetics of prion diseases in France. Neurology 1994;44:2347-51.

7. Hauw JJ, Sazdovitch V, Laplanche JL, et al. Neuropathologic variants of sporadic CreutzfeldtJakob disease and codon 129 of PrP gene. Neurology 2000;54:1641-6.

8. Haik S, Faucheux BA, Sazdovitch V, et al. The sympathetic nervous system is involved in variant Creutzfeldt-Jakob disease. Nature medicine 2003;9:1121-3.

9. Privat N, Laffont-Proust I, Faucheux BA, et al. Human prion diseases: from antibody screening to a standardized fast immunodiagnosis using automation. Mod Pathol 2008;21:140-9.

10. Levavasseur E, Laffont-Proust I, Morain E, et al. Regulating factors of PrP glycosylation in Creutzfeldt-Jakob disease--implications for the dissemination and the diagnosis of human prion strains. PloS one 2008;3:e2786.

11. Parchi P, Notari S, Weber P, et al. Inter-laboratory assessment of PrPSc typing in creutzfeldtjakob disease: a Western blot study within the NeuroPrion Consortium. Brain pathology 2009;19:384- 91.

12. McGuire LI, Poleggi A, Poggiolini I, et al. Cerebrospinal fluid real-time quaking-induced conversion is a robust and reliable test for sporadic creutzfeldt-jakob disease: An international study. Annals of neurology 2016;80:160-5.

snip...

https://www.nejm.org/doi/suppl/10.1056/NEJMc2000687/suppl_file/nejmc2000687_appendix.pdf

Variant Creutzfeldt–Jakob Disease Diagnosed 7.5 Years after Occupational Exposure

https://www.nejm.org/doi/full/10.1056/NEJMc2000687

THURSDAY, JULY 02, 2020

Variant Creutzfeldt–Jakob Disease Diagnosed 7.5 Years after Occupational Exposure

https://vcjd.blogspot.com/2020/07/variant-creutzfeldtjakob-disease.html

Japan

A nationwide trend analysis in the incidence and mortality of Creutzfeldt–Jakob disease in Japan between 2005 and 2014 increasing trends

Yoshito Nishimura, Ko Harada, Toshihiro Koyama, Hideharu Hagiya & Fumio Otsuka

Abstract

In the era of hyper-ageing, Creutzfeldt–Jakob disease (CJD) can become more prevalent as an important cause of dementia. This study aimed to evaluate the trends in crude and age-adjusted CJD-associated mortality and incidence rates in Japan using national vital statistics data on CJD-associated deaths among individuals aged over 50 years, as well as the government-funded nationwide CJD surveillance data (pertaining to the years 2005–2014) in Japan. The data were analysed using the Joinpoint Regression Program to estimate the long-term trends and average annual percentage changes (AAPCs). Overall, the AAPCs of age-adjusted CJD-associated mortality rates rose significantly over the study period (3.2%; 95% confidence interval [CI] 1.4–5.1%). The AAPC of the age-adjusted incidence rates also increased (overall 6.4%; 95% CI 4.7–8.1%). The CJD-associated increases in the mortality and incidence rates were especially prominent among adults over the age of 70 years. Given this trend in aging of population, the disease burden of CJD will continue to increase in severity. Our findings thus recommend that policymakers be aware of the importance of CJD and focus on preparing to address the increasing prevalence of dementia.

Snip...

Discussion

Our study revealed an increase in the absolute number of deaths, mortality rates, and incidence rates associated with CJD—even after age-adjustment—in Japan between 2005 and 2014. The significantly increasing trends in the CJD-associated mortality and incidence rates were especially prominent in the older age groups. Previous surveillance data and reviews have described that comparable increasing trends in both mortality and incidence of CJD have been observed globally. According to the latest report from the Creutzfeldt–Jakob Disease International Surveillance Network, annual mortality rates of sCJD had risen in the most participating countries from 1993 to 201821. In European countries including the Czech Republic, Slovakia, and the United Kingdom, increases in the sCJD incidence have been reported22,23,24. According to these studies and the current data, it should be noted that Japan might have had higher CJD incidence (more than 4.5 per million in 2014) than other countries. While CJD has been considered a rare disease, the phenomenon of population ageing may trigger a rise in the incidence of CJD and the attendant socioeconomic and healthcare burdens.

According to the previous CJD-associated mortality analysis conducted from 1979 to 2004 in Japan20, the crude mortality rate reached a peak of 1.3 per million in 2004. Our analysis indicates that the steep trend has continued, with 4.1 cases of CJD per million accounted for in 2014 (Supplementary Table S1). While the number of CJD-associated deaths was highest in the 70–79 years age group from 1979 to 2004 in Japan, our crude mortality analysis showed a predominant upward trend among individuals of over 80 years of age, indicating a shift in the CJD disease burden to the more aged population. Concerning the age-adjusted mortality, our results show a continuously increasing trend across the study period, with an APC of 3.7% among men and of 2.9% among females. These results agree with those found by Doi et al., with an age-adjusted mortality of 3.1% among men and 3.9% among women. This increasing trend suggests that CJD will soon aggravate the disease burden in the hyper-ageing Japanese society.

The increased CJD-associated mortality rates could be explained by the rise in the rate of CJD incidence. The prognosis of CJD is considered poor, with uniform fatality and a median life expectancy of about 6 months after diagnosis worldwide25,26. Hence, as was observed in the present study, the mortality and incidence rates are almost identical. Various factors could account for the increase in the rates of CJD incidence: e.g., increased awareness of the disease1, improvement in the accuracy of diagnostic tests2, and demographic changes characteristic of a hyper-ageing society. While the upward trends in the rates of mortality and incidence may be partly attributable to improvements in diagnosis, we propose the ageing of the population as an important contributor to the CJD trends in Japan.

According to the Japanese national statistics, the population of individuals of over 65 years of age was 35.58 million in 2018, accounting for 28.1% of the whole population27. The Japanese surveillance data indicates that approximately 80% of the CJD patients in Japan were sCJD, which is more common among older individuals28. Hence, if the increased CJD-related incidence and mortality are primarily attributable to sCJD, it follows that both rates would rise as the population ages. These observations are compatible with our study results, which suggest that the number of CJD-associated deaths was highest in the age groups of 70–74 and 75–79 years. From a pathophysiological perspective, age may increase the rate of prion protein conversion: the etiological agent of prion diseases, including CJD6,7,29. Also, in our study population, women experienced higher CJD-associated deaths and incidence than men, although it has been generally considered that there is no gender predilection for CJD12. A possible explanation for the differences in CJD according to sex may be postmenopausal decreased serum oestrogen levels, which could facilitate the maintenance of cellular pathological prion protein30. Hence, the cellular mechanism underlying prion diseases also suggests that the incidence and mortality of sCJD would increase in ageing populations.

Considering that dementia has been reported in almost all cases of CJD in Japan28, the increasing incidence of CJD is even more alarming. According to the latest WHO statistics, about 50 million people in the world are estimated to have dementia31, imposing a substantial worldwide socioeconomic burden; the global social costs due to dementia were estimated to be 1.1% of the global gross domestic product in 201532. Approximately 4.7 million people were living with dementia in Japan in 2015. This figure is projected to rapidly increase to 7 million people by 202533. Recognising the pressing global concern about dementia, the G20 Health Ministers stressed the importance of developing national strategies to improve the quality of care and life of the patients with dementia as well those of their caregivers17. It should further be noted that Japanese patients with CJD were reported to have a longer life expectancy (20.9 months on average) following diagnosis than those from other countries (approximately 6 months as noted above)28, which would pose additional socioeconomic impacts on the patients’ caregivers if the mortality and incidence rates continue to rise at the current rates34. While CJD still remains a rare disease, the trends identified by the present study warrant attention by public health authorities and indicate the need for effective policy measures to mitigate the disease burden of CJD, from caregiver’s perspectives in particular.

While this study benefits from being the first to use national vital statistics and surveillance data to perform a joinpoint regression analysis of trends in CJD-associated incidence and mortality in Japan, it is subject to several limitations. First, as we analysed the causes of death based on the information provided by death certificates, we may have underestimated the CJD-associated death rates. Second, the rate of CJD incidences could have been further underestimated due to the voluntary nature of the CJD surveillance. Third, we used a specific ICD-10 code (A81.0 “Creutzfeldt–Jakob disease”) from the vital statistics to obtain our data, which made it impossible to determine the accuracy of the recorded causes of death. Specifically, the patients with CJD may have a number of complications, such as infections, heart failure, and respiratory failure, common in the older populations. Hence, the attribution of the cause of death to CJD may have been recorded inappropriately in some cases. Despite the limitations, our present study underscores the significantly increasing trends in CJD-associated mortality and incidence across a 10-year period in the era of ageing.

In conclusion, we revealed the increasing trends of CJD-associated incidence and mortality using joinpoint regression analysis. The extent of increase was greater among individuals older than 70 years of age; hence, the increased rated of CJD-associated incidence and mortality may not only be attributable to increased disease awareness but also be attributable to the increasingly ageing population. The severe socioeconomic burdens on caregivers imposed by CJD-induced dementia also warrant the attention of policymakers and stress the need for a mitigative action plan with particular focus on preparations to handle an increase in the prevalence of dementia.

https://www.nature.com/articles/s41598-020-72519-0

SATURDAY, SEPTEMBER 26, 2020

A nationwide trend analysis in the incidence and mortality of Creutzfeldt–Jakob disease in Japan between 2005 and 2014 with increasing trends of incidence and mortality

https://creutzfeldt-jakob-disease.blogspot.com/2020/09/a-nationwide-trend-analysis-in.html

FRIDAY, OCTOBER 30, 2020

Analysis of Chinese patients with sporadic Creutzfeldt-Jakob disease

https://creutzfeldt-jakob-disease.blogspot.com/2020/10/analysis-of-chinese-patients-with.html

Sunday, November 1, 2020

Taiwan Incidence of and Mortality Due to Human TSE Prion Diseases Sees Significant Increase In Incidence After 2008

https://taiwancjd.blogspot.com/2020/11/taiwan-incidence-of-and-mortality-due.html

Australia CJD TSE Prion

Creutzfeldt-Jakob disease surveillance in Australia: update to 31 December 2019

Christiane Stehmann, Matteo Senesi, Shannon Sarros, Amelia McGlade, Marion Simpson, Genevieve Klug, Catriona McLean, Colin L Masters and Steven Collins

Abstract

Nationwide surveillance of Creutzfeldt-Jakob disease and other human prion diseases is performed by the Australian National Creutzfeldt-Jakob Disease Registry (ANCJDR). National surveillance encompasses the period since 1 January 1970, with prospective surveillance occurring from 1 October 1993. Over this prospective surveillance period, considerable developments have occurred in pre-mortem diagnostics; in the delineation of new disease subtypes; and in a heightened awareness of prion diseases in healthcare settings. Surveillance practices of the ANCJDR have evolved and adapted accordingly. This report summarises the activities of the ANCJDR during 2019.

Since the ANCJDR began offering diagnostic cerebrospinal fluid (CSF) 14-3-3 protein testing in Australia in September 1997, the annual number of referrals has steadily increased. In 2019, 513 domestic CSF specimens were referred for 14-3-3 protein testing and 85 persons with suspected human prion disease were formally added to the national register. As of 31 December 2019, just under half (42 cases) of the 85 suspect case notifications remain classified as ‘incomplete’; 16 cases were excluded through either detailed clinical follow-up (3 cases) or neuropathological examination (13 cases); 20 cases were classified as ‘definite’ and seven as ‘probable’ prion disease. For 2019, sixty-three percent of all suspected human prion disease related deaths in Australia underwent neuropathological examination. No cases of variant or iatrogenic CJD were identified. Two possibly causal novel prion protein gene (PRNP) sequence variations were identified.

snip...

Discussion

In 2019, the number of suspected prion disease referrals and confirmed cases broadly matched the long-term average (1997–2018). Australia continued to be free of vCJD and no further cases of iCJD were detected. By state and territory, generally only modest fluctuations in the number of suspected case referrals compared to the previous year were observed during 2019 which are within previously observed ranges. In 2017 and 2018 however, the highest recorded number of ‘definite’ and ‘probable’ prion disease cases in Queensland was observed contributing to an annual age-standardised mortality rate of 1.98 and 1.93 deaths per million in 2017 and 2018, respectively, for this state. Occasional high mortality rates have been reported previously in Queensland in 1999 and 2000. During 2012 and 2013, the reduced number of cases in Queensland was attributed to several possible factors including the temporary interruption of a facile suspected prion disease autopsy service, changes to the approach of recording suspected cases on the national case register for investigation by the ANCJDR, and natural fluctuations. Since the restoration of the routine suspected prion disease autopsy service through the Royal Brisbane Hospital towards the end of 2014, expected rates of prion disease-related post-mortems have been observed; a corresponding increase in statistical (‘definite’ or ‘probable’) cases has been observed. These findings illustrate the importance of brain autopsies to the accurate surveillance of prion disease in Australia.

Fluctuations in annual suspect case referrals and prion disease mortality rates are not surprising given the small absolute case numbers involved and the potential impact of extraneous factors. For example, higher referral rates were experienced in 1998 and 1999 when the 14-3-3 protein test was first introduced and in 2006 when notifiable disease legislation was completed in all states and territories; however, the higher number of case referrals in 2017 continued in 2018 and 2019 and, although likely to be an underestimate of final case classifications (until all post-mortem reports and case reviews are finalised), the currently observed rates are comparable to previous years and contribute to a period of stable case ascertainment. Increased case classifications since 2015 have also contributed to stabilising the number of ‘incomplete’ cases currently under investigation. Prior to 2015, the addition of new suspect cases considerably exceeded fully evaluated cases with an outcome.

Long-term national surveillance units report differing annual prion disease mortality rates, ranging from 0.24 to 4.56 per million population.4,5,10 Higher rates of human prion disease over short time frames have also been recognised and investigated in various global settings with inconclusive outcomes.10 The underlying basis for fluctuations and differences in national mortality rates is uncertain, although variation in case ascertainment is one potentially contributing factor.5

Spatio-temporal clustering of CJD has previously been recognised in NSW and Victoria.10,11 Detailed epidemiological assessment by the ANCJDR did not disclose any likely horizontal transmission event but instead uncovered a heightened intensity of surveillance.11 This more intense level of surveillance was reflected by the significantly higher rates of referrals of suspect prion disease cases for evaluation and diagnostic testing to the ANCJDR, as well as higher neuropathological examination rates in suspected patients.6,11,12 Monitoring of the geographical distribution of suspected case referrals and confirmed cases remains an important facet of ANCJDR national surveillance.

Notably, an upwards trajectory of incidence rates of prion disease has been reported from many countries with effective surveillance methods. This overall increase in sporadic CJD cases has also been observed in Australia and is most likely due to a combination of an ageing population, improved case ascertainment and diagnostic methodologies, and greater awareness of prion disease in the healthcare sector.13

Ascertainment mechanisms in 2019 were unchanged compared to recent years, with the majority of initial referrals coming through requests for diagnostic CSF 14-3-3 protein testing. Some proactive ascertainment mechanisms, such as state health department and tertiary hospital mortality data base searches, have ceased while other case detection methods have increased. In 2019, in addition to CSF 14-3-3 diagnostic testing requests, 18% of suspect case referrals to the ANCJDR were initially through direct communications from treating clinicians and hospitals, 14% through neuropathology referrals and 10% through communications with families or the CJD Support Group Network. The number of CSF referrals to the ANCJDR for diagnostic (14-3-3 protein) testing remained high for 2019. A 20% increase in diagnostic test referrals coincided with the introduction of CSF total-tau protein estimation in 2017. Estimation of total-tau protein in CSF is NATA/ILAC accredited and complementary to 14-3-3 protein testing to support a pre-mortem diagnosis of sporadic CJD. The identification of misfolded prion protein in CSF by RT-QuIC continues to be developed by the ANCJDR as a diagnostic test and is currently selectively performed for cases after discussion with clinicians. The addition of CSF total-tau protein estimation to 14-3-3 protein detection as a biomarker for the pre-mortem evaluation of suspected sCJD offers modestly enhanced diagnostic capacity while the ANCJDR completes imminent transition to clearly superior protein amplification techniques such as RT-QuIC.

The proportion of post-mortems being performed in suspect prion disease cases remains high and aligns with the long-term mean brain autopsy percentage of approximately 60% (of suspected case deaths) between 1993 and 2017. This contrasts with the findings of an Australian healthcare setting survey where the national hospital post-mortem rate was 12% in 2002–2003;14 more recently, a major Australian tertiary centre audit of hospital autopsy data has described an autopsy rate of 6.6% in 2011–2013.15 The high suspected prion disease-related post-mortem rate underpins the high and consistent number of confirmed Australian human prion disease cases recorded over the more recent prospective surveillance time period, and provides confident understanding of the cause of death in suspected cases ultimately determined as non-prion disease.

In 2019, two novel PRNP sequence variants of unknown pathogenicity were identified due to increased rates of referrals for PRNP gene sequencing in persons with suspected CJD, with such broader genetic screening informing the understanding of the true prevalence of genetic prion disease in Australia. A recent study by the ANCJDR of prion disease in Indigenous Australians8 has confirmed that sporadic CJD occurs in Indigenous Australians throughout Australia with a phenotype and incidence rate equivalent to non-Indigenous Australians, supporting the adequacy of national human prion disease surveillance.

Keywords: Creutzfeldt-Jakob disease, prion disease, transmissible spongiform encephalopathy, disease surveillance

https://www1.health.gov.au/internet/main/publishing.nsf/Content/AD2DF748753AFDE1CA2584E2008009BA/$File/creutzfeldt_jakob_disease_surveillance_in_australia_update_to_31_december_2019.docx

2019 Aug 15;43. doi: 10.33321/cdi.2019.43.35.

Creutzfeldt-Jakob disease surveillance in Australia: update to 31 December 2018

Christiane Stehmann 1, Matteo Senesi 1, Victoria Lewis 1, Mairin Ummi 2, Marion Simpson 2, Genevieve Klug 2, Catriona McLean 3, Colin Masters 1, Steven Collins 2

PMID: 31426734 DOI: 10.33321/cdi.2019.43.35

Abstract

Nationwide surveillance of human prion diseases (also known as transmissible spongiform encephalopathies), the most common being Creutzfeldt-Jakob disease (CJD), is performed by the Australian National Creutzfeldt-Jakob Disease Registry (ANCJDR), based at the University of Melbourne. National surveillance encompasses the period since 1 January 1970, with prospective surveillance occurring from 1 October 1993. Over this prospective surveillance period considerable developments have occurred in relation to pre-mortem diagnostics, the delineation of new disease subtypes and a heightened awareness of prion diseases in health care settings. Surveillance practices of the ANCJDR have evolved and adapted accordingly. This report summarises the activities of the ANCJDR from 1 January to 31 December 2018. Since the ANCJDR began offering diagnostic cerebrospinal fluid (CSF) 14-3-3 protein testing in Australia in September 1997, the annual number of referrals has steadily increased. In 2018, 465 domestic CSF specimens were referred for 14-3-3 protein testing and 78 persons with suspected human prion disease were formally added to the national register. The majority of the 78 suspect case notifications remain as of 31 December 2018 classified as "incomplete" (42 cases), while eleven cases were excluded by either detailed clinical follow-up (one case) or neuropathological examination (ten cases); 15 cases were classified as "definite" and ten as "probable" prion disease. Sixty-two percent of all suspected human prion disease related deaths underwent neuropathological examination. No cases of variant CJD were confirmed.

Keywords: Creutzfeldt-Jakob disease; disease surveillance; prion disease; transmissible spongiform encephalopathy.

https://pubmed.ncbi.nlm.nih.gov/31426734/

https://florey.edu.au/science-research/scientific-services-facilities/australian-national-cjd-registry

Russia Creutzfeldt-Jakob Disease CJD TSE Prion disease

In large cities of Russia, doctors are increasingly using rule patients with a presumptive diagnosis from the CJD to medical and scientific centers, where it is impossible to reliably confirm the diagnosis with the power of research on biological fluids. In this regard, in the media the helplessness of Russian doctors with regard to early diagnosis and organization the provision of assistance to patients and relatives. Until on the current time in Russia is not analyzed and registration of CJD cases. How can the situation be changed?

How many patients with Creutzfeldt-Jakob disease in Russia?

T.A. POLYAKOVAFGBOU

DPO "Russian Medical Academy of Continuing Professional Education", Moscow, Russia

The article provides epidemiological data on the prevalence of Creutzfeldt-Jakob disease in the world. Noted lack of relevant indicators in Russia due to the difficulties in diagnosing the disease using modern biological methods in the practice of a doctor. Modern methods of fast diagnosis of the disease and a general approach to the problem of prion diseases is discussed.

Key words: Creutzfeldt-Jakob disease, prion diseases, prions.

How many patients with Creutzfeldt — Jakob disease are there in Russia?

TA POLYAKOVA

Russian Medical Academy of Continued Professional Education, Moscow, Russia

The article presents epidemiological data on the prevalence of Creutzfeldt — Jakob disease in the world and modern techniques forthe rapid accurate diagnosis. The author discusses a national approach to this subject.

Keywords: Creutzfeldt — Jakob disease, prion diseases, prions

Human prion diseases representa group of rapidly progressing and constant but fatal neurodegenerative diseases, towhich include Creutzfeldt-Jakob disease(CJD), kuru, Gerstmann-Straussler syndrome—Scheinker and fatal familial insomnia. When-human diseases, including sporadic sky, hereditary and acquired forms, occur worldwide with a frequency of approximately 1-2cases per 1 million population per year [1]. These diseases attracted scientists and the public not only from for their significant threat to human health. Until now since there are no specific treatment and prevention activities for prion diseases. therefore so important for combating them and organizingnization of prevention has supervision over new cases of human prion diseases.

Since 1993, statistics have been kept in the world based onbased on the observation of CJD cases. There were organized long-term international projects projects aimed at obtaining epidemiological characteristics of various prion diseases of a person in different countries and regions. One of they concerned the CJP [2]. International research improvement of the epidemiological characteristics of sporadic CJD included 3,720 cases from 9 European countries, as well as from Australia and Canada. In the picture shows the countries in which monitoring is carried out treatment of CJD cases. It has been established that the total suitable mortality from CJD is 1.39 cases per 1 million population [3]. In Japan, the death rate The age-adjusted rate increased from 1979 to 2004. It is currently 1.48 cases per million population. China CJD Monitoring Service reported shila that the incidence rate in Beijing - 0.91cases per 1 million population per year. Death rates per million from sporadic CJD from 1993 to 2013 in some countries are shown in the figure.

Awareness needs to be raised first doctors about the signs of the disease and introduce methods, reliably confirming the diagnosis. In Russia a resource on the Internet was created (http: //www.prioncjbrussia.com) with which it should be promoted disease awareness and implemented remote assistance in difficult dia-gnostic cases. The use of the site is also considers the promotion of the goals of the public organization Creutzfeldt — Jakob Disease International Support Alliance (CJDISA) - International CJD Patient Support Alliance (http://cjdisa.com/), designed to solve problems of patient care there with CJD and their relatives...snip;

see full Russian Text ;

https://www.mediasphera.ru/issues/zhurnal-nevrologii-i-psikhiatrii-im-s-s-korsakova-2/2017/6/downloads/ru/1199772982017062041

sporadic creutzfeldt jakob disease sCJD as a zoonotic, zoonosis disease, what if?

2.3.2. New evidence on the zoonotic potential of atypical BSE and atypical scrapie prion strains

PLEASE NOTE;

2.3.2. New evidence on the zoonotic potential of atypical BSE and atypical scrapie prion strains

Olivier Andreoletti, INRA Research Director, Institut National de la Recherche Agronomique (INRA) – École Nationale Vétérinaire de Toulouse (ENVT), invited speaker, presented the results of two recently published scientific articles of interest, of which he is co-author: ‘Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice’ (MarinMoreno et al., 2020) and ‘The emergence of classical BSE from atypical/Nor98 scrapie’ (Huor et al., 2019).

In the first experimental study, H-type and L-type BSE were inoculated into transgenic mice expressing all three genotypes of the human PRNP at codon 129 and into adapted into ARQ and VRQ transgenic sheep mice. The results showed the alterations of the capacities to cross the human barrier species (mouse model) and emergence of sporadic CJD agents in Hu PrP expressing mice: type 2 sCJD in homozygous TgVal129 VRQ-passaged L-BSE, and type 1 sCJD in homozygous TgVal 129 and TgMet129 VRQ-passaged H-BSE.

https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/sp.efsa.2020.EN-1946

***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***

Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.

https://www.nature.com/articles/srep11573

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.

==============

https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf

***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.

http://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.

http://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.

http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160

1: J Infect Dis 1980 Aug;142(2):205-8

Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.

snip...

The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.

PMID: 6997404

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract

Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"

Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.

snip...

76/10.12/4.6

http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf

Nature. 1972 Mar 10;236(5341):73-4.

Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).

Gibbs CJ Jr, Gajdusek DC.

Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)

C. J. GIBBS jun. & D. C. GAJDUSEK

National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland

SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).

http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.html

http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html

Wednesday, February 16, 2011

IN CONFIDENCE

SCRAPIE TRANSMISSION TO CHIMPANZEES

IN CONFIDENCE

http://scrapie-usa.blogspot.com/2011/02/in-confidence-scrapie-transmission-to.html

FRIDAY, OCTOBER 23, 2020

Scrapie TSE Prion Zoonosis Zoonotic, what if?

https://transmissiblespongiformencephalopathy.blogspot.com/2020/10/scrapie-tse-prion-zoonosis-zoonotic.html

MONDAY, DECEMBER 16, 2019

Chronic Wasting Disease CWD TSE Prion aka mad cow type disease in cervid Zoonosis Update

***> ''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) <***

10. ZOONOTIC, ZOONOSIS, CHRONIC WASTING DISEASE CWD TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION AKA MAD DEER ELK DISEASE IN HUMANS, has it already happened, that should be the question...

''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)

EFSA Panel on Biological Hazards (BIOHAZ) Antonia Ricci Ana Allende Declan Bolton Marianne Chemaly Robert Davies Pablo Salvador Fernández Escámez ... See all authors

First published: 17 January 2018 https://doi.org/10.2903/j.efsa.2018.5132 ;

also, see;

8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data.

***> 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. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers.. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available.

snip...

The tissue distribution of infectivity in CWD‐infected cervids is now known to extend beyond CNS and lymphoid tissues. While the removal of these specific tissues from the food chain would reduce human dietary exposure to infectivity, exclusion from the food chain of the whole carcass of any infected animal would be required to eliminate human dietary exposure.

https://efsa.onlinelibrary.wiley.com/doi/full/10.2903/j.efsa.2018.5132

https://familialcjdtseprion.blogspot.com/2019/02/cwd-gss-tse-prion-spinal-cord-confucius.html

CJD FOUNDATION VIRTUAL CONFERENCE CJD Foundation Research Grant Recipient Reports Panel 2 Nov 3, 2020

zoonotic potential of PMCA-adapted CWD PrP 96SS inoculum

https://youtu.be/VfazuR7cjMc?t=1992

4 different CWD strains, and these 4 strains have different potential to induce any folding of the human prion protein.

https://youtu.be/VfazuR7cjMc?t=2019

***> PIGS, WILD BOAR, CWD <***

***> POPULATIONS OF WILD BOARS IN THE UNITED STATES INCREASING SUPSTANTUALLY AND IN MANY AREAS WE CAN SEE A HIGH DENSITY OF WILD BOARS AND HIGH INCIDENT OF CHRONIC WASTING DISEASE

HYPOTHOSIS AND SPECIFIC AIMS

HYPOTHOSIS

BSE, SCRAPIE, AND CWD, EXPOSED DOMESTIC PIGS ACCUMULATE DIFFERENT QUANTITIES AND STRAINS OF PRIONS IN PERIPHERAL TISSUES, EACH ONE OF THEM WITH PARTICULAR ZOONOTIC POTENTIALS

https://youtu.be/VfazuR7cjMc

Final Report – CJD Foundation Grant Program A.

Project Title: Systematic evaluation of the zoonotic potential of different CWD isolates. Principal Investigator: Rodrigo Morales, PhD.

https://cjdfoundation.org/sites/default/files/grant-downloads/Final%20Report%20-%20CJD%20Foundation%20-%20Morales.pdf

Systematic evaluation of the zoonotic potential of different CWD isolates

Rodrigo Morales, PhD Assistant Professor Protein Misfolding Disorders lab Mitchell Center for Alzheimer’s disease and Related Brain Disorders Department of Neurology University of Texas Health Science Center at Houston Washington DC. July 14th, 2018

Conclusions and Future Directions • We have developed a highly sensitive and specific CWD-PMCA platform to be used as a diagnostic tool. • Current PMCA set up allow us to mimic relevant prion inter-species transmission events. • Polymorphic changes at position 96 of the prion protein apparently alter strain properties and, consequently, the zoonotic potential of CWD isolates. • Inter-species and inter-polymorphic PrPC → PrPSc conversions further increase the spectrum of CWD isolates possibly present in nature. • CWD prions generated in 96SS PrPC substrate apparently have greater inter-species transmission potentials. • Future experiments will explore the zoonotic potential of CWD prions along different adaptation scenarios, including inter-species and inter-polymorphic.

https://cjdfoundation.org/files/Conf2018/Rodrigo%20Morales%202018.pdf

https://www.youtube.com/watch?v=CzQKemJRBlE&list=PLGXRDfDPg57yTYvn6tifH13NrSiLjv1d7&index=7&t=0s

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research

Title: Disease-associated prion protein detected in lymphoid tissues from pigs challenged with the agent of chronic wasting disease

Author item MOORE, SARAH - Orise Fellow item Kunkle, Robert item KONDRU, NAVEEN - Iowa State University item MANNE, SIREESHA - Iowa State University item SMITH, JODI - Iowa State University item KANTHASAMY, ANUMANTHA - Iowa State University item WEST GREENLEE, M - Iowa State University item Greenlee, Justin Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 3/15/2017 Publication Date: N/A Citation: N/A Interpretive Summary:

Technical Abstract: Aims: Chronic wasting disease (CWD) is a naturally-occurring, fatal neurodegenerative disease of cervids. We previously demonstrated that disease-associated prion protein (PrPSc) can be detected in the brain and retina from pigs challenged intracranially or orally with the CWD agent. In that study, neurological signs consistent with prion disease were observed only in one pig: an intracranially challenged pig that was euthanized at 64 months post-challenge. The purpose of this study was to use an antigen-capture immunoassay (EIA) and real-time quaking-induced conversion (QuIC) to determine whether PrPSc is present in lymphoid tissues from pigs challenged with the CWD agent.

Methods: At two months of age, crossbred pigs were challenged by the intracranial route (n=20), oral route (n=19), or were left unchallenged (n=9). At approximately 6 months of age, the time at which commercial pigs reach market weight, half of the pigs in each group were culled (<6 month challenge groups). The remaining pigs (>6 month challenge groups) were allowed to incubate for up to 73 months post challenge (mpc). The retropharyngeal lymph node (RPLN) was screened for the presence of PrPSc by EIA and immunohistochemistry (IHC). The RPLN, palatine tonsil, and mesenteric lymph node (MLN) from 6-7 pigs per challenge group were also tested using EIA and QuIC.

Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 month group was positive by EIA. PrPSc was detected by QuIC in at least one of the lymphoid tissues examined in 5/6 pigs in the intracranial <6 months group, 6/7 intracranial >6 months group, 5/6 pigs in the oral <6 months group, and 4/6 oral >6 months group. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%).

Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.

https://www.ars.usda.gov/research/publications/publication/?seqNo115=337105

https://www.ars.usda.gov/research/publications/publication/?seqNo115=326166

Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research

Title: The agent of chronic wasting disease from pigs is infectious in transgenic mice expressing human PRNP

Author item MOORE, S - Orise Fellow item Kokemuller, Robyn item WEST-GREENLEE, M - Iowa State University item BALKEMA-BUSCHMANN, ANNE - Friedrich-Loeffler-institut item GROSCHUP, MARTIN - Friedrich-Loeffler-institut item Greenlee, Justin Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: 5/10/2018 Publication Date: 5/22/2018 Citation: Moore, S.J., Kokemuller, R.D., West-Greenlee, M.H., Balkema-Buschmann, A., Groschup, M.H., Greenlee, J.J. 2018. The agent of chronic wasting disease from pigs is infectious in transgenic mice expressing human PRNP. Prion 2018, Santiago de Compostela, Spain, May 22-25, 2018. Paper No. WA15, page 44.

Interpretive Summary:

Technical Abstract: We have previously shown that the chronic wasting disease (CWD) agent from white-tailed deer can be transmitted to domestic pigs via intracranial or oral inoculation although with low attack rates and restricted PrPSc accumulation. The objective of this study was to assess the potential for cross-species transmission of pig-passaged CWD using bioassay in transgenic mice. Transgenic mice expressing human (Tg40), bovine (TgBovXV) or porcine (Tg002) PRNP were inoculated intracranially with 1% brain homogenate from a pig that had been intracranially inoculated with a pool of CWD from white-tailed deer. This pig developed neurological clinical signs, was euthanized at 64 months post-inoculation, and PrPSc was detected in the brain. Mice were monitored daily for clinical signs of disease until the end of the study. Mice were considered positive if PrPSc was detected in the brain using an enzyme immunoassay (EIA). In transgenic mice expressing porcine prion protein the average incubation period was 167 days post-inoculation (dpi) and 3/27 mice were EIA positive (attack rate = 11%). All 3 mice were found dead and clinical signs were not noted prior to death. One transgenic mouse expressing bovine prion protein was euthanized due to excessive scratching at 617 dpi and 2 mice culled at the end of the study at 700 dpi were EIA positive resulting in an overall attack rate of 3/16 (19%). None of the transgenic mice expressing human prion protein that died or were euthanized up to 769 dpi were EIA positive and at study end point at 800 dpi 2 mice had positive EIA results (overall attack rate = 2/20 = 10%). The EIA optical density (OD) readings for all positive mice were at the lower end of the reference range (positive mice range, OD = 0.266-0.438; test positive reference range, OD = 0.250-4.000). To the authors’ knowledge, cervid-derived CWD isolates have not been successfully transmitted to transgenic mice expressing human prion protein. The successful transmission of pig-passaged CWD to Tg40 mice reported here suggests that passage of the CWD agent through pigs results in a change of the transmission characteristics which reduces the transmission barrier of Tg40 mice to the CWD agent. If this biological behavior is recapitulated in the original host species, passage of the CWD agent through pigs could potentially lead to increased pathogenicity of the CWD agent in humans.

https://www.ars.usda.gov/research/publications/publication/?seqNo115=353091

cwd scrapie pigs oral routes

***> However, at 51 months of incubation or greater, 5 animals were positive by one or more diagnostic methods. Furthermore, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study) suggesting that swine are potential hosts for the agent of scrapie. <***

>*** Although the current U.S. feed ban is based on keeping tissues from TSE infected cattle from contaminating animal feed, swine rations in the U.S. could contain animal derived components including materials from scrapie infected sheep and goats. These results indicating the susceptibility of pigs to sheep scrapie, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health. <***

***> Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 month group was positive by EIA. PrPSc was detected by QuIC in at least one of the lymphoid tissues examined in 5/6 pigs in the intracranial <6 months group, 6/7 intracranial >6 months group, 5/6 pigs in the oral <6 months group, and 4/6 oral >6 months group. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%).

***> Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.

https://www.ars.usda.gov/research/publications/publication/?seqNo115=353091

https://www.ars.usda.gov/research/project/?accnNo=432011&fy=2017

https://www.ars.usda.gov/research/publications/publication/?seqNo115=337105

Experimental transmission of the chronic wasting disease agent to swine after oral or intracranial inoculation

S. Jo Moore1,2, M. Heather West Greenlee3, Naveen Kondru3, Sireesha Manne3, Jodi D. Smith1, Robert A. Kunkle1, Anumantha Kanthasamy3 and Justin J. Greenlee1* + Author Affiliations

1Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, Iowa, United States of America 2Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee, United States of America 3Department of Biomedical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa, United States of America

ABSTRACT

Chronic wasting disease (CWD) is a naturally occurring, fatal neurodegenerative disease of cervids. The potential for swine to serve as a host for the agent of chronic wasting disease is unknown. The purpose of this study was to investigate the susceptibility of swine to the CWD agent following experimental oral or intracranial inoculation. Crossbred piglets were assigned to one of three groups: intracranially inoculated (n=20), orally inoculated (n=19), or non-inoculated (n=9). At approximately the age at which commercial pigs reach market weight, half of the pigs in each group were culled (‘market weight’ groups). The remaining pigs (‘aged’ groups) were allowed to incubate for up to 73 months post inoculation (MPI). Tissues collected at necropsy were examined for disease-associated prion protein (PrPSc) by western blotting (WB), antigen-capture immunoassay (EIA), immunohistochemistry (IHC) and in vitro real-time quaking induced conversion (RT-QuIC). Brain samples from selected pigs were also bioassayed in mice expressing porcine prion protein. Four intracranially inoculated aged pigs and one orally inoculated aged pig were positive by EIA, IHC and/or WB. Using RT-QuIC, PrPSc was detected in lymphoid and/or brain tissue from one or more pigs in each inoculated group. Bioassay was positive in 4 out of 5 pigs assayed. This study demonstrates that pigs can support low-level amplification of CWD prions, although the species barrier to CWD infection is relatively high. However, detection of infectivity in orally inoculated pigs using mouse bioassay raises the possibility that naturally exposed pigs could act as a reservoir of CWD infectivity.

IMPORTANCE We challenged domestic swine with the chronic wasting disease agent by inoculation directly into the brain (intracranially) or by oral gavage (orally). Disease-associated prion protein (PrPSc) was detected in brain and lymphoid tissues from intracranially and orally inoculated pigs as early as 8 months of age (6 months post-inoculation). Only one pig developed clinical neurologic signs suggestive of prion disease. The amount of PrPSc in the brains and lymphoid tissues of positive pigs was small, especially in orally inoculated pigs. Regardless, positive results in orally inoculated pigs suggest that it may be possible for swine to serve as a reservoir for prion disease under natural conditions.

FOOTNOTES

↵*Corresponding author: Email: justin.greenlee@ars.usda.gov This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

http://jvi.asm.org/content/early/2017/07/06/JVI.00926-17.abstract

----Original Message-----

From: Terry Singeltary

To: Tracy.A.Nichols

Sent: Fri, Mar 30, 2018 12:51 pm

Subject: Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification Program Standards Singeltary Submission March 30, 2018

Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification Program Standards Singeltary Submission March 30, 2018

Greetings APHIS, USDA, Dr. Tracy Nichols, et al,

I wish to kindly submit my comments on the Docket No. APHIS-2018-0011 Chronic Wasting Disease Herd Certification Program Standards please. i have submitted online and sent a hard copy to Dr. Nichols via email. i know that my concern may not be the same concern as others, but ramifications from cwd tse prion can be long lasting, and science is still emerging. however, the science today warrants immediate and further actions be taken. my comments, with reference materials, are as follows, and will be formatted in such a way, i will address issues by numbers 1-10, and under each one of my comments by each number, i will reference my comments with science to back up what i am stating/asking...thank you kindly, terry

snip...see full text;

WEDNESDAY, NOVEMBER 4, 2020

CWD TSE PRION, SCRAPIE, BSE, AND PORCINE, PIGS, WILD BOAR, ZOONOTIC ZOONOSIS RISK FACTORS AND POTENTIALS

https://transmissiblespongiformencephalopathy.blogspot.com/2020/11/cwd-tse-prion-scrapie-bse-and-porcine.html

2.3.2. New evidence on the zoonotic potential of atypical BSE and atypical scrapie prion strains

PLEASE NOTE;

2.3.2. New evidence on the zoonotic potential of atypical BSE and atypical scrapie prion strains

https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/sp.efsa.2020.EN-1946

WEDNESDAY, OCTOBER 28, 2020

***> EFSA Annual report of the Scientific Network on BSE-TSE 2020 Singeltary Submission

https://efsaopinionbseanimalprotein.blogspot.com/2020/10/efsa-annual-report-of-scientific.html

SUNDAY, OCTOBER 11, 2020

Bovine adapted transmissible mink encephalopathy is similar to L-BSE after passage through sheep with the VRQ/VRQ genotype but not VRQ/ARQ

https://transmissible-mink-encephalopathy.blogspot.com/2020/10/bovine-adapted-transmissible-mink.html

THURSDAY, SEPTEMBER 24, 2020

The emergence of classical BSE from atypical/ Nor98 scrapie

https://nor-98.blogspot.com/2020/09/the-emergence-of-classical-bse-from.html

CWD TSE PRION AND ZOONOTIC, ZOONOSIS, POTENTIAL

Subject: Re: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY

Date: Fri, 18 Oct 2002 23:12:22 +0100

From: Steve Dealler

Reply-To: Bovine Spongiform Encephalopathy Organization: Netscape Online member

To: BSE-L@ References: <3daf5023 .4080804="" wt.net="">

Dear Terry,

An excellent piece of review as this literature is desparately difficult to get back from Government sites.

What happened with the deer was that an association between deer meat eating and sporadic CJD was found in about 1993. The evidence was not great but did not disappear after several years of asking CJD cases what they had eaten. I think that the work into deer disease largely stopped because it was not helpful to the UK industry...and no specific cases were reported. Well, if you dont look adequately like they are in USA currenly then you wont find any!

Steve Dealler ===============

https://caninespongiformencephalopathy.blogspot.com/2010/03/canine-spongiform-encephalopathy-aka.html

Stephen Dealler is a consultant medical microbiologist deal@airtime.co.uk

BSE Inquiry Steve Dealler

Management In Confidence

BSE: Private Submission of Bovine Brain Dealler

snip...see full text;

MONDAY, FEBRUARY 25, 2019

***> MAD DOGS AND ENGLISHMEN BSE, SCRAPIE, CWD, CJD, TSE PRION A REVIEW 2019

https://bseinquiry.blogspot.com/2019/02/mad-dogs-and-englishmen-bse-scrapie-cwd.html

> However, to date, no CWD infections have been reported in people.

key word here is ‘reported’. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can’t, and it’s as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it’s being misdiagnosed as sporadic CJD. …terry

*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***

*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***

http://www.tandfonline.com/doi/full/10.4161/pri.28124?src=recsys

http://www.tandfonline.com/doi/pdf/10.4161/pri.28124?needAccess=true

https://wwwnc.cdc.gov/eid/article/20/1/13-0858_article

Chronic Wasting Disease CWD TSE Prion aka mad deer disease zoonosis

We hypothesize that:

(1) The classic CWD prion strain can infect humans at low levels in the brain and peripheral lymphoid tissues;

(2) The cervid-to-human transmission barrier is dependent on the cervid prion strain and influenced by the host (human) prion protein (PrP) primary sequence;

(3) Reliable essays can be established to detect CWD infection in humans; and

(4) CWD transmission to humans has already occurred. We will test these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in vitro approaches.

http://grantome.com/grant/NIH/R01-NS088604-04

ZOONOTIC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE

Prion 2017 Conference

First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1

University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen

This is a progress report of a project which started in 2009. 21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves.

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.

At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation.

PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS

PRION 2018 CONFERENCE

Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice

Hermann M. Schatzl, Samia Hannaoui, Yo-Ching Cheng, Sabine Gilch (Calgary Prion Research Unit, University of Calgary, Calgary, Canada) Michael Beekes (RKI Berlin), Walter Schulz-Schaeffer (University of Homburg/Saar, Germany), Christiane Stahl-Hennig (German Primate Center) & Stefanie Czub (CFIA Lethbridge).

To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years.

After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were detected in spinal cord and brain of some euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and pre-clinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles.

Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate.

The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.
Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP.

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..

***> 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. <***

https://prion2018.org/

READING OVER THE PRION 2018 ABSTRACT BOOK, LOOKS LIKE THEY FOUND THAT from this study ;

P190 Human prion disease mortality rates by occurrence of chronic wasting disease in freeranging cervids, United States

Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1) (1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA..

SEEMS THAT THEY FOUND Highly endemic states had a higher rate of prion disease mortality compared to non-CWD
states.

AND ANOTHER STUDY;

P172 Peripheral Neuropathy in Patients with Prion Disease

Wang H(1), Cohen M(1), Appleby BS(1,2) (1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio..

IN THIS STUDY, THERE WERE autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017,

AND

included 104 patients. SEEMS THEY FOUND THAT The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%),

AND

THAT The Majority of cases were male (60%), AND half of them had exposure to wild game.

snip…

see more on Prion 2017 Macaque study from Prion 2017 Conference and other updated science on cwd tse prion zoonosis below…terry

https://prion2018.org/wp-content/uploads/2018/05/program.pdf

https://prion2018.org/

PRION 2019 ABSTRACTS

1. Interspecies transmission of the chronic wasting disease agent

Justin Greenlee

Virus and Prion Research Unit, National Animal Disease Center, USDA Agriculture Research Service

ABSTRACT

The presentation will summarize the results of various studies conducted at our research center that assess the transmissibility of the chronic wasting disease (CWD) agent to cattle, pigs, raccoons, goats, and sheep. This will include specifics of the relative attack rates, clinical signs, and microscopic lesions with emphasis on how to differentiate cross-species transmission of the CWD agent from the prion diseases that naturally occur in hosts such as cattle or sheep. Briefly, the relative difficulty of transmitting the CWD agent to sheep and goats will be contrasted with the relative ease of transmitting the scrapie agent to white-tailed deer.

53. Evaluation of the inter-species transmission potential of different CWD isolates

Rodrigo Moralesa, Carlos Kramma,b, Paulina Sotoa, Adam Lyona, Sandra Pritzkowa, Claudio Sotoa

aMitchell Center for Alzheimer’s disease and Related Brain Disorders, Dept. of Neurology, McGovern School of Medicine University of Texas Health Science Center at Houston, TX, USA; bFacultad de Medicina, Universidad de los Andes, Santiago, Chile

ABSTRACT

Chronic Wasting Disease (CWD) has reached epidemic proportions in North America and has been identified in South Korea and Northern Europe. CWD-susceptible cervid species are known to share habitats with humans and other animals entering the human food chain. At present, the potential of CWD to infect humans and other animal species is not completely clear. The exploration of this issue acquires further complexity considering the differences in the prion protein sequence due to species-specific variations and polymorphic changes within species. While several species of cervids are naturally affected by CWD, white-tailed deer (WTD) is perhaps the most relevant due to its extensive use in hunting and as a source of food. Evaluation of inter-species prion infections using animals or mouse models is costly and time consuming. We and others have shown that the Protein Misfolding Cyclic Amplification (PMCA) technology reproduces, in an accelerated and inexpensive manner, the inter-species transmission of prions while preserving the strain features of the input PrPSc. In this work, we tested the potential of different WTD-derived CWD isolates to transmit to humans and other animal species relevant for human consumption using PMCA. For these experiments, CWD isolates homozygous for the most common WTD-PrP polymorphic changes (G96S) were used (96SS variant obtained from a pre-symptomatic prion infected WTD). Briefly, 96GG and 96SS CWD prions were adapted in homologous or heterologous substrate by PMCA through several (15) rounds. End products, as well as intermediates across the process, were tested for their inter-species transmission potentials. A similar process was followed to assess seed-templated misfolding of ovine, porcine, and bovine PrPC. Our results show differences on the inter-species transmission potentials of the four adapted materials generated (PrPC/PrPSc polymorphic combinations), being the homologous combinations of seed/substrate the ones with the greater apparent zoonotic potential. Surprisingly, 96SS prions adapted in homologous substrate were the ones showing the easiest potential to template PrPC misfolding from other animal species. In summary, our results show that a plethora of different CWD isolates, each comprising different potentials for inter-species transmission, may exist in the environment. These experiments may help to clarify an uncertain and potentially worrisome public health issue. Additional research in this area may be useful to advise on the design of regulations intended to stop the spread of CWD and predict unwanted zoonotic events.

56. Understanding chronic wasting disease spread potential for at-risk species

Catherine I. Cullingham, Anh Dao, Debbie McKenzie and David W. Coltman

Department of Biological Sciences, University of Alberta, Edmonton AB, Canada

CONTACT Catherine I. Cullingham cathy.cullingham@ualberta.ca

ABSTRACT

Genetic variation can be linked to susceptibility or resistance to a disease, and this information can help to better understand spread-risk in a population. Wildlife disease incidence is increasing, and this is resulting in negative impacts on the economy, biodiversity, and in some instances, human health. If we can find genetic variation that helps to inform which individuals are susceptible, then we can use this information on at-risk populations to better manage negative consequences. Chronic wasting disease, a fatal, transmissible spongiform encephalopathy of cervids (both wild and captive), continues to spread geographically, which has resulted in an increasing host-range. The disease agent (PrPCWD) is a misfolded conformer of native cellular protein (PrPC). In Canada, the disease is endemic in Alberta and Saskatchewan, infecting primarily mule deer and white-tail deer, with a smaller impact on elk and moose populations. As the extent of the endemic area continues to expand, additional species will be exposed to this disease, including bison, bighorn sheep, mountain goat, and pronghorn antelope. To better understand the potential spread-risk among these species, we reviewed the current literature on species that have been orally exposed to CWD to identify susceptible and resistant species. We then compared the amino acid polymorphisms of PrPC among these species to determine whether any sites were linked to susceptibility or resistance to CWD infection. We sequenced the entire PrP coding region in 578 individuals across at-risk populations to evaluate their potential susceptibility. Three amino acid sites (97, 170, and 174; human numbering) were significantly associated with susceptibility, but these were not fully discriminating. All but one species among the resistant group shared the same haplotype, and the same for the susceptible species. For the at-risk species, bison had the resistant haplotype, while bighorn sheep and mountain goats were closely associated with the resistant type. Pronghorn antelope and a newly identified haplotype in moose differed from the susceptible haplotype, but were still closely associated with it. These data suggest pronghorn antelope will be susceptible to CWD while bison are likely to be resistant. Based on this data, recommendations can be made regarding species to be monitored for possible CWD infection.

KEYWORDS: Chronic wasting disease; Prnp; wildlife disease; population genetics; ungulates

Thursday, May 23, 2019

Prion 2019 Emerging Concepts CWD, BSE, SCRAPIE, CJD, SCIENTIFIC PROGRAM Schedule and Abstracts

https://prionconference.blogspot.com/2019/05/prion-2019-emerging-concepts-cwd-bse.html

see full Prion 2019 Conference Abstracts

https://www.tandfonline.com/doi/full/10.1080/19336896.2019.1615197

THURSDAY, OCTOBER 04, 2018

Cervid to human prion transmission 5R01NS088604-04 Update

http://grantome.com/grant/NIH/R01-NS088604-04

SATURDAY, FEBRUARY 09, 2019

Experts: Yes, chronic wasting disease in deer is a public health issue — for people

https://chronic-wasting-disease.blogspot.com/2019/02/experts-yes-chronic-wasting-disease-in.html

SATURDAY, FEBRUARY 23, 2019

Chronic Wasting Disease CWD TSE Prion and THE FEAST 2003 CDC an updated review of the science 2019

https://chronic-wasting-disease.blogspot.com/2019/02/chronic-wasting-disease-cwd-tse-prion.html

TUESDAY, NOVEMBER 04, 2014

Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: risk behaviours and health outcomes 2005–2011

Authors, though, acknowledged the study was limited in geography and sample size and so it couldn't draw a conclusion about the risk to humans. They recommended more study. Dr. Ermias Belay was the report's principal author but he said New York and Oneida County officials are following the proper course by not launching a study. "There's really nothing to monitor presently. No one's sick," Belay said, noting the disease's incubation period in deer and elk is measured in years. "

http://chronic-wasting-disease.blogspot.com/2014/11/six-year-follow-up-of-point-source.html

Transmission Studies

Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases {the following was written but with a single line marked through it ''first passage (by this route)}....TSS

resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculum (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in ALL of these species with the shortest incubation period in the ferret.

snip....

https://web.archive.org/web/20090506002237/http://www..bseinquiry.gov.uk/files/mb/m11b/tab01.pdf

Prion Infectivity in Fat of Deer with Chronic Wasting Disease▿

Brent Race#, Kimberly Meade-White#, Richard Race and Bruce Chesebro* + Author Affiliations

In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species.

http://jvi.asm.org/content/83/18/9608.full

Prions in Skeletal Muscles of Deer with Chronic Wasting Disease

Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure.

http://science.sciencemag.org/content/311/5764/1117..long

*** now, let’s see what the authors said about this casual link, personal communications years ago, and then the latest on the zoonotic potential from CWD to humans from the TOKYO PRION 2016 CONFERENCE.

see where it is stated NO STRONG evidence. so, does this mean there IS casual evidence ???? “Our conclusion stating that we found no strong evidence of CWD transmission to humans”

From: TSS

Subject: CWD aka MAD DEER/ELK TO HUMANS ???

Date: September 30, 2002 at 7:06 am PST

From: "Belay, Ermias"

To: Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"

Sent: Monday, September 30, 2002 9:22 AM

Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

Dear Sir/Madam,

In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD.. That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091). Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.

Ermias Belay, M.D. Centers for Disease Control and Prevention

-----Original Message-----

From: Sent: Sunday, September 29, 2002 10:15 AM

To: rr26k@nih.gov; rrace@niaid.nih.gov; ebb8@CDC.GOV

Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

Sunday, November 10, 2002 6:26 PM .......snip........end..............TSS

Thursday, April 03, 2008

A prion disease of cervids: Chronic wasting disease 2008 1: Vet Res. 2008 Apr 3;39(4):41 A prion disease of cervids: Chronic wasting disease Sigurdson CJ.

snip...

*** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,

snip... full text ;

http://chronic-wasting-disease.blogspot.com/2008/04/prion-disease-of-cervids-chronic.html

> However, to date, no CWD infections have been reported in people.

sporadic, spontaneous CJD, 85%+ of all human TSE, just not just happen. never in scientific literature has this been proven.

if one looks up the word sporadic or spontaneous at pubmed, you will get a laundry list of disease that are classified in such a way;

sporadic = 54,983 hits https://www.ncbi.nlm.nih.gov/pubmed/?term=sporadic

spontaneous = 325,650 hits https://www.ncbi.nlm.nih.gov/pubmed/?term=spontaneous

key word here is 'reported'. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can't, and it's as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it's being misdiagnosed as sporadic CJD. ...terry

*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***

http://www.tandfonline.com/doi/full/10.4161/pri.28124?src=recsys

http://www.tandfonline.com/doi/pdf/10.4161/pri.28124?needAccess=true

https://wwwnc.cdc.gov/eid/article/20/1/13-0858_article

FRIDAY, JULY 26, 2019

Chronic Wasting Disease in Cervids: Implications for Prion Transmission to Humans and Other Animal Species

https://chronic-wasting-disease.blogspot.com/2019/07/chronic-wasting-disease-in-cervids.html

TUESDAY, JANUARY 21, 2020

***> 2004 European Commission Chronic wasting disease AND TISSUES THAT MIGHT CARRY A RISK FOR HUMAN FOOD AND ANIMAL FEED CHAINS REPORT UPDATED 2020

https://chronic-wasting-disease.blogspot.com/2020/01/2004-european-commission-chronic.html

***> 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) <***

https://familialcjdtseprion.blogspot.com/2019/02/cwd-gss-tse-prion-spinal-cord-confucius.html

MONDAY, NOVEMBER 23, 2020

***> Chronic Wasting Disease CWD TSE Prion Cervid State by State and Global Update November 2020

https://chronic-wasting-disease.blogspot.com/2020/11/chronic-wasting-disease-cwd-tse-prion.html

TUESDAY, NOVEMBER 17, 2020

The European Union summary report on surveillance for the presence of transmissible spongiform encephalopathies (TSE) in 2019 First published 17 November 2020

https://efsaopinionbseanimalprotein.blogspot.com/2020/11/the-european-union-summary-report-on.html

MONDAY, NOVEMBER 30, 2020

***> REPORT OF THE MEETING OF THE OIE SCIENTIFIC COMMISSION FOR ANIMAL DISEASES Paris, 9–13 September 2019 BSE, TSE, PRION

https://animalhealthreportpriontse.blogspot.com/2020/11/report-of-meeting-of-oie-scientific.html

FRIDAY, DECEMBER 14, 2018

MAD COW USA FLASHBACK FRIDAY DECEMBER 14, 2018

https://madcowusda.blogspot.com/2018/12/mad-cow-usa-flashback-friday-december.html

2.3.2. New evidence on the zoonotic potential of atypical BSE and atypical scrapie prion strains

PLEASE NOTE;

2.3.2. New evidence on the zoonotic potential of atypical BSE and atypical scrapie prion strainsNo

https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/sp.efsa.2020.EN-1946

WEDNESDAY, OCTOBER 28, 2020

***> EFSA Annual report of the Scientific Network on BSE-TSE 2020 Singeltary Submission

https://efsaopinionbseanimalprotein.blogspot.com/2020/10/efsa-annual-report-of-scientific.html

SUNDAY, OCTOBER 11, 2020

Bovine adapted transmissible mink encephalopathy is similar to L-BSE after passage through sheep with the VRQ/VRQ genotype but not VRQ/ARQ

https://transmissible-mink-encephalopathy.blogspot.com/2020/10/bovine-adapted-transmissible-mink.html

THURSDAY, SEPTEMBER 24, 2020

The emergence of classical BSE from atypical/ Nor98 scrapie

https://nor-98.blogspot.com/2020/09/the-emergence-of-classical-bse-from.html

SUNDAY, OCTOBER 4, 2020

Cattle Meat and Offal Imported from the United States of America, Canada and Ireland to Japan (Prions) Food Safety Commission of Japan

https://animalhealthreportpriontse.blogspot.com/2020/10/cattle-meat-and-offal-imported-from.html

TUESDAY, SEPTEMBER 29, 2020

ISO's Updated 22442 Animal Tissue Standards — What Changed? TSE Prion!

https://animalhealthreportpriontse.blogspot.com/2020/09/isos-updated-22442-animal-tissue.html

WEDNESDAY, OCTOBER 21, 2020

Human Prion Disease Surveillance in Washington State, 2006-2017

https://creutzfeldt-jakob-disease.blogspot.com/2020/10/human-prion-disease-surveillance-in.html

FRIDAY, OCTOBER 23, 2020

Scrapie TSE Prion Zoonosis Zoonotic, what if?

https://transmissiblespongiformencephalopathy.blogspot.com/2020/10/scrapie-tse-prion-zoonosis-zoonotic.html

FRIDAY, OCTOBER 30, 2020

Efficient transmission of US scrapie agent by intralingual route to genetically susceptible sheep with a low dose inoculum

https://scrapie-usa.blogspot.com/2020/10/efficient-transmission-of-us-scrapie.html

MONDAY, OCTOBER 05, 2020

USA, UK, JAPAN, CJD TSE PRION STATISTICS UPDATE OCTOBER 2020

https://creutzfeldt-jakob-disease.blogspot.com/2020/10/usa-uk-japan-cjd-tse-prion-statistics.html

IATROGENIC TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY

Friendly fire, pass it forward, they call it iatrogenic cjd, or what i call 'tse prion poker', are you all in $$$

all iatrogenic cjd is, is sporadic cjd, before the iatrogenic event is discovered, traced back, proven, documented, put into the academic domain, and then finally the public domain, this very seldom happens, thus problem solved, it's all sporadic cjd, PLUS, SPORADIC CJD HAS NOW BEEN LINKED TO ATYPICAL AND TYPICAL BSE, SCRAPIE, AND NOW CWD. ...terry

Volume 26, Number 8—August 2020

Sporadic Creutzfeldt-Jakob Disease among Physicians, Germany, 1993–2018 high proportion of physicians with sCJD were surgeons

https://creutzfeldt-jakob-disease.blogspot.com/2020/08/sporadic-creutzfeldt-jakob-disease.html

SUNDAY, JULY 19, 2020

Joseph J. Zubak Orthopaedic surgeon passed away Monday, July 6, 2020, Creutzfeldt-Jakob Disease (CJD)

https://creutzfeldt-jakob-disease.blogspot.com/2020/07/joseph-j-zubak-orthopaedic-surgeon.html

Monday, September 14, 2020

Assessing the aggregated probability of entry of a novel prion disease agent into the United Kingdom

https://camelusprp.blogspot.com/2020/09/assessing-aggregated-probability-of.html

SUNDAY, OCTOBER 21, 2018

Surveillance for variant CJD: should more children with neurodegenerative diseases have autopsies? Singeltary Review

http://creutzfeldt-jakob-disease.blogspot.com/2018/10/surveillance-for-variant-cjd-should.html

TUESDAY, AUGUST 12, 2008

Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007 (occupational exposure to prion diseases)

http://creutzfeldt-jakob-disease.blogspot.com/2008/08/biosafety-in-microbiological-and.html

re-Human Prion Diseases in the United States Posted by flounder on 01 Jan 2010 at 18:11 GMT

https://journals.plos.org/plosone/article/comment?id=10.1371/annotation/04ce2b24-613d-46e6-9802-4131e2bfa6fd

Research articles Health professions and risk of sporadic Creutzfeldt– Jakob disease, 1965 to 2010

15. Terry S. Singeltary Sr. Doctor Antonio Ruiz Villaespesa, pathologist and CJD researcher deceased because of Creutzfeldt-Jakob Disease SPAIN. 21 Apr 2009. [Accessed 11 Apr 2012]. In: Monitoring the occurrence of emerging forms of CJD [blog]. Available from:

http://cjdusa.blogspot.com.es/2009/04/doctor-antonio-ruiz-villaespesa.html

https://www.eurosurveillance.org/images/dynamic/EE/V17N15/art20144.pdf

MONDAY, JANUARY 14, 2019

Evaluation of iatrogenic risk of CJD transmission associated with Chronic Wasting Disease TSE Prion in Texas TAHC TPWD

http://chronic-wasting-disease.blogspot.com/2019/01/evaluation-of-iatrogenic-risk-of-cjd.html

SUNDAY, OCTOBER 27, 2013

A Kiss of a Prion: New Implications for Oral Transmissibility

http://transmissiblespongiformencephalopathy.blogspot.com/2013/10/a-kiss-of-prion-new-implications-for.html

THURSDAY, MAY 17, 2012

Iatrogenic Creutzfeldt-Jakob Disease, Final Assessment Volume 18, Number 6—June 2012

http://transmissiblespongiformencephalopathy.blogspot.com/2012/05/iatrogenic-creutzfeldt-jakob-disease.html

Thursday, April 12, 2012

Health professions and risk of sporadic Creutzfeldt–Jakob disease, 1965 to 2010

Eurosurveillance, Volume 17, Issue 15, 12 April 2012

Research articles

http://creutzfeldt-jakob-disease.blogspot.com/2012/04/health-professions-and-risk-of-sporadic.html

Saturday, January 16, 2010

*** Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to Bramble et al

Evidence For CJD/TSE Transmission Via Endoscopes

From Terry S. Singletary, Sr flounder@wt.net 1-24-3

Terry S. Singeltary Sr., P.O. , 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

http://creutzfeldt-jakob-disease.blogspot.com/2010/01/evidence-for-cjd-tse-transmission-via.html

http://vcjd.blogspot.com/2014/07/

Wednesday, August 20, 2008

Tonometer disinfection practice in the United Kingdom: A national survey

http://creutzfeldt-jakob-disease.blogspot.com/2008/08/tonometer-disinfection-practice-in.html

Tuesday, August 12, 2008

Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007 (occupational exposure to prion diseases)

http://creutzfeldt-jakob-disease.blogspot.com/2008/08/biosafety-in-microbiological-and.html

Monday, December 31, 2007

Risk Assessment of Transmission of Sporadic Creutzfeldt-Jakob Disease in Endodontic Practice in Absence of Adequate Prion Inactivation

http://creutzfeldt-jakob-disease.blogspot.com/2007_12_01_archive.html

Subject: CJD: update for dental staff

Date: November 12, 2006 at 3:25 pm PST

1: Dent Update. 2006 Oct;33(8):454-6, 458-60.

CJD: update for dental staff.

http://seac992007.blogspot.com/2008/06/seac-2008-one-hundredth-meeting-of.html

http://vcjd.blogspot.com/2014/07/

FRIDAY, JANUARY 31, 2020

CJD TSE Prion Blood Products, iatrogenic transmission, Confucius is confused again, WHAT IF? Docket Number: FDA-2012-D-0307

http://creutzfeldt-jakob-disease.blogspot.com/2020/01/cjd-tse-prion-blood-products-iatrogenic.html

THURSDAY, DECEMBER 12, 2019

Heidenhain Variant Creutzfeldt Jakob Disease hvCJD, sporadic spontaneous CJD and the TSE Prion December 14, 2019

https://creutzfeldt-jakob-disease.blogspot.com/2019/12/heidenhain-variant-creutzfeldt-jakob.html

SUNDAY, DECEMBER 09, 2018

Creutzfeldt Jakob Disease CJD, BSE, Scrapie, CWD, TSE Prion Annual Report

December 14, 2018

https://creutzfeldt-jakob-disease.blogspot.com/2018/12/creutzfeldt-jakob-disease-cjd-bse.html

THURSDAY, DECEMBER 13, 2018

EFSA EU summary report trends and sources of zoonoses, zoonotic agents and food-borne outbreaks in 2017 and BSE TSE Prion Risk PAP December 14, 2018

https://efsaopinionbseanimalprotein.blogspot.com/2018/12/efsa-eu-summary-report-trends-and.html

TUESDAY, DECEMBER 12, 2017

Creutzfeldt Jakob Disease CJD National Prion Disease Pathology Surveillance Center Cases Examined to December 14, 2017

http://creutzfeldt-jakob-disease.blogspot.com/2017/12/creutzfeldt-jakob-disease-cjd-national.html

THURSDAY, JUNE 22, 2017

National Prion Disease Pathology Surveillance Center Cases Examined(1) (May 18, 2017)

http://prionunitusaupdate.blogspot.com/2017/06/national-prion-disease-pathology.html

MONDAY, AUGUST 22, 2016

CREUTZFELDT JAKOB DISEASE USA 2015 SPORADIC CJD TOTAL FIGURES REACHES HIGHEST ANNUAL COUNT TO DATE AT 239 CONFIRMED CASES

http://creutzfeldt-jakob-disease.blogspot.com/2016/08/creutzfeldt-jakob-disease-usa-2015.html

SATURDAY, MARCH 21, 2015

Canada and United States Creutzfeldt Jakob TSE Prion Disease Incidence Rates Increasing

http://creutzfeldt-jakob-disease.blogspot.com/2015/03/canada-and-united-states-creutzfeldt.html

Saturday, December 12, 2015

CREUTZFELDT JAKOB DISEASE CJD TSE PRION REPORT DECEMBER 14, 2015

http://creutzfeldt-jakob-disease.blogspot.com/2015/12/creutzfeldt-jakob-disease-cjd-tse-prion.html

SUNDAY, DECEMBER 14, 2014

ALERT new variant Creutzfeldt Jakob Disease nvCJD or vCJD, sporadic CJD strains, TSE prion aka Mad Cow Disease United States of America Update December 14, 2014

Report

https://transmissiblespongiformencephalopathy.blogspot.com/2014/12/alert-new-variant-creutzfeldt-jakob.html

SUNDAY, AUGUST 11, 2013

Creutzfeldt-Jakob Disease CJD cases rising North America updated report August 2013

http://creutzfeldt-jakob-disease.blogspot.com/2013/08/creutzfeldt-jakob-disease-cjd-cases.html

TEXAS CREUTZFELDT-JAKOB DISEASE CJD TSE PRION

Texas Creutzfeldt-Jakob Disease Case Counts by Type of Disease and Year (2009-2018)

Classifi-cation Trans-mission

Type Disease Type 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 Total Counts

Confirmed Acquired vCJD 1 1

Familial fCJD 2 2 3 1 2 10

FFI 2 2

Sporadic sCJD 10 16 12 10 10 11 14 18 15 21 137

sFI 1 1 2

VPSPr 1 1 1 3

Probable Familial fCJD 1 1 1 1 4

Sporadic sCJD 6 8 5 10 4 10 4 14 8 11 80

Possible Sporadic sCJD 2 1 1 4

Total Counts 20 28 18 22 14 27 20 33 25 36 243

vCJD: variant Creutzfeldt-Jakob Disease; fCJD: familial Creutzfeldt-Jakob Disease; FFI: Fatal Familial Insomnia; sCJD: sporadic Creutzfeldt-Jakob Disease; sFI: sporadic Fatal Insomnia; VPSP: variably protease-sensitive prionopathy

Texas Creutzfeldt-Jakob Disease Deaths and Death Rates per Year (2009-2018)

Case Year Case Counts Case Rate per

Million Population

2009 20 0.81

2010 28 1.11

2011 18 0.7

2012 22 0.84

2013 14 0.53

2014 27 0.99

2015 20 0.72

2016 33 1.17

2017 25 0.87

2018 36 1.22

Average 24.3 0.9

Average Number of Texas Cases per Year = 24.3

Average Rate of Deaths/Million Population/10 years = 0.9

SNIP...SEE FULL TEST;

https://www.dshs.state.tx.us/IDCU/disease/creutzfeldt_jakob/Data.aspx

THURSDAY, JULY 13, 2017

TEXAS CREUTZFELDT JAKOB DISEASE CJD TSE PRION

https://cjdtexas.blogspot.com/2017/07/texas-creutzfeldt-jakob-disease-cjd-tse.html

WEDNESDAY, DECEMBER 3, 2014

Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas in June 2014 confirmed as USA case NOT European Sunday, November 23, 2014

Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas in June 2014 confirmed as USA case NOT European

The completed investigation did not support the patient's having had extended travel to European countries, including the United Kingdom, or travel to Saudi Arabia. The specific overseas country where this patient’s infection occurred is less clear largely because the investigation did not definitely link him to a country where other known vCJD cases likely had been infected.

http://vcjd.blogspot.com/2014/11/confirmed-variant-creutzfeldt-jakob.html

http://vcjd.blogspot.com/2015/04/vcjd-texas-cdc-emerging-infectious.html

UPDATED TODAY WITH OLD HISTORY OF ANOTHER NVCJD CASE IN TEXAS IN 2005, AND PLEASE SEE HISTORY OF MAD COW CASES IN TEXAS THAT WAS COVERED UP BELOW TOWARD THE BOTTOM HERE, AND THE BANNED MAD COW FEED THAT WAS FED TO THEM...TSS

here is another record of a poor soul from Texas, that lived here for four years, and evidently never ate anything, just drank beer. odd how in Texas, you get these damn Brits with nvCJD, that come over to Texas and all they do is drink beer, and never eat, absolutely impossible to catch mad cow disease here in the USA, because it’s not here, and these Britts come here and never eat anything. what’s up with that. yet there are other strange cases of human TSE prion disease in Texas, the very young, long duration of illness till death, (see odd cases in original link post, and the cases of mad cow disease covered up in Texas, and the massive amount of banned mad cow feed, and what Texas claimed was o.k. i.e. 5.5 grams, because the steers were 600 lbs (more BSeee), see towards the bottom of original link. odd, back then when reported on nvCJD cases, you got the age, and extent of travel, diet, what not, but this June 2014 Texas human BSE vCJD case, not much information, just the same old BSeee, yada, yada, yada. ...tss

Date: 12/9/05

Texas Briton has vCJD Although likely infected in UK, case deemed U.S.

HOUSTON (AP)--A Briton who lived in Houston for four years has been diagnosed with variant Creutzfeldt-Jakob disease, the human form of bovine spongiform encephlopathy, the U.S. Centers for Disease Control said.

The 30-year-old man was diagnosed with the second U.S. case of variant Creutzfeldt-Jakob disease because his symptoms began while he lived in Houston, the CDC said Nov. 21.

Earlier this year, the man, who was not identified, returned to Britain, where his disease progressed and he is now receiving medical treatment for the fatal illness.

The U.K. National Creutzfeldt-Jakob Disease Surveillance Unit in Edinburgh, Scotland, informed the Atlanta-based CDC of the probable variant CJD diagnosis, and told the U.S. disease center that the case would need to be reported as a U.S. case since the symptoms appeared when he lived in Texas.

The man was born in the United Kingdom and lived there from 1980-1996, a period during which those living in the country were at risk of exposure to beef products infected with BSE.

The CDC said it was unlikely that he contracted the disease in the United States because his stay in the Texas was deemed "too brief relative to what is known about the incubation period for variant CJD," the CDC said. It is believed he was infected in the United Kingdom because the disease's incubation period can last years, sometimes decades.

"He lived in the United Kingdom for the whole time they had a problem," Lawrence B. Schonberger, a CDC medical epidemiologist, said. "Almost certainly, this case represents a continuation of the outbreak that is going on in the United Kingdom and it is just by convention that he happened to have gotten sick here."

The variant disease, which is contracted by eating the brain or other nervous system tissue of an animal infected with BSE, first was discovered in 1996 in the United Kingdom. It typically ends in death within a few years of diagnosis.

The man was not hospitalized while living in Houston and had not undergone any invasive medical procedures or received donated blood, the CDC said.

A total of 185 people from 11 countries have been diagnosed with variant CJD since 1996. A majority of the cases--158--have been diagnosed in Great Britain, while there have been 15 in France, three in Ireland and two in the United States. Canada, Italy, Japan, the Netherlands, Portugal, Saudi Arabia and Spain have each also reported a case.

The first U.S. case involved a woman from Britain who was living in Florida. She died last year, Schonberger said.

CDC spokesman David Daigle said there is no connection between the Briton's diagnosis with variant CJD and the presence of BSE found in a Texas cow earlier this year.

The 12-year-old Brahma-cross beef cow, which was born in Texas, was the first time a native-born case of the disease was discovered in the United States. The animal, which died in April on the farm where it lived, did not enter the human food or animal feed supply chain.

Date: 12/9/05

http://www.hpj.com/archives/2005/dec05/dec19/TexasBritonhasvCJD.cfm#.U48y9cJOWt8

see cdc report here ;

The second patient resided in Texas during 2001-2005. Symptoms began in early 2005 while the patient was in Texas. He then returned to the United Kingdom, where his illness progressed, and a diagnosis of variant CJD was made. The diagnosis was confirmed neuropathologically at the time of the patient's death. While living in the United States, the patient had no history of hospitalization, of having invasive medical procedures, or of donation or receipt of blood and blood products. The patient almost certainly acquired the disease in the United Kingdom. He was born in the United Kingdom and lived there throughout the defined period of risk (1980-1996) for human exposure to the agent of bovine spongiform encephalopathy (BSE, commonly known as "mad cow" disease). His stay in the United States was too brief relative to what is known about the incubation period for variant CJD. ...

see the other USA nvCJD cases here ;

http://www.cdc.gov/ncidod/dvrd/vcjd/factsheet_nvcjd.htm

*** remember what deep throat told me long ago ;

DEEP THROAT TO TSS 2000-2001 (take these old snips of emails with how ever many grains of salt you wish. ...tss)

The most frightening thing I have read all day is the report of Gambetti's finding of a new strain of sporadic cjd in young people...Dear God, what in the name of all that is holy is that!!! If the US has different strains of scrapie.....why????than the UK...then would the same mechanisms that make different strains of scrapie here make different strains of BSE...if the patterns are different in sheep and mice for scrapie.....could not the BSE be different in the cattle, in the mink, in the humans.......

I really think the slides or tissues and everything from these young people with the new strain of sporadic cjd should be put up to be analyzed by many, many experts in cjd........bse.....scrapie

Scrape the damn slide and put it into mice.....wait.....chop up the mouse brain and and spinal cord........put into some more mice.....dammit amplify the thing and start the damned research.....This is NOT rocket science...we need to use what we know and get off our butts and move....the whining about how long everything takes.....well it takes a whole lot longer if you whine for a year and then start the research!!!

Not sure where I read this but it was a recent press release or something like that: I thought I would fall out of my chair when I read about how there was no worry about infectivity from a histopath slide or tissues because they are preserved in formic acid, or formalin or formaldehyde.....for God's sake........ Ask any pathologist in the UK what the brain tissues in the formalin looks like after a year.......it is a big fat sponge...the agent continues to eat the brain ......you can't make slides anymore because the agent has never stopped........and the old slides that are stained with Hemolysin and Eosin......they get holier and holier and degenerate and continue...what you looked at 6 months ago is not there........Gambetti better be photographing every damned thing he is looking at.....

Okay, you need to know. You don't need to pass it on as nothing will come of it and there is not a damned thing anyone can do about it. Don't even hint at it as it will be denied and laughed at.......... USDA is gonna do as little as possible until there is actually a human case in the USA of the nvcjd........if you want to move this thing along and shake the earth....then we gotta get the victims families to make sure whoever is doing the autopsy is credible, trustworthy, and a saint with the courage of Joan of Arc........I am not kidding!!!! so, unless we get a human death from EXACTLY the same form with EXACTLY the same histopath lesions as seen in the UK nvcjd........forget any action........it is ALL gonna be sporadic!!!

And, if there is a case.......there is gonna be every effort to link it to international travel, international food, etc. etc. etc. etc. etc. They will go so far as to find out if a sex partner had ever traveled to the UK/europe, etc. etc. .... It is gonna be a long, lonely, dangerous twisted journey to the truth. They have all the cards, all the money, and are willing to threaten and carry out those threats....and this may be their biggest downfall...

Thanks as always for your help. (Recently had a very startling revelation from a rather senior person in government here..........knocked me out of my chair........you must keep pushing. If I was a power person....I would be demanding that there be a least a million bovine tested as soon as possible and agressively seeking this disease. The big players are coming out of the woodwork as there is money to be made!!! In short: "FIRE AT WILL"!!! for the very dumb....who's "will"! "Will be the burden to bare if there is any coverup!"

again it was said years ago and it should be taken seriously....BSE will NEVER be found in the US! As for the BSE conference call...I think you did a great service to freedom of information and making some people feign integrity...I find it scary to see that most of the "experts" are employed by the federal government or are supported on the "teat" of federal funds. A scary picture! I hope there is a confidential panel organized by the new government to really investigate this thing.

You need to watch your back........but keep picking at them.......like a buzzard to the bone...you just may get to the truth!!! (You probably have more support than you know. Too many people are afraid to show you or let anyone else know. I have heard a few things myself... you ask the questions that everyone else is too afraid to ask.)

END...TSS

UPDATED OLD HISTORY MYSTERIOUS CASES OF CJD TEXAS ;

CJD NE TEXAS CLUSTER

Creutzfeldt-Jakob Disease in Northeast Texas J.A. Rawlings,*1 K.A. Hendricks1, O.M. Nuno1, D.A. Brown1, D.A. Evans2, Texas Department of Health, 1Austin and 2Tyler, Texas

Creutzfeldt-Jacob Disease (CJD), a transmissible spongiform encephalopathy, is caused by prions composed of proteinaceous material devoid of nucleic acid. CJD occurs sporadically (generally 1 case/1,000,000 population per year) in older patients (average age of 65) and is characterized by rapidly progressive dementia, accompanied by severe muscle spasms and incoordination. Death usually occurs within 3 to 12 months (average 7 months). CJD activity in Texas, which has a population of nearly 19 million, appeared to be typical. The statewide death rate for 1995 and 1996 was just under 1/1,000,000. In April of 1997, the Texas Department of Health became aware of an increased number of possible CJD cases in a 23-county area of NE Texas with a population of just over one million. After review of medical and pathology records, four patients were identified with definite classic CJD and three were identified with probable CJD. Dates of death for the eight patients were from April, 1996 through mid-July 1997. The patients were from 46 through 65 years of age; four were male and three were female. A case-control study to identify risks for CJD in NE Texas has been initiated.

http://www.jifsan.umd.edu/tse/Rawlings.htm

http://vcjd.blogspot.com/2014/06/confirmed-variant-cjd-case-in-texas.html

SUNDAY, OCTOBER 13, 2013

Prion Disease Cases in Texas by Year, 2003-2012

http://cjdtexas.blogspot.com/2013/10/prion-disease-cases-in-texas-by-year_13.html

Sunday, February 12, 2012

National Prion Disease Pathology Surveillance Center Cases Examined1 (August 19, 2011) including Texas

http://transmissiblespongiformencephalopathy.blogspot.com/2012/02/national-prion-disease-pathology.html

WEDNESDAY, NOVEMBER 09, 2011

Case report Sporadic fatal insomnia in a young woman: A diagnostic challenge: Case Report TEXAS

HOW TO TURN A POTENTIAL MAD COW VICTIM IN THE USA, INTO A HAPPENSTANCE OF BAD LUCK, A SPONTANEOUS MUTATION FROM NOTHING.

OR WAS IT $$$

https://bmcneurol.biomedcentral.com/articles/10.1186/1471-2377-11-136

http://creutzfeldt-jakob-disease.blogspot.com/2011/11/case-report-sporadic-fatal-insomnia-in.html

TUESDAY, JUNE 1, 2010

USA cases of dpCJD rising with 24 cases so far in 2010

http://cjdtexas.blogspot.com/2010/06/usa-cases-of-dpcjd-rising-with-24-cases.html

>>> Up until about 6 years ago, the pt worked at Tyson foods where she worked on the assembly line, slaughtering cattle and preparing them for packaging. She was exposed to brain and spinal cord matter when she would euthanize the cattle. <<<

Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas

Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas. She left 6 Kids and a Husband.The Purpose of this web is to give information in Spanish to the Hispanic community, and to all the community who want's information about this terrible disease.- Physician Discharge Summary, Parkland Hospital, Dallas Texas Admit Date: 12/29/2009 Discharge Date: 1/20/2010 Attending Provider: Greenberg, Benjamin Morris; General Neurology Team: General Neurology Team Linda was a Hispanic female with no past medical history presents with 14 months of incresing/progressive altered mental status, generalized weakness, inability to walk, loss of appetite, inability to speak, tremor and bowel/blader incontinence.She was, in her usual state of health up until February, 2009, when her husbans notes that she began forgetting things like names and short term memories. He also noticed mild/vague personality changes such as increased aggression. In March, she was involved in a hit and run MVA,although she was not injured. The police tracked her down and ticketed her. At that time, her son deployed to Iraq with the Army and her husband assumed her mentation changes were due to stress over these two events. Also in March, she began to have weakness in her legs, making it difficult to walk. Over the next few months, her mentation and personality changes worsened, getting to a point where she could no longer recognized her children. She was eating less and less. She was losing more weight. In the last 2-3 months, she reached the point where she could not walk without an assist, then 1 month ago, she stopped talking, only making grunting/aggressive sounds when anyone came near her. She also became both bowel and bladder incontinent, having to wear diapers. Her '"tremor'" and body jerks worsened and her hands assumed a sort of permanent grip position, leading her family to put tennis balls in her hands to protect her fingers. The husband says that they have lived in Nebraska for the past 21 years. They had seen a doctor there during the summer time who prescribed her Seroquel and Lexapro, Thinking these were sx of a mood disorder. However, the medications did not help and she continued to deteriorate clinically. Up until about 6 years ago, the pt worked at Tyson foods where she worked on the assembly line, slaughtering cattle and preparing them for packaging. She was exposed to brain and spinal cord matter when she would euthanize the cattle. The husband says that he does not know any fellow workers with a similar illness. He also says that she did not have any preceeding illness or travel.

http://www.recordandoalinda.com/index.php?option=com_content&view=article&id=19:cjd-english-info&catid=9:cjd-ingles&Itemid=8

Irma Linda Andablo, victima de CJD

"...padeció durante un año de CJD Esporádico, Falleció a la edad de 38 años en la ciudad de Mesquite Texas un 6 de Febrero del año 2010" Irma Linda Martinez nació en el pueblo de Batesville Texas un 17 de mayo de 1971, padeció durante un año de CJD Esporádico (mal de la vaca loca conocido en español) Falleció a la edad de 38 años en la ciudad de Mesquite Texas un 6 de Febrero del año 2010. A continuación describiremos datos de su padecimiento: Se casó a la edad de 16 años con Everardo Andablo (Lalo) ella residió en Lexington Nebraska, desde ese entonces, trabajó aproximadamente 11 años en una compañia de matanza de vacas y procesadora de carne (Tyson) ella trabajaba en el rastro o el área de matanza, para el 2008 ella trabajaba como agente de seguridad para esta misma compañia, para ese entonces ella empezó a presentar cambios en su vida, su próximo trabajo fue en Subway dentro de una tienda comercial, donde los cambios de salud empezaron a ser muy notorios pues empezó a perder mucho peso, de 237 L de su peso normal empezó perdiendo 24 L en menos de un mes, esto era sorprendente!!! fué entonces cuando dejó el trabajo en febrero del 2009, de repente empezó a olvidar datos importantes. La siguiente información es una traducción pertenece al comunicado que el equipo de neurologia del hospital Parkland en la ciudad de Dallas Texas liberó a su salida, después de haber estado internada del 29 de diciembre del 2009 a enero 20 del 2010, en este comunicado se encuentra el historial tanto médico como de sintomas presentados en Linda: Physician Discharge Summary : (traducido y adaptado) "...Mujer de 38 años presento 10 meses de una estado mental progresivo y alterado, con debilidad general, temblor, inhabilidad para caminar, para hablar, con pérdida de apetito e incontinencia de esfínteres, ella empezó a mostrar debilidad en las piernas, durante los siguientes meses su estado mental se agravó al tanto que ella no conoció más a sus propios hijos" "El 29 de Diciembre del 2009 Fué admitida en el Hospital Parkland de Dallas por demencia de acuerdo a los síntomas de presentaba, Mujer de 38 años presentó 14 meses de una estado mental progresivo y alterado, con debilidad general, temblor, inhabilidad para caminar, para hablar, con pérdida de apetito e incontinencia de esfinteres. Ella empezó a olvidar los nombres de las personas que la rodeaban, datos importantes personales, también presentó algunos cambios de personalidad como incremento de agresión.Para el mes de Marzo del 2008 ella empezó a mostrar debilidad en las piernas, durante los siguientes meses su estado mental se agravó al tanto que ella no conoció más a sus propios hijos (6 hijos), ella cada vez comia menos, cada vez perdia más peso.Para el tiempo que ella arrivo a Dallas para la navidad del 2009 ella no caminaba en lo absoluto, no hablaba solo hacia sonidos agresivos cuando alguien se acercaba a ella, el temblor en sus manos empezó a ser más fuerte, sus manos solo tenian posición de sostener algo fuerte, ella siempre... Read more...

http://www.recordandoalinda.com/

"...padeció durante un año de CJD Esporádico, Falleció a la edad de 38 años en la ciudad de Mesquite Texas un 6 de Febrero del año 2010"

Irma Linda Martinez nació en el pueblo de Batesville Texas un 17 de mayo de 1971, padeció durante un año de CJD Esporádico (mal de la vaca loca conocido en español) Falleció a la edad de 38 años en la ciudad de Mesquite Texas un 6 de Febrero del año 2010.

A continuación describiremos datos de su padecimiento:

Se casó a la edad de 16 años con Everardo Andablo (Lalo) ella residió en Lexington Nebraska, desde ese entonces, trabajó aproximadamente 11 años en una compañia de matanza de vacas y procesadora de carne (Tyson) ella trabajaba en el rastro o el área de matanza, para el 2008 ella trabajaba como agente de seguridad para esta misma compañia, para ese entonces ella empezó a presentar cambios en su vida, su próximo trabajo fue en Subway dentro de una tienda comercial, donde los cambios de salud empezaron a ser muy notorios pues empezó a perder mucho peso, de 237 L de su peso normal empezó perdiendo 24 L en menos de un mes, esto era sorprendente!!! fué entonces cuando dejó el trabajo en febrero del 2009, de repente empezó a olvidar datos importantes.

La siguiente información es una traducción pertenece al comunicado que el equipo de neurologia del hospital Parkland en la ciudad de Dallas Texas liberó a su salida, después de haber estado internada del 29 de diciembre del 2009 a enero 20 del 2010, en este comunicado se encuentra el historial tanto médico como de sintomas presentados en Linda:

Physician Discharge Summary : (traducido y adaptado)

"...Mujer de 38 años presento 10 meses de una estado mental progresivo y alterado, con debilidad general, temblor, inhabilidad para caminar, para hablar, con pérdida de apetito e incontinencia de esfínteres, ella empezó a mostrar debilidad en las piernas, durante los siguientes meses su estado mental se agravó al tanto que ella no conoció más a sus propios hijos"

"El 29 de Diciembre del 2009 Fué admitida en el Hospital Parkland de Dallas por demencia de acuerdo a los síntomas de presentaba, Mujer de 38 años presentó 14 meses de una estado mental progresivo y alterado, con debilidad general, temblor, inhabilidad para caminar, para hablar, con pérdida de apetito e incontinencia de esfinteres. Ella empezó a olvidar los nombres de las personas que la rodeaban, datos importantes personales, también presentó algunos cambios de personalidad como incremento de agresión.Para el mes de Marzo del 2008 ella empezó a mostrar debilidad en las piernas, durante los siguientes meses su estado mental se agravó al tanto que ella no conoció más a sus propios hijos (6 hijos), ella cada vez comia menos, cada vez perdia más peso.Para el tiempo que ella arrivo a Dallas para la navidad del 2009 ella no caminaba en lo absoluto, no hablaba solo hacia sonidos agresivos cuando alguien se acercaba a ella, el temblor en sus manos empezó a ser más fuerte, sus manos solo tenian posición de sostener algo fuerte, ella siempre portaba pelotas pequeñas para que no se lastimara con sus propias uñas"

En terminos Médicos ella prensento un desorden mental con ansiedad y pérdida del habla y contracciones en los musculos que la inmobilizaba. Esto llevo a los médicos a predecir el diagnostico de CJD esporádico o variante, después de reuniones familiares se llego al acuerdo de no proseguir con los exámenes indicados como una biopsia cerebral debido al estado de debilidad y gravedad de ella, pues peligraba su vida y por consiguiente peligraban los médicos que le aplicarian el exámen ya que es demasiado contagioso.

Ella fué dada de alta con el diagnostico de CJD Esporádico, sin medicamento y con pocas esperanzas y semanas de vida.

http://www.recordandoalinda.com/index.php?option=com_content&view=article&id=2:frontpage&catid=1:frontpage

please see full text ;

Monday, March 29, 2010

Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas

http://creutzfeldt-jakob-disease.blogspot.com/2010/03/irma-linda-andablo-cjd-victim-she-died.html

MONDAY, APRIL 5, 2010

UPDATE - CJD TEXAS 38 YEAR OLD FEMALE WORKED SLAUGHTERING CATTLE EXPOSED TO BRAIN AND SPINAL CORD MATTER

http://prionunitusaupdate.blogspot.com/2010/04/update-cjd-texas-38-year-old-female.html

Sunday, July 11, 2010

CJD or prion disease 2 CASES McLennan County Texas population 230,213 both cases in their 40s

http://creutzfeldt-jakob-disease.blogspot.com/2010/07/cjd-2-cases-mclennan-county-texas.html

FRIDAY, OCTOBER 23, 2009

Creutzfeldt-Jakob Disease Surveillance Texas Data for Reporting Years 2000-2008

http://cjdtexas.blogspot.com/2009/10/creutzfeldt-jakob-disease-surveillance.html

http://cjdtexas.blogspot.com/2010/03/cjd-texas-38-year-old-female-worked.html

MONDAY, JULY 21, 2008

Officials await tests on man for human Mad Cow Disease (Texas)

don't these dummies know by now that the USA does not have any mad cow disease and or any human cjd ramifications from a mad cow, cause the USDA says so... NOT

there has been a decade old, systematic cover-up of corporate homicide just because of trade, futures and commodities. the elderly demented, your grandma and grandpa, mom and dad, sisters and brothers, are all expendable, due to the fact the American joe-cue-public is just to damn lazy to care. the elderly and demented are expendable. but mark my word here and now, it's here, and has been, call it what you like.....

http://cjdtexas.blogspot.com/2008/07/officials-await-tests-on-man-for-human.html

FRIDAY, NOVEMBER 21, 2008

Amarillo-area (suspect sporadic CJD) case linked to mad cow disease Rumor in Texas

http://cjdtexas.blogspot.com/2008/11/amarillo-area-suspect-sporadic-cjd-case.html

SUNDAY, DECEMBER 16, 2007

Creutzfeldt-Jakob Disease Surveillance in Texas 2000-2006

http://cjdtexas.blogspot.com/2007/12/creutzfeldt-jakob-disease-surveillance.html

http://cjdtexas.blogspot.com/

2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006

http://bse-atypical.blogspot.com/2006/08/bse-atypical-texas-and-alabama-update.html

http://sciencebushwhacked.blogspot.com/2011/08/rick-perry-texas-bse-aka-mad-cow.html

THURSDAY, OCTOBER 22, 2015

Former Ag Secretary Ann Veneman talks women in agriculture and we talk mad cow disease USDA and what really happened

http://madcowusda.blogspot.com/2015/10/former-ag-secretary-ann-veneman-talks.html

Volume 2: Science

4. The link between BSE and vCJD

Summary 4.29 The evidence discussed above that vCJD is caused by BSE seems overwhelming. Uncertainties exist about the cause of CJD in farmers, their wives and in several abattoir workers. It seems that farmers at least might be at higher risk than others in the general population. 1 Increased ascertainment (ie, increased identification of cases as a result of greater awareness of the condition) seems unlikely, as other groups exposed to risk, such as butchers and veterinarians, do not appear to have been affected. The CJD in farmers seems to be similar to other sporadic CJD in age of onset, in respect to glycosylation patterns, and in strain-typing in experimental mice. Some farmers are heterozygous for the methionine/valine variant at codon 129, and their lymphoreticular system (LRS) does not contain the high levels of PrPSc found in vCJD.

***>It remains a remote possibility that when older people contract CJD from BSE the resulting phenotype is like sporadic CJD and is distinct from the vCJD phenotype in younger people...end

BSE INQUIRY

https://bseinquiry.blogspot.com/2008/05/sporadic-cjd-in-farmers-farmers-wives.html

SATURDAY, JUNE 23, 2018

CDC

***> Diagnosis of Methionine/Valine Variant Creutzfeldt-Jakob Disease by Protein Misfolding Cyclic Amplification

Volume 24, Number 7—July 2018 Dispatch

https://wwwnc.cdc.gov/eid/article/24/7/17-2105_article

http://vcjd.blogspot.com/2018/06/diagnosis-of-methioninevaline-variant.html

TUESDAY, AUGUST 1, 2017

BSE INQUIRY DFA 17 Medicines and medical devices

http://bseinquiry.blogspot.com/2017/08/bse-inquiry-dfa-17-medicines-and.html

MONDAY, MAY 19, 2008

SPORADIC CJD IN FARMERS, FARMERS WIVES, FROM FARMS WITH BSE HERD AND ABATTOIRS

http://bseinquiry.blogspot.com/2008/05/sporadic-cjd-in-farmers-farmers-wives.html

BSE INQUIRY DFA 16 MID 1995 TO THE FINAL DAYS

https://bseinquiry.blogspot.com/2017/08/bse-inquiry-dfa-16-mid-1995-to-final.html

BSE Inquiry

http://bseinquiry.blogspot.com/

Singeltary communication statement to BSE Inquiry 1998

this is all in the world those 300k+ bovine that died with BSE were consuming, a nutritional supplement with srms, i.e. specified risk materials, the most highest risk tissue for the tse prion.

Sender: "Patricia Cantos"

To: "Terry S Singeltary Sr. (E-mail)"

Subject: Your submission to the Inquiry

Date: Fri, 3 Jul 1998 10:10:05 +0100

3 July 1998 Mr Terry S Singeltary Sr. E-Mail: Flounder at wt.net Ref: E2979

Dear Mr Singeltary,

Thank you for your E-mail message of the 30th of June 1998 providing the Inquiry with your further comments. Thank you for offering to provide the Inquiry with any test results on the nutritional supplements your mother was taking before she died.

As requested I am sending you our general Information Pack and a copy of the Chairman's letter. Please contact me if your system cannot read the attachments.

Regarding your question, the Inquiry is looking into many aspects of the scientific evidence on BSE and nvCJD. I would refer you to the transcripts of evidence we have already heard which are found on our internet site at http://www.bse.org.uk. Could you please provide the Inquiry with a copy of the press article you refer to in your e-mail? If not an approximate date for the article so that we can locate it? In the meantime, thank you for you comments. Please do not hesitate to contact me on 0171 261 8332 should you have any queries.

Yours sincerely Patricia Cantos Families Team Leader Attachments TSS

==============

-------- Original Message --------

Subject: re: METABOLIFE AND TSEs GAO-03-494 ''URGENT DATA''

Date: Thu, 01 May 2003 16:04:35 -0400

From: "Marcia G Crosse"

To: CC: "Charles W Davenport" , "Carolyn Feis Korman" , "Martin Gahart"

Mr. Singletary,

We were informed by representatives of Metabolife, Inc. that Metabolife 356 was reformulated to remove bovine complex as an ingredient in the product, approximately September 2001. We did not independently verify the contents of the product.

Sincerely, Marcia Crosse Acting Director Health CarePublic Health and Science Issues U.S. General Accounting Office 441 G Street, N.W. Washington, D.C. 20548

===================

-------- Original Message --------

Subject: Re: METABOLIFE AND TSEs GAO-03-494 ''URGENT DATA''

Date: Thu, 01 May 2003 15:48:52 -0500

From: "Terry S. Singeltary Sr."

To: Marcia G Crosse

CC: Charles W Davenport , Carolyn Feis Korman , Martin Gahart References:

THANK YOU!

MIRACLES DO HAPPEN! ;-)

snip...

NOW COMPARE BOVINE INGREDIENTS FROM;

2003 - 2004 Product Catalog

Standard Process Inc.

NATURAL COCOA STANDARDBAR (mad cow candy bar) (i will just list animal organs) bovine adrenal, bovine liver, bovine spleen, ovine spleen, bovine kidney...

NATURAL PEANUT BUTTER STANDARDBAR

bovine adrenal, bovine liver, bovine spleen, ovine spleen, bovine kidney...

USF (MAD COW) OINTMENT (RUB A DUB DUB, KURU ETC) ;

bovine orhic glandular extract

UTROPHIN PMG

bovine uterus PMG

VASCULIN

bovine heart PMG extract, veal bone PMG extract, bovine liever, porcine duodenum, bovine adrenal Cytosol extract, bovine spleen, ovine spleen (some yummy stuff)

IPLEX (neighbors mom died from CJD while taking these pills for years)

bovine eye PMG extract, veal bone PMG, bovine liver, porcine stomach, bovine adrenal, bovine kidney, bovine adrenal Cytosol extract, BOVINE BRAIN, bovine bone, veal bone meal

MYO-PLUS

bovine heart PMG, bovine liver, porcine stomach, bovine orchic extract, bovine spleen, ovine spleen, bovine adrenal Cytosol extract, BOVINE BRAIN

NEUROPLEX

bovine orchic Cytosol extract, bovine spleen, BOVINE BRAIN PMG EXTRACT, BOVINE ANTERIOR PITUITARY, bovine liver, BOVINE PITUITARY PMG EXTRACT, AND MORE BOVINE BRAIN... HOLY MAD COW IN A PILL !!!

NEUROTROPHIN PMG

BOVINE BRAIN PMG

NIACINAMIDE B6 VM

bovine liver, porcine stomach, bovine spleen ovine spleen, BOVINE BRAIN

OCULOTROPHIN PMG BOVINE EYE PMG

ORCHEX

bovine liver, bovine orchic Cytosol extract, porcine stomch, bovine spleen, ovine spleen, BOVINE BRAIN

OSTARPLEX

veal bone PMG extract, veal bone PMG extract, bovine liver, porcine stomach, bovine adrenal, bovine spleen, ovine spleen, BOVINE BRAIN

PARAPLEX

bovine pancreas PMG extract, porcine duodenum, bovine adrenal PMG, BOVINE PITUITARY PMG EXTRACT, bovine thyroid PMG extract

PITUITROPHIN PMG

RUMAPLEX

BOVINE BRAIN, veal bone PMG extract, bovine adrenal, bovine prostate Cytosol extract, veal bone meal, bovine liver PMG extract, bovine spleen, ovine spleen, bovine liver

SENAPLEX

bovine liver PMG extract, bovine adrenal, BOVNE BRAIN, veal bone meal, bovine kidney, bovine orchic extract, bovine spleen, ovine spleen ..........

THESE are just a few of MANY of just this ONE COMPANY...TSS

DEPARTMENT OF HEALTH AND HUMAN SERVICES

FOOD AND DRUG ADMINISTRATION CENTER FOR BIOLOGICS EVALUATION AND RESEARCH

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES ADVISORY COMMITTEE

Friday, January 19, 2001

Holiday Inn Bethesda Versailles I and II 8120 Wisconsin Avenue Bethesda, Maryland

2 PARTICIPANTS Paul W. Brown, M.D., Chairperson William Freas, Ph.D., Executive Secretary

VOTING MEMBERS Ermias D. Belay, M.D. David C. Bolton, Ph.D. Donald S. Burke, M.D. Dean O. Cliver, Ph.D. Bruce M. Ewenstein, M.D., Ph.D. Peter G. Lurie, M.D. Pedro Piccardo, M.D. Stanley B. Prusiner, M.D. Raymond P. Roos, M.D. Elizabeth S. Williams, D.V.M., Ph.D.

VOTING CONSULTANTS Linda A. Detwiler, D.V.M. David Gaylor, Ph.D.

Paul R. McCurdy, M.D. Kenrad E. Nelson, M.D.

NONVOTING CONSULTANT Susan Leitman, M.D.

GUESTS Richard Davey, M.D. Louis Katz, M.D.

snip...

page 501

253

1 DR. BOLTON: I have an additional question about

2 that. What is the assurance that additional locally sourced

3 tracheas are not added into that manufacturing process, thus

4 boosting the yield, if you will, but being returned to the

5 U.S. as being produced from U.S.-sourced raw material?

6 DR. McCURDY: Are there data to indicate how many

7 grams, or whatever, of infected brain are likely to infect

8 an organism, either animal or man, when taken orally?

9 DR. BROWN: If I am not mistaken, and I can be

10 corrected, I think a half a gram is enough in a cow, orally;

11 in other words, one good dietary-supplement pill.

12 DR. McCURDY: What I am driving at is the question

13 we are asked is really not do we wish to regulate these

14 things coming in. I think the statements about difficulties

15 in regulating things in the future or near future for new

16 regulations were probably accurate.

17 But I think that we could exhibit some quite

18 reasonable concern about blood donors who are taking dietary

19 supplements that contain a certain amount of unspecified-

20 origin brain, brain-related, brain and pituitary material.

21 If they have done this for more than a sniff or something

22 like that, then, perhaps, they should be deferred as blood

23 donors.

24 That is probably worse than spending six months in

25 the U.K.

1/19/01

3681t2.rtf(845) page 501

http://www.fda.gov/ohrms/dockets/ac/cber01.htm

Docket Management Docket: 96N-0417 - Current Good Manufacturing Practice in Manufacturing, Packing, or Holding Dietary Ingredients a Comment Number: EC -2 Accepted - Volume 7

http://www.fda.gov/ohrms/dockets/dailys/03/Mar03/031403/96N-0417-EC-2.htm

http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_07.pdf

snip...see full text and much more on nutritional supplements and the cjd tse prion;

http://creutzfeldt-jakob-disease.blogspot.com/2016/08/docket-no-fda-2011-d-0376-dietary.html

http://bovineprp.blogspot.com/2015/08/federal-judge-enters-permanent.html

http://transmissiblespongiformencephalopathy.blogspot.com/2013/03/gao-13-244-mar-18-2013-dietary.html

1996-12-04: BBC - Horizon BSE1 - The Invisible Enemy

https://histodb11.usz.ch/Images/videos/video-007/video-007.html

1996-12-04: BBC - Horizon BSE2 - The Invisible Enemy

https://histodb11.usz.ch/Images/videos/video-008/video-008.html

1997-11-10: Panorama - The british disease

https://histodb11.usz.ch/Images/videos/video-009/video-009.html

sporadic CJD, it too linked to mad cow disease? CBC NEWS Jeff Schwan sCJD and CWD

https://histodb11.usz.ch/Images/videos/video-004/video-004.html

http://creutzfeldt-jakob-disease.blogspot.com/2017/08/monitoring-occurrence-of-emerging-forms.html

https://chronic-wasting-disease.blogspot.com/2020/08/genetic-and-evolutionary-considerations.html

WEDNESDAY, AUGUST 5, 2020

1996-12-04: BBC - Horizon BSE1 - BSE2 The Invisible Enemy, The British Disease, CWD, sporadic CJD

https://transmissiblespongiformencephalopathy.blogspot.com/2020/08/1996-12-04-bbc-horizon-bse1-bse2.html

Sent: Sun, May 26, 2019 10:21 am

Subject: Arguments for Alzheimer’s and Parkinson’s diseases caused by prions Stanley B. Prusiner

''From a large array of bioassays, we conclude that AD, PD, MSA, and the frontotemporal dementias, including PSP and CBD, are all prion diseases'' 11.

Arguments for Alzheimer’s and Parkinson’s diseases caused by prions Stanley B. Prusiner Institute of Neurodegenerative Diseases, and Professor of Neurology and Biochemistry, University of California San Francisco ABSTRACT Arguments for Alzheimer’s (AD) and Parkinson’s diseases (PD) being caused by prions continue to advance with new evidence. Findings in the brains of deceased AD patients argue that both Aβ and tau prions can be demonstrated by bioassays in cultured cells as well as in transgenic (Tg) mice. Likewise, studies of the brains of deceased MSA patients have been found to contain α-synuclein prions by bioassays in cultured cells and Tg mice. Conversely, the brains of AD patients do not contain α-synuclein prions, and the brains of MSA patients do not contain Aβ or tau prions. Additionally, while the brains of patients who died of either progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD) contained tau prions, neither Aβ nor α-synuclein prions were detectable. Merely measuring the levels of Aβ, tau, and α-synuclein appears to give misleading information about the etiology and pathogenesis of neurodegenerative diseases (NDs). From a large array of bioassays, we conclude that AD, PD, MSA, and the frontotemporal dementias, including PSP and CBD, are all prion diseases. Our findings argue that changes in the conformations of Aβ, tau, and α-synuclein underlie the acquisition of prion infectivity in all of these NDs.

https://www.tandfonline.com/doi/full/10.1080/19336896.2019.1615197

''From a large array of bioassays, we conclude that AD, PD, MSA, and the frontotemporal dementias, including PSP and CBD, are all prion diseases''

Published: 09 September 2015

Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy

Zane Jaunmuktane, Simon Mead, Matthew Ellis, Jonathan D. F. Wadsworth, Andrew J. Nicoll, Joanna Kenny, Francesca Launchbury, Jacqueline Linehan, Angela Richard-Loendt, A. Sarah Walker, Peter Rudge, John Collinge & Sebastian Brandner

https://www.nature.com/articles/nature15369

>>> The only tenable public line will be that "more research is required’’ <<<

>>> possibility on a transmissible prion remains open<<<

O.K., so it’s about 23 years later, so somebody please tell me, when is "more research is required’’ enough time for evaluation ?

Re-Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy

Nature 525, 247?250 (10 September 2015) doi:10.1038/nature15369 Received 26 April 2015 Accepted 14 August 2015 Published online 09 September 2015 Updated online 11 September 2015 Erratum (October, 2015)

snip...see full Singeltary Nature comment here;

Alzheimer's disease

let's not forget the elephant in the room. curing Alzheimer's would be a great and wonderful thing, but for starters, why not start with the obvious, lets prove the cause or causes, and then start to stop that. think iatrogenic, friendly fire, or the pass it forward mode of transmission. think medical, surgical, dental, tissue, blood, related transmission. think transmissible spongiform encephalopathy aka tse prion disease aka mad cow type disease...

Commentary: Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy

http://journals.plos.org/plosone/article/comment?id=info:doi/10.1371/annotation/933cc83a-a384-45c3-b3b2-336882c30f9d

http://journals.plos.org/plosone/article/comments?id=10.1371/journal.pone.0111492

http://journals.plos.org/plosone/article/comment?id=10.1371/annotation/933cc83a-a384-45c3-b3b2-336882c30f9d

https://www.frontiersin.org/articles/10.3389/fnagi.2016.00005/full

Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease

*** Singeltary comment PLoS ***

Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?

Posted by flounder on 05 Nov 2014 at 21:27 GMT

http://www.plosone.org/annotation/listThread.action?root=82860

IN CONFIDENCE

5 NOVEMBER 1992

TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES

[9. Whilst this matter is not at the moment directly concerned with the iatrogenic CJD cases from hgH, there remains a possibility of litigation here, and this presents an added complication.

There are also results to be made available shortly

(1) concerning a farmer with CJD who had BSE animals,

(2) on the possible transmissibility of Alzheimer’s and

(3) a CMO letter on prevention of iatrogenic CJD transmission in neurosurgery, all of which will serve to increase media interest.]

https://web.archive.org/web/20170126060344/http://collections.europarchive.org/tna/20080102232842/http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf

https://web.archive.org/web/20040315075058/http://www.bseinquiry.gov.uk/files/yb/1992/12/16005001.pdf

https://web.archive.org/web/20040315075058/www.bseinquiry.gov.uk/files/yb/1992/12/16005001.pdf

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA Diagnosis and Reporting of Creutzfeldt-Jakob Disease

To the Editor:

In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally..

Terry S. Singeltary, Sr Bacliff, Tex

1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.

http://jama.jamanetwork.com/article.aspx?articleid=1031186

Tracking spongiform encephalopathies in North America

Xavier Bosch

Available online 29 July 2003.

Volume 3, Issue 8, August 2003, Page 463

“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem..” ............................

http://www.thelancet.com/journals/laninf/article/PIIS1473309903007151/fulltext

http://download.thelancet..com/pdfs/journals/1473-3099/PIIS1473309903007151.pdf

January 28, 2003; 60 (2) VIEWS & REVIEWS

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States

Ermias D. Belay, Ryan A. Maddox, Pierluigi Gambetti, Lawrence B. Schonberger

First published January 28, 2003, DOI: https://doi.org/10.1212/01.WNL.0000036913.87823.D6

Abstract

Transmissible spongiform encephalopathies (TSEs) attracted increased attention in the mid-1980s because of the emergence among UK cattle of bovine spongiform encephalopathy (BSE), which has been shown to be transmitted to humans, causing a variant form of Creutzfeldt-Jakob disease (vCJD). The BSE outbreak has been reported in 19 European countries, Israel, and Japan, and human cases have so far been identified in four European countries, and more recently in a Canadian resident and a US resident who each lived in Britain during the BSE outbreak. To monitor the occurrence of emerging forms of CJD, such as vCJD, in the United States, the Centers for Disease Control and Prevention has been conducting surveillance for human TSEs through several mechanisms, including the establishment of the National Prion Disease Pathology Surveillance Center. Physicians are encouraged to maintain a high index of suspicion for vCJD and use the free services of the pathology center to assess the neuropathology of clinically diagnosed and suspected cases of CJD or other TSEs.

Received May 7, 2002. Accepted August 28, 2002.

http://n.neurology.org/content/60/2/176.long

RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States

Terry S. Singeltary, retired (medically)

Published March 26, 2003

26 March 2003

Terry S. Singeltary, retired (medically) CJD WATCH

I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?

http://n.neurology.org/content/re-monitoring-occurrence-emerging-forms-creutzfeldt-jakob-disease-united-states

Reply to Singletary Ryan A. Maddox, MPH Other Contributors: Published March 26, 2003

Mr. Singletary raises several issues related to current Creutzfeldt- Jakob disease (CJD) surveillance activities. Although CJD is not a notifiable disease in most states, its unique characteristics, particularly its invariably fatal outcome within usually a year of onset, make routine mortality surveillance a useful surrogate for ongoing CJD surveillance.[1] In addition, because CJD is least accurately diagnosed early in the course of illness, notifiable-disease surveillance could be less accurate than, if not duplicative of, current mortality surveillance.[1] However, in states where making CJD officially notifiable would meaningfully facilitate the collection of data to monitor for variant CJD (vCJD) or other emerging prion diseases, CDC encourages the designation of CJD as a notifiable disease.[1] Moreover, CDC encourages physicians to report any diagnosed or suspected CJD cases that may be of special public health importance (e.g...., vCJD, iatrogenic CJD, unusual CJD clusters).

As noted in our article, strong evidence is lacking for a causal link between chronic wasting disease (CWD) of deer and elk and human disease,[2] but only limited data seeking such evidence exist. Overall, the previously published case-control studies that have evaluated environmental sources of infection for sporadic CJD have not consistently identified strong evidence for a common risk factor.[3] However, the power of a case-control study to detect a rare cause of CJD is limited, particularly given the relatively small number of subjects generally involved and its long incubation period, which may last for decades. Because only a very small proportion of the US population has been exposed to CWD, a targeted surveillance and investigation of unusual cases or case clusters of prion diseases among persons at increased risk of exposure to CWD is a more efficient approach to detecting the possible transmission of CWD to humans. In collaboration with appropriate local and state health departments and the National Prion Disease Pathology Surveillance Center, CDC is facilitating or conducting such surveillance and case- investigations, including related laboratory studies to characterize CJD and CWD prions.

Mr. Singletary also expresses concern over a recent publication by Asante and colleagues indicating the possibility that some sporadic CJD cases may be attributable to bovine spongiform encephalopathy (BSE).[4] The authors reported that transgenic mice expressing human prion protein homozygous for methionine at codon 129, when inoculated with BSE prions, developed a molecular phenotype consistent with a subtype of sporadic CJD. Although the authors implied that BSE might cause a sporadic CJD-like illness among persons homozygous for methionine, the results of their research with mice do not necessarily directly apply to the transmission of BSE to humans. If BSE causes a sporadic CJD-like illness in humans, an increase in sporadic CJD cases would be expected to first occur in the United Kingdom, where the vast majority of vCJD cases have been reported. In the United Kingdom during 1997 through 2002, however, the overall average annual mortality rate for sporadic CJD was not elevated; it was about 1 case per million population per year. In addition, during this most recent 6-year period following the first published description of vCJD in 1996, there was no increasing trend in the reported annual number of UK sporadic CJD deaths.[3, 5] Furthermore, surveillance in the UK has shown no increase in the proportion of sporadic CJD cases that are homozygous for methionine (Will RG, National CJD Surveillance Unit, United Kingdom, 2003; personal communication)..

References

1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Diagnosis and reporting of Creutzfeldt-Jakob disease. JAMA 2001;285:733-734.

2. Belay ED, Maddox RA, Gambetti P, Schonberger LB. Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States. Neurology 2003;60:176-181.

3. Belay ED. Transmissible spongiform encephalopathies in humans. Annu Rev Microbiol 1999;53:283-314.

4. Asante EA, Linehan JM, Desbruslais M, et al. BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein. EMBO J 2002;21:6358-6366.

5. The UK Creutzfeldt-Jakob Disease Surveillance Unit. CJD statistics. Available at: http://www.cjd.ed.ac.uk/figures.htm. Accessed February 18, 2003.

Competing Interests: None declared.

http://n.neurology.org/content/reply-singletary

Terry Singeltary, Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis

http://www.suprememastertv.tv/hl/?wr_id=159&page=1

Terry S. Singeltary Sr.