CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE U.K. 23rd ANNUAL REPORT
2014
23rd Annual Report 2014
(published 18th November 2015)
SUMMARY
The national surveillance programme for Creutzfeldt-Jakob disease (CJD) in
the UK was initiated in May 1990. In 1999, the National CJD Research &
Surveillance Unit (NCJDRSU) became a WHO Collaborative Centre for Reference and
Research on the surveillance and epidemiology of human transmissible spongiform
encephalopathies (TSEs). In September 2001, the National Care Team was formed in
response to concerns regarding the care of CJD patients. The team currently
comprises two care coordinators (who are senior nurses) with secretarial and
clinical neurological support from within the NCJDRSU where it is based.
The information provided in this 23rd Annual Report continues to indicate
that the annual mortality rates for sporadic CJD (sCJD) has remained around
1.4/million since 2008 (the data for 2014 may still be incomplete). Detailed
clinical and epidemiological information has been obtained for the great
majority of patients. Although the general autopsy rate in the UK is low, it
remains relatively high in suspected cases of CJD (being around 60% of all
referred cases to the NCJDRSU). The number of brain specimens examined for sCJD
in the neuropathology laboratory in 2014 was 30 (compared with 32 in
2013).
In 1990-2014 average annual mortality rates from sCJD in England, Wales,
Scotland and Northern Ireland were, respectively, 1.07, 1.33, 1.11 and
0.83/million/year. The differences between these rates are not statistically
significant (p=0.5). The mortality rates from sCJD in the UK are comparable to
those observed in most other European countries and elsewhere in the world,
including countries that are free of BSE.
Up to 31st December 2014, 177 cases of definite or probable variant CJD
(vCJD) had been identified in the UK (122 definite and 55 probable who did not
undergo post mortem). All 177 cases have died. The clinical, neuropathological
and epidemiological features of the cases of vCJD are remarkably uniform and
consistent with previous descriptions. Risk factors for the development of vCJD
include age, residence in the UK and methionine homozygosity at codon 129 of the
prion protein gene - all 160 clinically affected definite and probable cases of
vCJD with available genetic analysis have been methionine homozygotes. Analysis
of vCJD diagnoses and deaths from January 1994 to December 2011 indicates that a
peak has passed. While this is an encouraging finding, the incidence of vCJD may
increase again, particularly if different genetic subgroups with longer
incubation periods exist. The identification of an individual of the PRNP-129 MV
genotype as a possible case of vCJD (reported in the NCJDRSU 17th Annual Report,
2008) and, in a separate case, disease-related prion protein in the spleen of a
clinically unaffected blood recipient (reported in 2004) is consistent with such
a hypothesis. These cases, along with the report of the prevalence of abnormal
prion protein in the large study of appendix and tonsil tissues (two of the
positive specimens from VV individuals) suggests the possibility of a greater
number of asymptomatic infections (either preclinical or subclinical) in the
population than might be indicated by the present numbers of confirmed clinical
cases. Section
1 T 23rd Annual Report 2014 4
To help prevent any possible spread of CJD between people, we continue to
ask clinicians to refer all new suspect CJD cases to their local infection
control and health protection teams. This is important as a local response may
be required with respect to limiting potential secondary transmission, infection
control and other issues that may arise over time concerning the protection of
the wider community. The NCJDRSU continues to assist local health protection
teams in local audit and investigations of cases in response to local
concerns.
The NCJDRSU continues to collaborate with health departments and public
health teams throughout the UK in relation to a range of activities, for
example, in relation to the follow up of those identified as at increased risk
of CJD. The activities of the NCJDRSU are strengthened by collaboration with
other surveillance projects, including the Transfusion Medicine Epidemiology
Review and the study of Progressive Intellectual and Neurological Deterioration
in Children. The collaboration of our colleagues in these projects is greatly
appreciated; the effectiveness of this collaboration allowed the identification
in 2003 of a case of vCJD associated with blood transfusion and the
identification in 2004 of disease-related PrP in the spleen of a recipient of
blood donated by someone incubating vCJD. A patient was also identified in 2010
who had evidence of vCJD infection in the spleen (but no evidence of clinical
vCJD), considered probably due to blood products (treatment for
haemophilia).
The relatively recently described form of prion disease originally termed
Protease Sensitive Prionopathy and renamed Variably Protease Sensitive
Prionopathy, is of uncertain nosological significance but is presently
considered a form of sporadic prion disease, alongside sCJD. The NCJDRSU has so
far identified at total of 9 such cases in the UK and is continuing to monitor
this form of disease.
The data concerning CSF RT-QuIC are given in Section 3.5; the sensitivity
of CSF RT-QuIC for a diagnosis of sCJD is comparable with that of CSF 14-3-3.
The specificity is superior to that of CSF 14-3-3 with no positives in cases
with a confirmed alternate diagnosis.
The success of the National CJD Research & Surveillance Unit continues
to depend on the extraordinary level of co-operation from the neurology and
neuropathology communities and other medical and paramedical staff throughout
the UK. Ongoing support is provided by the Infectious Disease Epidemiology Unit,
London School of Hygiene and Tropical Medicine. We are also particularly
grateful to the relatives of patients for their collaboration.
snip...
Up to 31st December 2014, 177 cases of definite or probable variant CJD
(vCJD) had been identified in the UK (122 definite and 55 probable who did not
undergo post mortem). All 177 cases have died. The clinical, neuropathological
and epidemiological features of the cases of vCJD are remarkably uniform and
consistent with previous descriptions. Risk factors for the development of vCJD
include age, residence in the UK and methionine homozygosity at codon 129 of the
prion protein gene - all 160 clinically affected definite and probable cases of
vCJD with available genetic analysis have been methionine homozygotes. Analysis
of vCJD diagnoses and deaths from January 1994 to December 2011 indicates that a
peak has passed. While this is an encouraging finding, the incidence of vCJD may
increase again, particularly if different genetic subgroups with longer
incubation periods exist. The identification of an individual of the PRNP-129 MV
genotype as a possible case of vCJD (reported in the NCJDRSU 17th Annual Report,
2008) and, in a separate case, disease-related prion protein in the spleen of a
clinically unaffected blood recipient (reported in 2004) is consistent with such
a hypothesis. These cases, along with the report of the prevalence of abnormal
prion protein in the large study of appendix and tonsil tissues (two of the
positive specimens from VV individuals) suggests the possibility of a greater
number of asymptomatic infections (either preclinical or subclinical) in the
population than might be indicated by the present numbers of confirmed clinical
cases.
To help prevent any possible spread of CJD between people, we continue to
ask clinicians to refer all new suspect CJD cases to their local infection
control and health protection teams. This is important as a local response may
be required with respect to limiting potential secondary transmission, infection
control and other issues that may arise over time concerning the protection of
the wider community. The NCJDRSU continues to assist local health protection
teams in local audit and investigations of cases in response to local
concerns.
The NCJDRSU continues to collaborate with health departments and public
health teams throughout the UK in relation to a range of activities, for
example, in relation to the follow up of those identified as at increased risk
of CJD. The activities of the NCJDRSU are strengthened by collaboration with
other surveillance projects, including the Transfusion Medicine Epidemiology
Review and the study of Progressive Intellectual and Neurological Deterioration
in Children. The collaboration of our colleagues in these projects is greatly
appreciated; the effectiveness of this collaboration allowed the identification
in 2003 of a case of vCJD associated with blood transfusion and the
identification in 2004 of disease-related PrP in the spleen of a recipient of
blood donated by someone incubating vCJD. A patient was also identified in 2010
who had evidence of vCJD infection in the spleen (but no evidence of clinical
vCJD), considered probably due to blood products (treatment for
haemophilia).
The relatively recently described form of prion disease originally termed
Protease Sensitive Prionopathy and renamed Variably Protease Sensitive
Prionopathy, is of uncertain nosological significance but is presently
considered a form of sporadic prion disease, alongside sCJD. The NCJDRSU has so
far identified at total of 9 such cases in the UK and is continuing to monitor
this form of disease. The data concerning CSF RT-QuIC are given in Section 3.5;
the sensitivity of CSF RT-QuIC for a diagnosis of sCJD is comparable with that
of CSF 14-3-3. The specificity is superior to that of CSF 14-3-3 with no
positives in cases with a confirmed alternate diagnosis.
The success of the National CJD Research & Surveillance Unit continues
to depend on the extraordinary level of co-operation from the neurology and
neuropathology communities and other medical and paramedical staff throughout
the UK. Ongoing support is provided by the Infectious Disease Epidemiology Unit,
London School of Hygiene and Tropical Medicine. We are also particularly
grateful to the relatives of patients for their collaboration.
2.2 Sporadic Creutzfeldt-Jakob Disease
Between 1st January 1970 and 31st December 2014, 2012 cases of sCJD were
identified in the UK, of which 24 cases were alive on 31st December 2014 and one
case moved abroad after diagnosis and is therefore lost to follow-up. Of these
UK cases, 1425 (71%) were classified as definite cases with the remainder
classed as probable. Seven further cases have been identified: 3 in Jersey, 2 in
the Isle of Man and 2 cases who were repatriated to the UK when they became ill
but had been living abroad. These 7 cases are not included in the following UK
analyses.
Figure 2 shows the annual mortality rates from sCJD for the UK between 1985
and 2014. The number of deaths identified each year has increased over time. A
similar phenomenon has been observed in other European countries, and may
reflect improved case ascertainment, particularly in those aged over 70 years.
Figure 3 shows average annual age-specific mortality rates over the time
periods 1970-1984, 1985-1994, 1995-2004 and 2005-2014. These data also emphasise
the very small numbers of cases of sCJD occurring in individuals aged <50 0.02="" 40="" 50.="" 50="" 63="" 65-79="" 66="" 67="" 69="" age-specific="" age="" ages="" all="" an="" and="" are="" ascertainment="" at="" be="" below="" between="" but="" by="" case="" cases="" comparison="" consistent="" death="" decline="" declined.="" different="" div="" during="" elderly.="" explained="" extremely="" four="" greatest="" groups="" improved="" in="" increase="" increased="" indicate="" low="" median="" might="" million="" mortality="" most="" observations="" occurring="" of="" over="" periods="" rates="" recorded="" respectively.="" the="" then="" thereafter="" these="" this="" time="" to="" under-ascertainment="" up="" were="" with="" year="" years.="" years="">
snip...
2.3 Variant Creutzfeldt-Jakob Disease
Up to 31st December 2014, 177 cases of definite or probable vCJD had been
identified in the UK (122 definite and 55 probable cases who did not undergo
post mortem; no cases still alive). Seventy-five (43%) of the 176 cases were
female and 102 (58%) were male. The median age at onset of disease was 26 years
and the median age at death 28 years (compared with 67 years for the median age
at onset and 68 years for the median age at death for sCJD). The youngest case
was aged 12 years at onset while the oldest case was aged 74 years. The age- and
sex-specific mortality rates for vCJD over the time period 1 May 1995 to 31
December 2014 are shown in Figure 5. The median duration of illness from the
onset of first symptoms to death was 14 months (range 6-114) compared with a
median duration of illness for cases of sCJD of 4 months (range 1 to 74) during
the period 1990-2014.
www.cjd.ed.ac.uk/documents/report17.pdf). To date, no case of vCJD has
been identified in the UK in individuals born after 1989.
Deaths from variant CJD
Results from modelling the incidence of vCJD deaths indicate the epidemic
peaked in about the year 2000 when there were 28 deaths and has since declined1.
The last case of vCJD in the UK was
1 Analysis undertaken by N J Andrews, Senior Statistician, Statistics Unit,
Centre for Infections, Health Protection Agency. Further detail is available at
http://www.cjd.ed.ac.uk/cjdq72b.pdf
diagnosed in 2013 and died the same year; no cases have been reported
subsequently. Data were last reviewed in 2012 and further details are given in
the full report which is available at
www.cjd.ed.ac.uk/documents/cjdq72.pdf
It is important to note that although a peak has been passed, it is
possible that there will be future peaks, possibly in other genetic subgroups.
To date, however, there is no evidence of a second wave. There is also the
possibility of ongoing person to person spread as seen with 4 cases of
transfusion association vCJD infection to date, who received blood in 1999 or
earlier from donors who were later diagnosed with clinical vCJD.
Geographical distribution of variant CJD
Tables 2a and 2b present data on the geographical distribution by residence
at onset (for all 177 vCJD cases) and residence at death (for 174 vCJD cases who
had died by 31st December 2014 and were resident in the UK at death), along with
the crude mortality rate per million population per annum of each standard
region.
snip...
Cases have been widely spread throughout the UK. Age- and sex- standardised
incidence ratios (SIRs) based on cases' place of residence in 1991 (shortly
after the time when exposure to the BSE agent is assumed to have peaked) are
shown in Figure 6. There remains a relatively high incidence amongst those who
lived in the north (Scotland, North East, North West, Yorkshire &
Humberside; 16.9 million people, 74 vCJD cases) compared to the south (Wales,
East Midlands, West Midlands, South West, South East, London, East of England;
31.7 million people, 99 vCJD cases) of Great Britain in 1991.2 The rate ratio
controlling for age and sex is 1.41 (95% CI 1.04-1.90), ie individuals living in
the “North” in 1991 are about one and a half times more likely to have developed
vCJD than individuals who were living in the “South” in 1991.
Investigations into geographically associated cases of vCJD (either through
proximity of residence or through an occupational, educational or
social/recreational link with the same location) have found no convincing
evidence of factors that may have augmented local risks for vCJD3. Figure 6
Standardised variant CJD incidence ratios (SIRs) up to 31st December 2014, by
region of residence on 1st January 1991
snip...
2.4 Iatrogenic Creutzfeldt-Jakob disease
Since 1970, up to 31st December 2014, 84 cases of CJD attributable to
iatrogenic exposure have been identified, 8 in individuals receiving dura mater
implants, 75 in individuals who had received human-derived growth hormone (hGH)
and one in a recipient of human gonadotrophin (hGN) who was treated in
Australia. All these individuals have died (Figure 7). The mean age at death of
the hGH/hGN group was 35 years (with a range of 20-51 years) and for the dura
mater cases 46½ years (range 27-78 years).
Figure 7 Deaths from iatrogenic CJD, 1979-2014
The first identified iatrogenic case was a dura mater recipient who died in
1979. The first hGH-related death occurred in 1985. Since 1985 in the UK, human
pituitary-derived hormones have been replaced by synthetic preparations. Details
of the UK human pituitary-derived hormone cases, with a discussion of the
incubation periods, were published in 2003.4 A study of the accumulated UK
experience with dura mater-related CJD, including incubation periods, was
undertaken and the results published in 2006.5
Iatrogenic transmission of CJD/vCJD is also studied by the Unit through the
identification and investigation of surgical or other links between cases. The
Unit continues to collect risk factor information for all suspect cases of human
prion diseases referred to the Unit as part of its core work. 2.5 Transfusion
Medicine Epidemiology Review
The Transfusion Medicine Epidemiology Review (TMER) is a collaborative
project between the UK NCJDRSU and UK Blood Services (UKBS). The main purpose is
to investigate whether there is any evidence that CJD or vCJD may have been
transmitted via the blood supply. Cases (definite and probable) are notified to
the UKBS by NCJDRSU; a search establishes whether any have acted as donors or
received blood transfusions. Donation/transfusion records are checked and all
components traced through hospital records. Details of all identified
recipients/donors are forwarded to NCJDRSU for subsequent checking to ensure
none appear on the NCJDRSU database as a case of CJD. Further details are given
in the 19th Annual Report (www.cjd.ed.ac.uk/documents/report19.pdf)
4 Swerdlow AJ, Higgins CD, Adlard P, Jones ME, Preece MA. Creutzfeldt-Jakob
disease in United Kingdom patients treated with human pituitary growth hormone.
Neurology 2003; 61: 783-91.
5 Heath CA, Barker RA, Esmonde TFG, Harvey P, Trend P, Head MW, Smith C,
Bell JE, Ironside JW, Will RG, Knight RSG. Dura mater-associated
Creutzfeldt-Jakob disease: experience from surveillance in the UK. JNNP 2006;
77: 880-2.
snip...
2.6 Study of Progressive Intellectual & Neurological Deterioration
(PIND)
The aim of this project is to use the mechanism of the British Paediatric
Surveillance Unit to identify all cases of progressive intellectual and
neurological deterioration in children in the UK, particularly those with
features suggestive of vCJD. All cases are discussed by an Expert Neurological
Advisory Group comprising nine paediatric neurologists, one geneticist and a
representative from the National CJD Research & Surveillance Unit, which
allocates the cases to a diagnostic category10-11. As of 31st December 2014,
after nearly 18 years of surveillance, 3785 patients with suspected PIND had
been reported and the Expert Group had discussed 2491 of these. 1580 cases had a
confirmed underlying cause other than vCJD, being categorised into over 190
known neurodegenerative diseases3. There have been six cases of vCJD; four
definite and two probable. Three were reported in 1999, one in 2000 and 2 in
mid-2001. One girl was aged 12 at onset - the youngest UK case of vCJD
identified to date.
(Collaborators on this project: Dr C Verity, Prof A Nicoll, Ms L
Stellitano, Ms AM Winstone)
6 Llewelyn CA, Hewitt PA, Knight RSG, Amar K, Cousens S, Mackenzie J, Will
RG. Possible transmission of variant Creutzfeldt-Jakob disease by blood
transfusion. Lancet 2004; 363: 417-421.
7 Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW. Preclinical vCJD
after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 2004
364: 527-529.
8 Wroe SJ, Pal S, Siddique D, Hyare H, Macfarlane R, Joiner S, Linehan JM,
Brandner S, Wadsworth JD, Hewitt P, Collinge J. Clinical presentation and
pre-mortem diagnosis of variant Creutzfeldt-Jakob disease associated with blood
transfusion: a case report. Lancet 2006; 368: 2061-2067.
9 Health Protection Agency. Fourth case of transfusion-associated
variant-CJD. Health Protection Report 2007;1(3):
10 Verity CM, Nicoll A, Will RG, Devereux G, Stellitano L. Variant
Creutzfeldt-Jakob disease in UK children: a national surveillance study. Lancet
2000; 356: 1224-1227.
11 Devereux G, Stellitano L, Verity CM, Nicoll A, Will RG, Rogers P.
Variations in neurodegenerative disease across the UK: findings from the
national study of Progressive Intellectual and Neurological Deterioration
(PIND). Arch Dis Child 2004; 89: 8-12.
snip...
2.7 Surveillance of potential occupational exposure to CJD
Public Health England in collaboration with NCJDRSU have set up an
occupational surveillance study with two parts: 1) a registry for the
prospective long term monitoring of healthcare and laboratory workers who have
incurred occupational exposures to prion diseases and 2) the retrospective
review of possible occupational exposures of CJD cases who have been healthcare
or laboratory workers.
By the end of 2014, 2 healthcare workers and one laboratory worker had
reported prion-disease exposures as a result of needle stick/sharps injuries.
None have subsequently developed prion disease. Retrospective investigations of
possible occupational exposures of CJD cases continues to be undertaken to
determine if any exposure to prion disease occurred.12
(Collaborators on this project: K Sinka, J Thorpe)
2.8 Enhanced surveillance of individuals identified as at increased risk of
CJD
The potential for secondary transmission of CJD has led to collaborative
studies with the UK Haemophilia Centre Doctors Organisation, Institute of Child
Health (London), NHS Blood and Transplant, National Prion Clinic, Public Health
England, Health Protection Scotland aimed at identifying whether there is
evidence of clinical or sub-clinical infection in those judged to be at
increased risk of CJD, such evidence is investigated through review of clinical
records and medical histories, and through post-mortem investigations.
As at 31st December 2014, three cases of vCJD and one asymptomatic
infection had been identified in recipients of blood from donors who later
developed vCJD (see section 2.5 TMER) and one asymptomatic infection in a
bleeding-disorder patient who received UK sourced plasma products.13
(Collaborators on this project: P Adlard, O Blatchford, H Ward, C Creasey,
L Dewhurst, N Gill, C Hay, P Hewitt, M Makris, S Mead, P Minor, B Palmer, A
Rankin, K Sinka)
12 Thorpe J, Mackenzie J, Molesworth A, Sinka K, Will R. Occupational
exposures to prion diseases in healthcare and laboratory workers. Poster
presentation at Prion 2012, 9-12 May, Amsterdam.
13 Peden A, McCardle L, Head MW, Love S, Ward HJT, Cousens SN, Keeling DM,
Millar CM, Hill FGH, Ironside JW. Variant CJD infection in the spleen of a
neurologically asymptomatic UK adult patient with haemophilia. Haemophilia 2010;
16: 296-304.
snip...
3.4 Molecular Genetics
Genetic CJD
One hundred and forty-five cases of genetic CJD (excluding cases of GSS)
have been identified since 1970 by the NCJDRSU (these data are incomplete as
formal investigation of genetic CJD in the UK is undertaken by the National
Prion Clinic in London). Of the 145 cases, 128 were resident in England, 9 were
resident in Wales, 3 were resident in Northern Ireland and 5 were resident in
Scotland. Twenty-two cases were still alive as at 31st December 2014. Sixty-five
of the cases had insertions in the coding region of the PrP gene, 44 carried the
mutation at codon E200K, 15 at codon D178N, 4 at codon V210I, one at codon
D167G, 2 at codon V163STOP, one at codon G54S, one at codon E211Q and one at
codon E196K. The remaining 11 were identified as familial on the basis of
relatives known to have had CJD. The mean age at death was 55½ years (range
29-95 years).
PRNP Codon 129 distribution in sporadic CJD
The distribution of PRNP codon 129 genotypes in sCJD has been analysed
since the inception of the Unit in 1990. The overall distribution of PRNP codon
129 genotypes in sCJD is 62% MM, 19% MV, 19% VV (see Table 6). There appears to
be evidence (p=0.003) of a change in the PRNP codon 129 distribution in sCJD
between the periods 1990-1995 and 1996-2014. The explanation for this remains
unclear. It should be noted that not all cases are genotyped (data available on
62%) and, therefore, changes in PRNP codon 129 distribution may reflect changes
in the way in which cases are selected for analysis.
Table 6 PRNP codon 129 genotypes of cases of sporadic CJD in the UK,
1990-2014
snip...
see full report ;
O.05: Transmission of prions to primates after extended silent incubation
periods: Implications for BSE and scrapie risk assessment in human populations
Emmanuel Comoy, Jacqueline Mikol, Val erie Durand, Sophie Luccantoni,
Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys
Atomic Energy Commission; Fontenay-aux-Roses, France
Prion diseases (PD) are the unique neurodegenerative proteinopathies
reputed to be transmissible under field conditions since decades. The
transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that
an animal PD might be zoonotic under appropriate conditions. Contrarily, in the
absence of obvious (epidemiological or experimental) elements supporting a
transmission or genetic predispositions, PD, like the other proteinopathies, are
reputed to occur spontaneously (atpical animal prion strains, sporadic CJD
summing 80% of human prion cases). Non-human primate models provided the first
evidences supporting the transmissibiity of human prion strains and the zoonotic
potential of BSE. Among them, cynomolgus macaques brought major information for
BSE risk assessment for human health (Chen, 2014), according to their
phylogenetic proximity to humans and extended lifetime. We used this model to
assess the zoonotic potential of other animal PD from bovine, ovine and cervid
origins even after very long silent incubation periods.
*** We recently observed the direct transmission of a natural classical
scrapie isolate to macaque after a 10-year silent incubation period,
***with features similar to some reported for human cases of sporadic CJD,
albeit requiring fourfold longe incubation than BSE. Scrapie, as recently evoked
in humanized mice (Cassard, 2014),
***is the third potentially zoonotic PD (with BSE and L-type BSE),
***thus questioning the origin of human sporadic cases.
We will present an updated panorama of our different transmission studies
and discuss the implications of such extended incubation periods on risk
assessment of animal PD for human health.
===============
***thus questioning the origin of human sporadic cases...TSS
===============
==========================================
***our findings suggest that possible transmission risk of H-type BSE to
sheep and human. Bioassay will be required to determine whether the PMCA
products are infectious to these animals.
==========================================
PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS
*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***
O18
Zoonotic Potential of CWD Prions
Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1,
Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western Reserve
University, Cleveland, Ohio, USA, 2Second University of Naples, Naples, Italy,
3Encore Health Resources, Houston, Texas, USA
*** These results indicate that the CWD prion has the potential to infect
human CNS and peripheral lymphoid tissues and that there might be asymptomatic
human carriers of CWD infection.
==================
***These results indicate that the CWD prion has the potential to infect
human CNS and peripheral lymphoid tissues and that there might be asymptomatic
human carriers of CWD infection.***
==================
P.105: RT-QuIC models trans-species prion transmission
Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward Hoover
Prion Research Center; Colorado State University; Fort Collins, CO USA
Conversely, FSE maintained sufficient BSE characteristics to more
efficiently convert bovine rPrP than feline rPrP. Additionally, human rPrP was
competent for conversion by CWD and fCWD.
***This insinuates that, at the level of protein:protein interactions, the
barrier preventing transmission of CWD to humans is less robust than previously
estimated.
================
***This insinuates that, at the level of protein:protein interactions, the
barrier preventing transmission of CWD to humans is less robust than previously
estimated.***
================
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Title: Transmission of scrapie prions to primate after an extended silent
incubation period
Authors
item Comoy, Emmanuel - item Mikol, Jacqueline - item Luccantoni-Freire,
Sophie - item Correia, Evelyne - item Lescoutra-Etchegaray, Nathalie - item
Durand, Valérie - item Dehen, Capucine - item Andreoletti, Olivier - item
Casalone, Cristina - item Richt, Juergen item Greenlee, Justin item Baron,
Thierry - item Benestad, Sylvie - item Hills, Bob - item Brown, Paul - item
Deslys, Jean-Philippe -
Submitted to: Scientific Reports Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 28, 2015 Publication Date: June 30, 2015
Citation: Comoy, E.E., Mikol, J., Luccantoni-Freire, S., Correia, E.,
Lescoutra-Etchegaray, N., Durand, V., Dehen, C., Andreoletti, O., Casalone, C.,
Richt, J.A., Greenlee, J.J., Baron, T., Benestad, S., Brown, P., Deslys, J.
2015. Transmission of scrapie prions to primate after an extended silent
incubation period. Scientific Reports. 5:11573.
Interpretive Summary:
The transmissible spongiform encephalopathies (also called prion diseases)
are fatal neurodegenerative diseases that affect animals and humans. The agent
of prion diseases is a misfolded form of the prion protein that is resistant to
breakdown by the host cells. Since all mammals express prion protein on the
surface of various cells such as neurons, all mammals are, in theory, capable of
replicating prion diseases. One example of a prion disease, bovine spongiform
encephalopathy (BSE; also called mad cow disease), has been shown to infect
cattle, sheep, exotic undulates, cats, non-human primates, and humans when the
new host is exposed to feeds or foods contaminated with the disease agent. The
purpose of this study was to test whether non-human primates (cynomologous
macaque) are susceptible to the agent of sheep scrapie. After an incubation
period of approximately 10 years a macaque developed progressive clinical signs
suggestive of neurologic disease. Upon postmortem examination and microscopic
examination of tissues, there was a widespread distribution of lesions
consistent with a transmissible spongiform encephalopathy. This information will
have a scientific impact since it is the first study that demonstrates the
transmission of scrapie to a non-human primate with a close genetic relationship
to humans. This information is especially useful to regulatory officials and
those involved with risk assessment of the potential transmission of animal
prion diseases to humans.
Technical Abstract:
Classical bovine spongiform encephalopathy (c-BSE) is an animal prion
disease that also causes variant Creutzfeldt-Jakob disease in humans. Over the
past decades, c-BSE's zoonotic potential has been the driving force in
establishing extensive protective measures for animal and human health. In
complement to the recent demonstration that humanized mice are susceptible to
scrapie, we report here the first observation of direct transmission of a
natural classical scrapie isolate to a macaque after a 10-year incubation
period. Neuropathologic examination revealed all of the features of a prion
disease: spongiform change, neuronal loss, and accumulation of PrPres throughout
the CNS.
***This observation strengthens the questioning of the harmlessness of
scrapie to humans, at a time when protective measures for human and animal
health are being dismantled and reduced as c-BSE is considered controlled and
being eradicated. Our results underscore the importance of precautionary and
protective measures and the necessity for long-term experimental transmission
studies to assess the zoonotic potential of other animal prion strains.
Monday, November 16, 2015
*** Docket No. APHIS-2007-0127 Scrapie in Sheep and Goats Terry Singeltary
Sr. Submission ***
We have shown that cattle-adapted TME is the third cattle prion strain
(joining classical and L-type BSE) to be transmissible both to non-human
primates and transgenic mice overexpressing human PrP. However, the successful
transmission of raccoon TME to primate, inducing a disease with similar features
as cattle TME, extends this notion to TME-related strains independent of host
origin. Pathological, biochemical and bioassay investigations converged to
demonstrate the similarity between cattle-adapted TME and L-BSE.
***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67
PrPsc was not detected using rapid tests for BSE.
***Subsequent testing resulted in the detection of pathologic lesion in
unusual brain location and PrPsc detection by PMCA only.
IBNC Tauopathy or TSE Prion disease, it appears, no one is sure
Posted by flounder on 03 Jul 2015 at 16:53 GMT
AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to
other species will invariably present pathology typical of a scrapie-like
disease.
snip...
http://web.archive.org/web/20060307063542/http://www.bseinquiry.gov.uk/files/yb/1991/01/04004001.pdf
Wednesday, July 15, 2015
Additional BSE TSE prion testing detects pathologic lesion in unusual brain
location and PrPsc by PMCA only, how many cases have we missed?
Wednesday, September 23, 2015
*** NIH Availability for Licensing AGENCY: [FR Doc. 2015–24117 Filed
9–22–15; 8:45 am] Detection and Discrimination of Classical and Atypical L-Type
BSE Strains by RT-QuIC
Saturday, December 12, 2015
*** BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION REPORT DECEMBER 14, 2015
Tuesday, December 29, 2015
*** Congress repeals country-of-origin labeling rule for beef and pork
December 28, 2015 at 2:21am
*** Australian government assessing risk of importing beef from US, Japan
and the Netherlands
Thursday, December 24, 2015
Infectious disease spread is fueled by international trade
Monday, January 4, 2016
Long live the OIE, or time to close the doors on a failed entity?
Wednesday, December 16, 2015
*** Objects in contact with classical scrapie sheep act as a reservoir for
scrapie transmission
Saturday, December 12, 2015
CHRONIC WASTING DISEASE CWD TSE PRION REPORT DECEMBER 14, 2015
Friday, January 01, 2016
Bayesian Modeling of Prion Disease Dynamics in Mule Deer Using Population
Monitoring and Capture-Recapture Data
Tuesday, December 29, 2015
TEXAS MONTHLY CHRONIC WASTING DISEASE CWD JANUARY 2016 DEER BREEDERS STILL
DON'T GET IT $
Chronic Wasting Unease
The emergence of a deadly disease has wildlife officials and deer breeders
eyeing each other suspiciously.
Thursday, August 13, 2015
Iatrogenic CJD due to pituitary-derived growth hormone with genetically
determined incubation times of up to 40 years
Friday, October 09, 2015
An alarming presentation level II trauma center of Creutzfeldt-Jakob
disease following a self-inflicted gunshot wound to the head
Saturday, December 12, 2015
CREUTZFELDT JAKOB DISEASE CJD TSE PRION REPORT DECEMBER 14, 2015
Thursday, December 24, 2015
Revisiting the Heidenhain Variant of Creutzfeldt-Jakob Disease: Evidence
for Prion Type Variability Influencing Clinical Course and Laboratory Findings
Article type: Research Article
Thursday, September 10, 2015
25th Meeting of the Transmissible Spongiform Encephalopathies Advisory
Committee Food and Drug Administration Silver Spring, Maryland June 1, 2015
Friday, December 04, 2015
Iatrogenic and sporadic Creutzfeldt-Jakob disease in two sisters without
mutation in the prion protein gene
Monday, August 17, 2015
*** FDA Says Endoscope Makers Failed to Report Superbug Problems OLYMPUS
*** I told Olympus 15 years ago about these risk factors from endoscopy
equipment, disinfection, even spoke with the Doctor at Olympus, this was back in
1999. I tried to tell them that they were exposing patients to dangerous
pathogens such as the CJD TSE prion, because they could not properly clean them.
even presented my concern to a peer review journal GUT, that was going to
publish, but then it was pulled by Professor Michael Farthing et al... see ;
Monday, June 29, 2015
*** RESTRICTED – POLICY CJD IN ADOLESCENTS (16 year old Vickey Rimmer),
FARMERS WITH BSE HERDS, AND FARMERS WIFE with Sporadic CJD
Monday, February 03, 2014
CREUTZFELDT-JAKOB DISEASE T.S.E. PRION U.K. UPDATE As at 3rd February 2014
Sunday, January 19, 2014
National Prion Disease Pathology Surveillance Center Cases Examined1 as of
January 8, 2014
Friday, February 14, 2014
Creutzfeldt-Jakob disease (CJD) biannual update (February 2014), with
briefing on novel human prion disease National CJD Research and Surveillance
Unit NCJDRSU
Article | Open
Preclinical detection of infectivity and disease-specific PrP in blood
throughout the incubation period of prion disease
Elizabeth B. Sawyer , Julie Ann Edgeworth , Claire Thomas , John
Collinge
& Graham S. Jackson
Scientific Reports 5, Article number: 17742 (2015) doi:10.1038/srep17742
Download Citation Diagnostic markers | Experimental models of disease | Prion
diseases
Received:18 June 2015Accepted:06 November 2015Published online:03 December
2015
Abstract
Variant Creutzfeldt-Jakob disease (vCJD) is a fatal neurodegenerative
disorder characterised by accumulation of pathological isoforms of the prion
protein, PrP. Although cases of clinical vCJD are rare, there is evidence there
may be tens of thousands of infectious carriers in the United Kingdom alone.
This raises concern about the potential for perpetuation of infection via
medical procedures, in particular transfusion of contaminated blood products.
Accurate biochemical detection of prion infection is crucial to mitigate risk
and we have previously reported a blood assay for vCJD. This assay is sensitive
for abnormal PrP conformers at the earliest stages of preclinical prion disease
in mice and precedes the maximum infectious titre in blood. Not only does this
support the possibility of screening asymptomatic individuals, it will also
facilitate the elucidation of the complex relationship that exists between the
ensemble of abnormal PrP conformers present in blood and the relationship to
infectivity.
Discussion
The ability to accurately diagnose prion infection using biochemical
methods is crucial to protect public health from iatrogenic transmissions,
particularly arising from the transfusion of contaminated blood and blood
products10,11,12,33. In the United Kingdom (UK) measures taken to prevent
secondary infections of vCJD have included leucodepletion of donor blood,
sourcing of plasma from non-UK sources, exclusion of transfusion recipients from
donation, use of recombinant clotting factors for patients with bleeding
disorders and ceasing the use of UK plasma for fractionation and export34. We
have previously reported the development19 and validation20,35 of a blood test
for vCJD based upon the detection of abnormal disease-specific isoforms of PrP,
which is now in clinical use for the diagnosis of prion disease. The wider
application of this test, or indeed other emerging assays36,37, for screening
asymptomatic individuals for potential infection is confounded by an inability
to confirm that an assay detection limit is sufficient for the detection of
preclinical infections. This problem arises as there are currently no samples
available from individuals confirmed as sub-clinical carriers of vCJD with which
to assess either the prevalence of prionaemia in BSE prion-exposed populations
or the sensitivity of any potential blood tests. A definitive answer will
require prolonged longitudinal study of individuals testing positive to
determine what proportion of patients with vCJD prionaemia go on to develop
clinical vCJD and how many are chronic carriers38.
It has been suggested that carriers would have lower concentrations of
abnormal PrP compared to individuals with clinical CJD13, and this seems likely.
Despite potentially lower levels, animal models indicate clear preclinical blood
involvement23,24,39,40 and very efficient transmission of prion infection has
been demonstrated from blood taken from sheep in early preclinical stages of
scrapie9. The use of the RML-prion strain allows rapid and precise estimates of
low prion titre using cell-based assays41,42. Previous attempts to detect
infectivity in low titre sources have required either the use of large numbers
of recipient animals or the transfusion or large volumes of infected analyte in
large animals. By using the SSBA18 we have not only verified but accurately
quantified the presence of infectivity in blood even at the earliest stages of
preclinical prion disease. A comparison of RML-infected brain diluted into
either FVB/N-Prnp0/0 brain homogenate or blood showed that although the presence
of whole blood impacted on the overall detection limit of the assay, it remained
capable of detecting RML prions at concentrations of less than 1 LD50 units/ml.
Infectivity was found to rise by approximately 10–20-fold throughout the
incubation period (Fig. 4) as might be anticipated from historical estimates
derived from conventional large scale rodent bioassays26, albeit with
significant fluctuations approaching the clinical end-point of disease. The
significant increase in infectious titre in the last few days of the incubation
period are unexpected with the change in titre identifiable only as a result of
the high precision of SSBA and related cell-culture assays which are providing
unique insights into the replication of prion isoforms during pathogenesis43,44.
Levels of MMP-9 in serum provide an indication of BBB integrity and although
complicated by age-related decline45, sudden elevation towards the clinical end
point for prion disease (Fig. 5) may indicate a sudden perturbation leading to
exchange of prion material between the CNS and circulating blood and
fluctuations in the concentration of prion disease-related PrP isoforms in
blood.
Surprisingly, analysis of the same samples using our DDA assay revealed
relatively consistent positive signals throughout the RML incubation period
(Fig. 3). Positive detection was achieved from the earliest time point sampled
and could not be ascribed to the detection of residual inoculum as similar
signals were not observed in the blood of FVB/N-Prnp0/0 mice unable to replicate
prions (data not shown), and the half-life of prion-infected inocula has
previously been shown to be short: 36 hours in rodent brain tissue46 and less in
cell-culture47. The lack of correlation between DDA reactivity and infectivity
seen by SSBA indicates DDA is capable of detecting a wider ensemble of abnormal
PrP conformers associated with prion infection44,48 of which infectivity may
only constitute a minority component. Such observations are not without
precedent and there is increasing evidence to suggest that abnormal PrP
conformers may be as much as 106-fold more abundant than assayable
infectivity49. The ability to detect the plethora of abnormal PrP increases the
analytical sensitivity of assays and in the case of DDA an analytical
sensitivity equivalent to a 109-fold dilution of prion-infected brain is
sufficient for clinical sensitivity at the earliest stages of preclinical prion
disease.
Subject: CREUTZFELDT JAKOB DISEASE CJD TSE PRION REPORT DECEMBER 14,
2015
UNITED STATES OF AMERICA
National Prion Disease Pathology Surveillance Center Cases Examined1
(August 25, 2015)
Year Total Referrals2 Prion Disease Sporadic Familial Iatrogenic vCJD
1996 & earlier
56 35 31 4 0 0
1997 113 68 59 9 0 0
1998 89 53 45 7 1 0
1999 121 73 65 7 1 0
2000 144 101 89 12 0 0
2001 210 118 110 8 0 0
2002 242 144 125 17 2 0
2003 257 159 138 21 0 0
2004 314 180 162 17 0 13
2005 328 179 157 21 1 0
2006 369 182 163 17 0 24
2007 370 206 187 19 0 0
2008 387 223 207 16 0 0
2009 399 233 212 20 1 0
2010 403 247 218 29 0 0
2011 393 239 216 23 0 0
2012 409 241 218 23 0 0
2013 416 257 222 34 1 0
2014 355 210 187 21 0 15
2015 237 137 118 8 0 0 TOTAL 56126 32857 2929 3338 7 4
1 Listed based on the year of death or, if not available, on year of
referral;
2 Cases with suspected prion disease for which brain tissue was submitted;
3 Disease acquired in the United Kingdom;
4 Disease acquired in the United Kingdom in one case and in Saudi Arabia in
the other;
5 Disease possibly acquired in a Middle Eastern or Eastern European
country;
6 Includes 28 cases in which the diagnosis is pending, and 19 inconclusive
cases;
7 Includes 12 (11 from 2015) cases with type determination pending in which
the diagnosis of vCJD has been excluded. The sporadic cases include 2853 cases
of sporadic Creutzfeldt-Jakob disease (sCJD), 54 cases of Variably
Protease-Sensitive Prionopathy (VPSPr) and 22 cases of sporadic Fatal Insomnia
(sFI).
8 Total Excludes 194 familial blood only cases.
Rev 8/26/2015
Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas in
June 2014 confirmed as home grown case
Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in
Texas
Updated: October 7, 2014
CDC and the Texas Department of State Health Services (DSHS) have completed
the investigation of the recently reported fourth vCJD case in the United
States. It confirmed that the case was in a US citizen born outside the Americas
and indicated that the patient's exposure to the BSE/vCJD agent most likely
occurred before he moved to the United States; the patient had resided in
Kuwait, Russia and Lebanon. The completed investigation did not support the
patient's having had extended travel to European countries, including the United
Kingdom, or travel to Saudi Arabia. The specific overseas country where this
patient’s infection occurred is less clear largely because the investigation did
not definitely link him to a country where other known vCJD cases likely had
been infected.
>>>the patient had resided in Kuwait, Russia and Lebanon.
>>>The completed investigation did not support the patient's
having had extended travel to European countries, including the United Kingdom,
or travel to Saudi Arabia.
NOW we all know why the state of Texas or the CDC did not want to report
this case, because it was a home grown case of nvCJD right here in Texas...tss
Monday, June 02, 2014
Confirmed Variant CJD Case in Texas
Sunday, November 23, 2014
Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas in
June 2014 confirmed as USA case NOT European
Monday, November 3, 2014
USA CJD TSE PRION UNIT, TEXAS, SURVEILLANCE UPDATE NOVEMBER 2014
National Prion Disease Pathology Surveillance Center Cases Examined1
(October 7, 2014)
***6 Includes 11 cases in which the diagnosis is pending, and 19
inconclusive cases;
***7 Includes 12 (11 from 2014) cases with type determination pending in
which the diagnosis of vCJD has been excluded.
***The sporadic cases include 2660 cases of sporadic Creutzfeldt-Jakob
disease (sCJD),
***50 cases of Variably Protease-Sensitive Prionopathy (VPSPr)
***and 21 cases of sporadic Fatal Insomnia (sFI).
Sunday, December 14, 2014
ALERT new variant Creutzfeldt Jakob Disease nvCJD or vCJD, sporadic CJD
strains, TSE prion aka Mad Cow Disease United States of America Update December
14, 2014 Report
Sunday, August 11, 2013
Creutzfeldt-Jakob Disease CJD cases rising North America updated report
August 2013
http://creutzfeldt-jakob-disease.blogspot.com/2013/08/creutzfeldt-jakob-disease-cjd-cases.html
Risk.21
Monday, February 24, 2014
Sporadic Fatal Insomnia in an Adolescent
Friday, January 10, 2014
*** vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial
type prion disease, what it ???
>>> We concluded that VPSPr is transmissible; thus, it is an
authentic prion disease.
Sunday, November 23, 2014
Transmission Characteristics of Variably Protease-Sensitive Prionopathy
* We concluded that VPSPr is transmissible; thus, it is an authentic prion
disease.
Monday, November 3, 2014
The prion protein protease sensitivity, stability and seeding activity in
variably protease sensitive prionopathy brain tissue suggests molecular overlaps
with sporadic Creutzfeldt-Jakob disease
WHAT about the sporadic CJD TSE proteins ?
WE now know that some cases of sporadic CJD are linked to atypical BSE and
atypical Scrapie, so why are not MORE concerned about the sporadic CJD, and all
it’s sub-types $$$
Creutzfeldt-Jakob Disease CJD cases rising North America updated report
August 2013
*** Creutzfeldt-Jakob Disease CJD cases rising North America with Canada
seeing an extreme increase of 48% between 2008 and 2010 ***
Sunday, October 13, 2013
*** CJD TSE Prion Disease Cases in Texas by Year, 2003-2012
Wednesday, December 11, 2013
*** Detection of Infectivity in Blood of Persons with Variant and Sporadic
Creutzfeldt-Jakob Disease ***
07 02:27 AM
Terry S. Singeltary Sr. said:
re-Evidence for human transmission of amyloid-? pathology and cerebral
amyloid angiopathy
Nature 525, 247?250 (10 September 2015) doi:10.1038/nature15369 Received 26
April 2015 Accepted 14 August 2015 Published online 09 September 2015 Updated
online 11 September 2015 Erratum (October, 2015)
*** I would kindly like to comment on the Nature Paper, the Lancet reply,
and the newspaper articles.
snip...see full text ;
Subject: 1992 IN CONFIDENCE TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO
PRIMATES POSSIBILITY ON A TRANSMISSIBLE PRION REMAINS OPEN
BSE101/1 0136
IN CONFIDENCE
CMO
From: . Dr J S Metiers DCMO
4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have
recognised the public sensitivity of these findings and intend to report them in
their proper context. 'This hopefully will avoid misunderstanding and possible
distortion by the media to portray the results as having more greater
significance than the findings so far justify.
2. Using a highly unusual route of transmission (intra-cerebral injection)
the researchers have demonstrated the transmission of a pathological process
from two cases one of severe Alzheimer's disease the other of
Gerstmann-Straussler disease to marmosets. However they have not demonstrated
the transmission of either clinical condition as the "animals were behaving
normally when killed". As the report emphasises the unanswered question is
whether the disease condition would have revealed itself if the marmosets had
lived longer. They are planning further research to see if the conditions, as
opposed to the partial pathological process, is transmissible.
what are the implications for public health?
3. The route 'of transmission is very specific and in the natural state of
things highly unusual. However it could be argued that the results reveal a
potential risk, in that brain tissue from these two patients has been shown to
transmit a pathological process. Should therefore brain tissue from such cases
be regarded as potentially infective? Pathologists, morticians, neuro surgeons
and those assisting at neuro surgical procedures and others coming into contact
with "raw" human brain tissue could in theory be at risk. However, on a priori
grounds given the highly specific route of transmission in these experiments
that risk must be negligible if the usual precautions for handling brain tissue
are observed.
1
92/11.4/1.1
BSE101/1 0137
4. The other dimension to consider is the public reaction. To some extent
the GSS case demonstrates little more than the transmission of BSE to a pig by
intra-cerebral injection. If other prion diseases can be transmitted in this way
it is little surprise that some pathological findings observed in GSS were also
transmissible to a marmoset. But the transmission of features of Alzheimer's
pathology is a different matter, given the much greater frequency of this
disease and raises the unanswered question whether some cases are the result of
a transmissible prion. The only tenable public line will be that "more research
is required’’ before that hypothesis could be evaluated. The possibility on a
transmissible prion remains open. In the meantime MRC needs carefully to
consider the range and sequence of studies needed to follow through from the
preliminary observations in these two cases. Not a particularly comfortable
message, but until we know more about the causation of Alzheimer's disease the
total reassurance is not practical.
J S METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH
832 llllYc!eS 2 92/11.4/1.2
>>> The only tenable public line will be that "more research is
required’’ <<<
>>> possibility on a transmissible prion remains open<<<
O.K., so it’s about 23 years later, so somebody please tell me, when is
"more research is required’’ enough time for evaluation ?
Self-Propagative Replication of Ab Oligomers Suggests Potential
Transmissibility in Alzheimer Disease
Received July 24, 2014; Accepted September 16, 2014; Published November 3,
2014
*** Singeltary comment PLoS ***
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion
disease, Iatrogenic, what if ?
Posted by flounder on 05 Nov 2014 at 21:27 GMT
SINGELTARY PEER REVIEW
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14,
2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor: In their Research Letter, Dr Gibbons and colleagues1
reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD)
has been stable since 1985. These estimates, however, are based only on reported
cases, and do not include misdiagnosed or preclinical cases. It seems to me that
misdiagnosis alone would drastically change these figures. An unknown number of
persons with a diagnosis of Alzheimer disease in fact may have CJD, although
only a small number of these patients receive the postmortem examination
necessary to make this diagnosis. Furthermore, only a few states have made CJD
reportable. Human and animal transmissible spongiform encephalopathies should be
reportable nationwide and internationally.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob
disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.
26 March 2003
Terry S. Singeltary, retired (medically) CJD WATCH
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment
on the CDC's attempts to monitor the occurrence of emerging forms of CJD.
Asante, Collinge et al [1] have reported that BSE transmission to the
129-methionine genotype can lead to an alternate phenotype that is
indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD
and all human TSEs are not reportable nationally. CJD and all human TSEs must be
made reportable in every state and internationally. I hope that the CDC does not
continue to expect us to still believe that the 85%+ of all CJD cases which are
sporadic are all spontaneous, without route/source. We have many TSEs in the USA
in both animal and man. CWD in deer/elk is spreading rapidly and CWD does
transmit to mink, ferret, cattle, and squirrel monkey by intracerebral
inoculation. With the known incubation periods in other TSEs, oral transmission
studies of CWD may take much longer. Every victim/family of CJD/TSEs should be
asked about route and source of this agent. To prolong this will only spread the
agent and needlessly expose others. In light of the findings of Asante and
Collinge et al, there should be drastic measures to safeguard the medical and
surgical arena from sporadic CJDs and all human TSEs. I only ponder how many
sporadic CJDs in the USA are type 2 PrPSc?
The Lancet Infectious Diseases, Volume 3, Issue 8, Page 463, August 2003
doi:10.1016/S1473-3099(03)00715-1Cite or Link Using DOI
Tracking spongiform encephalopathies in North America
Original
Xavier Bosch
“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my
mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever
since. What I have found is that we have not been told the truth. CWD in deer
and elk is a small portion of a much bigger problem.” 49-year—old Singeltary is
one of a number of people who have remained largely unsatisfied after being told
that a close relative died from a rapidly progressive dementia compatible with
spontaneous Creutzfeldt—Jakob ...
Suspect symptoms
What if you can catch old-fashioned CJD by eating meat from a sheep
infected with scrapie?
28 Mar 01
Most doctors believe that sCJD is caused by a prion protein deforming by
chance into a killer. But Singeltary thinks otherwise. He is one of a number of
campaigners who say that some sCJD, like the variant CJD related to BSE, is
caused by eating meat from infected animals. Their suspicions have focused on
sheep carrying scrapie, a BSE-like disease that is widespread in flocks across
Europe and North America. Now scientists in France have stumbled across new
evidence that adds weight to the campaigners' fears. To their complete surprise,
the researchers found that one strain of scrapie causes the same brain damage in
mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by
some strains of scrapie," says team member Jean-Philippe Deslys of the French
Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses,
south-west of Paris. Hans Kretschmar of the University of Göttingen, who
coordinates CJD surveillance in Germany, is so concerned by the findings that he
now wants to trawl back through past sCJD cases to see if any might have been
caused by eating infected mutton or lamb...
2 January 2000
British Medical Journal
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well
15 November 1999
British Medical Journal
vCJD in the USA * BSE in U.S.
TSS