Saturday, December 12, 2015

CREUTZFELDT JAKOB DISEASE CJD TSE PRION REPORT DECEMBER 14, 2015

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

 

 

Referrals of Suspected CJD Reported by CJDSS, 1997-2015
As of October 31, 2015
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

CJD Deaths Reported by CJDSS, 1994-2015
As of October 31, 2015
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
CJD Cases by Province/Territory October 30, 2015


Incidence of CJD Deaths Reported by CJDSS in Canada
As of October 31, 2015
Year of Death Total CJD Cases Population of Canada Incidence Rate
Cases with definite & probable diagnosis to date.2014 Population SourceExternal Link
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

 


 

*** 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.

 


 

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

 

Number of Pages (including cover sheet):

 

Message:

 

*CONFIDENTIALITY NOTICE*

 

This document accompanying this transmission contains confidential information belonging to the sender that is legally privileged. This information is intended only for the use of the individual or entry names above. If you are not the intended recipient, you are hereby notified that any disclosure, copying distribution, or the taking of any action in reliances on the contents of this telefaxed information is strictly prohibited. If you received this telefax in error, please notify us by telephone immediately to arrange for return of the 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

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