Wednesday, January 06, 2016

CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE U.K. 23rd ANNUAL REPORT 2014 (published 18th November 2015)

CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE U.K. 23rd ANNUAL REPORT 2014

 

23rd Annual Report 2014

 

(published 18th November 2015)

 

SUMMARY

 

The national surveillance programme for Creutzfeldt-Jakob disease (CJD) in the UK was initiated in May 1990. In 1999, the National CJD Research & Surveillance Unit (NCJDRSU) became a WHO Collaborative Centre for Reference and Research on the surveillance and epidemiology of human transmissible spongiform encephalopathies (TSEs). In September 2001, the National Care Team was formed in response to concerns regarding the care of CJD patients. The team currently comprises two care coordinators (who are senior nurses) with secretarial and clinical neurological support from within the NCJDRSU where it is based.

 

The information provided in this 23rd Annual Report continues to indicate that the annual mortality rates for sporadic CJD (sCJD) has remained around 1.4/million since 2008 (the data for 2014 may still be incomplete). Detailed clinical and epidemiological information has been obtained for the great majority of patients. Although the general autopsy rate in the UK is low, it remains relatively high in suspected cases of CJD (being around 60% of all referred cases to the NCJDRSU). The number of brain specimens examined for sCJD in the neuropathology laboratory in 2014 was 30 (compared with 32 in 2013).

 

In 1990-2014 average annual mortality rates from sCJD in England, Wales, Scotland and Northern Ireland were, respectively, 1.07, 1.33, 1.11 and 0.83/million/year. The differences between these rates are not statistically significant (p=0.5). The mortality rates from sCJD in the UK are comparable to those observed in most other European countries and elsewhere in the world, including countries that are free of BSE.

 

Up to 31st December 2014, 177 cases of definite or probable variant CJD (vCJD) had been identified in the UK (122 definite and 55 probable who did not undergo post mortem). All 177 cases have died. The clinical, neuropathological and epidemiological features of the cases of vCJD are remarkably uniform and consistent with previous descriptions. Risk factors for the development of vCJD include age, residence in the UK and methionine homozygosity at codon 129 of the prion protein gene - all 160 clinically affected definite and probable cases of vCJD with available genetic analysis have been methionine homozygotes. Analysis of vCJD diagnoses and deaths from January 1994 to December 2011 indicates that a peak has passed. While this is an encouraging finding, the incidence of vCJD may increase again, particularly if different genetic subgroups with longer incubation periods exist. The identification of an individual of the PRNP-129 MV genotype as a possible case of vCJD (reported in the NCJDRSU 17th Annual Report, 2008) and, in a separate case, disease-related prion protein in the spleen of a clinically unaffected blood recipient (reported in 2004) is consistent with such a hypothesis. These cases, along with the report of the prevalence of abnormal prion protein in the large study of appendix and tonsil tissues (two of the positive specimens from VV individuals) suggests the possibility of a greater number of asymptomatic infections (either preclinical or subclinical) in the population than might be indicated by the present numbers of confirmed clinical cases. Section

 

1 T 23rd Annual Report 2014 4

 

To help prevent any possible spread of CJD between people, we continue to ask clinicians to refer all new suspect CJD cases to their local infection control and health protection teams. This is important as a local response may be required with respect to limiting potential secondary transmission, infection control and other issues that may arise over time concerning the protection of the wider community. The NCJDRSU continues to assist local health protection teams in local audit and investigations of cases in response to local concerns.

 

The NCJDRSU continues to collaborate with health departments and public health teams throughout the UK in relation to a range of activities, for example, in relation to the follow up of those identified as at increased risk of CJD. The activities of the NCJDRSU are strengthened by collaboration with other surveillance projects, including the Transfusion Medicine Epidemiology Review and the study of Progressive Intellectual and Neurological Deterioration in Children. The collaboration of our colleagues in these projects is greatly appreciated; the effectiveness of this collaboration allowed the identification in 2003 of a case of vCJD associated with blood transfusion and the identification in 2004 of disease-related PrP in the spleen of a recipient of blood donated by someone incubating vCJD. A patient was also identified in 2010 who had evidence of vCJD infection in the spleen (but no evidence of clinical vCJD), considered probably due to blood products (treatment for haemophilia).

 

The relatively recently described form of prion disease originally termed Protease Sensitive Prionopathy and renamed Variably Protease Sensitive Prionopathy, is of uncertain nosological significance but is presently considered a form of sporadic prion disease, alongside sCJD. The NCJDRSU has so far identified at total of 9 such cases in the UK and is continuing to monitor this form of disease.

 

The data concerning CSF RT-QuIC are given in Section 3.5; the sensitivity of CSF RT-QuIC for a diagnosis of sCJD is comparable with that of CSF 14-3-3. The specificity is superior to that of CSF 14-3-3 with no positives in cases with a confirmed alternate diagnosis.

 

The success of the National CJD Research & Surveillance Unit continues to depend on the extraordinary level of co-operation from the neurology and neuropathology communities and other medical and paramedical staff throughout the UK. Ongoing support is provided by the Infectious Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine. We are also particularly grateful to the relatives of patients for their collaboration.

 

snip...

 

Up to 31st December 2014, 177 cases of definite or probable variant CJD (vCJD) had been identified in the UK (122 definite and 55 probable who did not undergo post mortem). All 177 cases have died. The clinical, neuropathological and epidemiological features of the cases of vCJD are remarkably uniform and consistent with previous descriptions. Risk factors for the development of vCJD include age, residence in the UK and methionine homozygosity at codon 129 of the prion protein gene - all 160 clinically affected definite and probable cases of vCJD with available genetic analysis have been methionine homozygotes. Analysis of vCJD diagnoses and deaths from January 1994 to December 2011 indicates that a peak has passed. While this is an encouraging finding, the incidence of vCJD may increase again, particularly if different genetic subgroups with longer incubation periods exist. The identification of an individual of the PRNP-129 MV genotype as a possible case of vCJD (reported in the NCJDRSU 17th Annual Report, 2008) and, in a separate case, disease-related prion protein in the spleen of a clinically unaffected blood recipient (reported in 2004) is consistent with such a hypothesis. These cases, along with the report of the prevalence of abnormal prion protein in the large study of appendix and tonsil tissues (two of the positive specimens from VV individuals) suggests the possibility of a greater number of asymptomatic infections (either preclinical or subclinical) in the population than might be indicated by the present numbers of confirmed clinical cases.

 

To help prevent any possible spread of CJD between people, we continue to ask clinicians to refer all new suspect CJD cases to their local infection control and health protection teams. This is important as a local response may be required with respect to limiting potential secondary transmission, infection control and other issues that may arise over time concerning the protection of the wider community. The NCJDRSU continues to assist local health protection teams in local audit and investigations of cases in response to local concerns.

 

The NCJDRSU continues to collaborate with health departments and public health teams throughout the UK in relation to a range of activities, for example, in relation to the follow up of those identified as at increased risk of CJD. The activities of the NCJDRSU are strengthened by collaboration with other surveillance projects, including the Transfusion Medicine Epidemiology Review and the study of Progressive Intellectual and Neurological Deterioration in Children. The collaboration of our colleagues in these projects is greatly appreciated; the effectiveness of this collaboration allowed the identification in 2003 of a case of vCJD associated with blood transfusion and the identification in 2004 of disease-related PrP in the spleen of a recipient of blood donated by someone incubating vCJD. A patient was also identified in 2010 who had evidence of vCJD infection in the spleen (but no evidence of clinical vCJD), considered probably due to blood products (treatment for haemophilia).

 

The relatively recently described form of prion disease originally termed Protease Sensitive Prionopathy and renamed Variably Protease Sensitive Prionopathy, is of uncertain nosological significance but is presently considered a form of sporadic prion disease, alongside sCJD. The NCJDRSU has so far identified at total of 9 such cases in the UK and is continuing to monitor this form of disease. The data concerning CSF RT-QuIC are given in Section 3.5; the sensitivity of CSF RT-QuIC for a diagnosis of sCJD is comparable with that of CSF 14-3-3. The specificity is superior to that of CSF 14-3-3 with no positives in cases with a confirmed alternate diagnosis.

 

The success of the National CJD Research & Surveillance Unit continues to depend on the extraordinary level of co-operation from the neurology and neuropathology communities and other medical and paramedical staff throughout the UK. Ongoing support is provided by the Infectious Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine. We are also particularly grateful to the relatives of patients for their collaboration.

 

 2.2 Sporadic Creutzfeldt-Jakob Disease

 

Between 1st January 1970 and 31st December 2014, 2012 cases of sCJD were identified in the UK, of which 24 cases were alive on 31st December 2014 and one case moved abroad after diagnosis and is therefore lost to follow-up. Of these UK cases, 1425 (71%) were classified as definite cases with the remainder classed as probable. Seven further cases have been identified: 3 in Jersey, 2 in the Isle of Man and 2 cases who were repatriated to the UK when they became ill but had been living abroad. These 7 cases are not included in the following UK analyses.

 

Figure 2 shows the annual mortality rates from sCJD for the UK between 1985 and 2014. The number of deaths identified each year has increased over time. A similar phenomenon has been observed in other European countries, and may reflect improved case ascertainment, particularly in those aged over 70 years.

 

Figure 3 shows average annual age-specific mortality rates over the time periods 1970-1984, 1985-1994, 1995-2004 and 2005-2014. These data also emphasise the very small numbers of cases of sCJD occurring in individuals aged <50 0.02="" 40="" 50.="" 50="" 63="" 65-79="" 66="" 67="" 69="" age-specific="" age="" ages="" all="" an="" and="" are="" ascertainment="" at="" be="" below="" between="" but="" by="" case="" cases="" comparison="" consistent="" death="" decline="" declined.="" different="" div="" during="" elderly.="" explained="" extremely="" four="" greatest="" groups="" improved="" in="" increase="" increased="" indicate="" low="" median="" might="" million="" mortality="" most="" observations="" occurring="" of="" over="" periods="" rates="" recorded="" respectively.="" the="" then="" thereafter="" these="" this="" time="" to="" under-ascertainment="" up="" were="" with="" year="" years.="" years="">
 

snip...

 

2.3 Variant Creutzfeldt-Jakob Disease

 

Up to 31st December 2014, 177 cases of definite or probable vCJD had been identified in the UK (122 definite and 55 probable cases who did not undergo post mortem; no cases still alive). Seventy-five (43%) of the 176 cases were female and 102 (58%) were male. The median age at onset of disease was 26 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 2014 are shown in Figure 5. 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 74) during the period 1990-2014.

 

 www.cjd.ed.ac.uk/documents/report17.pdf). To date, no case of vCJD has been identified in the UK in individuals born after 1989.

 

Deaths from variant CJD

 

Results from modelling the incidence of vCJD deaths indicate the epidemic peaked in about the year 2000 when there were 28 deaths and has since declined1. The last case of vCJD in the UK was

 

1 Analysis undertaken by N J Andrews, Senior Statistician, Statistics Unit, Centre for Infections, Health Protection Agency. Further detail is available at http://www.cjd.ed.ac.uk/cjdq72b.pdf

 

 diagnosed in 2013 and died the same year; no cases have been reported subsequently. Data were last reviewed in 2012 and further details are given in the full report which is available at www.cjd.ed.ac.uk/documents/cjdq72.pdf

 

It is important to note that although a peak has been passed, it is possible that there will be future peaks, possibly in other genetic subgroups. To date, however, there is no evidence of a second wave. There is also the possibility of ongoing person to person spread as seen with 4 cases of transfusion association vCJD infection to date, who received blood in 1999 or earlier from donors who were later diagnosed with clinical vCJD.

 

Geographical distribution of variant CJD

 

Tables 2a and 2b present data on the geographical distribution by residence at onset (for all 177 vCJD cases) and residence at death (for 174 vCJD cases who had died by 31st December 2014 and were resident in the UK at death), along with the crude mortality rate per million population per annum of each standard region.

 

snip...

 

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 6. 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, 99 vCJD cases) of Great Britain in 1991.2 The rate ratio controlling for age and sex is 1.41 (95% CI 1.04-1.90), 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.

 

Investigations into geographically associated cases of vCJD (either through proximity of residence or through an occupational, educational or social/recreational link with the same location) have found no convincing evidence of factors that may have augmented local risks for vCJD3. Figure 6 Standardised variant CJD incidence ratios (SIRs) up to 31st December 2014, by region of residence on 1st January 1991

 

 snip...

 

2.4 Iatrogenic Creutzfeldt-Jakob disease

 

Since 1970, up to 31st December 2014, 84 cases of CJD attributable to iatrogenic exposure have been identified, 8 in individuals receiving dura mater implants, 75 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 these individuals have died (Figure 7). The mean age at death of the hGH/hGN group was 35 years (with a range of 20-51 years) and for the dura mater cases 46½ years (range 27-78 years).

 

Figure 7 Deaths from iatrogenic CJD, 1979-2014

 

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 2003.4 A study of the accumulated UK experience with dura mater-related CJD, including incubation periods, was undertaken and the results published in 2006.5

 

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. Further details are given in the 19th Annual Report (www.cjd.ed.ac.uk/documents/report19.pdf)

 

4 Swerdlow AJ, Higgins CD, Adlard P, Jones ME, Preece MA. Creutzfeldt-Jakob disease in United Kingdom patients treated with human pituitary growth hormone. Neurology 2003; 61: 783-91.

 

5 Heath CA, Barker RA, Esmonde TFG, Harvey P, Trend P, Head MW, Smith C, Bell JE, Ironside JW, Will RG, Knight RSG. Dura mater-associated Creutzfeldt-Jakob disease: experience from surveillance in the UK. JNNP 2006; 77: 880-2.

 

 snip...

 

 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 by an Expert Neurological Advisory Group comprising nine paediatric neurologists, one geneticist and a representative from the National CJD Research & Surveillance Unit, which allocates the cases to a diagnostic category10-11. As of 31st December 2014, after nearly 18 years of surveillance, 3785 patients with suspected PIND had been reported and the Expert Group had discussed 2491 of these. 1580 cases had a confirmed underlying cause other than vCJD, being categorised into over 190 known neurodegenerative diseases3. There have been six cases of vCJD; four definite and two probable. Three were reported in 1999, one in 2000 and 2 in mid-2001. One girl was aged 12 at onset - the youngest UK case of vCJD identified to date.

 

(Collaborators on this project: Dr C Verity, Prof A Nicoll, Ms L Stellitano, Ms AM Winstone)

 

6 Llewelyn CA, Hewitt PA, Knight RSG, Amar K, Cousens S, Mackenzie J, Will RG. Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Lancet 2004; 363: 417-421.

 

7 Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW. Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 2004 364: 527-529.

 

8 Wroe SJ, Pal S, Siddique D, Hyare H, Macfarlane R, Joiner S, Linehan JM, Brandner S, Wadsworth JD, Hewitt P, Collinge J. Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt-Jakob disease associated with blood transfusion: a case report. Lancet 2006; 368: 2061-2067.

 

9 Health Protection Agency. Fourth case of transfusion-associated variant-CJD. Health Protection Report 2007;1(3):

 

10 Verity CM, Nicoll A, Will RG, Devereux G, Stellitano L. Variant Creutzfeldt-Jakob disease in UK children: a national surveillance study. Lancet 2000; 356: 1224-1227.

 

11 Devereux G, Stellitano L, Verity CM, Nicoll A, Will RG, Rogers P. Variations in neurodegenerative disease across the UK: findings from the national study of Progressive Intellectual and Neurological Deterioration (PIND). Arch Dis Child 2004; 89: 8-12.

 

snip...

 

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 2014, 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 continues to be undertaken to determine if any exposure to prion disease occurred.12

 

(Collaborators on this project: K Sinka, J Thorpe)

 

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

 

The potential for secondary transmission of CJD has led to collaborative studies with the UK Haemophilia Centre Doctors Organisation, Institute of Child Health (London), NHS Blood and Transplant, National Prion Clinic, Public Health England, 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 investigations.

 

As at 31st December 2014, 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.13

 

(Collaborators on this project: P Adlard, O Blatchford, H Ward, C Creasey, L Dewhurst, N Gill, C Hay, P Hewitt, M Makris, S Mead, P Minor, B Palmer, A Rankin, K Sinka)

 

12 Thorpe J, Mackenzie J, Molesworth A, Sinka K, Will R. Occupational exposures to prion diseases in healthcare and laboratory workers. Poster presentation at Prion 2012, 9-12 May, Amsterdam.

 

13 Peden A, McCardle L, Head MW, Love S, Ward HJT, Cousens SN, Keeling DM, Millar CM, Hill FGH, Ironside JW. Variant CJD infection in the spleen of a neurologically asymptomatic UK adult patient with haemophilia. Haemophilia 2010; 16: 296-304.

 

snip...

 

3.4 Molecular Genetics

 

Genetic CJD

 

One hundred and forty-five cases of genetic CJD (excluding cases of GSS) have been identified since 1970 by the NCJDRSU (these data are incomplete as formal investigation of genetic CJD in the UK is undertaken by the National Prion Clinic in London). Of the 145 cases, 128 were resident in England, 9 were resident in Wales, 3 were resident in Northern Ireland and 5 were resident in Scotland. Twenty-two cases were still alive as at 31st December 2014. Sixty-five of the cases had insertions in the coding region of the PrP gene, 44 carried the mutation at codon E200K, 15 at codon D178N, 4 at codon V210I, one at codon D167G, 2 at codon V163STOP, one at codon G54S, one at codon E211Q and one at codon E196K. The remaining 11 were identified as familial on the basis of relatives known to have had CJD. The mean age at death was 55½ years (range 29-95 years).

 

PRNP Codon 129 distribution in sporadic CJD

 

The distribution of PRNP codon 129 genotypes in sCJD has been analysed since the inception of the Unit in 1990. The overall distribution of PRNP codon 129 genotypes in sCJD is 62% MM, 19% MV, 19% VV (see Table 6). There appears to be evidence (p=0.003) of a change in the PRNP codon 129 distribution in sCJD between the periods 1990-1995 and 1996-2014. The explanation for this remains unclear. It should be noted that not all cases are genotyped (data available on 62%) and, therefore, changes in PRNP codon 129 distribution may reflect changes in the way in which cases are selected for analysis.

 

Table 6 PRNP codon 129 genotypes of cases of sporadic CJD in the UK, 1990-2014

 

snip...

 

see full report ;

 


 

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, Val erie 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 longe 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...TSS

 

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

 


 

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

 

***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.

 

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

 

PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS

 

*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***

 

O18

 

Zoonotic Potential of CWD Prions

 

Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1, Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western Reserve University, Cleveland, Ohio, USA, 2Second University of Naples, Naples, Italy, 3Encore Health Resources, Houston, Texas, USA

 

*** These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.

 

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

 

***These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.***

 

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

 

P.105: RT-QuIC models trans-species prion transmission

 

Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward Hoover Prion Research Center; Colorado State University; Fort Collins, CO USA

 

Conversely, FSE maintained sufficient BSE characteristics to more efficiently convert bovine rPrP than feline rPrP. Additionally, human rPrP was competent for conversion by CWD and fCWD.

 

***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.

 

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

 

***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.***

 

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

 


 

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

 

Title: Transmission of scrapie prions to primate after an extended silent incubation period

 

Authors

 

item Comoy, Emmanuel - item Mikol, Jacqueline - item Luccantoni-Freire, Sophie - item Correia, Evelyne - item Lescoutra-Etchegaray, Nathalie - item Durand, Valérie - item Dehen, Capucine - item Andreoletti, Olivier - item Casalone, Cristina - item Richt, Juergen item Greenlee, Justin item Baron, Thierry - item Benestad, Sylvie - item Hills, Bob - item Brown, Paul - item Deslys, Jean-Philippe -

 

Submitted to: Scientific Reports Publication Type: Peer Reviewed Journal Publication Acceptance Date: May 28, 2015 Publication Date: June 30, 2015 Citation: Comoy, E.E., Mikol, J., Luccantoni-Freire, S., Correia, E., Lescoutra-Etchegaray, N., Durand, V., Dehen, C., Andreoletti, O., Casalone, C., Richt, J.A., Greenlee, J.J., Baron, T., Benestad, S., Brown, P., Deslys, J. 2015. Transmission of scrapie prions to primate after an extended silent incubation period. Scientific Reports. 5:11573.

 

Interpretive Summary:

 

The transmissible spongiform encephalopathies (also called prion diseases) are fatal neurodegenerative diseases that affect animals and humans. The agent of prion diseases is a misfolded form of the prion protein that is resistant to breakdown by the host cells. Since all mammals express prion protein on the surface of various cells such as neurons, all mammals are, in theory, capable of replicating prion diseases. One example of a prion disease, bovine spongiform encephalopathy (BSE; also called mad cow disease), has been shown to infect cattle, sheep, exotic undulates, cats, non-human primates, and humans when the new host is exposed to feeds or foods contaminated with the disease agent. The purpose of this study was to test whether non-human primates (cynomologous macaque) are susceptible to the agent of sheep scrapie. After an incubation period of approximately 10 years a macaque developed progressive clinical signs suggestive of neurologic disease. Upon postmortem examination and microscopic examination of tissues, there was a widespread distribution of lesions consistent with a transmissible spongiform encephalopathy. This information will have a scientific impact since it is the first study that demonstrates the transmission of scrapie to a non-human primate with a close genetic relationship to humans. This information is especially useful to regulatory officials and those involved with risk assessment of the potential transmission of animal prion diseases to humans.

 

Technical Abstract:

 

Classical bovine spongiform encephalopathy (c-BSE) is an animal prion disease that also causes variant Creutzfeldt-Jakob disease in humans. Over the past decades, c-BSE's zoonotic potential has been the driving force in establishing extensive protective measures for animal and human health. 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.

 


 

Monday, November 16, 2015

 

*** Docket No. APHIS-2007-0127 Scrapie in Sheep and Goats Terry Singeltary Sr. Submission ***

 


 


 

We have shown that cattle-adapted TME is the third cattle prion strain (joining classical and L-type BSE) to be transmissible both to non-human primates and transgenic mice overexpressing human PrP. However, the successful transmission of raccoon TME to primate, inducing a disease with similar features as cattle TME, extends this notion to TME-related strains independent of host origin. Pathological, biochemical and bioassay investigations converged to demonstrate the similarity between cattle-adapted TME and L-BSE.

 


 

***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67 PrPsc was not detected using rapid tests for BSE.

 

***Subsequent testing resulted in the detection of pathologic lesion in unusual brain location and PrPsc detection by PMCA only.

 

IBNC Tauopathy or TSE Prion disease, it appears, no one is sure

 

Posted by flounder on 03 Jul 2015 at 16:53 GMT

 


 

AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease.

 

snip...

 


 

Wednesday, July 15, 2015

 

Additional BSE TSE prion testing detects pathologic lesion in unusual brain location and PrPsc by PMCA only, how many cases have we missed?

 


 

Wednesday, September 23, 2015

 

*** NIH Availability for Licensing AGENCY: [FR Doc. 2015–24117 Filed 9–22–15; 8:45 am] Detection and Discrimination of Classical and Atypical L-Type BSE Strains by RT-QuIC

 


 

Saturday, December 12, 2015

 

*** BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION REPORT DECEMBER 14, 2015

 


 

Tuesday, December 29, 2015

 

*** Congress repeals country-of-origin labeling rule for beef and pork

 


 

December 28, 2015 at 2:21am

 

*** Australian government assessing risk of importing beef from US, Japan and the Netherlands

 


 

Thursday, December 24, 2015

 

Infectious disease spread is fueled by international trade

 


 

Monday, January 4, 2016

 

Long live the OIE, or time to close the doors on a failed entity?

 


 

Wednesday, December 16, 2015

 

*** Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission

 


 

Saturday, December 12, 2015

 

CHRONIC WASTING DISEASE CWD TSE PRION REPORT DECEMBER 14, 2015

 


 

Friday, January 01, 2016

 

Bayesian Modeling of Prion Disease Dynamics in Mule Deer Using Population Monitoring and Capture-Recapture Data

 


 

Tuesday, December 29, 2015

 

TEXAS MONTHLY CHRONIC WASTING DISEASE CWD JANUARY 2016 DEER BREEDERS STILL DON'T GET IT $

 

Chronic Wasting Unease

 

The emergence of a deadly disease has wildlife officials and deer breeders eyeing each other suspiciously.

 


 

Thursday, August 13, 2015

 

Iatrogenic CJD due to pituitary-derived growth hormone with genetically determined incubation times of up to 40 years

 


 

Friday, October 09, 2015

 

An alarming presentation level II trauma center of Creutzfeldt-Jakob disease following a self-inflicted gunshot wound to the head

 


 

Saturday, December 12, 2015

 

CREUTZFELDT JAKOB DISEASE CJD TSE PRION REPORT DECEMBER 14, 2015

 


 

Thursday, December 24, 2015

 

Revisiting the Heidenhain Variant of Creutzfeldt-Jakob Disease: Evidence for Prion Type Variability Influencing Clinical Course and Laboratory Findings

 

Article type: Research Article

 


 

Thursday, September 10, 2015

 

25th Meeting of the Transmissible Spongiform Encephalopathies Advisory Committee Food and Drug Administration Silver Spring, Maryland June 1, 2015

 


 

Friday, December 04, 2015

 

Iatrogenic and sporadic Creutzfeldt-Jakob disease in two sisters without mutation in the prion protein gene

 


 

Monday, August 17, 2015

 

*** FDA Says Endoscope Makers Failed to Report Superbug Problems OLYMPUS

 

*** I told Olympus 15 years ago about these risk factors from endoscopy equipment, disinfection, even spoke with the Doctor at Olympus, this was back in 1999. I tried to tell them that they were exposing patients to dangerous pathogens such as the CJD TSE prion, because they could not properly clean them. even presented my concern to a peer review journal GUT, that was going to publish, but then it was pulled by Professor Michael Farthing et al... see ;

 


 

Monday, June 29, 2015

 

*** RESTRICTED – POLICY CJD IN ADOLESCENTS (16 year old Vickey Rimmer), FARMERS WITH BSE HERDS, AND FARMERS WIFE with Sporadic CJD

 


 

Monday, February 03, 2014

 

CREUTZFELDT-JAKOB DISEASE T.S.E. PRION U.K. UPDATE As at 3rd February 2014

 


 

Sunday, January 19, 2014

 

National Prion Disease Pathology Surveillance Center Cases Examined1 as of January 8, 2014

 


 

Friday, February 14, 2014

 

Creutzfeldt-Jakob disease (CJD) biannual update (February 2014), with briefing on novel human prion disease National CJD Research and Surveillance Unit NCJDRSU

 


 

Article | Open

 

Preclinical detection of infectivity and disease-specific PrP in blood throughout the incubation period of prion disease

 

Elizabeth B. Sawyer , Julie Ann Edgeworth , Claire Thomas , John Collinge

 

& Graham S. Jackson

 

Scientific Reports 5, Article number: 17742 (2015) doi:10.1038/srep17742 Download Citation Diagnostic markers | Experimental models of disease | Prion diseases

 

Received:18 June 2015Accepted:06 November 2015Published online:03 December 2015

 

Abstract

 

Variant Creutzfeldt-Jakob disease (vCJD) is a fatal neurodegenerative disorder characterised by accumulation of pathological isoforms of the prion protein, PrP. Although cases of clinical vCJD are rare, there is evidence there may be tens of thousands of infectious carriers in the United Kingdom alone. This raises concern about the potential for perpetuation of infection via medical procedures, in particular transfusion of contaminated blood products. Accurate biochemical detection of prion infection is crucial to mitigate risk and we have previously reported a blood assay for vCJD. This assay is sensitive for abnormal PrP conformers at the earliest stages of preclinical prion disease in mice and precedes the maximum infectious titre in blood. Not only does this support the possibility of screening asymptomatic individuals, it will also facilitate the elucidation of the complex relationship that exists between the ensemble of abnormal PrP conformers present in blood and the relationship to infectivity.

 

Discussion

 

The ability to accurately diagnose prion infection using biochemical methods is crucial to protect public health from iatrogenic transmissions, particularly arising from the transfusion of contaminated blood and blood products10,11,12,33. In the United Kingdom (UK) measures taken to prevent secondary infections of vCJD have included leucodepletion of donor blood, sourcing of plasma from non-UK sources, exclusion of transfusion recipients from donation, use of recombinant clotting factors for patients with bleeding disorders and ceasing the use of UK plasma for fractionation and export34. We have previously reported the development19 and validation20,35 of a blood test for vCJD based upon the detection of abnormal disease-specific isoforms of PrP, which is now in clinical use for the diagnosis of prion disease. The wider application of this test, or indeed other emerging assays36,37, for screening asymptomatic individuals for potential infection is confounded by an inability to confirm that an assay detection limit is sufficient for the detection of preclinical infections. This problem arises as there are currently no samples available from individuals confirmed as sub-clinical carriers of vCJD with which to assess either the prevalence of prionaemia in BSE prion-exposed populations or the sensitivity of any potential blood tests. A definitive answer will require prolonged longitudinal study of individuals testing positive to determine what proportion of patients with vCJD prionaemia go on to develop clinical vCJD and how many are chronic carriers38.

 

It has been suggested that carriers would have lower concentrations of abnormal PrP compared to individuals with clinical CJD13, and this seems likely. Despite potentially lower levels, animal models indicate clear preclinical blood involvement23,24,39,40 and very efficient transmission of prion infection has been demonstrated from blood taken from sheep in early preclinical stages of scrapie9. The use of the RML-prion strain allows rapid and precise estimates of low prion titre using cell-based assays41,42. Previous attempts to detect infectivity in low titre sources have required either the use of large numbers of recipient animals or the transfusion or large volumes of infected analyte in large animals. By using the SSBA18 we have not only verified but accurately quantified the presence of infectivity in blood even at the earliest stages of preclinical prion disease. A comparison of RML-infected brain diluted into either FVB/N-Prnp0/0 brain homogenate or blood showed that although the presence of whole blood impacted on the overall detection limit of the assay, it remained capable of detecting RML prions at concentrations of less than 1 LD50 units/ml. Infectivity was found to rise by approximately 10–20-fold throughout the incubation period (Fig. 4) as might be anticipated from historical estimates derived from conventional large scale rodent bioassays26, albeit with significant fluctuations approaching the clinical end-point of disease. The significant increase in infectious titre in the last few days of the incubation period are unexpected with the change in titre identifiable only as a result of the high precision of SSBA and related cell-culture assays which are providing unique insights into the replication of prion isoforms during pathogenesis43,44. Levels of MMP-9 in serum provide an indication of BBB integrity and although complicated by age-related decline45, sudden elevation towards the clinical end point for prion disease (Fig. 5) may indicate a sudden perturbation leading to exchange of prion material between the CNS and circulating blood and fluctuations in the concentration of prion disease-related PrP isoforms in blood.

 

Surprisingly, analysis of the same samples using our DDA assay revealed relatively consistent positive signals throughout the RML incubation period (Fig. 3). Positive detection was achieved from the earliest time point sampled and could not be ascribed to the detection of residual inoculum as similar signals were not observed in the blood of FVB/N-Prnp0/0 mice unable to replicate prions (data not shown), and the half-life of prion-infected inocula has previously been shown to be short: 36 hours in rodent brain tissue46 and less in cell-culture47. The lack of correlation between DDA reactivity and infectivity seen by SSBA indicates DDA is capable of detecting a wider ensemble of abnormal PrP conformers associated with prion infection44,48 of which infectivity may only constitute a minority component. Such observations are not without precedent and there is increasing evidence to suggest that abnormal PrP conformers may be as much as 106-fold more abundant than assayable infectivity49. The ability to detect the plethora of abnormal PrP increases the analytical sensitivity of assays and in the case of DDA an analytical sensitivity equivalent to a 109-fold dilution of prion-infected brain is sufficient for clinical sensitivity at the earliest stages of preclinical prion disease.

 


 

Subject: CREUTZFELDT JAKOB DISEASE CJD TSE PRION REPORT DECEMBER 14, 2015

 

UNITED STATES OF AMERICA

 

National Prion Disease Pathology Surveillance Center Cases Examined1 (August 25, 2015)

 

Year Total Referrals2 Prion Disease Sporadic Familial Iatrogenic vCJD

 

1996 & earlier

 

56 35 31 4 0 0

 

1997 113 68 59 9 0 0

 

1998 89 53 45 7 1 0

 

1999 121 73 65 7 1 0

 

2000 144 101 89 12 0 0

 

2001 210 118 110 8 0 0

 

2002 242 144 125 17 2 0

 

2003 257 159 138 21 0 0

 

2004 314 180 162 17 0 13

 

2005 328 179 157 21 1 0

 

2006 369 182 163 17 0 24

 

2007 370 206 187 19 0 0

 

2008 387 223 207 16 0 0

 

2009 399 233 212 20 1 0

 

2010 403 247 218 29 0 0

 

2011 393 239 216 23 0 0

 

2012 409 241 218 23 0 0

 

2013 416 257 222 34 1 0

 

2014 355 210 187 21 0 15

 

2015 237 137 118 8 0 0 TOTAL 56126 32857 2929 3338 7 4

 

1 Listed based on the year of death or, if not available, on year of referral;

 

2 Cases with suspected prion disease for which brain tissue was submitted;

 

3 Disease acquired in the United Kingdom;

 

4 Disease acquired in the United Kingdom in one case and in Saudi Arabia in the other;

 

5 Disease possibly acquired in a Middle Eastern or Eastern European country;

 

6 Includes 28 cases in which the diagnosis is pending, and 19 inconclusive cases;

 

7 Includes 12 (11 from 2015) cases with type determination pending in which the diagnosis of vCJD has been excluded. The sporadic cases include 2853 cases of sporadic Creutzfeldt-Jakob disease (sCJD), 54 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 22 cases of sporadic Fatal Insomnia (sFI).

 

8 Total Excludes 194 familial blood only cases.

 

Rev 8/26/2015

 


 

Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas in June 2014 confirmed as home grown case

 

Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas

 

Updated: October 7, 2014

 

CDC and the Texas Department of State Health Services (DSHS) have completed the investigation of the recently reported fourth vCJD case in the United States. It confirmed that the case was in a US citizen born outside the Americas and indicated that the patient's exposure to the BSE/vCJD agent most likely occurred before he moved to the United States; the patient had resided in Kuwait, Russia and Lebanon. 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.

 


 

>>>the patient had resided in Kuwait, Russia and Lebanon.

 

>>>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.

 

NOW we all know why the state of Texas or the CDC did not want to report this case, because it was a home grown case of nvCJD right here in Texas...tss

 

Monday, June 02, 2014

 

Confirmed Variant CJD Case in Texas

 


 

Sunday, November 23, 2014

 

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

 


 

Monday, November 3, 2014

 

USA CJD TSE PRION UNIT, TEXAS, SURVEILLANCE UPDATE NOVEMBER 2014

 

National Prion Disease Pathology Surveillance Center Cases Examined1 (October 7, 2014)

 

***6 Includes 11 cases in which the diagnosis is pending, and 19 inconclusive cases;

 

***7 Includes 12 (11 from 2014) cases with type determination pending in which the diagnosis of vCJD has been excluded.

 

***The sporadic cases include 2660 cases of sporadic Creutzfeldt-Jakob disease (sCJD),

 

***50 cases of Variably Protease-Sensitive Prionopathy (VPSPr)

 

***and 21 cases of sporadic Fatal Insomnia (sFI).

 


 

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

 


 

Sunday, August 11, 2013

 

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

 


 

Monday, February 24, 2014

 

Sporadic Fatal Insomnia in an Adolescent

 


 

Friday, January 10, 2014

 

*** vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???

 


 

>>> We concluded that VPSPr is transmissible; thus, it is an authentic prion disease.

 

 Sunday, November 23, 2014

 

Transmission Characteristics of Variably Protease-Sensitive Prionopathy

 

* We concluded that VPSPr is transmissible; thus, it is an authentic prion disease.

 


 

Monday, November 3, 2014

 

The prion protein protease sensitivity, stability and seeding activity in variably protease sensitive prionopathy brain tissue suggests molecular overlaps with sporadic Creutzfeldt-Jakob disease

 


 


 

WHAT about the sporadic CJD TSE proteins ?

 

WE now know that some cases of sporadic CJD are linked to atypical BSE and atypical Scrapie, so why are not MORE concerned about the sporadic CJD, and all it’s sub-types $$$

 

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

 

*** Creutzfeldt-Jakob Disease CJD cases rising North America with Canada seeing an extreme increase of 48% between 2008 and 2010 ***

 


 

Sunday, October 13, 2013

 

*** CJD TSE Prion Disease Cases in Texas by Year, 2003-2012

 


 

Wednesday, December 11, 2013

 

*** Detection of Infectivity in Blood of Persons with Variant and Sporadic Creutzfeldt-Jakob Disease ***

 


 

 

 07 02:27 AM

 

Terry S. Singeltary Sr. said:

 

re-Evidence for human transmission of amyloid-? 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)

 


 

*** I would kindly like to comment on the Nature Paper, the Lancet reply, and the newspaper articles.

 

snip...see full text ;

 


 

Subject: 1992 IN CONFIDENCE TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES POSSIBILITY ON A TRANSMISSIBLE PRION REMAINS OPEN

 

BSE101/1 0136

 

IN CONFIDENCE

 

CMO

 

From: . Dr J S Metiers DCMO

 

4 November 1992

 

TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES

 

1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have recognised the public sensitivity of these findings and intend to report them in their proper context. 'This hopefully will avoid misunderstanding and possible distortion by the media to portray the results as having more greater significance than the findings so far justify.

 

2. Using a highly unusual route of transmission (intra-cerebral injection) the researchers have demonstrated the transmission of a pathological process from two cases one of severe Alzheimer's disease the other of Gerstmann-Straussler disease to marmosets. However they have not demonstrated the transmission of either clinical condition as the "animals were behaving normally when killed". As the report emphasises the unanswered question is whether the disease condition would have revealed itself if the marmosets had lived longer. They are planning further research to see if the conditions, as opposed to the partial pathological process, is transmissible.

 

what are the implications for public health?

 

3. The route 'of transmission is very specific and in the natural state of things highly unusual. However it could be argued that the results reveal a potential risk, in that brain tissue from these two patients has been shown to transmit a pathological process. Should therefore brain tissue from such cases be regarded as potentially infective? Pathologists, morticians, neuro surgeons and those assisting at neuro surgical procedures and others coming into contact with "raw" human brain tissue could in theory be at risk. However, on a priori grounds given the highly specific route of transmission in these experiments that risk must be negligible if the usual precautions for handling brain tissue are observed.

 

1

 

92/11.4/1.1

 

BSE101/1 0137

 

4. The other dimension to consider is the public reaction. To some extent the GSS case demonstrates little more than the transmission of BSE to a pig by intra-cerebral injection. If other prion diseases can be transmitted in this way it is little surprise that some pathological findings observed in GSS were also transmissible to a marmoset. But the transmission of features of Alzheimer's pathology is a different matter, given the much greater frequency of this disease and raises the unanswered question whether some cases are the result of a transmissible prion. The only tenable public line will be that "more research is required’’ before that hypothesis could be evaluated. The possibility on a transmissible prion remains open. In the meantime MRC needs carefully to consider the range and sequence of studies needed to follow through from the preliminary observations in these two cases. Not a particularly comfortable message, but until we know more about the causation of Alzheimer's disease the total reassurance is not practical.

 

J S METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH 832 llllYc!eS 2 92/11.4/1.2

 


 

>>> 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 ?

 

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

 

Received July 24, 2014; Accepted September 16, 2014; Published November 3, 2014

 


 

*** 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

 


 

SINGELTARY PEER REVIEW

 

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.

 


 

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?

 


 

The Lancet Infectious Diseases, Volume 3, Issue 8, Page 463, August 2003 doi:10.1016/S1473-3099(03)00715-1Cite or Link Using DOI

 

Tracking spongiform encephalopathies in North America

 

Original

 

Xavier Bosch

 

“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.” 49-year—old Singeltary is one of a number of people who have remained largely unsatisfied after being told that a close relative died from a rapidly progressive dementia compatible with spontaneous Creutzfeldt—Jakob ...

 


 

Suspect symptoms

 

What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?

 

28 Mar 01

 

Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America. Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.

 

"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb...

 


 

2 January 2000

 

British Medical Journal

 

U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well

 


 

15 November 1999

 

British Medical Journal

 

vCJD in the USA * BSE in U.S.

 


 

TSS

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