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: Thirty-Year Review of Prion Disease Surveillance in the United
States
Robert C. Holman,1,† Ryan A. Maddox,1 Arianne M. Folkema,1 Arialdi M.
Minino,2 Teresa A. Hammett,1 Kenneth D. Kochanek,2 James J. Sejvar,1 Ermias D.
Belay1 and Lawrence B. Schonberger,1
1CDC; Atlanta, GA USA; 2CDC; Hyattsville, MD USA†Presenting author; Email:
rholman@cdc.gov
Background. With the emergence of bovine spongiform encephalopathy/variant
Creutzfeldt-Jakob disease (vCJD) in the UK, the Centers for Disease Control and
Prevention began utilizing national mortality data with additional surveillance
mechanisms to monitor US occurrences of human prion disease.
Objectives. To review US prion disease surveillance data.
Methods. We analyzed national mortality data for prion disease deaths (a
surrogate for CJD incidence) among US residents for the 30 year period,
1979–2008, augmenting and extending these data through 2010 with information
from other surveillance mechanisms (e.g., national neuropathology surveillance).
We calculated age-adjusted and age-specific death rates per million persons;
race-specific rates used data available beginning 1981. We age-adjusted death
rates to the standard projected US 2000 population. www.landesbioscience.com
Prion 131
Results. A total of 7,615 deaths during 1979–2008 were identified for an
average annual age-adjusted rate of 0.98 cases per million persons. The highest
rate (1.15) was observed in 1997; the highest number of reported cases was in
2008 (348). By race, the rate (1.06) among whites, who constituted 95% of the
cases, was significantly higher than among blacks (0.40), Asian/Pacific
Islanders (0.63) and American Indians/Alaska Natives (0.42). The rate (4.0)
among persons ≥55 years old was strikingly higher than the rate (0.14) among
persons <55 2004-2006="" 2010="" 21="" 30="" age="" among="" arabia.="" as="" cell="" deaths="" decedent="" decedents="" deficiency="" disease.="" div="" during="" factor="" hereditary="" identified="" in="" infected="" ix="" likely="" none="" of="" old.="" only="" or="" period="" previously="" reported="" residents="" saudi="" sickle="" thalassemia="" the="" three="" through="" uk="" us="" vcjd="" viii="" was="" were="" who="" with="" year="" years.="" years="" youngest="">
Conclusion. The annual age-adjusted US CJD death rates remained relatively
stable over several decades although the most recent, complete, annual data show
the highest number of cases. The absence of CJD in persons <20 100="" absence="" age="" an="" and="" any="" at="" blood-related="" blood="" cell="" cjd="" current="" deserve="" despite="" differences="" disease="" div="" during="" estimated="" further="" hemophilia="" if="" in="" investigation.="" is="" likely="" low.="" magnitude="" many="" more="" of="" or="" period="" persons="" plus="" population="" products="" racial="" rates="" received="" recipients="" remained="" risk="" sickle="" such="" suggests="" surveillance="" thalassemia="" the="" times="" transfusion="" transmissions="" very="" who="" with="" years="" youngsters="">
Risk.27: Creutzfeldt-Jakob Disease Among Hispanics in the United States,
1997–2008
Ryan A. Maddox,1,† Robert C. Holman,1 Arianne M. Folkema,1 Arialdi M.
Minino,2 Teresa A. Hammett,1 Lawrence B. Schonberger1 and Ermias D. Belay1
1National Center for Zoonotic and Emerging Infectious Diseases; Centers for
Disease Control and Prevention; Atlanta, GA USA; 2National Center for Health
Statistics; Centers for Disease Control and Prevention; Hyattsville, MD
USA†Presenting author; Email: rmaddox@cdc.gov
Introduction. At 16% of the US population, Hispanics make up the largest
ethnic or racial minority in the country, and this proportion is expected to
increase in the coming decades. The occurrence of Creutzfeldt-Jakob disease
(CJD) among Americans of Hispanic ethnicity has not been widely
investigated.
Methods. Hispanic CJD decedents of any age were identified from the US
national multiple cause-of-death data and other sources for 1997–2008. Relevant
portions of medical records and results from neuropathologic and genetic testing
for Hispanic CJD decedents <55 age="" and="" as="" available.="" div="" obtained="" of="" reviewed="" were="" years="">
Results. During 1997–2008, 160 CJD decedents were identified as being of
Hispanic ethnicity, for an average annual age-adjusted incidence of 0.65 per
million population, an incidence significantly lower than that for non-Hispanics
(RR =0.6; 95% CI 0.5–0.7). While 27 states reported at least one Hispanic
decedent during the time period, almost half (47.5%) of the decedents were
residents of California or Texas, the states with the highest Hispanic
populations. A majority (55.0%) of the decedents were females, but the average
annual age-adjusted incidence was slightly higher for males, although the
difference was not significant. The median age at death was 64 years (range
36-93 years). Thirty-three Hispanic CJD decedents (20.6%) were <55 0.0001="" 0.17="" 12.1="" 21="" 33="" age-specific="" age="" among="" and="" annual="" available="" average="" cases="" cjd="" compared="" confirmation="" decedent="" decedents="" div="" familial="" fatal="" for="" group="" had="" hispanic="" hispanics="" however="" in="" incidence="" including="" insomnia.="" lower="" medical="" neuropathologic="" neuropathology="" non-hispanic="" non-hispanics="" of="" one="" or="" p="" records="" reports="" respectively="" review.="" significantly="" sporadic="" ten="" that="" the="" these="" three="" to="" was="" with="" years="" young="">
Conclusions. Between 1997 and 2008, the reported CJD incidence among
Hispanics in the US was significantly lower than that for non-Hispanics. This
lower incidence may be at least partly due to underreporting of Hispanic
ethnicity relative to surveys and censuses, and further study is warranted.
Analyses of brain tissue remain important, especially considering that
approximately half of the young Hispanic decedents with information available
lacked CJD confirmation.
Risk.26: Sex Effect in Prion Diseases
Corinne Loeillet,1,† Pierre-Yves Boelle,2 Catherine Lemaire-Vieille,1
Philippe Naquet,3 Pierre Chambon,4 Marie-France Cesbron-Delauw,1 Alain-Jacques
Valleron,2 Jean Gagnon1 and Jean-Yves Cesbron1
1CNRS LAPM 5163–Université Joseph Fourier; Grenoble, France; 2INSERM U
707–2 Université Pierre et Marie Curie–Paris 6; Paris, France; 3Centre
d’Immunologie de Marseille-Luminy, INSERM-CNRS; Marseille, France; 4Institut de
Génétique et de Biologie Moléculaire et Cellulaire, Université Louis Pasteur de
Strasbourg; Strasbourg, France†Presenting author; Email:
corinne.loeuillet@ujf-grenoble.fr
Despite large exposure to BSE in the UK, less than 180 patients had
developed clinical vCJD by October 2009. This figure was closely anticipated in
2001, thanks to an epidemiological model whose main assumptions was that the
risk of acquiring vCJD was exponentially decreasing during childhood, which was
consistent with the age distribution of vCJD. Further investigation of the
models showed that this decrease of risk during childhood could not be explained
by the age variation of meat consumption, and was likely a consequence of an age
dependent susceptibility to the disease. The more likely explanation for this
strong age-susceptibility relationship during childhood is hormonal.
In this context, we investigated if there was a sex difference in human
vCJD cases, and we used a mouse model to test a first hypothesis on the possible
role of sexual hormones on the risk of prion diseases.
In the 167 vCJD cases reported in the UK as of January 2009, age at onset
was significantly lower in women (two years) than in men after stratification on
birth cohort. In C57/BL6N mice infected with ME-7 scrapie strain, incubation was
shorter in females than in males. The incubation period increased in castrated
male mice after intraperitoneal infection, but not after intracerebral
inoculation. We also observed that androgen receptor deficient mice the
incubation period of prion disease also increased after intraperitoneal
inoculation. In contrast, in ovariectomised or estrogen receptor a defective
female mice, no effect was observed on the incubation period of mouse prion
disease.
These results show that androgens influence the prion diseases incubation
period in a peripheral site.1
References
1. Loeuillet C, Boelle PY, Lemaire-Vieille C, Baldazza M, Naquet P, Chambon
P, et al. Sex effect in mouse and human prion disease. J Infect Dis 2010;
202:648-54.
Risk.49: Creutzfeldt-Jakob Disease in Canada, 1998–2009
Zheng Wang,1,† Gerard Jansen,1, 2 Elina Olsen,1 Stacy Sabourin,1 Rolande
D’Amour,1 Tim Connolly,1 Jennifer Kruse,1 Neil Cashman3 and Michael
Coulthart1
1The Canadian Creutzfeldt-Jakob Disease Surveillance System; Public Health
Agency of Canada; Ottawa, ON Canada; 2Department of Pathology; Ottawa Hospital;
Ottawa, ON Canada; 3Brain Research Centre; University of British Columbia;
Vancouver, BC Canada†Presenting author; Email: zheng.wang@phac-aspc.gc.ca
Background. Creutzfeldt-Jakob Disease (CJD) is a fatal, transmissible
neurodegenerative disease with sporadic, genetic and acquired forms. In 1998,
Canada launched comprehensive national CJD surveillance to assess the
characteristics of CJD in Canada and its risks to the health of Canadians. This
study describes the broad characteristics of CJD in Canada from 1998–2009.
Methods. Case ascertainment was based on internationally accepted criteria.
Demographic information and risk-factor data were collected by standardized
questionnaire and medical chart review. Poisson regression, descriptive
analysis, and case investigation were employed.
Results. A total of 453 CJD deaths in Canadian residents were registered
from 1998–2009. Four hundred and fifteen (92%) were sporadic (sCJD), 33 (7%)
were genetic and five (1%) were acquired. Average annual sCJD mortality was 1.1
per million population, increasing gradually from 0.9 in 1999 to 1.4 in 2009 (P
= 0.27). All provinces saw average annual mortalities ranging from 1.0 to 1.5 (P
= 0.85), except three territories where population is small (~25,000 to
~45,000), sCJD occurred equally in both genders at 1.1. sCJD was rare under 50
years of age with only 11 cases identified (2.7%). Mortality increased after 50
and peaked at 8 per million in the 70–74 age group. Median age at death was 69
and median duration of illness was 4 months. Genetic TSE accounted for 33
deaths: 19 were GSS (P102L: 5, D202N: 2, P105T: 2, Q217R:1, A117V: 1, unknown
mutation: 8); 13 were familial CJD (E200K: 9, D178N: 2, V203I: 1, V189I:1); one
was FFI (D178N). Median age for genetic TSE was 59 and median duration of
illness was 27 months. For the five acquired cases of CJD, four were associated
with dura mater procedures (3 Lyodura, 1 Tutoplast) and were identified from
1998–2003 in patients aged 14–59. Investigation indicated the infections
possibly occurred from 1981–1992 with incubation times from 10–16 years. One
biochemically and neuropathologically confirmed variant CJD death occurred in
2002 in a person under 40 years old, likely acquired overseas.
Discussion and Conclusion. Characteristics of CJD in Canada are consistent
with those observed in other countries. The increase in sCJD mortality can be at
least partly attributed to increased awareness of CJD among referring
clinicians. The finding of four dura matter associated CJD cases and one
imported vCJD case in Canada demonstrate risks to Canadians from acquired CJD
exist. Continued surveillance for iatrogenic risks and novel forms of CJD is
warranted.
HD.23: Creutzfeldt-Jakob disease among American Indians and Alaska natives
in the United States, 1983–2009
Robert C. Holman, Ryan A. Maddox, Arianne M. Folkema, Arialdi M. Minino,
Ermias D. Belay and Lawrence B. Schonberger CDC; Atlanta, GA, USA
Background/Introduction. Creutzfeldt-Jakob disease (CJD) occurrence among
American Indians and Alaska Natives (AI/ ANs) is of special interest, in part
because of the high prevalence of hunting and venison consumption in this
population. Such behaviors could place AI/ANs at increased risk of prion disease
if chronic wasting disease (CWD) were found to transmit to humans.
Materials and Methods. Death records with CJD as anylisted cause of death
for US residents identified from the national multiple cause-of-death data and
other surveillance mechanisms for 1983 through 2009 were analyzed, and incidence
was calculated by race. Available death certificates and medical records were
collected and examined for AI/AN decedents.
Results. During 1983 through 2009, 15 decedents with CJD as a cause of
death were reported as AI/AN race. The average annual age-adjusted CJD incidence
for AI/ANs was 0.39 per 1,000,000 persons. The rate for whites (1.07) was higher
compared with that for AI/ANs (RR = 2.9, 95% CI = 1.8–4.9) and blacks were
similar (0.41; RR = 1.1, 95% CI = 0.7–1.9). The median age at death was 65 y
(range 39–85 y), similar to those for whites and blacks (68 and 66 y,
respectively); four (27%) AI/ AN decedents were younger than 55 y of age. Most
of the AI/AN decedents were males (60%). Decedents were reported from 13 states;
none resided in the states with the longest known presence of CWD, Colorado,
Wyoming, and Nebraska.
Conclusion. The reported CJD incidence for AI/ANs appears lower than that
for whites and similar to that for blacks, although the CJD incidence for AI/ANs
is likely underestimated due to racial misclassification of AI/ANs. Continued
monitoring of CJD occurrence in this population is important as CWD spreads into
new areas.
P.204: Creutzfeldt-Jakob disease in the aging United States
population
Ryan A Maddox,1 Marissa K Person,1 Arialdi M Minino,2 Janis E Blevins,3
Lawrence B Schonberger,1 and Ermias D Belay1
1National Center for Emerging and Zoonotic Infectious Diseases; Centers for
Disease Control and Prevention (CDC); Atlanta, GA USA; 2National Center for
Health Statistics, CDC; Hyattsville, MD USA; 3National Prion Disease Pathology
Surveillance Center (NPDPSC); Case Western Reserve University; Cleveland, OH
USA
Introduction. Creutzfeldt-Jakob disease (CJD) predominantly occurs among
older individuals. To describe the possible impact of changing demographics in
the US population on the occurrence of CJD, we reviewed data from the US census
and from national prion disease surveillance.
Methods. Prion disease decedents were identified from the US national
multiple cause-of-death data and the National Prion Disease Pathology
Surveillance Center database for 2008-2010. Incidence rates were calculated for
decedents ≥65 years and then applied to US census population estimates for 2030
to obtain projections of the number of CJD deaths in that year, assuming no
advances in treatment or prevention of these diseases.
Results. US census data projects that ≥65-year-olds will increase from
13.1% of the population in 2010 to 20.3% in 2030. The CJD incidence rates for
2008-2010 among decedents in the 65-74, 75-84, and 85+ year age groups were, in
cases per million population, 6.5, 7.2, and 3.1, respectively. Applying these
incidence rates to US census projections, in 2030 there may be 461 CJD decedents
≥65 years of age in the United States, an increase of more than 200 cases
compared to the 2008-2010 average for this age group. Of the 461 cases, 251 are
projected to be aged 65-74 years, 182 to be aged 75-84 years, and 28 to be aged
85 years or older.
Conclusions. Unless effective treatments for CJD are developed, the aging
population in the United States will likely result in an increase in CJD cases
due to its higher incidence among older adults. The increase in cases could
impact infection control policies and health care costs, among other
factors.
Friday, February 04, 2011
*** NMLB and USDA allow scrapie prion infected mutton to enter food chain
on the Navajo Reservation in New Mexico ***
HD.15: Prion disease among Asians and Pacific Islanders in the United
States, 2003–2009
Ryan A. Maddox,1 Robert C. Holman,1 Arialdi M. Minino,2 Janis E. Blevins,3
Lawrence B. Schonberger1 and Ermias D. Belay1
1National Center for Emerging and Zoonotic Infectious Diseases; Centers for
Disease Control and Prevention; Atlanta, GA USA; 2National Center for Health
Statistics; Centers for Disease Control and Prevention; Hyattsville, MD USA;
3National Prion Disease Pathology Surveillan ce Center (NPDPSC); Case Western
Reserve University; Cleveland, OH USA Introduction. Asians and Pacific Islanders
(APIs) comprise approximately 5% of the United States population. The occurrence
of Creutzfeldt-Jakob disease (CJD) and other prion diseases among APIs in the
United States has not been widely investigated.
Materials and Methods. API prion disease decedents were identified from the
United States national multiple cause-of-death data and the National Prion
Disease Pathology Surveillance Center database for 2003–2009. Relevant portions
of medical records and results from neuropathologic and genetic testing for API
prion disease decedents were obtained and reviewed, as available.
Results. During 2003–2009, 60 API prion disease decedents were identified;
34 of these decedents had additional race information available, with 15 API
decedents classified as Filipino (44%), 13 as Japanese (38%), 5 as Chinese (15%)
and 1 as Hawaiian (3%). The average annual age-adjusted incidence was 0.7 per
million population, significantly lower than that for whites (p < 0.001).
Over half (55%) of the API deaths occurred in California or Hawaii, the states
with the highest API populations. The median age at death was 66.5 y (range
40–87 y), similar to that for whites (68 y). Neuropathology reports and/ or
medical records were available for 24 of the decedents; for 20 cases with a
reported disease onset date, the median duration of illness was 4.5 mo (range
1–66 mo). Twenty of 22 decedents (91%) had sporadic CJD, while the remaining 2
decedents (9%) had familial CJD. All 20 decedents with genetic testing results
available were methionine homozygous at codon 129.
Conclusion. For 2003–2009, the reported prion disease incidence among APIs
in the United States was significantly lower than that for whites.
Underreporting of API race may contribute at least partly to this lower
incidence, but genetic factors may influence prion disease susceptibility as
well. Because the API race is heterogeneous, further study of prion diseases
among specific API ethnic groups is warranted.
The Pathological Protein:
Mad Cow, Chronic Wasting, and Other Deadly Prion Diseases
Philip Yam
*** ''Answering critics like Terry Singeltary, who feels that the US
undercounts CJD, Schonberger _conceded_ that the current surveillance system has
errors but stated that most of the errors will be confined to the older
population'' ***
CANADA
| Year of Reporting | Number of Referrals |
|---|---|
| 1997 | 4 |
| 1998 | 43 |
| 1999 | 63 |
| 2000 | 82 |
| 2001 | 101 |
| 2002 | 103 |
| 2003 | 75 |
| 2004 | 90 |
| 2005 | 97 |
| 2006 | 80 |
| 2007 | 101 |
| 2008 | 100 |
| 2009 | 104 |
| 2010 | 76 |
| 2011 | 102 |
| 2012 | 103 |
| 2013 | 99 |
| 2014 | 99 |
| 2015 | 80 |
| Total | 1602 |
| Deaths of Definite and Probable CJD | |||||||
| Year | Sporadic | Iatrogenic | Familial | GSS | FFI | vCJD | Total |
|---|---|---|---|---|---|---|---|
| Cases with definite & probable diagnosis to date. | |||||||
| 1994 | 2 | 0 | 0 | 1 | 0 | 0 | 3 |
| 1995 | 3 | 0 | 0 | 0 | 0 | 0 | 3 |
| 1996 | 13 | 0 | 0 | 0 | 0 | 0 | 13 |
| 1997 | 16 | 0 | 1 | 1 | 0 | 0 | 18 |
| 1998 | 22 | 1 | 0 | 1 | 0 | 0 | 24 |
| 1999 | 27 | 2 | 2 | 1 | 0 | 0 | 32 |
| 2000 | 32 | 0 | 0 | 3 | 0 | 0 | 35 |
| 2001 | 27 | 0 | 2 | 1 | 0 | 0 | 30 |
| 2002 | 31 | 0 | 2 | 2 | 0 | 1 | 36 |
| 2003 | 27 | 1 | 1 | 0 | 0 | 0 | 29 |
| 2004 | 42 | 0 | 1 | 1 | 0 | 0 | 44 |
| 2005 | 42 | 0 | 1 | 1 | 0 | 0 | 44 |
| 2006 | 39 | 0 | 1 | 3 | 1 | 0 | 44 |
| 2007 | 35 | 0 | 0 | 4 | 0 | 0 | 39 |
| 2008 | 48 | 0 | 1 | 0 | 0 | 0 | 49 |
| 2009 | 48 | 0 | 3 | 2 | 0 | 0 | 53 |
| 2010 | 35 | 0 | 3 | 0 | 0 | 0 | 38 |
| 2011 | 46 | 0 | 3 | 1 | 0 | 1 | 51 |
| 2012 | 62 | 0 | 1 | 0 | 0 | 0 | 63 |
| 2013 | 50 | 0 | 0 | 0 | 1 | 0 | 51 |
| 2014 | 49 | 0 | 4 | 0 | 1 | 0 | 54 |
| 2015 | 23 | 0 | 1 | 0 | 0 | 0 | 24 |
| Total | 719 | 4 | 27 | 22 | 3 | 2 | 777 |
CJD Cases
by Province/Territory October 31, 2015
| Year of Death | Total CJD Cases | Population of Canada | Incidence Rate |
|---|---|---|---|
Cases with definite
& probable diagnosis to date.2014 Population Source | |||
| 1999 | 32 | 30,492,106 | 1.05 |
| 2000 | 35 | 30,783,969 | 1.14 |
| 2001 | 30 | 31,130,030 | 0.96 |
| 2002 | 36 | 31,450,443 | 1.14 |
| 2003 | 29 | 31,734,851 | 0.91 |
| 2004 | 44 | 32,037,434 | 1.37 |
| 2005 | 44 | 32,352,233 | 1.36 |
| 2006 | 44 | 32,678,986 | 1.35 |
| 2007 | 39 | 33,001,076 | 1.18 |
| 2008 | 49 | 33,371,810 | 1.47 |
| 2009 | 53 | 33,756,714 | 1.57 |
| 2010 | 38 | 34,131,451 | 1.11 |
| 2011 | 51 | 34,472,304 | 1.48 |
| 2012 | 63 | 34,880,248 | 1.81 |
| 2013 | 51 | 35,289,003 | 1.45 |
| 2014 | 54 | 35,675,834 | 1.51 |
| 2015 | 24 | 35,702,707 | 0.81 |
Saturday, March 21, 2015
*** Canada and United States Creutzfeldt Jakob TSE Prion Disease Incidence
Rates Increasing
P.179: Sporadic Creutzfeldt-Jakob disease in Canada
Zheng Wang,1 Gerard Jansen,1,2 Stacy Sabourin,1 Rolande D’Amour,1 Tim
Connolly,1 Jennifer Kruse,1 David J Knox,3 Neil R Cashman,4 and Michael B
Coulthart1 1The Canadian Creutzfeldt-Jakob Disease Surveillance System; Public
Health Agency of Canada; Ottawa, ON Canada; 2Department of Pathology; Ottawa
Hospital; Ottawa, ON Canada; 3National Microbiology Laboratory; Public Health
Agency of Canada; Winnipeg, MB Canada; 4Brain Research Centre; University of
British Columbia; Vancouver, BC Canada
Background. Sporadic Creutzfeldt-Jakob Disease (sCJD) is a fatal,
transmissible neurodegenerative disease. Systematic surveillance has repeatedly
shown annual mortality in the range 1 to 2 per million population, has
elucidated key characteristics of sCJD, and led to recognition of a new form of
CJD, variant CJD (vCJD), which is associated with BSE. In 1998, Canada launched
comprehensive national CJD surveillance to assess the characteristics of CJD in
Canada, identify any acquired cases of CJD (such as vCJD, of which 2 imported
cases have been identified in Canada to date), and mitigate public health risks.
This study describes the epidemiology of sCJD in Canada from 1998 to 2012.
Methods. Case ascertainment was based on internationally accepted criteria.
Demographic and medical information were collected by standardized questionnaire
and medical chart review. Poisson regression and descriptive analysis were
employed.
Results. A total of 563 sCJD deaths (definite: 462, probable: 101) in
Canadian residents were registered from 1998 to 2012. Average annual sCJD
mortality was 1.2 per million population, increasing gradually from 0.9 in 1999
to 1.7 in 2012 (P = 0.0004). All provinces saw average annual mortalities
ranging from 1.0 to 1.6 (P = 0.25), except three territories where population is
small (~25,000 to ~45,000) and no cases were identified. sCJD occurred at
similar rates in males (1.1) and females (1.2) (P = 0.21). sCJD was rare under
50 years of age with only 11 cases identified (2.7%). Mortality increased after
50 and peaked at 7.4 per million in the 70–74 age group. Median age at death was
69 and median duration of illness was 4 months. Genotype at codon 129 (N = 358)
revealed that the MM subgroup accounted for 223 (62%, median age at death: 69,
duration: 4), the MV subgroup was 82 (23%, median age at death: 68, duration:
9), and the VV subgroup was 53 (23%, median age at death: 66, duration: 5).
Results of molecular typing (Parchi Scheme) for 256 cases are; MM1: 140, MM2:
11, MV1: 28, MV2: 18, VV1: 5, VV2: 25, Mixture: 29.
Conclusion. Characteristics of sCJD in Canada are consistent with those
observed in other countries. The increase in sCJD mortality can be partly
attributed to increased awareness of CJD among Canadian clinicians. These
findings support the conclusion that Canadian CJD surveillance system is
sufficiently sensitive to accurately characterize the epidemiology of sCJD in
Canada, and to detect potential additional cases of acquired CJD such as vCJD or
human chronic wasting disease.
Conclusion. Characteristics of sCJD in Canada are consistent with those
observed in other countries. The increase in sCJD mortality can be partly
attributed to increased awareness of CJD among Canadian clinicians. These
findings support the conclusion that Canadian CJD surveillance system is
sufficiently sensitive to accurately characterize the epidemiology of sCJD in
Canada, and to detect potential additional cases of acquired CJD such as vCJD or
human chronic wasting disease.
HD.18: Creutzfeldt-Jakob disease reporting in Canada
Zheng Wang,1 Gerard H. Jansen,1, 2 Elina Olsen,1 Rolande D’Amour,1 Stacy
Sabourin,1 Tim Connolly,1 Jennifer Kruse,1 Neil Cashman3 and Michael Coulthart1
1Public Health Agency of Canada; Ottawa, ON CA; 2Department of Pathology; Ottawa
Hospital; Ottawa, ON CA; 3Brain Research Centre; University of British Columbia;
Vancouver, BC CA
Background. To deal with risks of infectious transmission of
Creutzfeldt-Jakob disease (CJD), in 1998 the Government of Canada launched a
prospective national CJD surveillance system (CJDSS). In 2000, CJD became
nationally notifiable in Canada, and since then all Canadian Provinces and
Territories (P/Ts) have made CJD reportable. It has been recognized that the
CJDSS registers more cases of CJD than are reported to P/T Ministries of Health
(PTMH). Because the CJDSS may not legally share personal information with PTMH,
in 2008 the CJDSS began to systematically discuss the issue of CJD reporting
with referring health care professionals (HCP). The present study was undertaken
to estimate any changes in P/T CJD reporting from 2008, and to identify possible
areas for further improvement.
Materials and Methods. P/T CJD data were retrieved from the Public Health
Agency of Canada’s National Notifiable Disease System (NNDS) database, and
compared with CJDSS data. CJDSS intake sheets were examined, to determine if the
case had been reported to the PTMH at the time of notification.
Results. From 2005 to 2010, NNDS received complete data on CJD from 5 P/Ts.
During the same period, 134 cases of CJD (probable or neuropathologically
confirmed) were reported by the 5 P/Ts while 210 CJD deaths (probable or
definite) were recorded in the CJDSS from the same 5 P/Ts. Between 2008 and 2010
there was an increase of ~48% in P/T CJD reports compared with the period
2005–2007. In contrast, the CJDSS registered only ~12% more CJD deaths between
2008 and 2010 compared with 2005–2007, supporting an interpretation of improved
P/T reporting. Examination of intake sheets from 172 notifications that were
made to the CJDSS from the same 5 P/Ts between 2008 and 2010 revealed that 30
were known to have been reported to PTMH at the time of referring (24 were CJD,
5 were non-CJD, and 1 was unclassifiable). 142 were not reported or had unknown
reporting status. Reasons cited by HCPs for not reporting included (1)
uncertainty of the CJD diagnosis; (2) uncertainty regarding responsibility for
reporting; (3) lack of awareness that CJD is reportable; and (4) uncertainty
regarding when or how to report.
Conclusion. The considerable increase of CJD reports in P/Ts since 2008
occurred concurrently with efforts of the CJDSS to engage HCPs on the issue of
CJD reporting requirements. P/T CJD reports may include non-CJD cases.
Inter-jurisdiction collaboration is underway to further improve CJD reporting.
MEXICO
Tuesday, June 26, 2012
Creutzfeldt Jakob Disease Human TSE report update North America, Canada,
Mexico, and USDA PRION UNIT as of May 18, 2012
type determination pending Creutzfeldt Jakob Disease (tdpCJD), is on the
rise in Canada and the USA
Wednesday, June 13, 2012
MEXICO IS UNDER or MIS DIAGNOSING CREUTZFELDT JAKOB DISEASE AND OTHER PRION
DISEASE SOME WITH POSSIBLE nvCJD
Can prion disease suspicion be supported earlier? Clinical, radiological
and laboratory findings in a series of cases
Prion 5:3, 201-207; July/August/September 2011; © 2011 Landes
Bioscience
RESEARCH PAPER RESEARCH PAPER
*Correspondence to: Alejandra González-Duarte; Email:
gonzalezduarte@aol.com Submitted: 04/04/11; Accepted: 07/24/11 DOI:
10.4161/pri.5.3.16187
The subacute spongiform encephalopathies are prion diseases characterized
by acute and rapid neurodegeneration that lead to the death of the patient
within months to a few years. The epidemiology of CJD is complicated and the
frequency in Mexico is unknown. We aim to describe the cases of prion disease in
Mexico. Consecutive patients who met the diagnostic criteria by the WHO were
enrolled. We describe 26 patients with clinical manifestations, imaging and
laboratory studies compatible with prion disease. The mean age at onset was 52
years old. The main clinical manifestations were cognitive alterations (69%)
followed by extrapyramidal movements (50%), abnormal cerebellar function (46%),
behavioral alterations (46%), myoclonus (46%) and mood depression (23%), among
other features. Half of the patients progressed rapidly to a state of akinetic
mutism (53%). Only 2 (7.6%) patients had a family history of a similar disease.
Time interval between onset and diagnosis varied between 71 days to 24 months,
with a median of 6 months. The classical bilateral basal ganglia
hyperintensities were present in the very early stage of the disease. Protein
14-3-3 immuneassay in the CSF was positive in all measured cases. Bilateral
basal ganglia hyperintensities was the most important early finding, while
protein 14-3-3 was a late finding and the results were usually obtained after
the patient was discharged. Around 1.5 cases of CJD cases per year are reported
in our country. When suspected, MRI can support the diagnosis earlier than other
studies.
SNIP...
Conclusions
CJD is rarely recognized, however, the rapid development of signs and
symptoms in addition to abnormalities in the MRI and EEG will aid the diagnosis
in many cases despite not having timely access to CSF protein 14-3-3. Specially,
the early identification of new onset of depression, agitation, irritability or
memory loss should not be overlooked in middle age patients who do not have a
previous history of a psychiatric or neurologic illness. Unfortunately, there is
no treatment available, however, the recognition of more cases will allow us to
understand the epidemiology and pathophysiology of this rare and devastating
disease.
see earlier statistics for CJD in Mexico here ;
Friday, January 11, 2008
CJD HUMAN TSE REPORT UK, USA, CANADA, and Mexico JANUARY 2008
Neuropathology Volume 27 Issue 5 Page 419-428, October 2007
To cite this article: Leora Velásquez-Pérez, Daniel Rembao-Bojorquez, Jorge
Guevara, Rosa María Guadarrama-Torres, Araceli Trejo-Contreras (2007)
Creutzfeldt-Jakob disease in Mexico
Neuropathology 27 (5), 419–428. doi:10.1111/j.1440-1789.2007.00807.x
Abstract
Original Article
Creutzfeldt-Jakob disease in Mexico
snip...
UNITED KINGDOM
CREUTZFELDT-JAKOB DISEASE IN THE UK (By Calendar Year)
REFERRALS OF SUSPECT CJD DEATHS OF DEFINITE AND PROBABLE CJD
Year Referrals Year Sporadic1 Iatrogenic Genetic2 vCJD Total Deaths
1990 [53]† 1990 28 5 0 – 33
1991 75 1991 31 1 4 – 36
1992 96 1992 45 2 6 – 53
1993 79 1993 36 4 7 – 47
1994 119 1994 53 1 9 – 63
1995 87 1995 35 4 5 3 47
1996 132 1996 40 4 6 10 60 1997 163
1997 59 6 6 10 81
1998 155 1998 64 3 5 18 90
1999 170 1999 62 6 2 15 85
2000 178 2000 50 1 3 28 82
2001 179 2001 58 4 6 20 88
2002 164 2002 73 0 5 17 95
2003 162 2003 79 5 6 18 108
2004 114 2004 50 2 6 9 67
2005 124 2005 67 4 13 5 89
2006 112 2006 68 1 9 5 83
2007 119 2007 64 2 10 5 81
2008 150 2008 85 5 6 2 98
2009 153 2009 80 2 8 3 93
2010 150 2010 85 3 7 3 98
2011 158 2011 91 4 14 5 114
2012 127 2012 93 5 11 0 109
2013 151 2013 107 2 8 1 118
2014 128 2014 98 3 11 0 112
2015* 114 2015 73 0 3 0 76
Total Referrals 3412 Total Deaths 1674 79 176 177 2106 †
Referral figure for 1990 is from 1 May onwards * As at 2nd November 2015
Summary of vCJD cases
Deaths
Deaths from definite vCJD (confirmed): 122
Deaths from probable vCJD (without neuropathological confirmation): 55
Deaths from probable vCJD (neuropathological confirmation pending): 0
Number of deaths from definite or probable vCJD (as above): 177
Alive
Number of definite/probable vCJD cases still alive: 0
Total number of definite or probable vCJD (dead and alive): 177
1 There are in addition a total of 9 cases of VPSPr
(death in 1997(1 case),
2004(1),
2006(1),
2008(2),
2012(4)) not included in the above figures.
2 includes all genetic prion disease, including GSS.
Source: http://www.cjd.ed.ac.uk/documents/figs.pdf
- updated 02/11/2015
Thursday, July 30, 2015
*** Professor Lacey believes sporadic CJD itself originates from a cattle
infection number of cattle farmers falling victim to Creutzfeld-Jakob Disease is
much too high to be mere chance
ITALY
Monday, September 07, 2015
ITALY REPORTING INCREASE IN CASES OF MAD COW TYPE TSE PRION DISEASE IN
HUMANS CJD
AUSTRALIA
Saturday, November 09, 2013
Surveillance for creutzfeldt-Jakob disease in Australia: update to December
2012
BELGIUM
Research article
Overview and evaluation of 15 years of Creutzfeldt-Jakob disease
surveillance in Belgium, 1998-2012
Amber Litzroth12*, Patrick Cras34, Bart De Vil5 and Sophie Quoilin1
* Corresponding author: Amber Litzroth amber.litzroth@wiv-isp.be
Author Affiliations
1 Unit of Epidemiology of Infectious Diseases, Operational Directory Public
Health and Surveillance, Scientific Institute of Public Health, Juliette
Wytsmanstreet 14, Brussels, 1050, Belgium
2 European Programme for Intervention Epidemiology Training (EPIET),
European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden
3 Department of Neurology, Antwerp University Hospital, Wilrijkstreet 10,
Edegem, 2650, Belgium
4 Institute Born Bunge, University of Antwerp, Antwerp, Belgium
5 Laboratory of Neurology, Translational Neurosciences, Faculty of Medicine
and Health Sciences, University of Antwerp, Universiteitsplein 1,
Wilrijk-Antwerp, 2610, Belgium
For all author emails, please log on.
BMC Neurology 2015, 15:250 doi:10.1186/s12883-015-0507-x
The electronic version of this article is the complete one and can be found
online at: http://www.biomedcentral.com/1471-2377/15/250
Received: 12 February 2015 Accepted: 24 November 2015 Published: 2 December
2015
© 2015 Litzroth et al.
Open AccessThis article is distributed under the terms of the Creative
Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/),
which permits unrestricted use, distribution, and reproduction in any medium,
provided you give appropriate credit to the original author(s) and the source,
provide a link to the Creative Commons license, and indicate if changes were
made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/)
applies to the data made available in this article, unless otherwise stated.
Abstract Background
In 1998, following the detection of variant Creutzfeldt-Jakob disease
(vCJD) in the UK, Belgium installed a surveillance system for Creutzfeldt-Jakob
disease (CJD). The objectives of this system were to identify vCJD cases and
detect increases in CJD incidence. Diagnostic confirmation of CJD is based on
autopsy after referral by neurologists. Reference centres perform autopsies and
report to the surveillance system. The aim of this study was to assess whether
the system met its objectives and to assess its acceptability.
Methods For 1999–2010, we linked surveillance data with hospital discharge
data. We calculated the proportion of CJD suspected patients who died in
hospitals and were captured by the surveillance system. We surveyed stakeholders
on knowledge of the surveillance system, referral practices and acceptability.
We compared proportions using the chi-square test and investigated variables
associated with capture using a multivariable logistic regression model.
Results On average 60 % of hospitalised patients who died with suspected
CJD were captured by the surveillance system. This proportion did not
significantly differ over the years (p = 0.1). The odds of capture significantly
decreased with every 1 year increase in age (OR = 0.95, 95 % CI 0.92–0.98, p =
0.001). Eleven percent of surveyed neurologists would not refer suspect vCJD
cases for autopsy, nor contact a reference centre for diagnostic support.
Sixty-one percent of surveyed neurologists were not familiar with the
surveillance system. Awareness of the existence of the system did not impact
referral behaviour (p = 0.18). CJD and vCJD surveillance were considered
important by the majority of stakeholders.
Conclusions Although 40 % of the suspect CJD cases were not referred for
autopsy, our data suggest that the Belgian CJD surveillance system meets one of
its main objectives: it can detect changes in CJD incidence. However, we do not
have sufficient evidence to conclude that the system meets its second objective
of detecting vCJD cases arising in Belgium. Although not well known, the system
was considered acceptable by its stakeholders.
SNIP...
Conclusions In conclusion, the Belgian CJD surveillance system meets one of
its two main objectives: the system is capable of detecting changes in CJD
incidence in time, both at national and regional level. Although self-reported
referral behaviour of the Belgian neurologists indicates that vCJD cases are
likely to be captured by the surveillance system, this evaluation does not give
the necessary evidence that the system meets its second objective of capturing
vCJD cases. The system was acceptable to data providers and public health
officials. Nevertheless, data providers consider the lack of regular feedback
and the current way of reporting as the two main limitations to the system.
Moreover, we found that half of the suspect CJD cases were not referred for
autopsy and we found a decreasing trend in total capture over the years and a
decreasing capture with age. Therefore, we recommend to (a) revise the data
reporting through implementation of electronic tools (b) provide regular
feedback to reporting neurologists to enhance their contribution, and (c)
explore the reasons for not undergoing autopsy, for example by performing a
validation study on the CJD suspected deaths in hospital that do not undergo
autopsy.
Keywords: Creutzfeldt-Jakob disease; Evaluation; Surveillance; Variant
Creutzfeldt-Jakob disease; Acceptability; Belgium; Survey
U.K.
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
Monday, February 03, 2014
CREUTZFELDT-JAKOB DISEASE T.S.E. PRION U.K. UPDATE As at 3rd February 2014
KOREA
Characteristics of Korean patients with suspected Creutzfeldt-Jakob disease
with 14-3-3 protein in cerebrospinal fluid: Preliminary study of the Korean
Creutzfeldt-Jakob disease active surveillance program .
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DOI:10.1080/19336896.2015.1022020Jae-Sung Lima, Hyung-Min Kwona, Jae-Won
Jangb, Young-Ran Juc, SuYeon Kimc, Young Ho Parkd, So Young Parkd & SangYun
Kimde*
pages 136-143
Publishing models and article dates explained
Received: 22 Sep 2014 Accepted: 16 Feb 2015 Published online: 21 May 2015 .
.
Abstract
Although Korea had a national surveillance system for Creutzfeldt-Jakob
disease (CJD), it was mainly dependent on attending physician's reports. Thus,
little prospective data about the epidemiology, characteristics, and final
diagnoses of suspected patients were available. We have established a nationwide
network for the active surveillance of patients with suspected CJD. When the
requested cerebrospinal fluid (CSF) samples tested positive for 14-3-3 protein,
we investigated the clinical characteristics of the corresponding patients and
followed them until their final diagnoses were confirmed. A total of 218 samples
were requested for CSF assays from May 2010 to August 2012, and 106 (48.6%) were
positive for 14-3-3 protein. In 89 patients with complete clinical data, 38
(42.7%) were diagnosed with probable CJD and the estimated annual occurrence of
CJD was 16.3 persons-per-year. The most common diagnoses of the remainder were
central nervous system infection and any-cause encephalopathy. Non-CJD subjects
showed worse initial consciousness levels than CJD patients. This preliminary
study showed that the number of reported cases of CJD and the true positivity
rates of CSF 14-3-3 protein assays were both low in Korea. An active
surveillance system is urgently needed to provide the latest nationwide
epidemiological data of CJD.
HD.24: Surveillance of Creutzfeldt-Jakob disease in Korea: Establishing the
Korean National Creutzfeldt-Jakob disease Registry (KNCJDR)
Byoung-Hak Jeon,1 Hae-Kwan Cheong,1 Soo Eun Chung,1 Soo Chul Park,2 Sang
Yun Kim,4 Dong-Woo Lee,3 Si-Heon Kim,3 Young-Teak Kim3 and Je-Geun Chi5
1Sungkyunkwan University in Korea; Suwon, Gyeonggi-do, Korea; 2Yonsei
University; Seoul, Korea; 3Korea Centers for Disease Control and Prevention
(KCDC); Osong, Korea; 4Seoul National University Bundang Hospital; Bundang,
Korea; 5Seoul National University; Seoul, Korea
Keywords: prion diseases, Creutzfeldt-Jakob disease, surveillance,
epidemiology
Background. The Korean National Creutzfeldt-Jakob disease surveillance has
been operated by Korea Centers for Disease Control and Prevention (KCDC) since
2001. In accordance with the increasing public concern about CJD, updated and
comprehensive surveillance was conducted under the name of “Korean National
Creutzfeldt-Jakob Disease Registry (KNCJDR)”. Our study presents its setup
process and descriptive features of the Korean prion diseases registry.
Materials and Methods. The KNCJDR database has been established by merging
and reviewing all the available CJD cases from national notifiable infectious
diseases reports, previous surveillance database, mortality database by National
Statistics Office, and medical record survey by neurologists network. The KNCJDR
database consist of demographic findings, clinical signs (progressive dementia,
myoclonus, visual signs, cerebellar signs, pyramidal signs, extrapyramidal
signs, and akinetic mutism), test results (EEG, Brian MRI, and 14-3-3 protein
detection in cerebrospinal fluid) and result of pathologic study.
Results. Total number of cases merged to the KNCJDR database was 578 cases
since 1980. After excluding 155 cases with incomplete information 7.1%, 56.1%
and 10.0% was classified as definite, probable and possible CJD respectively.
The majority of Korean CJD cases were sporadic (about 80.4%). The range of the
incidence rate of nationwide CJD was 0.03–0.84 between 1980 and 2012. Mean age
of onset was 64.1 ± 9.8 y (63.2 y for males and 65.2 y for females) old. Mean
duration of illness was 10.3 ± 10.4 mo (range 1–79 mo). Annual incidence of CJD
has continuously increased during this period, and onset of symptom tends to be
acute or sub-acute.
Conclusion. Functioning KNCJDR is crucial for achieving effective
prevention and management of CJD. Although, this registry is contained in
currently available data, the authors expect that it is to be basic platform in
both academic research and national control plan for CJD.
Acknowledgments. This study was granted by Korea Centers for Disease
Control and Prevention (20120224307-00).
HD.25: Estimation of the size of iatrogenic Creutzfeldt-Jakob disease
associated with cadaveric dura mater transplantation in Korea
Byoung-Hak Jeon,1 Soo Eun Chung,1 Jinseob Kim,2 Kang Hyun Kim3 and Hae-Kwan
Cheong1 1Sungkyunkwan University in Korea; Suwon, Gyeonggi-do, Korea; 2Seoul
National University; Seoul, Korea; 3National Medical Center; Seoul, Korea
Keywords: prion diseases, iatrogenic Creutzfeldt-Jakob disease, dura graft,
modeling
Background. In Korea, a national Creutzfeldt-Jakob disease (CJD)
surveillance system was operated by the Korea Centers for Disease Control and
Prevention (KCDC) since 2001 and the Korean National Creutzfeldt-Jakob disease
Registry (KNCJDR) was established by the KCDC in December 2012. Since 1987, Dura
mater graft-associated iatrogenic Creutzfeldt-Jakob disease (iCJD) has been
reported in many countries. The first case of iCJD in Korea was reported in
2011. This study was conducted to estimate the overall size of iCJD from dura
graft in Korea using a mathematical model.
Materials and Methods. In order to estimate the overall size of the iCJD,
we assumed the annual cases of dura mater graft between 1980 and 2000 based on
the number of neurosurgery cases applying proportion of dura mater use estimated
from Health Insurance Review Agency (HIRA) claim data set in Korea. We designed
two mathematical projection models and there were two scenarios applied to
estimate exposure period to risk factor in each model. The incubation period
distribution was assumed to use the Weibull distribution with density function
and log-logistic distribution with density function. The overall size of iCJD
was estimated by Monte Carlo sensitivity analysis.
Results. Total number of neurosurgery during year 1980 and 2000 was
estimated to be 424,451. Among them, 23.9% was estimated to be grafted by dura
product. From 1980 until 2020, our model predicted the range of iCJD would be
approximately 13.4–50.9. The estimated range of the cumulative number of iCJD to
be caused by dura graft was approximately 12.4–44.8 until 2011.
Conclusion. We postulated that the occurrence of iCJD was expected to be in
sharp decline after 2012 until 2020. Acknowledgments. This study was granted by
Korea Centers for Disease Control and Prevention (20120224307–00).
JAPAN
APPS2015 Asian Pacific Prion Symposium 2015
An update on variant Creutzfeldt-Jakob disease
Prof. Robert Will (University of Edinburgh, Western General Hospital,
National CJD Research & Surveillance Unit Edinburgh, UK) Symposium 1
Surveillance of prion diseases Surveillance of prion diseases in the UK
Prof. Robert Will (University of Edinburgh, Western General Hospital,
National CJD Research & Surveillance Unit Edinburgh, UK) The CJD
surveillance characters of China
Dr. Qi ShiNational Institute for Viral Disease Control and Prevention,
Chinese Center for Disease Control and Prevention, China) Surveillance of prion
diseases in Korea
Prof. Yong-Sun Kim(Ilsong Institute of Life Science, Hallym University,
Korea) Australian Human Prion Disease Surveillance Update ... and some other
“bits and pieces”.
Prof. Steven John Collins (Australian National Creutzfeldt-Jakob Disease
Registry, Department of Pathology, The University of Melbourne, Australia)
Surveillance of prion diseases in Japan
Dr. Nobuo Sanjo(Department of Neurology and Neurological Science, Graduate
School, Tokyo Medical and Dental University, Japan) Day 2: Saturday September 5
Symposium 2 Amplification and detection of PrPSc Protein misfolding cyclic
amplification of PrPSc
Prof. Claudio Soto(Mitchell Center for Research in Alzheimer’s Disease and
Related Brain Disorders, University of Texas Medical School at Houston, USA)
Prion assembly and the detection of prions
Prof. Byron Caughey (Rocky Mountain Laboratories, National Institute of
Allergy and Infectious Disease, National Institute of Health, USA) Diagnostic
evaluation of real-time quaking-induced conversion for the detection of human
prion diseases
Dr. Ryuichiro Atarashi(Department of Molecular Microbiology and Immunology,
Graduate School of Biomedical Sciences, Nagasaki University, Japan)
P.184: Human prion diseases in Japan: a prospective surveillance from
1999
Nobuo Sanjo,1,2 Maya Higuma,1 Masaki Hizume,1 Fumiko Furukawa,1 Yosikazu
Nakamura,2 Tetsuyuki Kitamoto,2 Masahito Yamada,2 Kenji Sakai,2 Ichiro Nozaki,2
Moeko Noguchi-Shinohara,2 Tsuyoshi Hamaguchi,2 Fumio Moriwaka,2 Masashi Aoki,2
Fumiaki Tanaka,2 Masatoyo Nishizawa,2 Masatoshi Takeda,2 Takashi Inuzuka,2 Koji
Abe,2 Hiroyuki Murai,2 Shigeo Murayama,2 Masaki Takao,2 Katsuya Satoh,2 Masafumi
Harada,2 Nobuhito Saito,2 Ichirou Takumi,2 and Hidehiro Mizusawa,1,2
1Department of Neurology and Neurological Science; Tokyo Medical and Dental
University; Graduate School of Medical and Dental Sciences; Tokyo, Japan; 2
Prion disease Surveillance Committee; Tokyo, Japan
Introduction. A nationwide surveillance system for human prion diseases
(PrDs) was established in April 1999. The aim of this study is to describe the
features of epidemiology, clinical manifestations and CSF biomarkers of human
PrDs in Japan, including an additional period until September 2013. Patients and
Methods. We collected information on clinical, neuropathological, and molecular
genetic data of patients suspected as having PrDs and analyzed by the
Creutzfeldt-Jakob disease (CJD) Surveillance Committee, Japan, from April 1999
to September 2013.
Results. We have obtained the information of 4,281 patients. A total of
2,162 cases (50.5%) of PrDs was identified, including 1,655 cases of sporadic
CJD (sCJD) (76.5%), 325 cases of genetic CJD (15.0%), 85 cases of GSS (3.9%), 4
cases of fatal familial insomnia (FFI) (0.2%), 84 cases of dura mater
graft-associated CJD (dCJD) (3.9%), 1 case of variant CJD (vCJD) (0.04%), and 7
cases of unclassified CJD (0.3%). The overall annual incidence rate was 1.47
cases per million person-year. Genetic analysis was performed in 1,672 patients,
and revealed that 402 cases had mutations in prion protein (PRNP) gene. The most
frequent mutation was 187 cases of V180I mutation (46.5%), followed by 75 cases
of P102L (18.7%), 58 cases of M232R (14.4%), 55 cases of E200K (13.7%), 7 cases
of P105L, 5 cases of D178N, 2 cases of V203I, 1 case of R208H, 3 cases of
V180I+M232R, 6 cases of insertion. Autopsy was performed 16.6% of total 1,616
patients who had died. Of total 147 dCJD cases in Japan, 84 cases appeared in
this surveillance system. Only one case of vCJD with a history of a short stay
in UK was identified in 2005. V180I is the most frequently occurring mutation in
genetic PrDs in Japan, but has rarely been reported in other countries. P105L
mutation and a valine-encoding polymorphic codon 129 in the PRNP have been
reported only from Japan, and clinical features vary among patients.
Conclusion. Human PrDs in Japan were characterized by frequent occurrence
of dCJD and relatively larger amount of patients with genetic PrDs which were
composed of uncommon PRNP mutations in other countries.
References
1. Nozaki I, Hamaguchi T, Sanjo N, Noguchi-Shinohara M, Sakai K, Nakamura
Y, Sato T, Kitamoto T, Mizusawa H, Moriwaka F, et al. Prospective 10-year
surveillance of human prion diseases in Japan. Brain 2010; 133:3043-57;
PMID:20855418; http://dx.doi.org/10.1093/brain/awq216
2. Higuma M, Sanjo N, Satoh K, Shiga Y, Sakai K, Nozaki I, Hamaguchi T,
Nakamura Y, Kitamoto T, Shirabe S, et al. Relationships between
clinicopathological features and cerebrospinal fluid biomarkers in Japanese
patients with genetic prion diseases. PLoS One 2013; 8:e60003; PMID:23555862; http://dx.doi.org/10.1371/journal.
pone.0060003
3. Hamaguchi, et al. J Neurol Neurosurg Psychiatry, In press.
CHINA
Research Paper
Analysis of the advantage features of Beijing surveillance network for
Creutzfeldt-Jakob disease .
DOI:10.1080/19336896.2015.1075115Qi Shiab, Xiu-Chun Zhangc, Wei Zhoua, Kang
Xiaoa, Cao Chenab, Hai-Yan Zhangd, Jing-Yi Sune, Li-Na Chena, Xiao-Mei Zhanga,
Jun Hana & Xiao-Ping Dongabf*
pages 304-314
Publishing models and article dates explained
Received: 8 Jun 2015 Accepted: 14 Jul 2015 Accepted author version posted
online: 07 Aug 2015
Abstract
Since 2006, China has conducted the surveillance program for
Creutzfeldt-Jakob disease (CJD) and other subtypes of prion diseases covering 12
provinces. In this study, the characteristics and special role of Beijing CJD
surveillance network in the national CJD surveillance system were analyzed.
Based on the registered permanent resident places, all reporting suspected CJD
cases and diagnosed CJD cases via Beijing CJD surveillance network between 2006
and 2013 were grouped as the cases from Beijing and from outside of Beijing.
Both numbers of the suspected and diagnosed CJD cases via Beijing CJD
surveillance network constantly increased along with the years, totally 532
reporting cases and 192 diagnosed CJD cases were obtained in the past 8 y. About
75% of suspected and diagnosed CJD cases via Beijing CJD surveillance network
came from other provinces, mainly from neighboring provinces. Altogether, 46
different hospitals in the Beijing region have reported suspected CJD cases to
the CJD surveillance system during the period from 2006 to 2013. Five hospitals
continually reported suspected CJD cases during those 8 y and 5 other hospitals
had reported cases except for 1 to 2 y. Additionally, we found that the
diagnosed CJD patients from Beijing region had less numbers of hospital transfer
and shorter interval from the disease onset to the final diagnosis than those
outside of Beijing. It indicates that as the most important component, Beijing
CJD surveillance network functions more actively, which supplies the special
medical services not only for Beijing residents but also for patients from all
of China.
Keywords CJD, surveillance, network, Beijing, China
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Sunday, November 23, 2014
Transmission Characteristics of Variably Protease-Sensitive Prionopathy
* We concluded that VPSPr is transmissible; thus, it is an authentic prion
disease.
Friday, January 10, 2014
vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type
prion disease, what it ???
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
*** The discovery of previously unrecognized prion diseases in both humans
and animals (i.e., Nor98 in small ruminants) demonstrates that the range of
prion diseases might be wider than expected and raises crucial questions about
the epidemiology and strain properties of these new forms. We are investigating
this latter issue by molecular and biological comparison of VPSPr, GSS and
Nor98.
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE ...price of prion
poker goes up again $
OR-10: Variably protease-sensitive prionopathy is transmissible in bank
voles
Romolo Nonno,1 Michele Di Bari,1 Laura Pirisinu,1 Claudia D’Agostino,1
Stefano Marcon,1 Geraldina Riccardi,1 Gabriele Vaccari,1 Piero Parchi,2 Wenquan
Zou,3 Pierluigi Gambetti,3 Umberto Agrimi1 1Istituto Superiore di Sanità; Rome,
Italy; 2Dipartimento di Scienze Neurologiche, Università di Bologna; Bologna,
Italy; 3Case Western Reserve University; Cleveland, OH USA
Background. Variably protease-sensitive prionopathy (VPSPr) is a recently
described “sporadic”neurodegenerative disease involving prion protein
aggregation, which has clinical similarities with non-Alzheimer dementias, such
as fronto-temporal dementia. Currently, 30 cases of VPSPr have been reported in
Europe and USA, of which 19 cases were homozygous for valine at codon 129 of the
prion protein (VV), 8 were MV and 3 were MM. A distinctive feature of VPSPr is
the electrophoretic pattern of PrPSc after digestion with proteinase K (PK).
After PK-treatment, PrP from VPSPr forms a ladder-like electrophoretic pattern
similar to that described in GSS cases. The clinical and pathological features
of VPSPr raised the question of the correct classification of VPSPr among prion
diseases or other forms of neurodegenerative disorders. Here we report
preliminary data on the transmissibility and pathological features of VPSPr
cases in bank voles.
Materials and Methods. Seven VPSPr cases were inoculated in two genetic
lines of bank voles, carrying either methionine or isoleucine at codon 109 of
the prion protein (named BvM109 and BvI109, respectively). Among the VPSPr cases
selected, 2 were VV at PrP codon 129, 3 were MV and 2 were MM. Clinical
diagnosis in voles was confirmed by brain pathological assessment and western
blot for PK-resistant PrPSc (PrPres) with mAbs SAF32, SAF84, 12B2 and 9A2.
Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission
in BvM109. Overall, 3 voles were positive with survival time between 290 and 588
d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form
of the typical PrP27–30, which was indistinguishable to that previously observed
in BvM109 inoculated with sCJDMM1 cases.
In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission until
now. Overall, 5 voles were positive with survival time between 281 and 596
d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like
PrPSc electrophoretic pattern, characterized by low molecular weight PrPres.
These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative
with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus
and the N-terminus. Second passages are in progress from these first successful
transmissions.
Conclusions. Preliminary results from transmission studies in bank voles
strongly support the notion that VPSPr is a transmissible prion disease.
Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of
voles, with sCJD-like features in BvM109 and GSS-like properties in BvI109.
The discovery of previously unrecognized prion diseases in both humans and
animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion
diseases might be wider than expected and raises crucial questions about the
epidemiology and strain properties of these new forms. We are investigating this
latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.
Monday, August 9, 2010
Variably protease-sensitive prionopathy: A new sporadic disease of the
prion protein or just more Prionbaloney ?
Wednesday, March 28, 2012
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE ...price of prion
poker goes up again $
OR-10 15:25 - 15:40 VARIABLY PROTEASE-SENSITIVE PRIONOPATHY IS
TRANSMISSIBLE IN BANK VOLES Nonno
Monday, February 24, 2014
Sporadic Fatal Insomnia in an Adolescent
Tuesday, September 1, 2015
Evidence for α-synuclein prions causing multiple system atrophy in humans
with parkinsonism
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
Thursday, October 1, 2015
*** Alzheimergate, re-Evidence for human transmission of amyloid-β
pathology and cerebral amyloid angiopathy, Singeltary Submission to Nature ***
2015-12-07 02:27 AM
Comment #67381
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.
Wednesday, September 2, 2015
*** Clinically Unsuspected Prion Disease Among Patients With Dementia
Diagnoses in an Alzheimer’s Disease Database
March 1989
COMMERCIAL IN CONFIDENCE
INACTIVATION OF SCRAPIE-LIKE AGENTS Some implications for the use of bovine
material in sterile medical devices in the UK
To the best of our knowledge, this is the first case of CJD combined with
Lewy body disease and argirophilic grain disease. Furthermore, we believe this
case is an extremely rare combination of MM2-cortical-type and MM2-thalamic-type
sporadic CJD (sCJD), which explains the broad spectrum of MM2-type sCJD findings
and symptoms. Moreover, histological features of possible Alzheimer's disease
were also reported.
Wednesday, September 03, 2014
Coexistence of mixed phenotype Creutzfeldt-Jakob disease, Lewy body disease
and argyrophilic grain disease plus histological features of possible
Alzheimer's disease: A multi-protein disorder in an autopsy case
P197
Misfolded prion protein (PrPTSE) can be detected in the blood of squirrel
monkeys infected with variant Creutzfeldt-Jakob disease (vCJD)
Larisa Cervenakova1, Oksana Yakovleva1, Paula Saá1, David M. Asher2, Thomas
R. Kreil3, Susan Gibson4, Christian Abee5, James W. Ironside6, Paul W. Brown7
1Scientific Affairs, American Red Cross, Rockville, MD, USA, 2Office of Blood
Research and Review, Center for Biologics Evaluation and Research, FDA, Silver
Prion2015 Program Guide
36
Prion 2015 Fort Collins Spring, MD, USA, 3Global Pathogen Safety, Baxter
BioScience, Vienna, Austria, 4University of South Alabama, Mobile, AL
(deceased), USA, 5University of Texas, Anderson Cancer Center, Bastrop, TX, USA,
6National CJD Surveillance Unit, Edinburgh, UK, 7NINDS, National Institutes of
Health, Bethesda, MD (retired), USA
Variant CJD infections have been recognized in 4 recipients of
non-leukocyte-depleted red blood cell (RBC) transfusions (and in a hemophilia
patient treated with a plasmaderived coagulation factor). In the UK, PrPTSE has
been detected in blood of 70% of vCJD patients and in appendices of as many as 1
in 2000 asymptomatic individuals. Reliable tests are needed to detect blood
donors infected with vCJD before the appearance of overt illness to protect
transfusion recipients. We previously reported the co-localization of PrPTSE
with extracellular vesicles (EVs) in plasma of vCJD-infected mice. Here we
report detecting PrPTSE in EVs from archived plasma samples of vCJD-infected
squirrel monkeys. Blood was collected from infected and uninfected monkeys into
anticoagulant every 3 months and separated into RBCs, buffy coat and plasma. EVs
were extracted from plasma using ExoQuickTM. PMCA was performed using uninfected
TgHu mouse brain homogenate as PrPC substrate. We tested samples of blood from 2
groups of monkeys inoculated intracerebrally with vCJD brain diluted 10-1 (4
monkeys) or 10-3 (3 monkeys) and from 4 control monkeys inoculated with 10-1
normal human brain. PrPTSE was detected in plasma EV of 5 of 7 vCJD-inoculated
monkeys (3/4 10-1 and 2/3 10-3). Multiple tests of control plasma EV samples
from the 4 control monkeys were all negative. Whole blood collected from 4
monkeys during incubation and clinical stages of vCJD was transfused into
individual recipient monkeys. We continue to test archived plasma samples from
donor and transfusion-recipient monkeys. Baxter and FABS funded the study.
prion2013
iatrogenic CJD
*** all iatrogenic cjd is, is sporadic cjd until the iatrogenic event is
discovered, documented, put into the academic and then the public domain,which
very seldom happens due to lack of trace back efforts.
Friday, December 04, 2015
Iatrogenic and sporadic Creutzfeldt-Jakob disease in two sisters without
mutation in the prion protein gene
Friday, October 09, 2015
An alarming presentation level II trauma center of Creutzfeldt-Jakob
disease following a self-inflicted gunshot wound to the head
http://creutzfeldt-jakob-disease.blogspot.com/2015/10/an-alarming-presentation-level-ii.html
Monday, November 23, 2015
*** Blood transmission studies of prion infectivity in the squirrel monkey
(Saimiri sciureus): the Baxter study
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.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract
Sunday, November 22, 2015
*** Effect of heating on the stability of amyloid A (AA) fibrils and the
intra- and cross-species transmission of AA amyloidosis ***
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 ;
Tuesday, May 26, 2015
*** Minimise transmission risk of CJD and vCJD in healthcare settings
***
Last updated 15 May 2015
Monday, November 23, 2015
1992 IN CONFIDENCE TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
POSSIBILITY ON A TRANSMISSIBLE PRION REMAINS OPEN
>>> 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 ?
Friday, October 23, 2015
*** CJD FOUNDATION CREUTZFELDT JAKOB DISEASE TSE PRION QUESTIONNAIRE UPDATE
OCTOBER 2015 ***
Thursday, September 10, 2015
25th Meeting of the Transmissible Spongiform Encephalopathies Advisory
Committee Food and Drug Administration Silver Spring, Maryland June 1, 2015
Friday, November 13, 2015
No evidence of asymptomatic variant CJD infection in immunodeficiency
patients treated with UK-sourced immunoglobulin ?
Thursday, August 13, 2015
Iatrogenic CJD due to pituitary-derived growth hormone with genetically
determined incubation times of up to 40 years
Tuesday, August 4, 2015
FDA U.S. Measures to Protect Against BSE
P.85: Improving Creutzfeldt-Jakob disease incidence estimates by
incorporating results of neuropathological analyses, United States,
2003–2011
Ryan Maddox1, Marissa Person1, Arialdi Minino2, Janis Blevins3, Lawrence
Schonberger1, and Ermias Belay1
1National Center for Emerging and Zoonotic Infectious Diseases; Centers for
Disease Control and Prevention, Atlanta GA USA; 2National Center for Health
Statistics; Centers for Disease Control and Prevention; Hyattsville, MD USA;
3National Prion Disease Pathology Surveillance Center; Case Western Reserve
University; Cleveland, OH USA
Introduction. The incidence of invariably fatal prion diseases such as
Creutzfeldt-Jakob disease (CJD) can be estimated by analyzing death certificate
data, but there are limitations.
Methods. Prion disease decedents were identified from the US national
multiple cause-ofdeath data and the National Prion Disease Pathology
Surveillance Center (NPDPSC) database for 2003–2011. Due to limited personal
identifying information, an algorithm was constructed to determine likely
decedent matches between the 2 databases. NPDPSC decedents with a positive prion
disease autopsy or biopsy result or genetic mutation for whom no match was found
in the multiple cause-of-death data were added as cases for incidence
calculations; those with negative neuropathology results but Prion 2015 Poster
Abstracts S55 with a death certificate indicating prion disease were removed.
The resulting average annual age-adjusted incidence was then calculated.
Results. A total of 2986 decedents were identified as having prion disease
indicated as a cause of death in the multiple cause-of-death data; 469
additional NPDPSC decedents were identified with positive neuropathology and/or
genetic findings, while 140 decedents with death certificates indicating prion
disease had negative neuropathology results. Incorporating the matched data, the
average annual ageadjusted incidence of CJD in the United States was 1.2 per
million.
Conclusion. Analysis of multiple cause-of death data is an efficient means
of conducting CJD surveillance. However, not all decedents are captured as the
death certificate may not list the diagnosis; conversely, a CJD diagnosis on the
certificate may be contradicted by neuropathology results. Incorporating
findings from NPDPSC neuropathological and genetic analyses produces an estimate
closer to the true incidence of the disease.
The Pathological Protein:
Mad Cow, Chronic Wasting, and Other Deadly Prion Diseases
Philip Yam
''Answering critics like Terry Singeltary, who feels that the US
undercounts CJD, Schonberger _conceded_ that the current surveillance system has
errors but stated that most of the errors will be confined to the older
population''....end
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?
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.
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...
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
Saturday, December 12, 2015
BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION REPORT DECEMBER 14, 2015
Saturday, December 12, 2015
CHRONIC WASTING DISEASE CWD TSE PRION REPORT DECEMBER 14, 2015
Saturday, December 12, 2015
NOTICE: Environmental Impact Statement on Large Livestock Carcasses TSE
Prion REPORT December 14, 2015
these blogs are for educational use. I do not advertise or make money from
them.
MOM DOD 12/14/97 confirmed hvCJD, just made a promise to mom, never forget,
and never let them forget...
Heidenhain Variant Creutzfeldt Jakob Disease autopsy case report
'MOM'
DIVISION OF NEUROPATHOLOGY University of Texas Medical Branch 114
McCullough Bldg. Galveston, Texas 77555-0785
FAX COVER SHEET
DATE: 4-23-98
TO: Mr. Terry Singeltary @ -------
FROM: Gerald Campbell
FAX: (409) 772-5315 PHONE: (409) 772-2881
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*CONFIDENTIALITY NOTICE*
This document accompanying this transmission contains confidential
information belonging to the sender that is legally privileged. This information
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original documents. -------------------------- Patient Account: 90000014-518
Med. Rec. No.: (0160)118511Q Patient Name: POULTER, BARBARA Age: 63 YRS DOB:
10/17/34 Sex: F Admitting Race: C
Attending Dr.: Date / Time Admitted : 12/14/97 1228 Copies to:
UTMB University of Texas Medical Branch Galveston, Texas 77555-0543 (409)
772-1238 Fax (409) 772-5683 Pathology Report
FINAL AUTOPSY DIAGNOSIS Autopsy' Office (409)772-2858
Autopsy NO.: AU-97-00435
AUTOPSY INFORMATION: Occupation: Unknown Birthplace: Unknown Residence:
Crystal Beach Date/Time of Death: 12/14/97 13:30 Date/Time of Autopsy: 12/15/97
15:00 Pathologist/Resident: Pencil/Fernandez Service: Private Restriction: Brain
only
FINAL AUTOPSY DIAGNOSIS
I. Brain: Creutzfeldt-Jakob disease, Heidenhain variant.
Terry S. Singeltary Sr. Bacliff, Texas USA 77518 flounder9@verizon.net