Accelerated, Spleen-Based Titration of Variant Creutzfeldt-Jakob Disease Infectivity in Transgenic Mice Expressing Human Prion Protein with Sensitivity Comparable to That of Survival Time Bioassay
Accelerated, Spleen-Based Titration of Variant Creutzfeldt-Jakob Disease
Infectivity in Transgenic Mice Expressing Human Prion Protein with Sensitivity
Comparable to That of Survival Time Bioassay
Sophie Hallieza, Fabienne Reinea, Laetitia Herzoga, Emilie Jaumaina,
Stéphane Haïkb,c,d, Human Rezaeia, Jean-Luc Vilottee, Hubert Laudea and Vincent
Béringuea aINRA (Institut National de la Recherche Agronomique), UR892,
Virologie Immunologie Moléculaires, Jouy-en-Josas, France bINSERM, Equipe
maladie d'Alzheimer et maladies à Prions, CRicm, UMRS 975, CNRS UMR7225, UPMC.
R., Hôpital de la Salpêtrière, Paris, France cInVS, Centre national de référence
des Agents Transmissibles Non Conventionnels, Hôpital de la Salpêtrière, Paris,
France dAP-HP, Laboratoire de Neuropathologie, Hôpital de la Salpêtrière, Paris,
France eINRA, UMR1313, Génétique Animale et Biologie Intégrative, Jouy-en-Josas,
France B. W. Caughey, Editor + Author Affiliations
ABSTRACT The dietary exposure of the human population to the prions
responsible for the bovine spongiform encephalopathy (BSE) epizooty has led to
the emergence of variant Creutzfeldt-Jakob disease (vCJD). This fatal,
untreatable neurodegenerative disorder is a growing public health concern
because the prevalence of the infection seems much greater than the disease
incidence and because secondary transmission of vCJD by blood transfusion or use
of blood products has occurred. A current limitation in variant CJD risk
assessment is the lack of quantitative information on the infectivity of
contaminated tissues. To address this limitation, we tested the potential of a
transgenic mouse line overexpressing human prion protein (PrP), which was
previously reported to propagate vCJD prions. Endpoint titration of vCJD
infectivity in different tissues was evaluated by two different methods: (i) the
“classical” bioassay, based on the appearance of clinical symptoms and the
detection of pathological prion protein in tissues of the inoculated mouse, and
(ii) a shortened bioassay based on the detection of the protein in the mouse
spleen at defined time points. The two methods proved equally sensitive in
quantifying infectivity, even after very-low-dose inoculation of infected
material, but the time schedule was shortened from ∼2.5 years to ∼1 year with
the spleen bioassay. Compared to the “gold-standard” RIII model routinely used
for endpoint titration of vCJD/BSE prions, either method improved the
sensitivity by >2 orders of magnitude and allowed reevaluating the infectious
titer of spleen from a vCJD individual at disease end stage to
>1,000-fold-higher values.
IMPORTANCE Here, we provide key reevaluation of the infectious titer of
variant CJD brain and spleen tissues. The highly sensitive, accelerated
spleen-based assay should thus constitute a key advance for variant CJD
epidemiological and risk assessment purposes and should greatly facilitate
future titration studies, including, for example, those aimed at validating
decontamination procedures. The overlooked notion that the lymphoid tissue
exhibits a higher capacity than the brain to replicate prions even after
low-dose infection raises new questions about the molecular and/or cellular
determinant(s) involved, a key issue regarding potent silent carriers of variant
CJD in the lymphoid tissue.
FOOTNOTES Received 18 April 2014. Accepted 16 May 2014. Address
correspondence to Vincent Béringue, vincent.beringue@jouy.inra.fr. Published
ahead of print 21 May 2014
Copyright © 2014, American Society for Microbiology. All Rights
Reserved.
Monday, June 16, 2014
Preclinical Detection of Variant CJD and BSE Prions in Blood
Sunday, April 06, 2014
SPORADIC CJD and the potential for zoonotic transmission there from, either
directly or indirectly via friendly fire iatrogenic mode, evidence to date
Friday, January 10, 2014
vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type
prion disease, what it ???
Monday, May 19, 2014
Variant CJD: 18 years of research and surveillance
Monday, June 02, 2014
Confirmed Variant CJD Case in Texas
Friday, April 25, 2014
Accuracy of administrative diagnostic data for pathologically confirmed
cases of Creutzfeldt-Jakob disease CJD
Article in Press
U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
Wednesday, October 09, 2013
WHY THE UKBSEnvCJD ONLY THEORY IS SO POPULAR IN IT'S FALLACY, £41,078,281
in compensation REVISED
Tuesday, March 11, 2014
Science and Technology Committee Oral evidence: Blood, tissue and organ
screening, HC 990 Wednesday 5 March 2014 SPORADIC CJD
Actually, it is nearer 2 per million per year of the population will
develop sporadic CJD, but your lifetime risk of developing sporadic CJD is about
1 in 30,000. So that has not really changed. When people talk about 1 per
million, often they interpret that as thinking it is incredibly rare. They think
they have a 1-in-a-million chance of developing this disease. You haven’t.
You’ve got about a 1-in-30,000 chance of developing it.
Sunday, March 09, 2014
A Creutzfeldt-Jakob Disease (CJD) Lookback Study: Assessing the Risk of
Blood Borne Transmission of Classic Forms of Creutzfeldt-Jakob Disease
FDA TSEAC CIRCUS AND TRAVELING ROAD SHOW FOR THE TSE PRION DISEASES
Friday, February 14, 2014
Creutzfeldt-Jakob disease (CJD) biannual update (February 2014), with
briefing on novel human prion disease National CJD Research and Surveillance
Unit NCJDRSU
Tuesday, February 11, 2014
Novant Health Forsyth Medical Center Information on potential CJD exposure
Thursday, April 17, 2014
Novant: Three more may have been exposed to disease CJD
Wednesday, January 15, 2014
*** INFECTION PREVENTION AND CONTROL OF CJD, VCJD AND OTHER HUMAN PRION
DISEASES IN HEALTHCARE AND COMMUNITY SETTINGS Variably Protease-Sensitive
Prionopathy (VPSPr) January 15, 2014
*** 1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8
Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes
contaminated during neurosurgery.
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.
Laboratory of Central Nervous System Studies, National Institute of
Neurological Disorders and Stroke, National Institutes of Health,
Bethesda, MD 20892.
Stereotactic multicontact electrodes used to probe the cerebral cortex of a
middle aged woman with progressive dementia were previously implicated in the
accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger
patients. The diagnoses of CJD have been confirmed for all three cases. More
than two years after their last use in humans, after three cleanings and
repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were
implanted in the cortex of a chimpanzee. Eighteen months later the animal became
ill with CJD. This finding serves to re-emphasise the potential danger posed by
reuse of instruments contaminated with the agents of spongiform
encephalopathies, even after scrupulous attempts to clean them.
PMID: 8006664 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract
New studies on the heat resistance of hamster-adapted scrapie agent:
Threshold survival after ashing at 600°C suggests an inorganic template of
replication
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel
Production
Detection of protease-resistant cervid prion protein in water from a
CWD-endemic area
A Quantitative Assessment of the Amount of Prion Diverted to Category 1
Materials and Wastewater During Processing
Rapid assessment of bovine spongiform encephalopathy prion inactivation by
heat treatment in yellow grease produced in the industrial manufacturing process
of meat and bone meals
PPo4-4:
Survival and Limited Spread of TSE Infectivity after Burial
*** 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.
Saturday, November 16, 2013
Management of neurosurgical instruments and patients exposed to
creutzfeldt-jakob disease 2013 December
Infect Control Hosp Epidemiol.
Tuesday, May 28, 2013
Late-in-life surgery associated with Creutzfeldt-Jakob disease: a
methodological outline for evidence-based guidance
Wednesday, January 15, 2014
*** INFECTION PREVENTION AND CONTROL OF CJD, VCJD AND OTHER HUMAN PRION
DISEASES IN HEALTHCARE AND COMMUNITY SETTINGS Variably Protease-Sensitive
Prionopathy (VPSPr) January 15, 2014
Wednesday, November 27, 2013
NHS failed to sterilise surgical instruments contaminated with 'mad cow'
disease
Thursday, January 23, 2014
Medical Devices Containing Materials Derived from Animal Sources (Except
for In Vitro Diagnostic Devices) [Docket No. FDA–2013–D–1574]
Thursday, April 12, 2012
Health professions and risk of sporadic Creutzfeldt–Jakob disease, 1965 to
2010
Eurosurveillance, Volume 17, Issue 15, 12 April 2012
Research articles
Tuesday, May 28, 2013
Late-in-life surgery associated with Creutzfeldt-Jakob disease: a
methodological outline for evidence-based guidance
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
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
Thursday, October 25, 2012
Current limitations about the cleaning of luminal endoscopes and TSE prion
risk factors there from
Article in Press
Saturday, January 16, 2010
Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to
Bramble et al
Evidence For CJD/TSE Transmission Via Endoscopes
From Terry S. Singletary, Sr flounder@wt.net 1-24-3
Terry S. Singeltary Sr., P.O. BOX 42, Bacliff, Texas 77518 USA
Professor Michael Farthing wrote:
Louise Send this to Bramble (author) for a comment before we post. Michael
Tuesday, July 31, 2012
11 patients may have been exposed to fatal disease Creutzfeldt-Jakob
Disease CJD Greenville Memorial Hospital
Thursday, August 02, 2012
CJD case in Saint John prompts letter to patients Canada CJD case in Saint
John prompts letter to patients
Saturday, February 12, 2011
Another Pathologists dies from CJD, another potential occupational death ?
another happenstance of bad luck, a spontaneous event from nothing, or
friendly fire ???
Thursday, July 08, 2010
GLOBAL CLUSTERS OF CREUTZFELDT JAKOB DISEASE - A REVIEW 2010
Sunday, May 10, 2009
Meeting of the Transmissible Spongiform Encephalopathies Committee On June
12, 2009 (Singeltary submission)
Thursday, January 29, 2009
Medical Procedures and Risk for Sporadic Creutzfeldt-Jakob Disease, Japan,
1999-2008 (WARNING TO Neurosurgeons and Ophthalmologists) Volume 15, Number
2-February 2009 Research
Wednesday, August 20, 2008
Tonometer disinfection practice in the United Kingdom: A national survey
Tuesday, August 12, 2008
Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007
(occupational exposure to prion diseases)
Monday, December 31, 2007
Risk Assessment of Transmission of Sporadic Creutzfeldt-Jakob Disease in
Endodontic Practice in Absence of Adequate Prion Inactivation
Subject: CJD: update for dental staff
Date: November 12, 2006 at 3:25 pm PST
1: Dent Update. 2006 Oct;33(8):454-6, 458-60.
CJD: update for dental staff.
Friday, July 19, 2013
Beaumont Hospital in Dublin assessing patients for CJD
Saturday, September 21, 2013
CJD CONFIRMED in patient at New Hampshire Department of Health and Human
Services (DHHS), Catholic Medical Center (CMC), and the Manchester Health
Department (MHD)
Thursday, September 26, 2013
Minimise transmission risk of CJD and vCJD in healthcare settings Guidance
Sunday, October 27, 2013
A Kiss of a Prion: New Implications for Oral Transmissibility
Saturday, April 19, 2014
Human prion diseases and the risk of their transmission during anatomical
dissection
Wednesday, October 09, 2013
WHY THE UKBSEnvCJD ONLY THEORY IS SO POPULAR IN IT'S FALLACY, £41,078,281
in compensation REVISED
Tuesday, March 11, 2014
Science and Technology Committee Oral evidence: Blood, tissue and organ
screening, HC 990 Wednesday 5 March 2014 SPORADIC CJD
Actually, it is nearer 2 per million per year of the population will
develop sporadic CJD, but your lifetime risk of developing sporadic CJD is about
1 in 30,000. So that has not really changed. When people talk about 1 per
million, often they interpret that as thinking it is incredibly rare. They think
they have a 1-in-a-million chance of developing this disease. You haven’t.
You’ve got about a 1-in-30,000 chance of developing it.
Monday, June 23, 2014
*** PRION 2014 CONFERENCE CHRONIC WASTING DISEASE CWD
Monday, June 23, 2014
PRION 2014 CONFERENCE TYPICAL AND ATYPICAL BSE AND CJD REPORT UPDATES
Sunday, June 29, 2014
Transmissible Spongiform Encephalopathy TSE Prion Disease North America
2014
TSS
posted by Terry S. Singeltary Sr. | 1:44 PM
0 Comments:
Post a Comment
Subscribe to Post Comments [Atom]
<< Home