Evaluation of a test for its suitability in the diagnosis of variant Creutzfeldt–Jakob disease
Original Paper
Evaluation of a test for its suitability in the diagnosis of variant
Creutzfeldt–Jakob disease J. K. Cooper1,*, N. Andrews2, K. Ladhani1, E. Bujaki1,
P. D. Minor1Article first published online: 16 JUN 2013
DOI: 10.1111/vox.12037
Keywords: blood collection, Prions, transfusion, transmissible infections
Background and Objectives Evaluation of variant Creutzfeldt–Jakob disease
(vCJD) diagnostic/donor screening tests is made complicated by the very limited
supply of blood samples from clinically confirmed cases of vCJD. To determine
appropriate access for test developers to rare Creutzfeldt–Jakob disease (CJD)
blood samples, the oversight committee of the NIBSC CJD Resource Centre has
developed a process and protocols detailing minimum requirements for both test
sensitivity and specificity. This protocol is broadly similar to that outlined
in the common technical specification (European Directive 98/79/EC).
Materials and Methods Tests are subjected to a stepwise evaluation (step
1). vCJD tissue homogenates spiked into pooled human plasma (step 2). Blood
samples from animals known to be incubating (Transmissible spongiform
encephalopathy) TSE disease (scrapie/Bovine Spongiform encephalopathy
(BSE)-infected sheep, BSE-infected primates) and appropriate controls (step 3).
Fresh or frozen plasma from normal UK blood donors and (step 4). Plasma samples
from individuals with confirmed clinical stage variant CJD (transfusion
transmission) or sporadic CJD (no evidence of blood transmission).
Results The assay evaluated performed with good sensitivity with
vCJD-spiked tissue homogenates, poor sensitivity for ovine TSE-infected blood
samples and failed with plasma from BSE-infected non-human primates and with
true vCJD clinical samples.
Conclusions The test evaluated here is currently unsuitable for use in
blood donor screening or diagnosis using blood.
Tuesday, May 21, 2013
CJD, TSE, PRION, BLOOD Abstracts of the 23rd Regional Congress of the
International Society of Blood Transfusion, Amsterdam, The Netherlands, June
2-5, 2013
Sunday, June 9, 2013
TSEAC March 14, 2013: Transmissible Spongiform Encephalopathies Advisory
Committee Meeting Webcast
Thursday, June 13, 2013
Experimental interspecies transmission studies of the transmissible
spongiform encephalopathies to cattle: comparison to bovine spongiform
encephalopathy in cattle
Tuesday, May 28, 2013
Late-in-life surgery associated with Creutzfeldt-Jakob disease: a
methodological outline for evidence-based guidance
FC5.1.1 Transmission Results in Squirrel Monkeys Inoculated with Human
sCJD, vCJD, and GSS Blood Specimens: the Baxter Study
Brown, P1; Gibson, S2; Williams, L3; Ironside, J4; Will, R4; Kreil, T5;
Abee, C3 1Fondation Alliance BioSecure, France; 2University of South Alabama,
USA; 3University of Texas MD Anderson Cancer Center, USA; 4Western General
Hospital, UK; 5Baxter BioSience, Austria
Background: Rodent and sheep models of Transmissible Spongiform
Encephalopathy (TSE) have documented blood infectivity in both the pre-clinical
and clinical phases of disease. Results in a (presumably more appropriate)
non-human primate model have not been reported. Objective: To determine if blood
components (red cells, white cells, platelets, and plasma) from various forms of
human TSE are infectious.
Methods: Blood components were inoculated intra-cerebrally (0.1 ml) and
intravenously (0.5 ml) into squirrel monkeys from 2 patients with sporadic
Creutzfeldt- Jakob disease (sCJD) and 3 patients with variant Creutzfeldt-Jakob
disease (vCJD). Additional monkeys were inoculated with buffy coat or plasma
samples from chimpanzees infected with either sCJD or
Gerstmann-Sträussler-Scheinker disease (GSS). Animals were monitored for a
period of 5 years, and all dying or sacrificed animals had post-mortem
neuropathological examinations and Western blots to determine the presence or
absence of the misfolded prion protein (PrPTSE).
Results: No transmissions occurred in any of the animals inoculated with
blood components from patients with sporadic or variant CJD. All donor
chimpanzees (sCJD and GSS) became symptomatic within 6 weeks of their
pre-clinical phase plasmapheresis, several months earlier than the expected
onset of illness. One monkey inoculated with purified leukocytes from a
pre-clinical GSS chimpanzee developed disease after 36 months.
Conclusion: No infectivity was found in small volumes of blood components
from 4 patients with sporadic CJD and 3 patients with variant CJD. ***However, a
single transmission from a chimpanzee-passaged strain of GSS shows that
infectivity may be present in leukocytes, and the shock of general anaesthesia
and plasmspheresis appears to have triggered the onset of illness in
pre-clinical donor chimpanzees.
Saturday, September 5, 2009 TSEAC MEETING FEBRUARY 12, 2004 THE BAXTER
STUDY GSS
snip...
Saturday, September 5, 2009
TSEAC MEETING FEBRUARY 12, 2004 THE BAXTER STUDY GSS
snip...see full text ;
Monday, May 6, 2013 Warning of mad cow disease threat to blood transfusions
*** The potential impact of prion diseases on human health was greatly
magnified by the recognition that interspecies transfer of BSE to humans by beef
ingestion resulted in vCJD. While changes in animal feed constituents and
slaughter practices appear to have curtailed vCJD, there is concern that CWD of
free-ranging deer and elk in the U.S. might also cross the species barrier.
Thus, consuming venison could be a source of human prion disease. Whether BSE
and CWD represent interspecies scrapie transfer or are newly arisen prion
diseases is unknown. Therefore, the possibility of transmission of prion disease
through other food animals cannot be ruled out. There is evidence that vCJD can
be transmitted through blood transfusion. There is likely a pool of unknown size
of asymptomatic individuals infected with vCJD, and there may be asymptomatic
individuals infected with the CWD equivalent. These circumstances represent a
potential threat to blood, blood products, and plasma supplies.
TSS
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