Author Information
1The National CJD Research & Surveillance Unit, University of
Edinburgh, Edinburgh, Scotland, UK
2Bristol Institute for Transfusion Sciences, NHS Blood and Transplant,
Bristol, UK
3Laboratory of Persistent Viral Disease, NIAID Rocky Mountain Laboratories,
National Institutes of Health, Montana, USA ‡Ph: + 44 (0)131 537 3075; Fax: + 44
(0) 131 343 1404
Email: Alison J.E. Green PhD (Alison.Green@ed.ac.uk)
*The National CJD Research & Surveillance Unit, University of
Edinburgh, Western, General Hospital, Edinburgh, United Kingdom, EH4 2XU
†Conflicts of Interest There were no conflicts of interest
Publication History Accepted manuscript online: 15 MAR 2012 11:52PM EST
Manuscript Accepted: 9 MAR 2012 Manuscript Revised: 24 FEB 2012 Manuscript
Received: 30 MAY 2011
Funded by University of Edinburgh Development Trust Scottish Government's
Chief Scientists Office Government of Scotland National CJD Research &
Surveillance Department of Health and the Scottish Home Office Department of
Health Intramural Research Program of the NIAID NIH Department of Health
(England) Medical Research Council. Grant Number: G1000681
Research Article
RT-QuIC analysis of cerebrospinal fluid in sporadic Creutzfeldt-Jakob
disease†
Lynne I. McGuire PhD1, Alexander H. Peden PhD1, Christina D. Orrú PhD3,
Jason M. Wilham PhD3, Nigel E. Appleford Cbiol2, Gary Mallinson PhD2, Mary
Andrews BSc1, Mark W. Head PhD1, Byron Caughey PhD3, Robert G. Will FRCP1,
Richard S.G. Knight FRCP1, Alison J.E. Green PhD1,‡,*DOI:
10.1002/ana.23589
Copyright © 2012 American Neurological Association
Abstract
Objective:
Current cerebrospinal fluid (CSF) tests for sporadic Creutzfeldt-Jakob
disease (sCJD) are based on the detection of surrogate markers of neuronal
damage such as CSF 14-3-3 which are not specific for sCJD. A number of prion
protein conversion assays have been developed, including real-time quaking
induced conversion (RT-QuIC). The objective of this study is to investigate
whether CSF RT-QuIC analysis could be used as a diagnostic test in sCJD.
Methods:
An exploratory study was undertaken which analysed 108 CSF samples from
patients with neuropathologically confirmed sCJD or from control patients. Of
the 108 CSF samples 55 were from sCJD patients (30 female, 25 male, aged 31-84
years; 62.1 ± 13.5 years) and 53 were from control patients (26 female, 27 male,
aged 43-84 years; 67.8 ± 10.4 years). A confirmatory group of 118 patients were
subsequently examined which consisted of 67 cases of neuropathologically
confirmed sCJD (33 female, 34 male, aged 39-82 years; 67.5 ± 9.0 years) and 51
control cases (26 female, 25 male, aged 36-87 years; 63.5 ± 11.6 years).
Results:
The exploratory study showed that RT-QuIC analysis had a sensitivity of 91%
and a specificity of 98% for the diagnosis of sCJD. These results were confirmed
in the confirmatory study which showed that CSF RT-QuIC analysis had a
sensitivity and specificity of 87% and 100% respectively.
Interpretation:
This study shows that CSF RT-QuIC analysis has the potential to be a more
specific diagnostic test for sCJD than current CSF tests. ANN NEUROL 2012
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE
RISE IN NORTH AMERICA
Sunday, February 12, 2012
National Prion Disease Pathology Surveillance Center Cases Examined1
(August 19, 2011) including Texas
Terry S. Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health
Crisis
MAD COW USDA ATYPICAL L-TYPE BASE BSE, the rest of the story...
***Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate
Model
***Infectivity in skeletal muscle of BASE-infected cattle
***feedstuffs- It also suggests a similar cause or source for atypical BSE
in these countries.
***Also, a link is suspected between atypical BSE and some apparently
sporadic cases of Creutzfeldt-Jakob disease in humans.
Friday, May 11, 2012
Experimental H-type bovine spongiform encephalopathy characterized by
plaques and glial- and stellate-type prion protein deposits
***support risk assessments in some peripheral tissues derived from cattle
affected with H-type BSE
Friday, May 4, 2012
May 2, 2012: Update from APHIS Regarding a Detection of Bovine Spongiform
Encephalopathy (BSE) in the United States
Sunday, May 6, 2012
Bovine Spongiform Encephalopathy Mad Cow Disease, BSE May 2, 2012 IOWA
State University OIE
Sunday, March 11, 2012
APHIS Proposes New Bovine Spongiform Encephalopathy Import Regulations in
Line with International Animal Health Standards Proposal Aims to Ensure Health
of the U.S. Beef Herd, Assist in Negotiations
Friday, May 25, 2012
R-CALF USDA’s New BSE Rule Eliminates Important Protections Needed to
Prevent BSE Spread
Saturday, May 26, 2012
Are USDA assurances on mad cow case 'gross oversimplification'?
SNIP...
What irks many scientists is the USDA’s April 25 statement that the rare
disease is “not generally associated with an animal consuming infected feed.”
The USDA’s conclusion is a “gross oversimplification,” said Dr. Paul Brown,
one of the world’s experts on this type of disease who retired recently from the
National Institutes of Health. "(The agency) has no foundation on which to base
that statement.”
“We can’t say it’s not feed related,” agreed Dr. Linda Detwiler, an
official with the USDA during the Clinton Administration now at Mississippi
State.
In the May 1 email to me, USDA’s Cole backed off a bit. “No one knows the
origins of atypical cases of BSE,” she said
The argument about feed is critical because if feed is the cause, not a
spontaneous mutation, the California cow could be part of a larger outbreak.
SNIP...
Sunday, May 27, 2012
CANADA PLANS TO IMPRISON ANYONE SPEAKING ABOUT MAD COW or ANY OTHER DISEASE
OUTBREAK
CENSORSHIP IS A TERRIBLE THING
Sunday, May 27, 2012
GAIN REPORT BSE Case in United States Will Not Affect Trade, States
Canadian Food Inspection Agency
PO-028: Oral transmission of L-type bovine spongiform encephalopathy
(L-BSE) in primate model Microcebus murinus
Nadine Mestre-Frances,1 Simon Nicot,2 Sylvie Rouland,1 Anne-Gaëlle
Biacabe,2 Isabelle Quadrio,3 Armand Perret-Liaudet,3 Thierry Baron,2 Jean-Michel
Verdier1
1IN SER M UM2; Montpellier, France; 2Anses; Lyon, France; 3Hopitaux Civils
de Lyon; Lyon, France
An atypical form of bovine spongiform encephalopathy has been identified in
cattle in Europe, North America and Japan and was designed as L-type BSE (L-BSE)
due to the lower apparent molecular mass of the unglycosylated,
protease-resistant prion protein (PrPres) detected by western blot compared with
classical BSE. Experimental evidences from studies in transgenic mice expressing
human PrP and in primate models suggest a higher risk of transmission to humans
of the L-BSE form than for classical BSE agent. However, a major unresolved
issue concerns the potential transmissibility of the L-BSE agent by oral route.
To address this question, we infected mouse lemurs (Microcebus murinus), a
non-human primate model, with L-BSE by intracerebral or oral route.
Four adult lemurs were intracerebrally (IC) inoculated with 5mg of L-BSE
infected brain homogenate of an atypical French BSE case (02-2528). Four young
and four adult animals were fed with 5 mg or 50 mg of infected brain. After
sacrifice, the brain tissues were biochemically and immunocytochemically
investigated for PrPres.
The 4 animals IC inoculated died at 19 and 22 months postinoculation (mpi).
They developed blindness, tremor, abnormal posture, incoordinated movements,
balance loss. Symptoms get worse according to the disease progression, until
severe ataxia. Severe spongiosis was evidenced into the thalamus, the striatum,
the mesencephalon, and the brainstem, whereas into the cortex the vacuolisation
was weaker. Strong deposits of PrPres were detected into the thalamus, the
striatum, and the hippocampus whereas in the cerebral cortex, PrPres was
prominently accumulated in plaques.
The orally inoculated animals showed similar clinical symptoms occurring
between 27 and 34 mpi. Disease was characterized by progressive prostration,
loss of appetite and poor appearance of the fur. Only one adult animal showed
disequilibrium. PrPres was strongly accumulated only in the striatum and
thalamus and weakly into the cortex. No plaques were evidenced. Two animals that
were orally challenged at the age of two years are still alive and healthy 34
months after inoculation. The western blot analysis showed uniform molecular
profiles, irrespective of the route or dose of infection, and included notably a
PrPres form with low apparent molecular mass (~19 kDa) similar to the PrPres in
the original cattle brain. However, the PrPres profile in lemurs was
characterized by a higher proportion of di- and mono-glycosylated species (up to
95% of the total signal) than in the bovine L-BSE inoculum (~80%). In addition,
small amounts of PrPres were detected by western blotting in the spleen of three
animals (one intra-cerebrally inoculated and two fed with 5 mg of cattle brain).
Here, we demonstrate that the L-BSE agent can be transmitted by oral route
from cattle to young and adult mouse lemurs. In comparison to IC inoculated
animals, orally challenged lemurs were characterized by longer survival periods
as expected with this route of infection.
Wednesday, April 25, 2012
USA MAD COW DISEASE AND CJD THERE FROM SINGELTARY ET AL 1999 – 2012
TSS