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.
posted by Terry S. Singeltary Sr. at
4:08 PM
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