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From: TSS ()
Subject: PRIONS IN PLASMA OF PATIENTS WITH SPORADIC CJD, ATYPICAL VCJD IN 73 YEAR OLD HUMAN BLOOD TRANSFUSION RECIPIENT AND MACAQUE, ENHANCED SURVEILLANCE
Date: September 30, 2007 at 1:17 pm PST

P04.49


Case Report of Variant Creutzfeldt-Jakob Disease in a Macaque after Blood
Transfusion


Lescoutra-Etchegaray, N1; Ruchoux, MM1; Correia, E1; Jolit, A1; Freire, S1;
Lasmezas,
CI2; Deslys, JP1; Comoy, E1 1CEA/DSV/IMETI/SEPIA, France; 2Scripps Florida,
USA

A fourth human case of probable transmission of vCJD through transfusion has
now
been reported but a number of features affecting transfusion-related
infection remain
imprecise, including infectious dose, length of incubation period and
critical infectious
window of blood donors.


We report here the first case of experimental transmission of vCJD in
primates by
blood transfusion. Experimental infection of Cynomolgus macaque has been
demonstrated to be a sensitive model for the investigation of human prion
diseases,
inducing similar distribution of infectivity in peripheral lymphoid tissues
and equivalent
brain pathology. In our study, transfusion was performed with 40 ml of whole
blood
drawn from a vCJD-infected macaque at the terminal stage of the disease.
Clinical
symptoms of vCJD appeared in the recipient animal after five years of
incubation. The
total amount of infectivity in the transfused blood was approximately 106
fold lower
than in the brain (titration still in progress). In several animals infected
intravenously
with brain homogenate, the presence of PrPres in serial lymph nodes biopsies
and in
other organs at autopsy was examined and results will be presented.


http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf


P04.51


Atypical Presentation of Variant Creutzfeldt-Jakob Disease in a 73 Year Old
Blood Transfusion Recipient


Wroe, S1; Pal, S1; Webb, T1; Alner, K2; Hewitt, P3; Brander, S4; Wadsworth,
JD5; Collinge, J1 1National Hospital for Neurology and Neurosurgery,
National Prion Clinic,
UK; 2National Hospital for Neurology and Neurosurgery, Department of
Neuropsychology, UK;
3Health Protection Agency, UK; 4National Hospital for Neurology and
Neurosurgery,
Department of Neuropathology, UK; 5Institute of Neurology, UCL, UK

We report atypical presentation of variant Creutzfeldt-Jakob Disease (vCJD)
identified
ante-mortem in a 73 year-old recipient of blood products. This patient was
transfused
following orthopaedic surgery in December 1997. Tracing of blood products
identified
a single unit of non-leucodepleted red cells from an individual who
developed
neuropathologically confirmed vCJD eleven months after donation. Nine years
post
transfusion, this individual was referred to the National Prion Clinic for
specialist
investigation. Six years post transfusion the recipient complained of
fluctuating fatigue
and impaired concentration. At this time neurological examination and MRI
brain
(T1/T2 weighted/DWI) were normal. Progressive symptoms emerged six months
later
with imbalance and deteriorating cognition. Examination two months after
onset of
neurological symptoms demonstrated cognitive deficits, dyspraxia or
visuospatial
dysfunction and normal motor, sensory and gait examination. Six weeks later
cognitive
impairment was identified alongside tremulousness, impaired manual dexterity
and
limb ataxia. Serological investigations were normal. MRI (T1/T2
weighted/FLAIR/DWI)
demonstrated prominent signal change throughout the dorsal thalamus,
consistent
with vCJD. PRNP genotyping revealed no mutations and homozygosity for
methionine
at codon 129. The prolonged incubation period of vCJD and possibility of
asymptomatic carrier states pose major public health concerns. This case
highlights
the significant risk encountered by recipients of contaminated blood
products and the
necessity for their specialist monitoring.


http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf

P04.36

Enhanced Surveillance of Persons Identified as at Increased Risk of CJD Due
to
Blood Transfusion or Healthcare Procedures

Brookes, D1; Chow, Y1; Ward, HJT2; Will, RG2; Hewitt, P3; Gill, ON1
1HPA, CJD, UK; 2National CJD Surveillance Unit, UK; 3Colindale, NHS Blood
and Tissue, UK


Introduction:

Reports of four iatrogenic transmissions of variant-CJD (vCJD) infection
in the UK (all due to transfusion of blood from donors who later developed
vCJD),
evidence from iatrogenic transmissions of sporadic CJD and experimental work
on
CJD infectivity in tissues and on healthcare instruments have given rise to
concern
about the risks of iatrogenic transmission of CJD. This risk warrants a)
certain public
health precautions, and b) follow-up of individuals with identified risks in
order to gain
evidence about their risks and ensure appropriate management of these risks.
Evidence of transmission via iatrogenic routes is important to inform public
health
measures and so prevent ongoing transmission of CJD.


Methods:


The Health Protection Agency and Health Protection Scotland holds details
of persons identified as ‘at-risk’ of vCJD due to blood transfusion and of
persons identified as ‘at-risk’ of CJD (of any type) from other healthcare
procedures. The GPs/clinicians of all persons identified as ‘at-risk’ for
public health
purposes are provided with: information; risk assessment updates; advice on
public health
precautions and advice on referral to specialist care. Procedures are being
established to obtain enhanced surveillance data on these individuals,
including:
clinical status updates, date and cause of death, surplus tissue and blood
specimens, and
postmortem investigations.


Results:


Persons ‘at-risk’ of CJD have experienced a range of exposures. Estimated
risks are uncertain and overlapping. Some individuals - recipients of vCJD
implicated blood components - are considered to be at a clearly higher risk
of
infection: active follow-up is currently conducted for these individuals. In
time, the
enhanced surveillance of persons at increased risk of CJD will provide
estimates of
transmission risks and of the impact of iatrogenic exposures on mortality.
Conclusion: Knowledge about iatrogenic transmission of CJD is being gained
by the follow-up of individuals who have been identified as ‘at-risk’ of CJD
in the
UK. This enhanced surveillance may need to be sustained for many years.


http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf


Prions in Plasma of Patients with Sporadic Creutzfeldt-Jakob Disease
Safar, J.G1,3, Geschwindm M.D2,3, Letessier, F1,
Kuo, A1, Pomeroy, K1, Deering, C1, Serban, A1,
Groth, D1, Miller, B.L2,3, DeArmond, S.J1,4,
Prusiner, S.B1,3,5
1Institute for Neurodegenerative Diseases,
2Memory and Aging Center, Departments of
3Neurology, 4Pathology, and 5Biochemistry
and Biophysics, University of California,
San Francisco, California 94143


http://www.prion2007.com/pdf/Prion%20Friday.pdf

http://www.prion2007.com/pdf/Prion%20Thursday.pdf

http://www.prion2007.com/pdf/Prion%20Wednesday.pdf


P04.33


Diagnostic Utility of CSF Biomarkers and General CSF Findings in a U.S
Sporadic CJD Cohort


Geschwind, MD; Haman, A; Torres-Chae, C; Raudabaugh, BJ; Devereux, G;
Miller, BL
University of California, San Francisco, USA


Background:

The diagnostic utility of CSF biomarkers, including 14-3-3 protein,
neuron-specific enolase (NSE), AB42, total Tau (T-Tau), and phosphorylated
Tau (PTau)/ T-Tau ratio are often are used for sporadic CJD (sCJD) diagnosis
is
controversial. We have previously reported the CSF 14-3-3 protein to have
poor sensitivity
for CJD diagnosis. In this study, now report the sensitivity and specificity
of
several CSF biomarkers and general characteristics in a U.S. cohort of sCJD
and
non-prion rapidly progressive dementia (RPD) controls (Non-CJD cohort)
subjects.

Design/Methods:


Clinical diagnoses are made through review of medical
records, clinical evaluation, and in many cases pathology. Data is stored in
a secure
clinical relational database, which was queried for various CSF findings,
including
cell count, protein, IgG index, oligoclonal bands (OCBs), 14-3-3, NSE, T-Tau
in patients
with probable or definite sporadic CJD and non-prion rapidly progressive
dementias (RPD),
most of whom were referred to our center with a potential diagnosis of CJD.
For probable sCJD diagnosis, we used UCSF criteria that are modified from
WHO to
substitute MRI for 14-3-3. T-Tau and NSE were considered positive if > 1300
pg/ml and > 35 ng/ml, respectively. For this analysis, ambiguous 14-3-3
results were
considered as negative.


Results:

14-3-3 protein (n=149) sensitivity was only 48% (47% for definite; 50% for
probable sCJD). NSE (n=49) sensitivity was 63% (66% for definite; 59% for
probable
sCJD). T-Tau (n=28) was the most sensitive at 68% (69% for definite; 67% for
probable
sCJD). The specificity of these biomarkers among our CJD and RPD controls
(n=72)
was 66% for 14-3-3 (n=47), 81% for NSE (n=21), and 100% for T-Tau (n=7). The
14-3-3 had the lowest sensitivity and specificity. Mildly elevated CSF
protein
(<100 mg/dl) is common in sCJD; High WBC; >20, is uncommon in sCJD.


Conclusions/Relevance:


In a cohort from a major U.S. CJD referral center, the 14-3-3
is neither sensitive nor specific for sCJD. NSE and T-Tau also show poor
sensitivity for
sCJD. T-Tau may be more specific than 14-3-3 and NSE, but our “n” is small.
WHO
sCJD criteria should be revised; by eliminating 14-3-3 and including brain
MRI into the
criteria. We are currently analyzing the effects of disease duration and
codon 129
polymorphism on these CSF biomarker results.

http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf


TSS




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