Monday, March 02, 2015

Rapid and Sensitive RT-QuIC Detection of Human Creutzfeldt-Jakob Disease Using Cerebrospinal Fluid

Rapid and Sensitive RT-QuIC Detection of Human Creutzfeldt-Jakob Disease Using Cerebrospinal Fluid

 

Christina D. Orrúa, Bradley R. Grovemana, Andrew G. Hughsona, Gianluigi Zanussob, Michael B. Coulthartc, Byron Caugheya

 

+ Author Affiliations aLaboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA bDepartment of Neurological and Movement Sciences, University of Verona, Verona, Italy cCanadian CJD Surveillance System, Public Health Agency of Canada, Ottawa, Ontario, Canada Address correspondence to Byron Caughey, bcaughey@nih.gov.

 

C.D.O., B.R.G., and A.G.H. contributed equally to this study.

 

Editor Reed B. Wickner, National Institutes of Health

 

ABSTRACT

 

Fast, definitive diagnosis of Creutzfeldt-Jakob disease (CJD) is important in assessing patient care options and transmission risks. Real-time quaking-induced conversion (RT-QuIC) assays of cerebrospinal fluid (CSF) and nasal-brushing specimens are valuable in distinguishing CJD from non-CJD conditions but have required 2.5 to 5 days. Here, an improved RT-QuIC assay is described which identified positive CSF samples within 4 to 14 h with better analytical sensitivity. Moreover, analysis of 11 CJD patients demonstrated that while 7 were RT-QuIC positive using the previous conditions, 10 were positive using the new assay. In these and further analyses, a total of 46 of 48 CSF samples from sporadic CJD patients were positive, while all 39 non-CJD patients were negative, giving 95.8% diagnostic sensitivity and 100% specificity. This second-generation RT-QuIC assay markedly improved the speed and sensitivity of detecting prion seeds in CSF specimens from CJD patients. This should enhance prospects for rapid and accurate ante mortem CJD diagnosis.

 

Importance A long-standing problem in dealing with various neurodegenerative protein misfolding diseases is early and accurate diagnosis. This issue is particularly important with human prion diseases, such as CJD, because prions are deadly, transmissible, and unusually resistant to decontamination. The recently developed RT-QuIC test allows for highly sensitive and specific detection of CJD in human cerebrospinal fluid and is being broadly implemented as a key diagnostic tool. However, as currently applied, RT-QuIC takes 2.5 to 5 days and misses 11 to 23% of CJD cases. Now, we have markedly improved RT-QuIC analysis of human CSF such that CJD and non-CJD patients can be discriminated in a matter of hours rather than days with enhanced sensitivity. These improvements should allow for much faster, more accurate, and practical testing for CJD. In broader terms, our study provides a prototype for tests for misfolded protein aggregates that cause many important amyloid diseases, such as Alzheimer’s, Parkinson’s, and tauopathies.

 

Footnotes

 

Citation Orrú CD, Groveman BR, Hughson AG, Zanusso G, Coulthart MB, Caughey B. 2015. Rapid and sensitive RT-QuIC detection of human Creutzfeldt-Jakob disease using cerebrospinal fluid. mBio 6(1):e02451-14. doi:10.1128/mBio.02451-14.

 

This article is a direct contribution from a Fellow of the American Academy of Microbiology.

 

Received 5 December 2014 Accepted 9 December 2014 Published 20 January 2015 Copyright © 2015 Orrú et al.

 

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

 


 


 

nvCJD CONFIRMED TEXAS USA 2014

 

‘’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.’’

 

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.

 


 

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).

 


 

Thursday, January 15, 2015

 

41-year-old Navy Commander with sporadic Creutzfeldt–Jakob disease CJD TSE Prion: Case Report

 


 

Subject: *** Becky Lockhart 46, Utah’s first female House speaker, dies diagnosed with the extremely rare Creutzfeldt-Jakob disease aka mad cow type disease

 

what is CJD ? just ask USDA inc., and the OIE, they are still feeding the public and the media industry fed junk science that is 30 years old.

 

why doesn’t some of you try reading the facts, instead of rubber stamping everything the USDA inc says.

 

sporadic CJD has now been linked to BSE aka mad cow disease, Scrapie, and there is much concern now for CWD and risk factor for humans.

 

My sincere condolences to the family and friends of the House Speaker Becky Lockhart. I am deeply saddened hear this.

 

with that said, with great respect, I must ask each and every one of you Politicians that are so deeply saddened to hear of this needless death of the Honorable House Speaker Becky Lockhart, really, cry me a friggen river. I am seriously going to ask you all this...I have been diplomatic for about 17 years and it has got no where. people are still dying. so, are you all stupid or what??? how many more need to die ??? how much is global trade of beef and other meat products that are not tested for the TSE prion disease, how much and how many bodies is this market worth?

 

Saturday, January 17, 2015

 

*** Becky Lockhart 46, Utah’s first female House speaker, dies diagnosed with the extremely rare Creutzfeldt-Jakob disease

 


 

*** 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 ***

 


 

Tuesday, November 04, 2014

 

Towards an Age-Dependent Transmission Model of Acquired and Sporadic Creutzfeldt-Jakob Disease

 


 

Thursday, January 22, 2015

 

Transmission properties of atypical Creutzfeldt-Jakob disease: a clue to disease etiology?

 


 


 

Sunday, July 06, 2014

 

Dietary Risk Factors for Sporadic Creutzfeldt-Jakob Disease: A Confirmatory Case-Control Study

 

Conclusions—The a priori hypotheses were supported.

 

*Consumption of various meat products may be one method of transmission of the infectious agent for sCJD.

 


 

PLEASE REMEMBER ;

 

The Akron, Ohio-based CJD Foundation said the Center for Disease Control revised that number in October of 2004 to about one in 9,000 CJD cases per year in the population group age 55 and older.

 

HAVE YOU GOT YOUR CJD QUESTIONNAIRE ASKING REAL QUESTIONS PERTAINING TO ROUTE AND SOURCE OF THE TSE AGENT THAT KILLED YOUR LOVED ONE ???

 

if not, why not...

 

Friday, November 30, 2007

 

CJD QUESTIONNAIRE USA CWRU AND CJD FOUNDATION

 


 


 

 

Friday, January 10, 2014

 

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

 


 


 

 Sunday, February 08, 2015

 

FDA SCIENCE BOARD TO THE FOOD AND DRUG ADMINISTRATION BOVINE HEPARIN BSE CJD TSE PRION Wednesday, June 4, 2014

 


 

Tuesday, March 5, 2013

 

Use of Materials Derived From Cattle in Human Food and Cosmetics; Reopening of the Comment Period FDA-2004-N-0188-0051 (TSS SUBMISSION)

 

FDA believes current regulation protects the public from BSE but reopens comment period due to new studies

 


 

Wednesday, June 19, 2013

 

Spreading of tau pathology in Alzheimer's disease by cell-to-cell transmission

 


 

Wednesday, January 28, 2015

 

Another new prion disease: relationship with central and peripheral amyloidoses

 

here we go again...

 


 


 


 


 


 


 


 


 


 


 


 


 


 

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 ;

 


 

Saturday, December 13, 2014

 

*** Terry S. Singeltary Sr. Publications TSE prion disease Peer Review ***

 

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

 

Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA

 

snip...

 


 

Monday, February 23, 2015

 

*** 20th BSE Case Raises New Concerns about Canada's Feeding Practices and Voluntary Testing Program; Highlights Importance of COOL

 


 

Saturday, February 28, 2015

 

*** BSE CANADA UPDATE Transcript - Technical Briefing to Provide an Update on Investigation of Bovine Spongiform Encephalopathy in Alberta February 27, 2015 4:00 p.m.

 


 

 Tuesday, February 17, 2015

 

*** Could we spot the next BSE?, asks BVA President

 


 

Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. *** This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada. *** It also suggests a similar cause or source for atypical BSE in these countries. ***

 

see page 176 of 201 pages...tss

 


 

*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply ;

 


 

ruminant feed ban for cervids in the United States ?

 

31 Jan 2015 at 20:14 GMT

 

Terry S. Singeltary Sr.

 


 

 

Terry S. Singeltary Sr.

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