vCJD With Extremely Low Lymphoreticular Deposition of Prion Protein MAY NOT HAVE BEEN DETECTABLE
Case Report/Case Series | January 20, 2014
Variant Creutzfeldt-Jakob Disease With Extremely Low Lymphoreticular
Deposition of Prion Protein
ONLINE FIRST
Simon Mead, PhD1,2; Jonathan D. F. Wadsworth, PhD2; Marie-Claire Porter,
MRCP1; Jacqueline M. Linehan, BSc2; Wojciech Pietkiewicz, MD3; Graham S.
Jackson, PhD2; Sebastian Brandner, MD, FRCPath4; John Collinge, MD, FRCP, FRS1,2
[+] Author Affiliations
JAMA Neurol. Published online January 20, 2014.
doi:10.1001/jamaneurol.2013.5378
ABSTRACT
Importance Human transmission of bovine spongiform encephalopathy causes
the fatal neurodegenerative condition variant Creutzfeldt-Jakob disease (vCJD)
and, based on recent human prevalence studies, significant subclinical prion
infection of the UK population. To date, all clinical cases have been fatal,
totaling 228 mostly young adults residing in the United Kingdom.
Observations Here we describe the investigation and case history of a
patient recently diagnosed as having vCJD in the United Kingdom. Although his
presentation, imaging findings, cerebrospinal fluid investigation results, and
clinical progression were typical of other cases, tonsillar biopsy and
subsequent examination of multiple tissues at autopsy showed minimal deposition
of disease-associated prion protein in peripheral lymphoreticular tissue. The
result of a blood test for vCJD, the Direct Detection Assay for vCJD, was
negative.
Conclusions and Relevance These findings suggest that some patients with
vCJD have very low peripheral prion colonization and therefore may not have
detectable prion deposition in diagnostic tonsillar biopsy or markers of prion
infection in blood. These results have implications for accurate interpretation
of diagnostic tests and prevalence studies based on lymphoreticular tissue or
blood.
<<>>
not good, this is not good. makes one wonder about the final figures on the
previous estimates from tonsils tissue samples and results there from ??? ...tss
An earlier study of appendix and some tonsil tissue, from operations
conducted between 1995 and 1999, found three positive samples out of 12,674
screened for abnormal prion protein using the IHC method [5]. The prevalence
estimate calculated from this study was 237 per million overall (95% CI: 49-692
per million) – or 380 per million (95% CI=80-1120 per million) in those born
between 1961 and 1985. This prevalence estimate equals to one infection per
4,000 of the population in the 1961 to 1985 birth cohort, the cohort in which
most vCJD cases have arisen.
In 2008, the Spongiform Encephalopathy Advisory Committee (SEAC) considered
the available NATA data [6]. At that time no abnormal prion protein positive
samples had been found in nearly 55,000 samples, analysed by the high throughput
dual EIA screening technique, including about 11,000 samples from the 1961 to
1985 birth cohort [7]. This translated to a prevalence estimate of zero per
million (95% CI=0-324 per million) in this birth cohort. Statistical analysis of
the data from the previous appendix survey and NATA showed the prevalence rates
were consistent with each other.
To further investigate the prevalence of abnormal prion protein in the NATA
samples from patients in the 1961 to 1985 birth cohort, the IHC technique was
applied to screen 9,160 samples within that cohort; these samples which had
already been shown to be negative when screened by the dual EIA technique [8].
One specimen showed a single strongly positive follicle. The specimen was
negative when further investigated by EIA, IHC, and immunoblotting. This finding
of 1 in 9,160 gives a prevalence estimate of 109 infections per million (95% CI:
3-608 per million) in those born between 1961 and 1985 which is not
statistically different from the prevalence estimate based on the previous
appendix study (exact p =0.64).
The results of NATA and the “IHC screening” sub-study were considered by
SEAC in 2010 [9]. The committee agreed that “even though the positive sample
suggested a possible prevalence of 1:10,000, the result from the Hilton data of
1:4,000 would still remain the most precautionary figure for risk management
purposes”.
The Health Protection Agency is also coordinating a second Appendix Survey
in order to test for abnormal prion protein in archived appendix tissues in two
birth cohorts of individuals[10]. The study is an unlinked anonymous survey
testing approximately 20,000 samples from individuals born between 1961 and 1985
and 10,000 from those born between 1941 and 1960. The study is continuing but
the interim data shows that four out of 13,878 suitable samples across both
birth cohorts have tested positive for disease associated prion protein (PrP CJD
). This translates to a prevalence estimate of 288 per million (95% CI=79-738
per million). Two of the four positive samples were from the 1941-1960 birth
cohort resulting in a prevalence estimate of 641 per million (95% CI=78-2314 per
million) compared to 186 per million (95% CI=23-671 per million) in the younger
cohort of individuals. The interim data has been reviewed by the ACDP TSE Risk
Assessment Sub-Group [11].
snip...see ;
Friday, February 10, 2012
Creutzfeldt-Jakob disease (CJD) biannual update (2012/1) potential
iatrogenic (healthcare-acquired) exposure to CJD, and on the National Anonymous
Tonsil Archive
Monday, August 13, 2012
Summary results of the second national survey of abnormal prion prevalence
in archived appendix specimens August 2012
Tuesday, October 05, 2010
Large-scale immunohistochemical examination for lymphoreticular prion
protein in tonsil specimens collected in Britain
05 Oct 2010 14:46
Monday, October 14, 2013
Researchers estimate one in 2,000 people in the UK carry variant CJD
proteins
WHAT about the sporadic CJD TSE proteins ?
WE now know that some cases of sporadic CJD are linked to atypical BSE and
atypical Scrapie, so why are not MORE concerned about the sporadic CJD, and all
it’s sub-types $$$
Creutzfeldt-Jakob Disease CJD cases rising North America updated report
August 2013
*** Creutzfeldt-Jakob Disease CJD cases rising North America with Canada
seeing an extreme increase of 48% between 2008 and 2010 ***
Sunday, October 13, 2013
*** CJD TSE Prion Disease Cases in Texas by Year, 2003-2012
Monday, December 02, 2013
*** A parliamentary inquiry has been launched today into the safety of
blood, tissue and organ screening following fears that vCJD – the human form of
‘mad cow’ disease – may be being spread by medical procedures
Wednesday, December 11, 2013
Detection of Infectivity in Blood of Persons with Variant and Sporadic
Creutzfeldt-Jakob Disease
Thursday, January 2, 2014
*** CWD TSE Prion in cervids to hTGmice, Heidenhain Variant
Creutzfeldt-Jacob Disease MM1 genotype, and iatrogenic CJD ???
Friday, January 10, 2014
*** vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial
type prion disease, what it ???
Monday, January 13, 2014
*** Prions in Variably Protease-Sensitive Prionopathy: An Update Pathogens
2013
Pathogens 2013, 2, 457-471; doi:10.3390/pathogens2030457
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
Sunday, January 19, 2014
*** National Prion Disease Pathology Surveillance Center Cases Examined1 as
of January 8, 2014 ***
Thursday, January 23, 2014
Medical Devices Containing Materials Derived from Animal Sources (Except
for In Vitro Diagnostic Devices) [Docket No. FDA–2013–D–1574]
kind regards,
terry
posted by Terry S. Singeltary Sr. | 1:08 PM
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