27th ANNUAL REPORT 2018 CREUTZFELDT-JAKOB DISEASE SURVEILLANCE IN THE UK
27th ANNUAL REPORT 2018 CREUTZFELDT-JAKOB DISEASE SURVEILLANCE IN THE UK
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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 on the surveillance, diagnosis 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 annual mortality rate for sporadic CJD (sCJD) was 2.06 cases/million in 2018. Although the data for 2018 may still be incomplete, detailed clinical and epidemiological information has been obtained for the great majority of patients. Although the autopsy rate in cases of suspected CJD has decreased in recent years, it remains relatively high in comparison to the general autopsy rate in the UK. The number of brain tissue specimens examined for sCJD in the neuropathology laboratory in 2018 was 36 cases (compared with 33 cases in 2017).
Over the period 1990-2018 average annual mortality rates from sCJD in England, Wales, Scotland and Northern Ireland were, respectively, 1.20, 1.52, 1.22 and 0.90/million/year. The differences between these rates are not statistically significant (p=0.29). The mortality rates of 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.
Variably Protease Sensitive Prionopathy (VPSPr), is of uncertain nosological significance but is presently considered a form of sporadic prion disease, alongside sCJD. The NCJDRSU has so far identified a total of 17 such cases in the UK and is continuing to monitor this form of disease.
Up to 31st December 2018, 178 cases of definite or probable variant CJD (vCJD) had been identified in the UK (123 definite and 55 probable cases who did not undergo post mortem). All 178 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 – of 161 clinically affected definite and probable cases of vCJD with available genetic analysis, 160 have been methionine homozygotes and one methionine-valine heterozygous at Codon 129 of the PRNP gene. Analysis of vCJD diagnoses and deaths from January 1994 continues to indicate that the peak has passed. While this is an encouraging finding, the incidence of vCJD may increase again, particularly if further cases in different genetic subgroups with longer incubation periods exist. The identification of an individual of the PRNP-129 MV genotype as a confirmed case of vCJD (in addition to the possible case of vCJD reported in the NCJDRSU 17th Annual Report, 2008) and the finding of 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 results of large scale surveys of the prevalence of abnormal prion protein in appendix and tonsil tissues suggest 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 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 also continues to collaborate with government health departments and the UK public health authorities, including Public Health England and Health Protection Scotland, in relation to a range of activities 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, Prion Surveillance in Primary Immunodeficiency Patients, the study of Progressive Intellectual and Neurological Deterioration in Children and the CJD International Surveillance Network. 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 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.
Providing information to the public is an important aspect of the NCJDRSU’s activities. We held a Family Day in 2018. We liaise closely with the CJD Support Network, providing articles for their newsletter, updating their information booklets and giving presentations to their Annual Family Day meetings. Professor Knight is the current Chair of the Network’s Management Committee and is also a member of the CJD International Alliance of CJD support organisations.
CLINICAL SURVEILLANCE
The 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 2018 (based on data ascertained up to 10th July 2018). 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
Cases classified as definite or probable are included in all analyses from Section 2.2 onwards.
2.1 Referrals to NCJDRSU
The NCJDRSU receives referrals of suspect cases of CJD and a proportion of these will turn out not to have CJD. Referrals of suspect cases increased after the present surveillance system began in 1990, particularly following the description of vCJD in 1996. Numbers of referrals fluctuate over time, and may be attributed to variation in case ascertainment and reporting practice, including changes in the number of non-CJD cases referred to the NCJDRSU (see Figure 1)
Figure 1 Referrals to NCJDRSU: UK 1 May 1990 – 31st December 2018
In addition to formal referrals of suspected CJD as shown above, the NCJDRSU also receives enquiries from clinicians for advice or to utilise the CSF tests available at the Unit. In 2018, in addition to the 167 formal referrals of suspected cases of CJD, there were a further 249 enquiries where advice was sought by clinicians on individual patients. The NCJDRSU also receives a number of enquiries from relatives of patients, members of the public and professional bodies both in the UK and worldwide seeking advice in relation to CJD. In 2018, over 150 such email enquiries were received via the contact details displayed our website (http://www.cjd.ed.ac.uk/contact-us).
Nationally across the UK rates of post-mortem examinations have been decreasing over time, and this includes for suspected cases of CJD (Figure 2). Although increasing diagnostic certainty can now be offered by biomarker tests (MRI, RT-QuIC), the fall in post-mortem rate may potentially impact on our ability to confirm the different types of prion disease, particularly in cases where prion disease may not have been considered or otherwise atypical of CJD.
Figure 2 Post-mortem rate in all referrals of suspected CJD to NCJDRSU: UK 1 May 1990 – 31st December 2018
2.2 Sporadic Creutzfeldt-Jakob Disease
Between 1st January 1970 and 31st December 2018, 2494 cases of sCJD were identified (268 in England and Wales from 1970-1984 and 2226 in the UK from 1985-2018), of which 20 cases were alive on 31st December 2018. Two cases moved abroad after diagnosis and are therefore lost to follow-up. Of these 2494 cases, 1604 (64%) were classified as definite cases with the remainder classed as probable. 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, along with the 2 cases lost to follow up, are not included in the following UK analyses.
Figure 3 shows the annual mortality rates from sCJD for the UK between 1985 and 2018. 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, and also following revised diagnostic criteria in January 2017, the impact of which is under investigation.
Figure 3 Mortality Rates from sCJD, UK, 1985-2018
Figure 4 shows average annual age-specific mortality rates over the time periods 1970-1984, 1985- 1994, 1995-2004, 2005-2014 and subsequently. These data also emphasise the very small numbers of cases of sCJD occurring in individuals aged <50 0.04="" 40="" 50.="" 50="" 63="" 65-79="" 65="" 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="" during="" elderly.="" explained="" five="" for="" greatest="" groups="" improved="" in="" increase="" increased="" indicate="" low="" median="" might="" million="" mortality="" most="" observations="" occurring="" of="" over="" part="" periods="" rates="" reasons="" recorded="" respectively.="" span="" the="" then="" thereafter="" these="" this="" time="" to="" unclear="" under-ascertainment="" up="" were="" with="" year="" years.="" years="">
Figure 4 Age-specific mortality rates from sporadic CJD in the UK 1970-2018 (note: from 1970-1984 only England and Wales, thereafter UK)
Geographical distribution of sCJD
Over the period 1990-2018 the average crude annual mortality rates from sCJD per million population were 1.20 in England, 1.52 in Wales, 1.22 in Scotland and 0.90 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=0.29).
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 2018 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=0.15).
Figure 5 Standardised sporadic CJD mortality ratios (SMRs) 1 January 1990 - 31 December 2018, by region of residence at death
Table 1a Deaths from definite and probable sporadic CJD in England (shown by region and local authority of residence at death). 1 st January 1990 to 31st December 2018
Table 1b Deaths from definite and probable sporadic CJD: Wales, Scotland and NI 1 st January 1990 to 31st December 2018
2.3 Variant Creutzfeldt-Jakob Disease
Up to 31st December 2018, 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 2018 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 74) during the period 1990-2018. The last known UK case of vCJD was reported in 2016 with onset in 2014.
Figure 6 Age- and sex-specific mortality rates from variant CJD in the UK 1 May 1995 - 31st December 2018
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 2018 and were resident in the UK at death), along with the crude mortality rate per million population per annum of each standard region.
1 Kaski D, Mead S, Hyare H, Cooper S, Jampana R, Overell J, Knight R, Collinge J, Rudge P: Variant CJD in an individual heterozygous for PRNP Codon 129. Lancet 2009;374:2128.
Table 2a Cases of definite and probable variant CJD shown by residence at onset (n=143) and residence at death (n=144†) in England (region & local authority)
Table 2b Cases of definite and probable variant CJD shown by residence at onset (n=35) and residence at death (n=31): Wales, Scotland and NI
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.
Figure 7 Standardised variant CJD incidence ratios (SIRs) up to 31st December 2018, by region of residence on 1st January 1991
2.4 Iatrogenic Creutzfeldt-Jakob disease
Since 1970, up to 31st December 2018, 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. Eighty-seven of these individuals have died (Figure 8). The mean age at death of the hGH/hGN group was 35½ years (with a range of 20-51 years) and for the dura mater cases 46½ years (range 27-78 years).
Figure 8 Deaths from iatrogenic CJD, 1979-2018
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.
3 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.
4 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.
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.
As look-back studies of blood transfusion in Creutzfeldt-Jakob disease commonly rely on reported history from surrogate witnesses, data from the TMER project were analysed to determine the accuracy of blood donation history provided by the relatives of cases. The results showed that only a small percentage of cases were found to be registered as donors on UKBS databases when there was no family report of blood donation. In contrast, a history of reported donation was less accurate10. As there are potential public health implications of even a small percentage of CJD blood donors not being identified, a revision to the protocol of the CJD arm of the project has recently being made whereby all cases of CJD (definite and probable) will be notified to UKBS regardless of their reported donation history.
(External collaborators on this project: Dr P Hewitt, Dr H Harvala Simmonds, Ms C Reynolds).
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.11, 12, 13
5 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. 6 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. 7 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. 8 Health Protection Agency. Fourth case of transfusion-associated variant-CJD. Health Protection Report 2007;1(3): 9 Urwin PJ, Mackenzie JM, Llewelyn CA, Will RG, Hewitt PE. Creutzfeldt-Jakob disease and blood transfusion: updated results of the UK Transfusion Medicine Epidemiology Review Study. Vox Sang 2016; 110: 310-316. 10 Mackenzie JM, Turner M, Morris K, Field S, Molesworth AM, Pal S, Will RG, Llewelyn CA, Hewitt PE. Accuracy of a history of blood donation from surrogate witnesses: data from the UK TMER study. Vox Sang 2018; 113(5): 489-491. 11 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. 12 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. 13 Verity C, Winstone AM, Stellitano L, Will R, Nicoll, A. The epidemiology of progressive intellectual and neurological deterioration in childhood. Arch Dis Child 2010; 95:361-364 deterioration in childhood. Arch Dis Child 2010; 95:361-364.
As of 31st December 2018, after nearly 22 years of surveillance, 4467 patients with suspected PIND had been reported and the Expert Group had discussed 2919 of these. There have been six cases of vCJD: four definite and two probable. Three were reported in 1999, one in 2000 and two in mid2001. The youngest UK case of vCJD identified to date was aged 12 at onset. A total of 1945 cases had a confirmed underlying cause other than vCJD, being categorised into over 190 known neurodegenerative diseases.
(External collaborators on this project:: Dr C Verity, Dr A Powell, 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 2018, 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. 14 15 (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 2000.16
By the end of March 2019, a total of 79 patients registered in 17 immunology centres across Great Britain had participated in the study. Of these, 18 had died with a further 8 lost to follow up, leaving 53 participants registered over 12 sites. Participants had been followed up for approximately 1466 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 tested17.
(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, S Murng, P Wood, M Browning, T Garcez, A Herwadkor, D Lowe, M Thomas)
14 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.
15 Mackenzie JM, Urwin P, Mackenzie G, Knight RSG, Will RG, Molesworth AM. Occupations of cases of vCJD in the UK. Poster presentation at Prion 2017, 23-26 May, Edinburgh.
16 Helbert MR, Bangs C, Bishop M, Molesworth A, Ironside J. No evidence of asymptomatic variant CJD infection in immunodeficiency patients treated with UK-sourced immunoglobulin. Vox Sang 2016; 110(3): 382-4.
17 http://www.cjd.ed.ac.uk/sites/default/files/PID%20Study%20Steering%20Group%20report_2018_0.pdf
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 investigations18.
As at 31st December 2018, 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
Laboratory investigations are part of the internationally-agreed diagnostic criteria for CJD, both during life (CSF protein analysis, PrP genetic studies, brain biopsy neuropathology and prion protein studies) and post-mortem (autopsy neuropathology and prion protein studies). The NCJDRSU has facilities to perform all of these investigations, which aid the timely and accurate diagnosis of all forms of CJD and are essential for surveillance purposes.
3.1 Neuropathology – Statement of Progress and Surveillance Activities
The neuropathology laboratory in the NCJDRSU continues to maintain its diagnostic and research activities, with most of the cases investigated referred from other centres across the UK (see Table 3). The laboratory maintains close links with other neuropathology centres across the UK and overseas with scientific, medical, technical and student visitors over the past year for specialist training purposes. The laboratory has continued to maintain an active research programme both in-house and by collaboration with other research centres in UK, Europe and across the world and provides tissues to researchers through the CJD Brain and Tissue Bank, which is part of the MRC-funded Edinburgh Brain Bank.
In the contemporary referrals for 2018, the numbers of cases diagnosed as prion diseases was similar to those in the previous year; the numbers of cases in which there was no evidence of CJD or an alternative diagnosis was made was higher in 2018. No cases of vCJD were identified in the UK and none were referred from outside the UK.
In addition to the UK CJD surveillance work, the neuropathology laboratory is involved in a number of collaborative research and surveillance studies in relation to neuropathological diagnosis of CJD and other human prion diseases.
The laboratory and its staff continue to participate in a range of EQA activities related to both technical and diagnostic neuropathology. As before, the laboratory continues to act as a source of information to a wide range of professionals involved in health and safety issues relating to CJD. We are most grateful to all neuropathologists, general pathologists and their technical, secretarial and autopsy room staff for their continuing support of the NCJDRSU. We are also grateful to the relatives of patients with CJD for allowing us to study this group of devastating disorders.
Table 3 Breakdown of Laboratory Activities: 1 st January 2017– 31st December 2018
3.2 Protein Biochemistry Laboratory
Prion protein detection and typing
Prion protein typing is carried out as a routine diagnostic test on all suspected cases of CJD from which frozen brain tissue is received by the NCJDRSU. Small quantities of cerebral cortex or cerebellum are homogenised, treated with protease and the size and relative abundance of the protease resistant prion protein (PrPres) fragments determined by Western blot analysis. The recognised PrPres types, their nomenclature and their association with different human prion diseases are shown in Figure 9 and described in the accompanying legend. In cases from which only peripheral tissues are available (such as those in which diagnostic tonsil biopsy is performed), or in cases in which the patient is thought to have been at risk of developing CJD due to potential iatrogenic exposure and is enrolled in a UK prion screening study, a modified Western blot procedure is used which employs centrifugal concentration or sodium phosphotungstic acid precipitation to enrich for PrPres and increase the sensitivity of the test.
Figure 9
Figure 9 shows the diagrammatic representation of the main protease resistant prion protein (PrPres) types found in the human prion disease brain as determined by proteinase K digestion and Western blot analysis. The classification of the banding pattern has two components, one numerical depending on the migration of the bands and the other alphabetical depending on their relative abundance. The pattern is termed type 1 if the non-glycosylated (bottom) band is ~21kDa, type 2 if the non-glycosylated band is ~19kDa or type 1+2 if both bands are found. In cases and samples in which both types are present but one type predominates the less abundant type is placed in parentheses [ie type 1(+2) or type 2(+1)]. The pattern is given the suffix A if the middle or bottom (mono-, or non-glycosylated) bands predominate, B if the top (di-glycosylated) band predominates or A/B if the glycosylated bands (middle and top) predominate at the expense of the non-glycosylated (bottom) band. A pattern dominated by a low molecular mass unglycosylated band is here termed 8kDa. The faint ladder of bands that sometimes accompanies the 8kDa band is shown in grey. Types 1A, 2A, 1+2(A) are characteristic of sporadic and iatrogenic CJD. Type 2B is associated with variant CJD and is a consistent feature present in all cases so far examined. However, a protein isotype resembling type 2B can also be found in cases of FFI and fCJDE200K. Types 1B, 1A/B and 2A/B are often found in genetic CJD, GSS and FFI. The 8kDa pattern is characteristic of some cases of GSS and of Variably protease-sensitive prionopathy (VPSPr). VPSPr can present with multiple isotypes, one of which includes an intermediate band also associated with iatrogenic CJD.
UK Referrals
A total of 44 UK cases with frozen tissue were received and analysed in 2018. The results of the analysis were as follows:
Table 4 Breakdown of cases analysed in 2018
Table 5 PrPres type / PRNP genotype breakdown of CJD cases analysed in 2018
Table 6 Non-UK Referrals
3.3 Brain banking activities
The bank of fixed and frozen tissues in the Research and Surveillance Unit was used extensively in 2018 for diagnostic and collaborative research purposes with colleagues in the UK and overseas. Funding from MRC was renewed in 2013 to support the activities of the CJD bank as part of the Edinburgh Brain Bank (Director – Professor Colin Smith) for a further 5 years. The Edinburgh Brain Bank is a member of the MRC Network of UK Brain Banks, which works to strengthen banking activities and ensure uniform high standards of operation. The Bank has a website, on which further details are available including instructions on how to request tissue samples for research (http://www.ed.ac.uk/clinical-brain-sciences/research/edinburgh-brain-and-tissue-bank).
The activities of the Bank comply with current guidelines from the Royal College of Pathologists, the Human Tissue (Scotland) Act 2006 and the Human Tissue Act 2004.
3.4 Molecular Genetics
Genetic CJD
One hundred and seventy-one 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 171 cases, 151 were resident in England, 11 were resident in Wales, 3 were resident in Northern Ireland and 6 were resident in Scotland. Thirteen cases were still alive as at 31st December 2018. Seventy-two of the cases had insertions in the coding region of the PrP gene, 56 carried the mutation at codon E200K, 17 at codon D178N, 4 at codon V210I, one at codon D167G, 2 at codon V163STOP, one at codon G54S, one at codon E211Q and 2 at codon E196K. The remaining 15 were identified as genetic on the basis of relatives known to have had CJD. The mean and median age at death was 56 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 61% MM, 19% MV, 20% VV (see Table 7). There appears to be evidence (p<0 .05="" 129="" 63="" a="" all="" analysis.="" and="" are="" available="" be="" between="" cases="" change="" changes="" codon="" data="" distribution="" explanation="" first="" for="" genotyped="" in="" it="" may="" not="" noted="" of="" on="" periods.="" prnp="" reflect="" remains="" scjd="" selected="" should="" span="" subsequent="" that="" the="" therefore="" this="" unclear.="" way="" which="">
Table 7 PRNP Codon 129 genotypes of cases of sporadic CJD in the UK, 1990-2018
PRNP Codon 129 distribution in variant CJD
In clinical cases for whom genetic data are available (n=161, 90%), 160 were methionine homozygotes at PRNP Codon 129 of the PrP gene and one case was heterozygous at PRNP Codon 129 of the PrP gene.
The genetic laboratory undertakes genetic analysis on a national and international basis.
19 Bishop et al. PRNP variation in UK sporadic and variant Creutzfeldt-Jakob disease highlights genetic risk factors and a novel non-synonymous polymorphism. BMC Medical Genetics 2009;10:146-155.
3.5 CSF RT-QuIC, 14-3-3 and other brain specific proteins
Introduction
During the period January-December 2018, the laboratory received 304 cerebrospinal fluid (CSF) from suspected CJD patients residing in the UK, 65 samples from suspected CJD patients residing outwith the UK and 37 from young onset dementia patients (Table 8).
Table 8 Origin of CSF samples sent to the NCJDRSU for CSF 14-3-3 analysis from January 2018 – December 2018
Results of 14-3-3 and RT-QuIC analysis on the 304 cases of suspected CJD in the UK is shown in Table 9.
Table 9 CSF 14-3-3 and RT-QuIC results in 304 CSF samples from suspected CJD cases in the UK
NATIONAL CJD CARE TEAM
Established by the Department of Health and Social Care, the National CJD Care Team is based within the National CJD Research & Surveillance Unit and was formed in order to optimise the care of patients suffering from all forms of CJD. The national care coordinator post was established in February 2000, and the National CJD Care Team formed in September 2001. The present team consists of two care co-ordinators who are senior nurses.
All new referrals with suspected CJD are assessed by care co-ordinators in person whenever possible. Co-ordinators work closely with family and local healthcare professionals in assisting care planning. Referrals are also received from The Institute of Child Health in London (iatrogenic CJD linked to human growth hormone treatment) and from the National Prion Clinic (genetic cases). Care coordinators are able to meet with patients, families and local professionals depending on individual need. They provide valuable expertise in nursing patients with CJD and in anticipation and prevention of problems that may arise. Care co-ordinators are available to provide advice and education on diagnosis, prognosis, discharge planning, symptom management, infection control and any other questions in relation to the care of patients with CJD. Contact is maintained in person, by telephone, or email.
The National CJD Care Team works in close liaison with NHS England and provides access to the CJD Care Package. This provides funding to assist local authorities with the care of patients suffering from all forms of CJD. Care packages are flexible and can change quickly to meet the rapidly changing needs of patients. The aim is to provide a package of care that will meet the needs both for the patient and their family in a timely manner. In addition to collaborations with national organisations in the United Kingdom, the Care Team liaises closely with international organisations, including the Australian and American CJD Support Groups and is an Official Friend of the CJD International Support Alliance.
A breakdown of new referrals and educational and professional presentations during 2018 is shown in Table 10. Care Fund payments from 1st April 2018 – 31st March 2019 are shown in Table 11.
Table 10 New Patients and Education: 1 st January 2018 to 31st December 2018
Table 11 Care Fund Payments: 1 st April 2018 – 31st March 2019
PUBLICATIONS IN 2018
1. Abu-Rumeileh S, Redaelli V, Baiardi S, Mackenzie G, Windl O, Ritchie DL, Didato G, Hernandez-Vara J, Rossi M, Capellari S, Imperiale D, Rizzone MG, Belotti A, Sorbi S, Rozemuller AJM, Cortelli P, Gelpi E, Will RG, Zerr I, Giaccone G, Parchi P. Sporadic Fatal Insomnia in Europe: Phenotypic Features and Diagnostic Challenges. Ann Neurol. 2018;84(3):347-360.
2. Areškevičiūtė A, Melchior LC, Broholm H, Krarup LH, Granhoj Lindquist S, Johansen P, McKenzie N, Green A, Nielsen JE, Laursen H, Lobner Lund E. Sporadic Creutzfeldt-Jakob Disease in a woman married into a Gerstmann-Straussler-Scheinker family: an investigation of prion transmission via microchimerism. J Neuropatholo Exp Neurol 2018;77(8):673-684.
3. Barria MA, Libori A, Mitchell G, Head MW. Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions. Emerg Infect Dis. 2018;24(8):1482- 1489.
4. Barria MA, Lee A, Green AJ, Knight R, Head MW. Rapid amplification of prions from variant Creutzfeldt-Jakob disease cerebrospinal fluid. J Pathol Clin Res. 2018;4(2):86-92.
5. Bougard D, Bélondrade M, Mayran C, Bruyère-Ostells L, Lehmann S, Fournier-Wirth C, Knight RS, Will RG, Green AJE. Diagnosis of Methionine/Valine Variant CreutzfeldtJakob Disease by Protein Misfolding Cyclic Amplification. Emerg Infect Dis. 2018;24(7):1364-1366.
6. Brandel JP, Knight R. Variant Creutzfeldt-Jakob disease. Handb Clin Neurol. 2018;153:191-205.
7. De Icaza Valenzuela MM, Bak TH, Pal S, Abrahams S. The Edinburgh Cognitive and Behavioural ALS screen: relationship to age, education, IQ and the Addenbrooke’s Cognitive Examination-III. Amyotrophic Lateral Sclerosis and Frontotemporal Degneration 2018;19(7-8):585-590.
8. De Sousa PA, Ritchie D, Green A, Chandran S, Knight R, Head MW. Renewed assessment of the risk of emergent advanced cell therapies to transmit neuroproteinopathies. Acta Neuropath Epub 2018, Nov 27 doi:10.1007/s00401-018- 1941-9
9. Gibson LM, Chappell FM, Summers D, Collie DA, Sellar R, Best J, Knight R, Ironside JW, Wardlaw JM. Post-mortem magnetic resonance imaging in patients with suspected prion disease: Pathological confirmation, sensitivity, specificity and observer reliability. A national registry. PLoS One. 2018 Aug 7;13(8):e0201434.
10. Green AJE and Zanusso G. Prion Protein Amplification Techniques. In: Pocchiari M, Manson J, eds. Human Prion Diseases. San Diego: Elsevier BV, 2018;153:357-370.
11. Mabbott NA, Alibhai JD, Manson J. The role of the immune system in prion infection. Handb Clin Neurol. 2018;153:85-107.
12. Mackenzie JM, Turner M, Morris K, Field S, Molesworth AM, Pal S, Will RG, Llewelyn CA, Hewitt PE. Accuracy of a history of blood donation from surrogate witnesses: data from the UK TMER study. Vox Sang. 2018;113(5):489-491.
13. Majumder V, Gregory JM, Barria MA, Green A, Pal S. TDP-43 as a potential biomarker for amyotrophic lateral sclerosis: a systematic review and meta-analysis. BMC Neurol. 2018;18(1):90.
14. Soane T, Schott JM, Stone J, Smith C, Pal S, Davenport RJ. Clinicopathological case: progressive somnolence and dementia in an accountant: when the shine rubs off the gold standard. Practical Neurology 2018;18(6):505-512.
15. Verity C, Winstone AM, Will R, Powell A, Baxter P, de Sousa C, Gissen P, Kurian M, Livingston J, McFarland R, Pal S, Pike M, Robinson R, Wassmer E, Zuberi S. Surveillance for variant CJD: should more children with neurodegenerative diseases have autopsies? Arch Dis Child. Epub 2018 Oct 18 doi:10.1136/archdischild-2018-315458.
16. Ward H, Molesworth A, Holmes S, Sinka K. Public health: surveillance, infection prevention, and control. In: Pocchiari M, Manson J, eds. Human Prion Diseases. San Diego: Elsevier BV, 2018:153;473-484.
Staff based at the National CJD Research & Surveillance Unit, Edinburgh in 2018
Dr C Smith Director, NCJDRSU, Professor of Clinical Neuropathology Dr AM Molesworth Deputy Director, NCJDRSU, Senior Epidemiologist Dr A Green Reader (CSF analysis) Dr S Pal Senior Clinical Lecturer in Neurology and Honorary Consultant Neurologist Dr M Barria Group Leader/Research Fellow Professor RSG Knight Consultant Neurologist, Professor of Clinical Neurology Professor RG Will Consultant Neurologist, Professor of Clinical Neurology Dr D Summers Consultant Neuroradiologist Dr G Mackenzie Dr G Langlands Clinical Research Fellow Clinical Research Fellow Dr J Lumsden Clinical Research Fellow Dr A Peden Postdoctoral Research Fellow Ms J Mackenzie Surveillance Co-ordinator Ms T Lindsay European Study Co-ordinator Mrs B Smith-Bathgate National Care Co-ordinator and Senior Nurse Ms M Leitch National Care Co-ordinator and Senior Nurse Mr N Attwood Database Manager Dr D Ritchie Postdoctoral Research Fellow Dr N McKenzie Postdoctoral Research Fellow Mr J Alibhai Postdoctoral Research Fellow Dr S Suleiman Postdoctoral Research Scientist Ms S Lowrie Senior Biomedical Scientist Mrs M Le Grice Senior Biomedical Scientist Mrs M Andrews Senior Biomedical Scientist Ms H Yull Senior Research Technician Mr G Fairfoul Research Technician Ms K Burns Neuropathology Technical Officer Ms L Banks Research Technician Ms A Libori Research Technician Ms A Chong Research Technical Officer Mrs Elaine Lord Senior Administrative Manager Mrs F Frame Secretariat Mrs C Donaldson Secretariat/Data Handler Ms L Bond Secretariat Mrs A Kuchnowski Research Nurse Mrs K Karekwaivanane Research Nurse Dr S Cudmore Data Analyst Mr G Piconi PhD Student Ms C Wardhaugh Research Assistant Ms K McGoohan Research Assistant Mr S Singh Research Assistant
SATURDAY, OCTOBER 05, 2019
Creutzfeldt-Jakob disease (CJD) biannual update (August 2019) Health Protection Report Volume 13 Number 28 9 August 2019
MONDAY, OCTOBER 22, 2018
26th ANNUAL REPORT 2017 CREUTZFELDT-JAKOB DISEASE SURVEILLANCE IN THE UK
SUNDAY, MARCH 10, 2019
National Prion Disease Pathology Surveillance Center Cases Examined¹ Updated Feb 1, 2019 Variably protease-sensitive prionopathy VPSPr
MONDAY, AUGUST 26, 2019
Creutzfeldt Jakob Disease CJD, TSE, Prion, Surveillance Update August 2019
SATURDAY, AUGUST 24, 2019
Creutzfeldt-Jakob disease surveillance in Australia: update to 31 December 2018
SATURDAY, SEPTEMBER 21, 2019
National Variability in Prion Disease–Related Safety Policies for Neurologic Procedures
Friday, September 27, 2019
Prion disease and recommended procedures for flexible endoscope reprocessing – a review of policies worldwide and proposal for a simplified approach
FRIDAY, SEPTEMBER 06, 2019
Disinfection of Multi-Use Ocular Equipment for Ophthalmological Procedures: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines
THURSDAY, SEPTEMBER 26, 2019
Veterinary Biologics Guideline 3.32E: Guideline for minimising the risk of introducing transmissible spongiform encephalopathy prions and other infectious agents through veterinary biologics
Wednesday, September 11, 2019
Is the re-use of sterilized implant abutments safe enough? (Implant abutment safety) iatrogenic TSE Prion
New Variant Creutzfeldt Jakob Disease nvCJD or what is call now variant Creutzfeldt Jakob Disease or vCJD
atypical and typical BSE and Scrapie Zoonosis
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.
==============
***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.
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
Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France
Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion... Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.
To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.
These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.
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.
***> why do we not want to do TSE transmission studies on chimpanzees $
5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man.
***> I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough.
***> Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.
snip...
R. BRADLEY
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.
***> 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. <***
Transmission of scrapie prions to primate after an extended silent incubation period
Emmanuel E. Comoy, Jacqueline Mikol, Sophie Luccantoni-Freire, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Valérie Durand, Capucine Dehen, Olivier Andreoletti, Cristina Casalone, Juergen A. Richt, Justin J. Greenlee, Thierry Baron, Sylvie L. Benestad, Paul Brown & Jean-Philippe Deslys Scientific Reports volume 5, Article number: 11573 (2015) | Download Citation
Abstract
Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans and having guided protective measures for animal and human health against animal prion diseases. Recently, partial transmissions to humanized mice showed that the zoonotic potential of scrapie might be similar to c-BSE. We here report the direct transmission of a natural classical scrapie isolate to cynomolgus macaque, a highly relevant model for human prion diseases, after a 10-year silent incubation period, with features similar to those reported for human cases of sporadic CJD. Scrapie is thus actually transmissible to primates with incubation periods compatible with their life expectancy, although fourfold longer than BSE. Long-term experimental transmission studies are necessary to better assess the zoonotic potential of other prion diseases with high prevalence, notably Chronic Wasting Disease of deer and elk and atypical/Nor98 scrapie.
SNIP...
Discussion We describe the transmission of spongiform encephalopathy in a non-human primate inoculated 10 years earlier with a strain of sheep c-scrapie. Because of this extended incubation period in a facility in which other prion diseases are under study, we are obliged to consider two alternative possibilities that might explain its occurrence. We first considered the possibility of a sporadic origin (like CJD in humans). Such an event is extremely improbable because the inoculated animal was 14 years old when the clinical signs appeared, i.e. about 40% through the expected natural lifetime of this species, compared to a peak age incidence of 60–65 years in human sporadic CJD, or about 80% through their expected lifetimes. 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.
The second possibility is a laboratory cross-contamination. Three facts make this possibility equally unlikely. First, handling of specimens in our laboratory is performed with fastidious attention to the avoidance of any such cross-contamination. Second, no laboratory cross-contamination has ever been documented in other primate laboratories, including the NIH, even between infected and uninfected animals housed in the same or adjacent cages with daily intimate contact (P. Brown, personal communication). Third, the cerebral lesion profile is different from all the other prion diseases we have studied in this model19, with a correlation between cerebellar lesions (massive spongiform change of Purkinje cells, intense PrPres staining and reactive gliosis26) and ataxia. The iron deposits present in the globus pallidus are a non specific finding that have been reported previously in neurodegenerative diseases and aging27. Conversely, the thalamic lesion was reminiscent of a metabolic disease due to thiamine deficiency28 but blood thiamine levels were within normal limits (data not shown). The preferential distribution of spongiform change in cortex associated with a limited distribution in the brainstem is reminiscent of the lesion profile in MM2c and VV1 sCJD patients29, but interspecies comparison of lesion profiles should be interpreted with caution. It is of note that the same classical scrapie isolate induced TSE in C57Bl/6 mice with similar incubation periods and lesional profiles as a sample derived from a MM1 sCJD patient30.
We are therefore confident that the illness in this cynomolgus macaque represents a true transmission of a sheep c-scrapie isolate directly to an old-world monkey, which taxonomically resides in the primate subdivision (parvorder of catarrhini) that includes humans. With an homology of its PrP protein with humans of 96.4%31, cynomolgus macaque constitutes a highly relevant model for assessing zoonotic risk of prion diseases. Since our initial aim was to show the absence of transmission of scrapie to macaques in the worst-case scenario, we obtained materials from a flock of naturally-infected sheep, affecting animals with different genotypes32. This c-scrapie isolate exhibited complete transmission in ARQ/ARQ sheep (332 ± 56 days) and Tg338 transgenic mice expressing ovine VRQ/VRQ prion protein (220 ± 5 days) (O. Andreoletti, personal communication). From the standpoint of zoonotic risk, it is important to note that sheep with c-scrapie (including the isolate used in our study) have demonstrable infectivity throughout their lymphoreticular system early in the incubation period of the disease (3 months-old for all the lymphoid organs, and as early as 2 months-old in gut-associated lymph nodes)33. In addition, scrapie infectivity has been identified in blood34, milk35 and skeletal muscle36 from asymptomatic but scrapie infected small ruminants which implies a potential dietary exposure for consumers.
Two earlier studies have reported the occurrence of clinical TSE in cynomolgus macaques after exposures to scrapie isolates. In the first study, the “Compton” scrapie isolate (derived from an English sheep) and serially propagated for 9 passages in goats did not transmit TSE in cynomolgus macaque, rhesus macaque or chimpanzee within 7 years following intracerebral challenge1; conversely, after 8 supplementary passages in conventional mice, this “Compton” isolate induced TSE in a cynomolgus macaque 5 years after intracerebral challenge, but rhesus macaques and chimpanzee remained asymptomatic 8.5 years post-exposure8. However, multiple successive passages that are classically used to select laboratory-adapted prion strains can significantly modify the initial properties of a scrapie isolate, thus questioning the relevance of zoonotic potential for the initial sheep-derived isolate. The same isolate had also induced disease into squirrel monkeys (new-world monkey)9. A second historical observation reported that a cynomolgus macaque developed TSE 6 years post-inoculation with brain homogenate from a scrapie-infected Suffolk ewe (derived from USA), whereas a rhesus macaque and a chimpanzee exposed to the same inoculum remained healthy 9 years post-exposure1. This inoculum also induced TSE in squirrel monkeys after 4 passages in mice. Other scrapie transmission attempts in macaque failed but had more shorter periods of observation in comparison to the current study. Further, it is possible that there are differences in the zoonotic potential of different scrapie strains.
The most striking observation in our study is the extended incubation period of scrapie in the macaque model, which has several implications. Firstly, our observations constitute experimental evidence in favor of the zoonotic potential of c-scrapie, at least for this isolate that has been extensively studied32,33,34,35,36. The cross-species zoonotic ability of this isolate should be confirmed by performing duplicate intracerebral exposures and assessing the transmissibility by the oral route (a successful transmission of prion strains through the intracerebral route may not necessarily indicate the potential for oral transmission37). However, such confirmatory experiments may require more than one decade, which is hardly compatible with current general management and support of scientific projects; thus this study should be rather considered as a case report.
Secondly, transmission of c-BSE to primates occurred within 8 years post exposure for the lowest doses able to transmit the disease (the survival period after inoculation is inversely proportional to the initial amount of infectious inoculum). The occurrence of scrapie 10 years after exposure to a high dose (25 mg) of scrapie-infected sheep brain suggests that the macaque has a higher species barrier for sheep c-scrapie than c-BSE, although it is notable that previous studies based on in vitro conversion of PrP suggested that BSE and scrapie prions would have a similar conversion potential for human PrP38.
Thirdly, prion diseases typically have longer incubation periods after oral exposure than after intracerebral inoculations: since humans can develop Kuru 47 years after oral exposure39, an incubation time of several decades after oral exposure to scrapie would therefore be expected, leading the disease to occur in older adults, i.e. the peak age for cases considered to be sporadic disease, and making a distinction between scrapie-associated and truly sporadic disease extremely difficult to appreciate.
Fourthly, epidemiologic evidence is necessary to confirm the zoonotic potential of an animal disease suggested by experimental studies. A relatively short incubation period and a peculiar epidemiological situation (e.g., all the first vCJD cases occurring in the country with the most important ongoing c-BSE epizootic) led to a high degree of suspicion that c-BSE was the cause of vCJD. Sporadic CJD are considered spontaneous diseases with an almost stable and constant worldwide prevalence (0.5–2 cases per million inhabitants per year), and previous epidemiological studies were unable to draw a link between sCJD and classical scrapie6,7,40,41, even though external causes were hypothesized to explain the occurrence of some sCJD clusters42,43,44. However, extended incubation periods exceeding several decades would impair the predictive values of epidemiological surveillance for prion diseases, already weakened by a limited prevalence of prion diseases and the multiplicity of isolates gathered under the phenotypes of “scrapie” and “sporadic CJD”.
Fifthly, considering this 10 year-long incubation period, together with both laboratory and epidemiological evidence of decade or longer intervals between infection and clinical onset of disease, no premature conclusions should be drawn from negative transmission studies in cynomolgus macaques with less than a decade of observation, as in the aforementioned historical transmission studies of scrapie to primates1,8,9. Our observations and those of others45,46 to date are unable to provide definitive evidence regarding the zoonotic potential of CWD, atypical/Nor98 scrapie or H-type BSE. The extended incubation period of the scrapie-affected macaque in the current study also underscores the limitations of rodent models expressing human PrP for assessing the zoonotic potential of some prion diseases since their lifespan remains limited to approximately two years21,47,48. This point is illustrated by the fact that the recently reported transmission of scrapie to humanized mice was not associated with clinical signs for up to 750 days and occurred in an extreme minority of mice with only a marginal increase in attack rate upon second passage13. The low attack rate in these studies is certainly linked to the limited lifespan of mice compared to the very long periods of observation necessary to demonstrate the development of scrapie. Alternatively, one could estimate that a successful second passage is the result of strain adaptation to the species barrier, thus poorly relevant of the real zoonotic potential of the original scrapie isolate of sheep origin49. The development of scrapie in this primate after an incubation period compatible with its lifespan complements the study conducted in transgenic (humanized) mice; taken together these studies suggest that some isolates of sheep scrapie can promote misfolding of the human prion protein and that scrapie can develop within the lifespan of some primate species.
In addition to previous studies on scrapie transmission to primate1,8,9 and the recently published study on transgenic humanized mice13, our results constitute new evidence for recommending that the potential risk of scrapie for human health should not be dismissed. Indeed, human PrP transgenic mice and primates are the most relevant models for investigating the human transmission barrier. To what extent such models are informative for measuring the zoonotic potential of an animal TSE under field exposure conditions is unknown. During the past decades, many protective measures have been successfully implemented to protect cattle from the spread of c-BSE, and some of these measures have been extended to sheep and goats to protect from scrapie according to the principle of precaution. Since cases of c-BSE have greatly reduced in number, those protective measures are currently being challenged and relaxed in the absence of other known zoonotic animal prion disease. We recommend that risk managers should be aware of the long term potential risk to human health of at least certain scrapie isolates, notably for lymphotropic strains like the classical scrapie strain used in the current study. Relatively high amounts of infectivity in peripheral lymphoid organs in animals infected with these strains could lead to contamination of food products produced for human consumption. Efforts should also be maintained to further assess the zoonotic potential of other animal prion strains in long-term studies, notably lymphotropic strains with high prevalence like CWD, which is spreading across North America, and atypical/Nor98 scrapie (Nor98)50 that was first detected in the past two decades and now represents approximately half of all reported cases of prion diseases in small ruminants worldwide, including territories previously considered as scrapie free... 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.
FRIDAY, OCTOBER 11, 2019
CattleTrace to Host First-Ever Industry Symposium
U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
Subject: BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001
Date: Tue, 9 Jan 2001 16:49:00 -0800
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
snip...
[host Richard Barns] and now a question from Terry S. Singeltary of CJD Watch.
[TSS] yes, thank you, U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?
[no answer, you could hear in the back ground, mumbling and 'we can't. have him ask the question again.]
[host Richard] could you repeat the question?
[TSS] U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?
[not sure whom ask this] what group are you with?
[TSS] CJD Watch, my Mom died from hvCJD and we are tracking CJD world-wide.
[not sure who is speaking] could you please disconnect Mr. Singeltary
[TSS] you are not going to answer my question?
[not sure whom speaking] NO
snip...see full archive and more of this;
THURSDAY, SEPTEMBER 26, 2019
Veterinary Biologics Guideline 3.32E: Guideline for minimising the risk of introducing transmissible spongiform encephalopathy prions and other infectious agents through veterinary biologics
Tuesday, September 10, 2019
FSIS [Docket No. FSIS–2019–0021] Notice of Request To Renew an Approved Information Collection: Specified Risk Materials Singeltary Submission
MONDAY, JUNE 24, 2019
APHIS, FSIS, USDA, FDA, Transmissible Spongiform Encephalopathy TSE, BSE, CWD, Scrapie, Camel TSE Prion Disease, CJD Humans
Chronic Wasting Disease In Cervids: Zoonosis there from, has it already happened, and is it being misdiagnosed as sporadic cjd?
> 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).***
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.
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.
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. <***
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.
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
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
see full Prion 2019 Conference Abstracts
THURSDAY, OCTOBER 04, 2018
Cervid to human prion transmission 5R01NS088604-04 Update
snip…full text;
SATURDAY, FEBRUARY 09, 2019
Experts: Yes, chronic wasting disease in deer is a public health issue — for people
FRIDAY, JULY 26, 2019
Chronic Wasting Disease in Cervids: Implications for Prion Transmission to Humans and Other Animal Species
THE FULL MONTY
***> MAD DOGS AND ENGLISHMEN BSE, SCRAPIE, CWD, CJD, TSE PRION A REVIEW 2019
BSE INQUIRY EVIDENCE
Why did the appearance of new TSEs in animals matter so much? It has always been known that TSEs will transfer across species boundaries. The reason for this was never known until the genetic nature of the prion gene was fully investigated and found to be involved. The gene is found to have well preserved sites and as such there is a similar gene throughout the animal kingdom...and indeed a similar gene is found in insects! It is NOT clear that the precise close nature of the PrP gene structure is essention for low species barriers. Indeed it is probably easier to infect cats with BSE than it is to infect sheep. As such it is not clear that simply because it is possible to infect BSE from cattle into certain monkeys then other apes will necessarily be infectable with the disease. One factor has stood out, however, and that is that BSE, when inoculated into mice would retain its apparent nature of disease strain, and hence when it was inoculated back into cattle, then the same disease was produced. Similarly if the TSE from kudu was inoculated into mice then a similar distribution of disease in the brain of the mouse is seen as if BSE had been inoculated into the mouse. This phenomenon was not true with scrapie, in which the transmission across a species barrier was known to lose many of the scrapie strain phenomena in terms of incubation period or disease histopathology. This also suggested that BSE was not derived from scrapie originally but we probably will never know.
------------------------------------------------------------------------
TSE in wild UK deer? The first case of BSE (as we now realise) was in a nyala in London zoo and the further zoo cases in ungulates were simply thought of as being interesting transmissions of scrapie initially. The big problem started to appear with animals in 1993-5 when it became clear that there was an increase in the CJD cases in people that had eaten deer although the statistics involved must have been questionable. The reason for this was that the CJD Surveillance was well funded to look into the diet of people dying of CJD. This effect is not clear with vCJD...if only because the numbers involved are much smaller and hence it is difficult to gain enough statistics. They found that many other foods did not appear to have much association at all but that deer certainly did and as years went by the association actually became clearer. The appearance of vCJD in 1996 made all this much more difficult in that it was suddenly clearer that the cases of sporadic CJD that they had been checking up until then probably had nothing to do with beef...and the study decreased. During the period there was an increasing worry that deer were involved with CJD..
see references:
DEER BRAIN SURVEY
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="" a="" fg_scanned="1" href="http://wt.net/" nbsp="" rel="noopener noreferrer" shape="rect" style="color: blue; cursor: pointer;" target="_blank">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 ===============
BSE Inquiry Steve Dealler
Management In Confidence
BSE: Private Submission of Bovine Brain Dealler
reports of sheep and calf carcasses dumped...
re-scrapie to cattle GAH Wells BSE Inquiry
https://web.archive.org/web/20090506043931/http://www.bseinquiry.gov.uk/files/yb/1993/12/09001001.pdf
https://web.archive.org/web/20090506065716/http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf
Dr. Dealler goes rogue to confirm BSE
Confirmation BSE Dealler's mad cow
BSE vertical transmission
1993 cjd report finds relationship with eat venison and cjd increases 9 fold, let the cover up begin...tss
FINDINGS
*** The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). ***
*** The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). ***
*** The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). ***
There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY OF LAMB EATING (p = 0.02)..
The evidence for such an association between beef eating and CJD is weaker (p = 0.14). When only controls for whom a relative was interviewed are included, this evidence becomes a little STRONGER (p = 0.08).
snip...
It was found that when veal was included in the model with another exposure, the association between veal and CJD remained statistically significant (p = < 0.05 for all exposures), while the other exposures ceased to be statistically significant (p = > 0.05).
snip...
In conclusion, an analysis of dietary histories revealed statistical associations between various meats/animal products and INCREASED RISK OF CJD. When some account was taken of possible confounding, the association between VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS STATISTICALLY. ...
snip...
In the study in the USA, a range of foodstuffs were associated with an increased risk of CJD, including liver consumption which was associated with an apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3 studies in relation to this particular dietary factor, the risk of liver consumption became non-significant with an odds ratio of 1.2 (PERSONAL COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS)
snip...see full report ;
GAME FARM INDUSTRY WANTS TO COVER UP FINDINGS OF INCREASE RISK TO CJD FROM CERVID
BSE INQUIRY
CJD9/10022
October 1994
Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane
BerksWell Coventry CV7 7BZ
Dear Mr Elmhirst,
CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT
Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published.
The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended.. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication.
The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department.
The statistical results reqarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme.
I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all.
The BSE Inquiry / Statement No 324
Dr James Kirkwood (not scheduled to give oral evidence)
Statement to the BSE Inquiry
James K Kirkwood BVSc PhD FIBiol MRCVS
[This witness has not been asked to give oral evidence in Phase 1 of the Inquiry]
1. I became involved in the field of TSEs through my work as Head of the Veterinary Science Group at the Zoological Society of London’s Institute of Zoology. I held this post from November 1984 until June 1996, when I took up my present post at UFAW. During this time, concurrent with the BSE epidemic, cases of scrapie-like spongiform encephalopathies occurred in animals at the Zoological Society of London’s collections at Regent’s Park and Whipsnade and in other zoos. It was appropriate to investigate the epidemiology of these cases in order to try to determine the possible impact on zoo animals and breeding programmes, and to consider how the disease in zoo animals might be controlled.
2. Throughout the period from 1985 to March 1996, I worked at the Institute of Zoology (IoZ). I was Head of the Veterinary Science Group of the IoZ and Senior Veterinary Officer of the Zoological Society of London (ZSL). I was responsible for the provision of the veterinary service for the ZSL collections.
3. During the period from 1985 to March 1996, scrapie-like spongiform encephalopathies were diagnosed in the following animals which died, or were euthanased, at London Zoo and Whipsnade:
Animal Sex Date of Death Age (mos)
Arabian Oryx Oryx leucoryx F 24.3.89 38
Greater kudu Tragelaphus strepsiceros (Linda) F 18.8.89 30
Greater kudu (Karla) F 13.11.90 19 Greater kudu (Kaz) M 6.6.91 37
Greater kudu (Bambi) M 24.10.91 36
Greater kudu (346/90) M 26.2.92 18
Greater kudu (324/90) F 22.11.92 38
Cheetah Acinonyx jubatus (Michelle) F 22.12.93 91
All these cases were described in papers published in the scientific literature (as cited below).
EYES, RETINA, SHOULD NOT BE USED IN SCHOOLS, BAB, SOB, MRM,
BSE, PET FOOD, CRUSHED HEADS
IN PARTICULAR CRUSHED HEADS
YOU explained that imported crushed heads were extensively used in the petfood industry...
In particular I do not believe one can say that the levels of the scrapie agent in pet food are so low that domestic animals are not exposed.
BSE IN PETFOOD
1. The Secretary asked on 19 April whether I was content with the advice in para 3 of the record of the meeting on 17 March with the Parliamentary Secretary (Mr Thompson). The simple answer is ''not entirely''.
2. On occasions, material obtained from slaughterhouses will be derived from sheep affected with scrapie or cattle that may be incubating BSE for use in petfood manufacture. Some of this material must be classified as high risk since it contains brain, spinal cord, spleen or lymphatic glands.
Meldrum's notes on pet foods and materials used
IN CONFIDENCE CJD TO CATS...
It should be noted that under experimental conditions cats succumb to an encephalopathy after intracerebral inoculation of material derived from patients affected with Creutzfeldt-Jakob Disease.
Confidential BSE and __________________
3. I have thought very hard about whether the Branch should carry out a similar exercise with meat and meat products for human foods. On balance I do NOT think we should undertake it, but a final decision has not been taken and you may wish to discuss this further. ...
1st case natural FSE
NATURAL SPONGIFORM ENCEPHALOPATHY IN A DOMESTIC CAT
1. We have heard from MAFF that a domestic Siamese cat from the Bristol area has had spongiform encephalopathy confirmed. Although there are previous instances of experimental infection in cats, there have been no previous natural infections reported. The assumption must be the cat became infected by scrapie/BSE agent in it's food. ...
FSE and pharmaceuticals
1. An analysis by MCA Professional staff of the results to the questionnaire sent out to industry to obtain additional data about the use of animal materials of any origin in the manufacture of pharmaceutical products for human use, reveals that material of feline or canine origin is used in only two licensed products. In both instances the material is sourced from outside the U.K. and from areas currently believed to be free from B.S.E.
CONFIDENTIAL
Confidential cats/dogs and unsatisfactory posture MAFFs failure to assure key research
3. First, I am very uneasy about the relative lack of urgency and interest that MAFF appear to hold for getting the necessary research programme on BSE and related encephalopathies started, and getting it going fast. FOR EXAMPLE, MR BRADLEY of CVL said that there were difficulties in organizing transmission experiments from the brain of the cat which died of an encephalopathy in Bristol. There were arguments going on about who should pay for this work. Should it be MAFF, the Bristol Veterinary School or someone else? Dr. Tyrrell was clearly exasperated.
snip...
11. The Committee were even LESS FORTHCOMING on what their reaction might be if an encephalopathy is found in another species, perhaps in DOGS. Their first reaction was that, as with the cats, the first step could be to investigate whether this was really a new disease, or simply one that had not previously been recognized and to see whether it has any links to BSE, scrapie or other transmissible encephalopathies. Indeed, some members of the Committee seem to regard the whole question of another species as a hypothetical question to be addressed only when it happened. A rather UNSATISFACTORY POSTURE.
12. In advance of your meeting with Dr Tyrrell on Monday morning, I have not voiced my ANXIETIES about the support the Committee is receiving from MAFF to anyone OTHER THAN DR PICKLES. ...
SPONGIFORM ENCEPHALOPATHY IN A CAPTIVE PUMA
an article in yesterday's Times (attached) which suggested that the puma concerned had never ''eaten any part of a cow or sheep which, in the opinion of Government Scientists, could transmit the species to a different species''.
3. You explained to me that this was INCORRECT. The position was as set out in the briefing for Prime Minister's questions attached to Mr Taylor's note. The puma had probably been fed low quality beef meat in the form of split carcasses. ...
Subject: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY Date: Thu, 17 Oct 2002 17:04:51 -0700 From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy To: BSE-L
Greetings BSE-L,
is there any other CWD surveys/testing in the UK on their deer? what sort of testing has been done to date on UK/EU deer? any input would be helpful... thank you
DEER SPONGIFORM ENCEPHALOPATHY SURVEY
3. This will be a low key study with no publicity to avoid unnecessary media interest. It will be carried out in two stages ;
(I) A small scale examination of around 30 deer brains to establish the normal histology of the healthy brain; and
(II) A larger scale random examination of 300 or more adult deer brains drawn from both deer farms and parks to establish whether there is any evidence of a cervine spongiform encephalopathy. ...
Ministry of Agriculture Fisheries and Food Veterinary Investigation Centre West House. Station Road. Thirsk Y07 IPZ Telephone: 0845·522065 Fax: 0845·525224
Your reference
Our reference RJH/ASB
Date 4 November 1992
DEER SPONGIFORM ENCEPHALOPATHY SURVEY
Dear Paul
I have now found time to review the 10 deer- brains collected from Mr Walker farm··via Winchester Via Winchester VIC. In answer to your specific question was there sufficient difference in preservation of brain tissue to warrant the extra effort involved in rapid brain removal on the farm, the answer is definitely "Yes." The original five brains (Winchester ref M487/11) showed varying degrees of autolytic vacuolation affecting both white and grey matter throughout the brain. vacuolation and separation of Purkinje cells and marked perivascular spaces. These artifacts made interpretation of subtle, specific pathological vacuolation more difficult. By contrast the second submission (Winchester reference N736/2) showed excellent preservation of white and grey matter. Any vacuolar Change present could be confidently interpreted as pathological albeit of unknown pathogenesis.
I can only reiterate the comments made by Gerald Wells and myself at the preliminary discussion at Weybridge in Autumn 1991. If the survey's purpose is an accurate histopathological interpretation of brain tissue. the material must be collected in a pristine state. This is particularly valid when looking for ar unrecognised and undefined spongiform encephalopathy in a new species. Deer brains are very large structures which take a lot of fixation and therefore must be handled sympathetically from the start. We have already seen the problems encountered in comparatively smaller hound brains where delayed fixation was a major limitation on interpretation of true pathological change.
The bottom line must be that if a pathologist's expertise is to be used, it is critical to collect artefact free brain material. If the politics or economics do not allow this, then I would suggest that an electron microscopy survey involving detection of scrapie associated fibrils would be much more appropriate.
Best wishes Yours sincerely
R J HIGGINS VIO 92/11.4/2.1
HOUND SURVEY
I am sorry, but I really could have been a co-signatory of Gerald's minute.
I do NOT think that we can justify devoting any resources to this study, especially as larger and more important projects such as the pathogenesis study will be quite demanding.
If there is a POLITICAL need to continue with the examination of hound brains then it should be passed entirely to the VI Service.
J W WILESMITH Epidemiology Unit 18 October 1991
Mr. R Bradley
cc: Mr. G A H Wells
***> 3.3. Mr R J Higgins in conjunction with Mr G A Wells and Mr A C Scott would by the end of the year, identify the three brains that were from the ''POSITIVE'' end of the lesion spectrum.
HOUND SURVEY PATHOLOGICAL REPORT (see positive results) and MAD DOGS AND ENGLISHMAN...
ya'll thought i was making this stuff up didn't ya...i don't make this stuff up!
It is clear that the designing scientists must also have shared Mr Bradley's surprise at the results because all the dose levels right down to 1 gram triggered infection.
second supplementary
Why did the appearance of new TSEs in animals matter so much? It has always been known that TSEs will transfer across species boundaries. The reason for this was never known until the genetic nature of the prion gene was fully investigated and found to be involved. The gene is found to have well preserved sites and as such there is a similar gene throughout the animal kingdom...and indeed a similar gene is found in insects! It is NOT clear that the precise close nature of the PrP gene structure is essention for low species barriers. Indeed it is probably easier to infect cats with BSE than it is to infect sheep. As such it is not clear that simply because it is possible to infect BSE from cattle into certain monkeys then other apes will necessarily be infectable with the disease. One factor has stood out, however, and that is that BSE, when inoculated into mice would retain its apparent nature of disease strain, and hence when it was inoculated back into cattle, then the same disease was produced. Similarly if the TSE from kudu was inoculated into mice then a similar distribution of disease in the brain of the mouse is seen as if BSE had been inoculated into the mouse. This phenomenon was not true with scrapie, in which the transmission across a species barrier was known to lose many of the scrapie strain phenomena in terms of incubation period or disease histopathology. This also suggested that BSE was not derived from scrapie originally but we probably will never know.
------------------------------------------------------------------------
TSE in wild UK deer? The first case of BSE (as we now realise) was in a nyala in London zoo and the further zoo cases in ungulates were simply thought of as being interesting transmissions of scrapie initially. The big problem started to appear with animals in 1993-5 when it became clear that there was an increase in the CJD cases in people that had eaten deer although the statistics involved must have been questionable. The reason for this was that the CJD Surveillance was well funded to look into the diet of people dying of CJD. This effect is not clear with vCJD...if only because the numbers involved are much smaller and hence it is difficult to gain enough statistics. They found that many other foods did not appear to have much association at all but that deer certainly did and as years went by the association actually became clearer. The appearance of vCJD in 1996 made all this much more difficult in that it was suddenly clearer that the cases of sporadic CJD that they had been checking up until then probably had nothing to do with beef...and the study decreased. During the period there was an increasing worry that deer were involved with CJD..
see references:
DEER BRAIN SURVEY
1993 cjd report finds relationship with eat venison and cjd increases 9 fold, let the cover up begin...tss
FINDINGS
*** The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). ***
There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY OF LAMB EATING (p = 0.02)..
The evidence for such an association between beef eating and CJD is weaker (p = 0.14). When only controls for whom a relative was interviewed are included, this evidence becomes a little STRONGER (p = 0.08).
snip...
It was found that when veal was included in the model with another exposure, the association between veal and CJD remained statistically significant (p = < 0.05 for all exposures), while the other exposures ceased to be statistically significant (p = > 0.05).
snip...
In conclusion, an analysis of dietary histories revealed statistical associations between various meats/animal products and INCREASED RISK OF CJD. When some account was taken of possible confounding, the association between VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS STATISTICALLY. ...
snip...
In the study in the USA, a range of foodstuffs were associated with an increased risk of CJD, including liver consumption which was associated with an apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3 studies in relation to this particular dietary factor, the risk of liver consumption became non-significant with an odds ratio of 1.2 (PERSONAL COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS)
snip...see full report ;
GAME FARM INDUSTRY WANTS TO COVER UP FINDINGS OF INCREASE RISK TO CJD FROM CERVID
BSE INQUIRY
CJD9/10022
October 1994
Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane
BerksWell Coventry CV7 7BZ
Dear Mr Elmhirst,
CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT
Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published.
The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended.. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication.
The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department.
The statistical results reqarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme.
I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all.
http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf
Management In Confidence
BSE: Private Submission of Bovine Brain Dealler
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="" a="" fg_scanned="1" href="http://wt.net/" nbsp="" rel="noopener noreferrer" shape="rect" style="color: blue; cursor: pointer;" target="_blank">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
Stephen Dealler is a consultant medical microbiologist deal@airtime.co.uk
===============
https://caninespongiformencephalopathy.blogspot.com/2010/03/canine-spongiform-encephalopathy-aka.html
*** DEFRA TO SINGELTARY ON HOUND STUDY AND BSE 2001 ***
DEFRA Department for Environment, Food & Rural Affairs Area 307, London, SW1P 4PQ Telephone: 0207 904 6000 Direct line: 0207 904 6287 E-mail: h.mcdonagh.defra.gsi.gov.uk GTN: FAX: Mr T S Singeltary P.O. Box Bacliff Texas USA 77518 21 November 2001
Dear Mr Singeltary
TSE IN HOUNDS Thank you for e-mail regarding the hounds survey. I am sorry for the long delay in responding. As you note, the hound survey remains unpublished. However the Spongiform Encephalopathy Advisory Committee (SEAC), the UK Government's independent Advisory Committee on all aspects related to BSE-like disease, gave the hound study detailed consideration at their meeting in January 1994. As a summary of this meeting published in the BSE inquiry noted, the Committee were clearly concerned about the work that had been carried out, concluding that there had clearly been problems with it, particularly the control on the histology, and that it was more or less inconclusive. However was agreed that there should be a re-evaluation of the pathological material in the study.
Later, at their meeting in June 95, The Committee re-evaluated the hound study to see if any useful results could be gained from it. The Chairman concluded that there were varying opinions within the Committee on further work. It did not suggest any further transmission studies and thought that the lack of clinical data was a major weakness.
Overall, it is clear that SEAC had major concerns about the survey as conducted. As a result it is likely that the authors felt that it would not stand up to peer review and hence it was never published. As noted above, and in the detailed minutes of the SEAC meeting in June 95, SEAC considered whether additional work should be performed to examine dogs for evidence of TSE infection. Although the Committee had mixed views about the merits of conducting further work, the Chairman noted that when the Southwood Committee made their recommendation to complete an assessment of possible spongiform disease in dogs, no TSEs had been identified in other species and hence dogs were perceived as a high risk population and worthy of study. However subsequent to the original recommendation, made in 1990, a number of other species had been identified with TSE ( e.g. cats) so a study in hounds was less critical.
For more details see- http://www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf
new url;
As this study remains unpublished, my understanding is that the ownership of the data essentially remains with the original researchers. Thus unfortunately, I am unable to help with your request to supply information on the hound survey directly. My only suggestion is that you contact one of the researchers originally involved in the project, such as Gerald Wells. He can be contacted at the following address. Dr Gerald Wells, Veterinary Laboratories Agency, New Haw, Addlestone, Surrey, KT 15 3NB, UK
You may also wish to be aware that since November 1994 all suspected cases of spongiform encephalopathy in animals and poultry were made notifiable. Hence since that date there has been a requirement for vets to report any su
===============
U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
Subject: BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001
Date: Tue, 9 Jan 2001 16:49:00 -0800
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
snip...
[host Richard Barns] and now a question from Terry S. Singeltary of CJD Watch.
[TSS] yes, thank you, U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?
[no answer, you could hear in the back ground, mumbling and 'we can't. have him ask the question again.]
[host Richard] could you repeat the question?
[TSS] U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?
[not sure whom ask this] what group are you with?
[TSS] CJD Watch, my Mom died from hvCJD and we are tracking CJD world-wide.
[not sure who is speaking] could you please disconnect Mr. Singeltary
[TSS] you are not going to answer my question?
[not sure whom speaking] NO
snip...see full archive and more of this;
===============
THURSDAY, SEPTEMBER 26, 2019
Veterinary Biologics Guideline 3.32E: Guideline for minimising the risk of introducing transmissible spongiform encephalopathy prions and other infectious agents through veterinary biologics
MONDAY, FEBRUARY 25, 2019
MAD DOGS AND ENGLISHMEN BSE, SCRAPIE, CWD, CJD, TSE PRION A REVIEW 2019
SATURDAY, FEBRUARY 23, 2019
Chronic Wasting Disease CWD TSE Prion and THE FEAST 2003 CDC an updated review of the science 2019
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. "
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....
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.
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.
*** 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 (216-119-163-189.ipset45.wt.net)
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
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 ;
> 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 $$$ ***
*** 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).***
MONDAY, FEBRUARY 25, 2019
MAD DOGS AND ENGLISHMEN BSE, SCRAPIE, CWD, CJD, TSE PRION A REVIEW 2019
FRIDAY, OCTOBER 25, 2019
Experts testify United States is underprepared for bioterrorism threats Transmissible Spongiform Encephalopathy TSE Prion disease
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.
doi:10.1016/S1473-3099(03)00715-1 Copyright © 2003 Published by Elsevier Ltd. Newsdesk
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..” ...
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.
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?
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.
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
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
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
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 hvCJD in the USA * BSE in U.S.
Terry S. Singeltary Sr.
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply
IBNC BSE TSE Prion mad cow disease
***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 Terry S. Singeltary Sr. on 03 Jul 2015 at 16:53 GMT
*** 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
TUESDAY, JANUARY 1, 2019
CHILDHOOD EXPOSURE TO CADAVERIC DURA https://betaamyloidcjd.blogspot.com/2019/01/childhood-exposure-to-cadaveric-dura.html
SUNDAY, OCTOBER 21, 2018
Surveillance for variant CJD: should more children with neurodegenerative diseases have autopsies? Singeltary Review
FRIDAY, DECEMBER 14, 2018
Transmission of amyloid-β protein pathology from cadaveric pituitary growth hormone December 14, 2018
Tuesday, December 12, 2017
Neuropathology of iatrogenic Creutzfeldt–Jakob disease and immunoassay of French cadaver-sourced growth hormone batches suggest possible transmission of tauopathy and long incubation periods for the transmission of Abeta pathology
SUNDAY, MAY 26, 2019
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''
Friday, January 10, 2014
vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???
Re-Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy
>>> 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
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
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.]
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)
1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8
***> Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery.
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.
Laboratory of Central Nervous System Studies, National Institute of
Neurological Disorders and Stroke, National Institutes of Health,
Bethesda, MD 20892.
Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.
PMID: 8006664 [PubMed - indexed for MEDLINE]
SUNDAY, AUGUST 09, 2009
CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009
TUESDAY, AUGUST 18, 2009
BSE-The Untold Story - joe gibbs and singeltary 1999 - 2009
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. at
3:13 PM
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