Multiorgan Detection and Characterization of Protease-Resistant Prion Protein in a Case of Variant CJD Examined in the United States

PLoS One. 2010; 5(1): e8765. Published online 2010 January 19. doi: 10.1371/journal.pone.0008765. PMCID: PMC2808239

Copyright Notari et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Multiorgan Detection and Characterization of Protease-Resistant Prion Protein in a Case of Variant CJD Examined in the United States

Silvio Notari,#1 Francisco J. Moleres,#1 Stephen B. Hunter,2 Ermias D. Belay,3 Lawrence B. Schonberger,3 Ignazio Cali,1 Piero Parchi,4 Wun-Ju Shieh,3 Paul Brown,5 Sherif Zaki,3 Wen-Quan Zou,1 and Pierluigi Gambetti1* 1Institute of Pathology, Case Western Reserve University, Cleveland, Ohio, United States of America 2Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, Georgia, United States of America 3National Center for Zoonotic, Vector-Borne, and Enteric Diseases, Center for Disease Control and Prevention, Atlanta, Georgia, United States of America 4Dipartimento di Scienze Neurologiche, Universita' di Bologna, Italy 5CEA/DSV/iMETI/SEPIA, France Delia Goletti, Editor National Institute for Infectious Diseases L. Spallanzani, Italy #Contributed equally. * E-mail: pxg13@case.edu Conceived and designed the experiments: SN FJM PG. Performed the experiments: SN FJM IC. Analyzed the data: SN FJM PB WQZ PG. Contributed reagents/materials/analysis tools: SBH WJS SZ PG. Wrote the paper: SN FJM SBH EDB LBS IC PP WJS PB SZ WQZ PG. Received October 19, 2009; Accepted December 18, 2009.

ABSTRACT

Background Variant Creutzfeldt–Jakob disease (vCJD) is a prion disease thought to be acquired by the consumption of prion-contaminated beef products. To date, over 200 cases have been identified around the world, but mainly in the United Kingdom. Three cases have been identified in the United States; however, these subjects were likely exposed to prion infection elsewhere. Here we report on the first of these subjects.

Methodology/Principal Findings Neuropathological and genetic examinations were carried out using standard procedures. We assessed the presence and characteristics of protease-resistant prion protein (PrPres) in brain and 23 other organs and tissues using immunoblots performed directly on total homogenate or following sodium phosphotungstate precipitation to increase PrPres detectability. The brain showed a lack of typical spongiform degeneration and had large plaques, likely stemming from the extensive neuronal loss caused by the long duration (32 months) of the disease. The PrPres found in the brain had the typical characteristics of the PrPres present in vCJD. In addition to the brain and other organs known to be prion positive in vCJD, such as the lymphoreticular system, pituitary and adrenal glands, and gastrointestinal tract, PrPres was also detected for the first time in the dura mater, liver, pancreas, kidney, ovary, uterus, and skin.

Conclusions/Significance Our results indicate that the number of organs affected in vCJD is greater than previously realized and further underscore the risk of iatrogenic transmission in vCJD.

snip...

The oral route of prion infection in vCJD raised the possibility that tissues and organs, beside the central nervous system (CNS), might also be affected. To date, PrPres has been reported in several tissues and organs outside the CNS of vCJD patients (Table 1) [14–19, P. Brown, unpublished data].

Although the amount of PrPres in non-neural tissues is small compared to that in the brain, the risk posed by the spread of even small amounts of PrPres has been underscored by the iatrogenic transmission of vCJD from blood donors in the preclinical phase of the disease [20].

We examined the main characteristics and tissue distribution of PrPres in a case of vCJD, in which the disease was most likely acquired in the UK but which is officially referred to as an American case because illness onset occurred in the US [21]. In an extensive autopsy examination, sodium phosphotungstate (NaPTA) precipitation, a highly sensitive method of PrPres detection [14,22], was used to establish the presence and estimate the relative amounts of PrPres in several organs and tissues made available to the National Prion Disease Pathology Surveillance Center (NPDPSC).

snip...

Results Clinical History Clinical data on the present patient have been reported in detail [21]. Briefly, the patient lived in Britain until the age of 13 and immigrated to the US in 1992. In early November 2001, at the age of 22 years, the patient was evaluated for depression, emotional instability and memory loss, followed one month later by involuntary movements, gait disturbances and incontinence. During the ensuing three months, the patient’s motor and cognitive deficits worsened, and confusion, hallucination, dysarthria, bradykinesia, and spasticity also occurred. The diagnosis of vCJD was made following brain magnetic resonance imaging and confirmed by immunoblot and immunohistochemistry of tonsil tissue. She received an experimental treatment with quinacrine for 3 months, but showed only minimal and transitory improvement. The patient died in June 2004, 32 months after the clinical onset.

snip...

Discussion Our study confirms the diagnosis of vCJD in the present case, based on the characteristics of the PrPres and the methionine homozygosity at codon 129 of the PrP gene, the last feature being invariably present in vCJD [32]. However, we also observed two unusual features in this case. The first is the long disease duration of 32 months, which is more than twice the 14 month mean duration of the British cases of vCJD [3]. However, cases of up to 40 months duration after the diseases onset have been reported [3,33]. The second unusual feature is the absence of typical spongiform degeneration which likely stemmed from the long duration of the disease. The long disease duration likely led to extensive loss of neurons, in which most of the vacuoles are formed, with ensuing astroglial scar [34].

As previously reported [21], the BSE exposure most likely occurred between the early eighties, when the BSE epidemic emerged in the UK, and 1992, when the patient immigrated to the US. This assumption is consistent with an incubation period of 9 to 21 years, which correlates well with the medium incubation period of 17 years estimated for the UK cases of vCJD [35]. The brain PrPres of the present case displayed the glycoform ratio and electrophoretic mobility characteristic of the PrPres associated with vCJD [5]. One exception is the cerebellum where the monoglycosylated and unglycosylated PrPres isoform migrated slightly faster than the PrPres from other brain regions and resolved in three bands. The variation in PrPres electrophoretic characteristics between the cerebellum and the cerebral cortex is not surprising for it has also been observed in sCJD [36]. Yet to our knowledge it has never been reported in vCJD. Finally, contrary to previous reports [29], PrPres type 1 did not co-occur with type 2. This discrepancy might stem from our rigorous PrP digestion with PK and from the use of different antibodies, an approach that rules out the possibility that partially cleaved fragments derived by the incomplete digestion of PrPSc be misinterpreted as the type 1 fragment [30,37].

The major finding of the present study is the demonstration that PrPres is present in a number of non-CNS tissues and organs which previous studies had reported as free of PrPres (Table 1 and 2) [14– 19, P. Brown, unpublished data]. These tissues include the dura mater, skin, liver, kidney, pancreas, descending colon, uterus and ovary (Table 2 and Fig. 3). The use of NaPTA, along with the long disease duration, may both have contributed to the undisputed detection of PrPres in these organs in this case. The glycoform ratio of the brain PrPres was not retained in every peripheral organ examined (Fig. 4). In the pituitary gland and the skin the diglycosylated and monoglycosylated PrPres isoforms were about equally represented thus the diglycosylated isoform was not dominant. On the other hand, electrophoretic mobility appeared to match that of the brain. Variations in the glycoform ratio could be assessed only on the TH because the glycoform ratio, as well the electrophoretic mobility, is affected by NaPTA enrichment [14].

The presence of prion in the human dura mater is not surprising because sCJD has been transmitted following transplantation of dura obtained from sCJD-affected cases [38]. However, to our knowledge this is the first immunoblot demonstration of PrPres in the dura mater in any prion disease. The detection of relatively large amounts of PrPres in the dura mater raises the possibility of contamination with brain tissue at autopsy. Although this possibility cannot be completely ruled out, extensive rinses in PBS were performed before homogenization in some experiments without observing a reduction in the amount of the PrPres detected.

Prion infectivity of kidney and liver has been demonstrated by bioassay in other human prion diseases [39], and PrPres has been observed in the kidney of scrapie infected sheep [40]. The presence of PrPres has also been reported in kidney, liver and pancreas of scrapie infected mice in association with lymphofollicular proliferation [41]. This last finding is relevant to the present case in which multiple lymphocytic infiltrates with follicular pattern were present in the kidney. However, contrary to this report, we observed no significant inflammatory reaction in any of the other tissues which contained PrPres. A puzzling finding of our study is the presence of PrPres albeit in small amounts in the kidney but not in the urinary bladder. This apparent discrepancy is relevant to the recent demonstrations of prion infectivity in urine

of animals carrying experimental or naturally occurring prion diseases [42–46]. It would indicate that prion infectivity in urine is acquired from the kidney while the urinary bladder acts as a bystander. However the amount of PrPres we observed in the kidney was minimal, and might have not been sufficient to infect the urine and to propagate to the bladder in detectable amounts. Indeed we failed to demonstrate PrPres in the urine in the present case even after hundred-fold urine concentration (data not shown). Obviously more studies are needed to clarify this issue. The present study also demonstrates for the first time the presence of PrPres in the skin in a human prion disease. Previously, PrPres has been detected in the skin from animals with experimental or naturally occurring scrapie [47] as well as in the antler velvet of elk affected by CWD [48].

Furthermore, it is remarkable that we observed PrPres in the uterus and the ovary, a finding which implicates the reproductive system, thereby raising the possibility of maternal transmission of vCJD. Vertical transmissibility of prion infection has been demonstrated in transgenic mice infected with BSE [49]. Related literature on human prion diseases is very scanty. Pregnancy completed to delivery has been reported in sCJD, iatrogenic CJD and vCJD [50,51]; however, transmission to the progeny has not been examined in detail or confirmed in any of these cases. The first detailed determination of PrPC and PrPres in the reproductive and gestational tissues from a sCJD patient has been carried out only recently [51]. Although this study failed to detect PrPres, remarkably it showed that, in uterine tissue obtained at biopsy, most of the PK-sensitive PrP is truncated at the N-terminus and matches the C-terminal PrPC fragment C1 which is generated during normal PrPC metabolism [51]. Similarly, in the present case we observed that the C1-like fragment was largely predominant over the full-length PrPC in the uterus, and it was easily digested by PK but it was present along with a significant amount of characteristic vCJD PrPres (Fig. 4). Since the Nterminus of the PrPres type 2 associated with vCJD is at residues 92–99, the uterine PrPres must have formed from the full length PrPC rather than from C1, the N-terminus of which is at residues 111–112 [31,52]. These findings raise the question of the origin of the PrPres found in the uterus, a question that is currently unanswered. A similar question may be raised for the urine, in

which although the prion infectivity has been demonstrated in animals by bioassay [42–46], the only detected form of PrP under normal condition in animals and humans, is a fragment matching the C1 [53, 54, Notari et al., unpublished data].

All these considerations notwithstanding, the widespread presence of PrPres in visceral organs that we observed in the present case further reinforces the concerns over iatrogenic transmission of vCJD. These concerns are already compelling given the multiple reports of vCJD transmission by blood transfusion.


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2808239/pdf/pone.0008765.pdf





Wednesday, January 27, 2010


Fast, broad-range disinfection of bacteria, fungi, viruses and prions


http://creutzfeldt-jakob-disease.blogspot.com/2010/01/fast-broad-range-disinfection-of.html




Saturday, January 23, 2010


Experimental Verification of a Traceback Phenomenon in Prion Infection


http://creutzfeldt-jakob-disease.blogspot.com/2010/01/experimental-verification-of-traceback.html




Sunday, January 17, 2010


CJD Following up: Patients never contracted brain disorder UW Hospital patients


http://creutzfeldt-jakob-disease.blogspot.com/2010/01/cjd-following-up-patients-never.html




Sunday, January 17, 2010


Human tissue, recovered from a donor history indicated increased risk factors for Creutzfeldt-Jacob disease Lions Eye Bank


http://creutzfeldt-jakob-disease.blogspot.com/2010/01/human-tissue-recovered-from-donor.html




Saturday, January 16, 2010


Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to Bramble et al


http://creutzfeldt-jakob-disease.blogspot.com/2010/01/evidence-for-cjd-tse-transmission-via.html




Sunday, August 09, 2009

CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009


http://creutzfeldt-jakob-disease.blogspot.com/2009/08/cjdstraight-talk-withjames.html



Tuesday, August 18,

2009 BSE-The Untold Story - joe gibbs and singeltary 1999 - 2009


http://madcowusda.blogspot.com/2009/08/bse-untold-story-joe-gibbs-and.html



R.I.P. MOM hvCJD confirmed DECEMBER 14, 1997

Monday, December 14, 2009

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types


http://nor-98.blogspot.com/2009/12/similarities-between-forms-of-sheep.html



Saturday, January 2, 2010

Human Prion Diseases in the United States January 1, 2010 ***FINAL***


http://prionunitusaupdate2008.blogspot.com/2010/01/human-prion-diseases-in-united-states.html


my comments to PLosone here ;


http://www.plosone.org/annotation/listThread.action?inReplyTo=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd&root=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd



TSS

Variant Creutzfeldt–Jakob disease: the first confirmed case from Portugal shows early onset, long duration and unusual pathology

J Neurol Neurosurg Psychiatry 2010;81:112-114 doi:10.1136/jnnp.2009.164293

Short report

Variant Creutzfeldt–Jakob disease: the first confirmed case from Portugal shows early onset, long duration and unusual pathology

C Barbot1, L Castro2, C Oliveira3, S Carpenter2 + Author Affiliations

1Department of Neuropaediatrics, Hospital Maria Pia, Porto, Portugal 2Anatomical Pathology Service, Hospital S João, Porto, Portugal 3Neurochemistry Laboratory, Department of Neurology, Hospitals of the University of Coimbra, Coimbra, Portugal Correspondence to Dr S Carpenter, Anatomic Pathology Service, Hospital São João, Alamêda Professor Hernani Monteiro, 4202-451 Porto, Portugal; scarpenter@mail.telepac.pt Received 2 October 2008 Revised 14 February 2009 Accepted 20 February 2009

Abstract

We present clinical and autopsy findings in the first case of variant Creutzfeldt–Jakob disease diagnosed and confirmed in Portugal. Onset was at 11 years, the earliest onset reported, and the course (32 months) relatively long. Western blot showed protease resistant prion protein, mainly of type 4 (2B) isoform. The cerebral cortex revealed severe spongiform change with numerous amyloid plaques, which did not fit the definition of florid plaques. In the striatum, spongiform change was limited but the extracellular space was dilated. Other reports have found marked spongiform change in the striatum and little in the cortex. Massive neuronal loss, in excess of what has been described, was found in the thalamus and pontine grey. The cerebellum showed, as expected, severe loss of granule cells, moderate loss of Purkinje cells and marked immunopositivity for the prion protein. Differences between our findings and previous ones probably result from the patient’s long survival.



http://jnnp.bmj.com/content/81/1/112.abstract




Thursday, December 3, 2009


FINAL REPORT OF A MISSION CARRIED OUT IN PORTUGAL FROM 11 TO 20 MAY 2009 IN ORDER TO EVALUATE MEASURES CONCERNING BOVINE SPONGIFORM ENCEPHALOPATHY


http://docket-aphis-2006-0041.blogspot.com/2009/12/final-report-of-mission-carried-out-in.html



Thursday, December 17, 2009

An Unusual Case of Variant CJD 18 December 2009


http://creutzfeldt-jakob-disease.blogspot.com/2009/12/unusual-case-of-variant-cjd-18-december.html




Saturday, June 13, 2009

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009

http://cjdusa.blogspot.com/2009/06/monitoring-occurrence-of-emerging-forms.html




TSS

An Unusual Case of Variant CJD 18 December 2009

An Unusual Case of Variant CJD 18 December 2009

A Case Report published in this week’s The Lancet, written by Professor John Collinge, MRC Prion Unit and National Prion Clinic, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, reports the particular genetic make-up of a 30-year old man who has died of variant Creutzfeldt–Jakob disease (vCJD). The case report suggests that there could be other people with the condition who at the moment have no symptoms.

vCJD is caused by infectious agents called prions, which are made primarily of protein. The prions which cause vCJD are the same as those that cause bovine spongiform encephalopathy (BSE, also known as mad cow disease) in cows. Prion diseases affect the structure of the brain or other neural tissue, and all are currently untreatable and eventually fatal. Disease-causing prions are thought to consist of abnormally folded proteins that spread by encouraging the normal healthy prion protein found on the surface of most cells in the body to change shape. Prion diseases share similar disease mechanisms with Alzheimer’s, Parkinson’s, and other neurodegenerative brain diseases.

The 30-year-old man was admitted to hospital in June, 2008, with a 13-month history of personality change, progressive unsteadiness, and intellectual decline. He complained of severe leg pain and poor memory. Two months later he developed visual hallucinations. His symptoms worsened over the next three months. An MRI scan and other tests led to a diagnosis of vCJD. The man died in January 2009.

The case is unusual because tests showed the man had a particular genotype at his human prion protein gene (PRNP 129 codon), which can code for the amino acids valine (V) or methionine (M). People can be VV (homozygous), MM (again homozygous), or MV (heterozygous). Since 1994, around 200 cases of vCJD have been identified worldwide, and all those tested have been MM homozygous. However, the man in this Case Report was heterozygous.

Other prion diseases such as kuru or CJD associated with the use of pituitary hormones tend to have longer incubation periods in people who are PRNP heterozygous than those who are MM homozygous. The authors have recently reported some heterozygous patients with kuru had been incubating the disease over 50 years. Thus the authors believe there could be other cases like this one in which people are infected with vCJD but experiencing a long incubation period.

The authors say:

“The majority of the UK population have potentially been exposed to BSE prions but the extent of clinically silent infection remains unclear. About a third of the UK population are PRNP codon 129 methionine homozygous. If individuals with other genotypes are similarly susceptible to developing prion disease after BSE prion exposure, but with longer incubation periods, further cases, which may or may not meet diagnostic criteria for vCJD, would be expected in these PRNP codon 129 genotypes.”

They conclude:

“However, prion disease susceptibility and incubation periods are also affected by other genetic loci, and the possibility remains that cases of vCJD to date may have unusual combinations of genotypes at these loci, yet to be fully characterised.”

Press contact: 020 7637 6011 press.office@headoffice.mrc.ac.uk


http://www.mrc.ac.uk/Newspublications/News/MRC006556



Case Report

Variant CJD in an individual heterozygous for PRNP codon 129

Diego Kaski, Simon Mead, Harpreet Hyare, Sarah Cooper, Ravi Jampana, James Overell, Richard Knight, John Collinge, Peter Rudge

A 30-year-old man was admitted to hospital in June, 2008, with a 13-month history of personality change, progressive unsteadiness, and intellectual decline. He complained of severe leg pain and poor memory. 2 months later he de-veloped visual hallucinations and falsely believed he had an abdominal tumour. Symptoms worsened over the next 3 months. In October, 2008, his score on the mini mental state examination was 26/30. Pursuit eye movements were saccadic. He had a pout reflex. There was mild ataxia in the arms. His legs were severely ataxic with brisk tendon reflexes and a left extensor plantar response. He needed two crutches to walk. Medical history included tonsillectomy and removal of a cervical lymph node 15 years previously but he had never had a blood trans-fusion or received implantation of other human tissues.

EEG showed slow wave activity. CSF protein, glucose, and cell count were normal but the 14-3-3 protein was positive. MRI of the brain was consistent with the pulvinar sign (figure A). Although not all neuroradiologists con-sulted considered the pulvinar sign positive, quantitative assessment showed symmetrical higher signal in the pul-vinar nuclei than the caudate nuclei (figure B). Extensive screens for genetic, metabolic, and autoimmune diseases, including those induced by neoplasia, were negative. PRNP analysis did not show any known disease-associated mutations; codon 129 was heterozygous. A clinical diag-nosis of variant Creutzfeldt-Jakob disease (vCJD) was made on the basis of a characteristic clinical onset and progres-sion, exclusion of other diagnoses, and MRI findings. Sporadic CJD was judged unlikely given the combination of young age, clinical features, MRI findings, and absence of pseudoperiodic complexes on EEG. His carers did not want further investigation. His condition deteriorated and he died in January, 2009. Autopsy was not done.

Human prion diseases have acquired, sporadic, and inherited aetiologies, show wide phenotypic heterogeneity, and are associated with propagation of infectious prions of many distinct strain types.1 Since 1994, about 200 cases of vCJD, causally related to exposure to bovine spongiform encephalopathy (BSE) prions, have been identified world-wide. vCJD is generally seen in young adults, has charac-teristic neuropathological features and tissue distribution of infectivity, and a distinctive type 4 (London classifica-tion) molecular strain type.1 A polymorphism at codon 129 (encoding methionine or valine) of the human prion protein gene (PRNP), constitutes a powerful susceptibility factor in all types of prion disease. In vCJD, every case genotyped to date has been methionine homozygous. In the other acquired prion diseases, cases have occurred in all genotypes but with different mean incubation periods,1 which can span decades;2 PRNP codon 129 heterozygotes generally have the longest incubation periods. There is a report of a recipient of a blood transfusion from a donor incubating vCJD who died of unrelated causes but showed signs of prion infection at autopsy and was PRNP codon 129 heterozygous.3 Animal studies have suggested that different clinicopathological phenotypes could occur in people with various PRNP codon 129 genotypes.4,5 The majority of the UK population have potentially been exposed to BSE prions but the extent of clinically silent infection remains unclear. About a third of the UK population are PRNP codon 129 methionine homozygous. If individuals with other genotypes are similarly susceptible to developing prion disease after BSE prion exposure, but with longer incubation periods, further cases, which may or may not meet diagnostic criteria for vCJD, would be expected in these PRNP codon 129 genotypes. However, prion disease susceptibility and incubation periods are also affected by other genetic loci, and the possibility remains that cases of vCJD to date may have unusual combinations of genotypes at these loci, yet to be fully characterised.

Figure: MRI (A) Increased signal intensity in the pulvinar nucleus bilaterally (arrow). (B) MR signal intensity in the pulvinar (Pu) is higher than in the head of the caudate nuclei (C), putamen (P), and right frontal white matter (FWM).

Contributors

All authors were involved in discussion about diagnosis, care of the patient, and preparation of the report. Written consent to publish was obtained.

Conflicts of interest

JC is a director and shareholder of D-Gen Ltd, an academic spin-out company in the field of prion disease diagnosis, decontamination, and therapy. The other authors declare that they have no conflicts of interest.

References

1 Collinge J. Prion diseases of humans and animals: their causes and molecular basis. Annu Rev Neurosci 2001; 24: 519–50.

2 Collinge J, Whitfield J, McKintosh E, et al. Kuru in the 21st century–an acquired human prion disease with very long incubation periods. Lancet 2006; 367: 2068–74.

3 Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW. Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 2004; 364: 527–29.

4 Asante E, Linehan J, Gowland I, et al. Dissociation of pathological and molecular phenotype of variant Creutzfeldt-Jakob disease in transgenic human prion protein 129 heterozygous mice. Proc Natl Acad Sci USA 2006; 103: 10759–64.

5 Wadsworth JD, Asante E, Desbruslais M, et al. Human prion protein with valine 129 prevents expression of variant CJD phenotype. Science 2004; 306: 1793–96.


http://press.thelancet.com/vcjd.pdf



Tuesday, December 15, 2009

Intraspecies transmission of L-type-like bovine spongiform encephalopathy detected in Japan

NOTE


http://bse-atypical.blogspot.com/2009/12/intraspecies-transmission-of-l-type.html



Monday, October 19, 2009

Atypical BSE, BSE, and other human and animal TSE in North America Update October 19, 2009


http://bse-atypical.blogspot.com/2009/10/atypical-bse-bse-and-other-human-and.html




2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006


http://bse-atypical.blogspot.com/2006/08/bse-atypical-texas-and-alabama-update.html




Monday, December 14, 2009 R.I.P. MOM hvCJD December 14, 1997

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

http://nor-98.blogspot.com/2009/12/similarities-between-forms-of-sheep.html



Saturday, December 05, 2009

Molecular Model of Prion Transmission to Humans


http://creutzfeldt-jakob-disease.blogspot.com/2009/12/molecular-model-of-prion-transmission.html



Tuesday, August 11, 2009

Characteristics of Established and Proposed Sporadic Creutzfeldt-Jakob Disease Variants


http://creutzfeldt-jakob-disease.blogspot.com/2009/08/characteristics-of-established-and.html



Friday, December 11, 2009 Sporadic Creutzfeldt-Jakob disease causing a 2-years slowly progressive isolated dementia


http://creutzfeldt-jakob-disease.blogspot.com/2009/12/sporadic-creutzfeldt-jakob-disease.html



Sunday, August 09, 2009

CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009


http://creutzfeldt-jakob-disease.blogspot.com/2009/08/cjdstraight-talk-withjames.html



Saturday, June 13, 2009

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009


http://cjdusa.blogspot.com/2009/06/monitoring-occurrence-of-emerging-forms.html



TSS

NATIONAL CREUTZFELDT-JAKOB DISEASE SURVEILLANCE UNIT SCIENTIFIC REPORT 2007/08

NCJDSU Scientific Report 2008

SPORADIC CJD

Question 7. What is the cause of sporadic CJD (sCJD) ?

What are the risks of secondary transmission of sCJD?

Case control studies

Risk factor information has been collected for cases of sporadic CJD since before the Unit was established in 1990. Over the years various control groups have been recruited; the method chosen depending on the resources available and anticipated validity. These have been detailed in various previous NCJDSU Annual Reports.

Since 1990 there have been five papers published examining risk factors for sCJD that the Unit has either led or collaborated in:-

1) Wientjens et al, Neurology 1996. A meta analysis of three case control studies (178 CJD cases and 333 controls). The results showed an elevated risk of CJD for those with a family history of dementia, a history of poliomyelitis, those employed as health professionals and those exposed to cows and sheep. There was no association with consumption of animal organs, including brain.

2) van Duijn et al, Lancet 1998- this compared 405 CJD cases and 405 hospital controls recruited as part of the 1993-95 EU collaborative studies of CJD in Europe. The findings suggested that genetic factors other than CJD mutations may play an important part in CJD. Iatrogenic transmission seemed rare in the population studied. There was little evidence of association between the risk of CJD and animal exposure or consumption of processed bovine meat or milk products for the period studied.

3) Zerr I et al, J Clin Epid 2000- medical risk factors were examined using the 405 CJD cases and 405 hospital controls recruited as part of the 1993-95 EU collaborative studies of CJD in Europe. The study failed to identify any common medical risk factor for CJD.

4) Ward et al, Neurology 2002- Surgical risk factors from 326 sCJD cases recruited as part of the 1993-95 EU collaborative studies of CJD in Europe were compared with 326 community controls recruited by telephone in 2000. A history of surgery was associated with risk of sCJD and the results supported the hypothesis that sCJD may result from hitherto unrecognised surgical contamination events.

42

NCJDSU Scientific Report 2008

5) Ward et al, Annals of Neurology 2007- Medical risk factors for 431 sCJD cases resident in the UK and referred to NCJDSU between 1998-2006 were compared with 454 general population control subjects recruited 2002-2003 (see NatCen controls in Appendix 6). This study found some evidence for a link between increased risk of sCJD and surgery, however there was no convincing evidence of temporal-geographical links between cases undergoing neurosurgery or gynaecological surgery. It concluded that it was unlikely that a high proportion of UK sCJD cases were the result of surgical transmission, but the possibility of such transmission cannot be excluded.

As for vCJD (see Questions 2 and 5 above), further work examining data from general practitioner records of cases and controls needs to be carried out in order to accurately determine risk for sCJD associated with medical or surgical procedures. This is on-going, though the priority has been given to vCJD at present.

Blood transfusion

An analysis of the potential for blood transfusion to be a risk factor for the development of sporadic CJD has been undertaken collaboratively by the major EU countries (coordinator M Pocchiari). A prospective study is under consideration.

Genetic factors

Possible genetic factors related to sCJD are being investigated by the Unit, both internally and through external collaboration (see Question 8 below).

Geographical distribution

The investigation of the geographical distribution of sporadic CJD by genetic and molecular subtype is on-going in the Unit.

43

NCJDSU Scientific Report 2008

Question 8: What are the clinico-pathological, genetic & molecular features of sporadic CJD and how are they related?

While this is an interesting question in its own right, it has an extremely important bearing on the Unit’s core surveillance function, particularly in relation to vCJD. This is because the most important and potentially difficult differential diagnosis of vCJD is sCJD; many initial reports of suspect cases of vCJD in the UK and elsewhere, have been found to be atypical cases of sCJD. A full characterisation of the clinico- pathological, epidemiological and molecular phenotypes of sCJD is therefore clearly essential, which the Unit has continued to carry out within the UK.
Atypical clinical presentations, disease courses and pathological findings are found in only a small percentage of sCJD cases and so are difficult to characterise, even in the UK population of 50-60 million. This is of particular importance in relation to any attempt to recognise new clinical disease phenotypes either related to BSE or, potentially, to other animal diseases. Therefore, our international collaborations have contributed greatly to the analysis of clinical, epidemiological and pathological data. For example, within the NEUROCJD collaboration, a detailed study was undertaken of particular presentations of sporadic CJD, such as pure cerebellar ataxia and Heidenhain’s syndrome (currently being prepared for publication). Studies of atypical forms and cases with young age of onset are in progress (Murray et al, J Neurol Neurosurg Psychiatry 2008). The large number of cases of sCJD accumulated within the system allowed a detailed study of the factors that separately influence disease duration (Pocchiari et al, Brain 2004).
It is well established that the clinico-pathological features of sCJD vary with PRNP-129 genotype and PrP protein type. Both the Unit’s Molecular Genetic and Protein Laboratories contribute to the full clinico-pathological-molecular characterisation of sCJD cases and research is being undertaken into these correlations. Research into possible genetic factors that affect susceptibility and disease phenotype in sCJD has been described above in Question 3.
The differentiation of atypical sCJD from vCJD is potentially aided by prion protein molecular data. However, the relationship between PrP protein type and CJD strain is not as straightforward as it initially seemed and, in particular, the Unit has been active in research into the phenomenon of the co-occurrence of prion types in individual cases of

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NCJDSU Scientific Report 2008

CJD. Work carried out by the Prion Protein Laboratory used a type 1 specific antibody (12B2) to show that type 1 PrPres is a minor component in brains of sporadic CJD cases previously classified as type 2 and also that a minority type 1 component is present in BSE brain, in all tested cases of vCJD and in vCJD transmitted to wild-type mice (Yull et al, Am J Pathol 2006). Whilst this work provoked interest and a study with similar conclusions was published by the Aguzzi laboratory (University Hospital, Zurich), the findings are somewhat controversial. To address this, the Unit has conducted a detailed study of the WHO CJD standard reference materials (available from the UK National Institute for Biological Standards and Control) to compare the PrPres mixtures in cases of sporadic CJD that are acknowledged to be genuine mixtures, to those of vCJD where antibodies such as 12B2 are needed to detect the type 1 component. A paper is in preparation for publication. The distribution of disease-related prion protein in extra-neural tissues (such as skeletal muscle and pituitary) in cases of sCJD is an area of developing interest (Peden et al, Am J Pathol 2006; J Gen Virol 2007), which the Prion Protein Laboratory plans to continue to pursue in the future.

The protein laboratory studies have also included work on other forms of CJD. The study of iatrogenic CJD shows the presence of types 1 and/or type 2 PrPres, similar to those found in sporadic CJD, but with a very different protein type and codon 129 genotype distribution. These data, and that on panencephalopathic CJD, have been correlated with clinico-pathological data and are currently being prepared for publication and provide valuable comparisons with the sporadic and variant forms of CJD.

The relationship between PrPres type and agent strain is being investigated by ongoing analysis of transmission to wild-type mice in collaboration with the Neuropathogenesis Division, Roslin Institute. Studies of the transmission characteristics of subtypes of sporadic CJD in a human transgenic model have also been completed (J Manson) and provide important information on the extent of strain variation in sCJD and the influence of codon 129 genotype and prion protein type. This later project is harmonised with the EU funded HUMTRANS project which aims at identifying strain variation in all forms of human prion disease, including ’atypical’ cases (J Manson).

Complementing animal transmission studies the Prion Protein Laboratory aims to model the transmission of human prions, and prion protein conversion, by comparing the

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NCJDSU Scientific Report 2008

results of mouse transmission studies with the infection of cell cultures (including human stem cells) and the cell-free protein misfolding cyclic amplification (PMCA) method. The results of initial studies using PMCA indicate that amplification depends on both host and agent factors and that PrPres types are amplified with fidelity from sCJD brain (Jones & Head, unpublished observation). ...

snip...


http://www.cjd.ed.ac.uk/scientificreport.pdf





Sunday, August 09, 2009


CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009


http://creutzfeldt-jakob-disease.blogspot.com/2009/08/cjdstraight-talk-withjames.html




also see ;





Further characterisation of the prion protein molecular types detectable in the NIBSC CreutzfeldteJakob disease brain reference materials

1.4. Mixed PrP types The co-occurrence of types 1 and 2 in cases of sCJD is now a well recognised phenomenon [5,10,11,12] and several independent studies have each concluded that when an extensive brain sampling protocol is employed 20-50% of sCJD cases can be seen to contain both type 1 and type 2 PrPres [7,10,13,14,15].

AMAZING !!!

terry




Further characterisation of the prion protein molecular types detectable in the NIBSC CreutzfeldteJakob disease brain reference materials

Helen M. Yull, James W. Ironside, Mark W. Head* National CJD Surveillance Unit, School of Molecular & Clinical Medicine (Pathology), University of Edinburgh, Edinburgh, United Kingdom

Received 17 November 2008; revised 29 December 2008; accepted 23 January 2009

Abstract

Sporadic and variant CreutzfeldteJakob disease brain reference materials available from the UK National Institute for Biological Standards and Control have been subjected to further characterisation by Western blot analysis, with particular reference to the co-occurrence of different abnormal disease-associated prion protein (PrPSc) types. The results confirm the presence of genuine type 1 and type 2 protease-resistant PrP (PrPres) in each of the three sporadic CreutzfeldteJakob disease reagents, and provide evidence supporting the lower level presence of type 1 PrPres in the variant CreutzfeldteJakob disease reagents. We conclude that these reagents provide a valuable resource for future research and development.


snip...


1.4. Mixed PrP types The co-occurrence of types 1 and 2 in cases of sCJD is now a well recognised phenomenon [5,10,11,12] and several independent studies have each concluded that when an extensive brain sampling protocol is employed 20-50% of sCJD cases can be seen to contain both type 1 and type 2 PrPres [7,10,13,14,15].

snip...


On a superficial level the presence of more than one PrPSc type in individual CJD brains may seem at variance with the molecular strain typing hypothesis, which proposes that individual prion strains are enciphered by unique and self-perpetuating conformations and glycosylation states. However, this is not necessarily the case. It has long been known that multiple strains may be derived in mice from individual scrapie isolates, and cross-species transmission can, on occasion lead to an abrupt change in apparent strain characteristics.


snip...see full text ;


2009 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved. Keywords: CreutzfeldteJakob disease; Standards; Prion protein; Molecular typing; Co-occurrence



http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WBS-4VRWNKF-3&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=5a0c2f13b5476b0ddfea5bf9882300df




Beyond PrPres Type 1/Type 2 Dichotomy in Creutzfeldt-Jakob Disease

ArticleRelated ContentComments: 0.Formal Correction: This article has been formally corrected to address the following errors.

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Abstract Author Summary Introduction Materials and Methods Results Discussion Author Contributions References Emmanuelle Uro-Coste1#, Hervé Cassard2#, Stéphanie Simon3, Séverine Lugan2, Jean-Marc Bilheude4, Armand Perret-Liaudet5, James W. Ironside6, Stéphane Haik7,8, Christelle Basset-Leobon1, Caroline Lacroux2, Katell Peoch'9, Nathalie Streichenberger5, Jan Langeveld10, Mark W. Head6, Jacques Grassi3, Jean-Jacques Hauw8, Francois Schelcher2, Marie Bernadette Delisle1, Olivier Andréoletti2*

1 INSERM U858, Institut de Médecine Moléculaire de Rangueil and Service d'Anatomie Pathologique et Histologie-Cytologie, C.H.U. Rangueil, Toulouse, France, 2 UMR Institut National de la Recherche Agronomique (INRA)/Ecole Nationale Vétérinaire de Toulouse (ENVT) 1225, Interactions Hôtes Agents Pathogènes, ENVT, Toulouse, France, 3 Commissariat à l'Energie Atomique (CEA), Service de Pharmacologie et d'Immunologie, DRM, CEA/Saclay, Gif sur Yvette, France, 4 Bio-Rad, Research and Development Department, Marnes-la-Coquette, France, 5 Hôpital Neurologique, Services de Neurochimie et de Pathologie, Bron, France, 6 National Creutzfeldt-Jakob Disease Surveillance Unit, Division of Pathology, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom, 7 INSERM, Equipe Avenir, Maladies à Prions chez l'Homme, Paris, France, 8 Neuropathology Laboratory, Salpêtrière Hospital, AP-HP, Paris, France, 9 Service de Biochimie et Biologie Moléculaire, Hôpital Lariboisière, Paris (Laboratoire associé au CNR “ATNC”) et EA 3621 Faculté de Pharmacie, Paris, France, 10 Central Institute for Animal Disease Control CIDC-Lelystad, Lelystad, The Netherlands

Abstract Top Sporadic Creutzfeldt-Jakob disease (sCJD) cases are currently subclassified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the proteinase K (PK) digested abnormal prion protein (PrPres) identified on Western blotting (type 1 or type 2). These biochemically distinct PrPres types have been considered to represent potential distinct prion strains. However, since cases of CJD show co-occurrence of type 1 and type 2 PrPres in the brain, the basis of this classification system and its relationship to agent strain are under discussion. Different brain areas from 41 sCJD and 12 iatrogenic CJD (iCJD) cases were investigated, using Western blotting for PrPres and two other biochemical assays reflecting the behaviour of the disease-associated form of the prion protein (PrPSc) under variable PK digestion conditions. In 30% of cases, both type 1 and type 2 PrPres were identified. Despite this, the other two biochemical assays found that PrPSc from an individual patient demonstrated uniform biochemical properties. Moreover, in sCJD, four distinct biochemical PrPSc subgroups were identified that correlated with the current sCJD clinico-pathological classification. In iCJD, four similar biochemical clusters were observed, but these did not correlate to any particular PRNP 129 polymorphism or western blot PrPres pattern. The identification of four different PrPSc biochemical subgroups in sCJD and iCJD, irrespective of the PRNP polymorphism at codon 129 and the PrPres isoform provides an alternative biochemical definition of PrPSc diversity and new insight in the perception of Human TSE agents variability.

snip...

Discussion Top Coexistence of Different PrPres Types in the Same Subject In this study, detection, by WB, of the coexistence of two PrPres types in about 30% (13/41) of cases is consistent with already published data [12],[14]. This observation could suggest the existence in brain from a single patient of different abnormal PrP species. Although two main PK cleavage sites are associated with PrPres type 1 and type 2 (respectively amino acid 82 and 97), N-terminal sequencing revealed in all investigated cases the presence of a whole spectrum of overlapping cleavage sites. Moreover in a part of investigated cases this technique demonstrated the presence (i) of variable but consistent level of type 1 PrPres in patients classified type 2 using WB and (ii) in some patient classified type 1, of low amount of type 2 PrPres [10]. These observations could suggest that, rather than a pure type 1 or type 2 PrPres, PK digestion of a PrPSc specific conformer generate variable mixture of PrPres fragments (with presence of dominant or sub dominant type 1 or type 2 PrPres), which WB usually failed to reveal accurately because its intrinsic technical limits [14]. Antibodies either harbouring higher affinity to PrP (like Sha31) [18] or probing specifically type 1 PrPres (like 12B2) [20], now allow a better perception of such mixture. However, investigations carried out using artificial mixture of type 1 and type 2 brain homogenate, even using high affinity anti-PrP antibodies, clearly indicate the current limits of WB discriminative power [14]. Together, these data suggest that WB analysis of PrPres on its own could be misleading for adequate discrimination between PrPSc variants in CJD.

Both PrPSc PK resistance ELISA and strain typing ELISA are based on the characterization the N terminal part of the PrPSc PK digestion either by increasing PK amount or modifying detergent conditions. While WB profile could be compared to a snapshot picture of PrPres fragments generated by PK digestion process, these assays reflect the dynamics of the PK cleavage rather than its final result (different forms of PrPres). Consequently they could provide different but also more accurate perception of the PrPSc conformers.

Our findings from the PrPSc capture immunoassays clearly indicate that in a single patient, irrespective of brain area, sCJD associated PrPSc displays uniform biochemical properties, regardless of the regional variation of type 1 and type 2 isoforms determined by WB. Such findings support the idea of the presence of a specific TSE agent in each brain and the accumulation of a single associated PrPSc conformer.

sCJD Classification Because the limited size of our cohort of cases, an in depth comparison between the PrPSc signature (as established in this study) and the Parchi classification system is not possible.

However, despite this limitation, two major groups were identified in our panel according to the PrPSc properties. The first major group was constituted with patients harbouring a highly PK resistant PrPSc (MM1 and MV1 patients). The second group included patients harboring a PK labile PrPSc (VV2 and MV2 patients). Using both lesion profile and clinical parameters [2], two major forms of sCJD are commonly recognized. The first sCJD form, named “classical”, is characterized by a “rapid evolution” (usually around 4 months), and affects most of the MM1 and MV1 patients. The second sCJD form, named “atypical”, affects VV2 and MV2 with a longer symptomatic evolution (usually longer than 6 months) and a late dementia. Despite inter-individual variations, sCJD Groups 1 and 2, as we defined them on biochemical criteria were consistent with this classification.

Both VV1 and MM2 sCJD cases are extremely rare; they respectively represent 1% and 4% of the identified sCJD cases. According to the literature, these patients have clinical features and lesion profiles that are very different from other sCJD patients [2]. However, in our study as in previously published studies, WB did not identify any distinct biochemical difference from other type 1 and type 2 cases. In contrast, both the strain typing ELISA and PrPSc resistance assays clearly differentiated these cases from Group 1 and Group 2 cases. This finding, which is consistent with clinico/pathological observations carried out in patients, could indicate that there are indeed differences in PrPSc that distinguish these VV1 and MM2 cases from other sCJD groups.

Prion Strains and PrPSc Phenotype Although prion strains can only be identified definitively by bioassay, molecular in vitro tools to characterize PrPSc are more and more widely used for the rapid identification of particular agents, such as BSE in cattle, sheep, rodent and humans (vCJD) [20],[21]. This has come to be termed “molecular strain typing” and although widely employed, the exact relationship between PrPSc biochemistry and the biological properties of the agents responsible remain to be determined. In sCJD, the presence of four distinct PrPSc biochemical forms apparently correlated to clinico-pathological phenotypes as defined by Parchi et al. [2] could be an indication of the involvement of different TSE agents.

iCJD cases are a consequence of accidental human to human TSE transmission, most likely representing transmission of sCJD. The identification in iCJD cases of the four PrPSc signatures identified in sCJD is consistent with the existence of distinct prions associated with these biochemical forms.

Three examples of human-to-human transmission of variant CJD through blood transfusion have now been identified. While all blood donors were MM at codon 129 PRNP, the recipients had either a MM (n = 2) or a MV genotype (n = 1). Despite this genotype difference there appears to have been conservation of the disease phenotype and PrPres type in all “secondary” vCJD cases [22]–[25]. These observations could suggest that in case of inter-human transmission, difference in donor/recipient genotype could result in un-altered abnormal PrP signature.

Our identification of MM GH iCJD cases harbouring similar PrPSc signature as a VV1 sCJD case or of a VV dura mater iCJD case similar to MM2 sCJD might indicate preservation of a specific PrPSc biochemical signature after human to human transmission between individuals of different codon 129 genotypes.

Treatment with extracts of GH contaminated by CJD has lead to a high number of iCJD cases in France and the UK. The codon 129 genotypes of the affected individuals in the two countries differ, with the French cohort predominantly MM and MV and the British cohort MV and VV [26]. In the absence of any clear explanation for this finding, it was suggested that it might be due to contamination of different batches of GH with different prion strains from individuals of differing PRNP codon 129 genotypes. Our identification of different biochemical forms of PrPSc in GH French patients and in UK patients is consistent with this hypothesis. The variability observed within the French GH cases could signify involvement of different prion strains, consistent with multiple contaminated GH batches in the French epidemic.

Conclusion The identification in this study of different PrPSc species in CJD patients with the same PRNP polymorphism at codon 129 and WB PrPres profile offers a new perspective on our understanding of the relationship between PrP biochemistry, prion disease phenotype and agent strain. We highlight two novel approaches to analysing PrPSc in sCJD and iCJD and offer evidence that these analyses provide potentially-strain associated information, which appears to be lacking from the conventional WB assay.



http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000029




Saturday, April 04, 2009 An unusually presenting case of sCJD—The VV1 subtype Volume 111, Issue 3, Pages 282-291 (April 2009)

An unusually presenting case of sCJD—The VV1 subtype

Kaloyan S. Taneva, Mimi Yilmab

Received 16 November 2007; received in revised form 4 September 2008; accepted 12 September 2008.

Abstract Creutzfeldt–Jakob disease (CJD) is a rapidly progressive neurodegenerative disease caused by prions. Typically CJD presents with a triad of rapidly progressive dementia, abnormal movements (e.g., myoclonus) and electroencephalographic (EEG) changes. Recently, CJD has been subdivided into subtypes based on host genetic polymorphisms and the characteristics of the pathological prion protein. Different subtypes likely have different clinical and laboratory presentations. We describe a case of sporadic CJD of the VV1 subtype. We describe our patient's clinical symptoms, time course, laboratory workup, structural and functional neuroimaging data, EEG data and CJD biomarkers. Our patient presented with clinical symptoms atypical for CJD. Because of that, her clinical symptoms were initially attributed to psychiatric reasons. After extensive clinical and laboratory investigation, we concluded that the patient probably had CJD. Postmortem neuropathological results confirmed this clinical hypothesis. We compare our patient's clinical, laboratory and neuroimaging data to the data on typical CJD as well as the data on the few CJD VV1 cases described in the literature. We discuss our case's relevance to the diagnosis of CJD.

Keywords: Creutzfeldt–Jakob disease, Dementia, Neuroimaging, Magnetic resonance imaging, Electroencephalography, Biomarkers, Prion diseases a Department of Psychiatry, Massachusetts General Hospital, 55 Fruit Street, Warren 1220/Blake 11, Boston, MA 02114, United States

b University of Connecticut Health Center, Farmington, CT, United States

Corresponding author. Tel.: +1 617 726 7511; fax: +1 617 724 9155.

PII: S0303-8467(08)00320-X

doi:10.1016/j.clineuro.2008.09.017

© 2008 Elsevier B.V. All rights reserved.

http://www.clineu-journal.com/article/S0303-8467(08)00320-X/abstract


rare atypical strain of sporadic cjd ??? seems these rare strains are increasing ???

Wednesday, February 04, 2009

Creutzfeldt-Jacob disease presenting as severe depression: a case report

http://creutzfeldt-jakob-disease.blogspot.com/2009/02/creutzfeldt-jacob-disease-presenting-as.html


A case-control study of sporadic Creutzfeldt-Jakob disease in Switzerland: analysis of potential risk factors with regard to an increased CJD incidence in the years 2001-2004

http://creutzfeldt-jakob-disease.blogspot.com/2009/02/case-control-study-of-sporadic.html


Thursday, July 10, 2008

A New Prionopathy update July 10, 2008

snip...

DOES ANYONE BESIDES ME SEE A PATTERN YET ???

Vickey Rimmer, 16, DID NOT DIE FROM nvCJD, she died from a form of sporadic CJD, whatever the hell that is. and there have been 16 year old die from sporadic CJD in the USA as well.

SIMPLY PUT, the ukbsenvcjd only theory was wrong from day one. the elderly are expendable, pets and kids are not.

Science was dictated by 'big buisness' after the Vickey Rimmer case with the ukbsenvcjd only myth.

snip...

Sporadic creutzfeldt-jakob disease in two adolescents

http://jnnp.bmj.com/cgi/content/abstract/jnnp.2006.104570v1


see full text sporadic CJD the big lie;

snip...

IT seems we have come full circle from the 'ORIGINAL 10' i.e. the 1st 10 adolescents in the UKBSEnvCJD only theory. and now we find us at the 1st 10 in USA, or is it the first 10, or the tip of the iceburg, many that went undocumented ???

lets look at the full circle, to date ;

http://cjdmadcowbaseoct2007.blogspot.com/2008/07/new-prionopathy-update-july-10-2008.html


Sunday, August 10, 2008

A New Prionopathy OR more of the same old BSe and sporadic CJD

http://creutzfeldt-jakob-disease.blogspot.com/2008/08/new-prionopathy-or-more-of-same-old-bse.html



full text ;


http://creutzfeldt-jakob-disease.blogspot.com/2009/04/unusually-presenting-case-of-scjdthe.html




Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009

Saturday, July, 18, 2009

Greetings,

I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena’s. North America seems to have the most species with documented Transmissible Spongiform Encephalopathy's, most all of which have been rendered and fed back to food producing animals and to humans for years. If you look at the statistics, sporadic CJD seems to be rising in the USA, and has been, with atypical cases of the sCJD. I find deeply disturbing in the year of 2009, that Human Transmissible Spongiform Encephalopathy of any strain and or phenotype, of all age groups, and I stress all age groups, because human TSE's do not know age, and they do not know borders. someone 56 years old, that has a human TSE, that has surgery, can pass this TSE agent on i.e. friendly fire, and or passing it forward, and there have been documented nvCJD in a 74 year old. Remembering also that only sporadic CJD has been documented to transmit via iatrogenic routes, until recently with the 4 cases of blood related transmission, of which the origin is thought to be nvCJD donors. However most Iatrogenic CJD cases are nothing more than sporadic CJD, until the source is proven, then it becomes Iatrogenic. An oxymoron of sorts, because all sporadic CJD is, are multiple forms, or strains, or phenotypes of Creutzfeldt Jakob Disease, that the route and source and species have not been confirmed and or documented. When will the myth of the UKBSEnvCJD only theory be put to bed for good. This theory in my opinion, and the following there from, as the GOLD STANDARD, has done nothing more than help spread this agent around the globe. Politics and money have caused the terrible consequences to date, and the fact that TSEs are a slow incubating death, but a death that is 100% certain for those that are exposed and live long enough to go clinical. once clinical, there is no recourse, to date. But, while sub-clinical, how many can one exposed human infect? Can humans exposed to CWD and scrapie strains pass it forward as some form of sporadic CJD in the surgical and medical arenas? why must we wait decades and decades to prove this point, only to expose millions needlessly, only for the sake of the industries involved? would it not have been prudent from the beginning to just include all TSE's, and rule them out from there with transmission studies and change policies there from, as opposed to doing just the opposite? The science of TSE's have been nothing more than a political circus since the beginning, and for anyone to still believe in this one strain, one group of bovines, in one geographical location, with only one age group of human TSE i.e. nvCJD myth, for anyone to believe this today only enhances to spreading of these human and animal TSE's. This is exactly why we have been in this quagmire.

The ones that believe that there is a spontaneous CJD in 85%+ of all cases of human TSE, and the ones that do not believe that cattle can have this same phenomenon, are two of the same, the industry, and so goes the political science aspect of this tobacco and or asbestos scenario i.e. follow the money. I could go into all angles of this man made nightmare, the real facts and science, for instance, the continuing rendering technology and slow cooking with low temps that brewed this stew up, and the fact that THE USA HAD THIS TECHNOLOGY FIRST AND SHIPPED IT TO THE U.K. SOME 5 YEARS BEFORE THE U.S. STARTED USING THE SAME TECHNOLOGY, to save on fuel cost. This is what supposedly amplified the TSE agent via sheep scrapie, and spread via feed in the U.K. bovine, and other countries exporting the tainted product. BUT most everyone ignores this fact, and the fact that the U.S. has been recycling more TSE, from more species with TSEs, than any other country documented, but yet, it's all spontaneous, and the rise in sporadic CJD in the U.S. is a happenstance of bad luck ??? I respectfully disagree. To top that all off, the infamous BSE-FIREWALL that the USDA always brags about was nothing more than ink on paper, and I can prove this. YOU can ignore it, but this is FACT (see source, as late as 2007, in one recall alone, some 10,000,000 MILLION POUNDS OF BANNED MAD COW FEED WENT OUT INTO COMMERCE TO BE FED OUT, and most was never recovered. This was banned blood laced, meat and bone meal. 2006 was a banner year for banned mad cow protein going into commerce in the U.S. (see source of FDA feed ban warning letter below). I stress that the August 4, 1997 USA mad cow feed ban and this infamous BSE firewall, was nothing more than ink on paper, it was never enforceable.

I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route. This would further have to be broken down to strain of species and then the route of transmission would further have to be broken down. Accumulation and Transmission are key to the threshold from sub-clinical to clinical disease, and key to all this, is to stop the amplification and transmission of this agent, the spreading of, no matter what strain. In my opinion, to continue with this myth that the U.K. strain of BSE one strain TSE in cows, and the nv/v CJD one strain TSE humans, and the one geographical location source i.e. U.K., and that all the rest of human TSE are just one single strain i.e. sporadic CJD, a happenstance of bad luck that just happens due to a twisted protein that just twisted the wrong way, IN 85%+ OF ALL HUMAN TSEs, when to date there are 6 different phenotypes of sCJD, and growing per Gambetti et al, and that no other animal TSE transmits to humans ??? With all due respect to all Scientist that believe this, I beg to differ. To continue with this masquerade will only continue to spread, expose, and kill, who knows how many more in the years and decades to come. ONE was enough for me, My Mom, hvCJD i.e. Heidenhain Variant CJD, DOD 12/14/97 confirmed, which is nothing more than another mans name added to CJD, like CJD itself, Jakob and Creutzfeldt, or Gerstmann-Straussler-Scheinker syndrome, just another CJD or human TSE, named after another human. WE are only kidding ourselves with the current diagnostic criteria for human and animal TSE, especially differentiating between the nvCJD vs the sporadic CJD strains and then the GSS strains and also the FFI fatal familial insomnia strains or the ones that mimics one or the other of those TSE? Tissue infectivity and strain typing of the many variants of the human and animal TSEs are paramount in all variants of all TSE. There must be a proper classification that will differentiate between all these human TSE in order to do this. With the CDI and other more sensitive testing coming about, I only hope that my proposal will some day be taken seriously. ...

please see history, and the ever evolving TSE science to date ;

Saturday, June 13, 2009

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009

http://cjdusa.blogspot.com/2009/06/monitoring-occurrence-of-emerging-forms.html


SEE THE DAMNING VIDEO NOW AT THE BOTTOM OF THE BLOG BELOW ;

http://creutzfeldt-jakob-disease.blogspot.com/2009/07/usa-hiding-mad-cow-disease-victims-as.html



Saturday, August 01, 2009 Cases of Early-Onset Sporadic Creutzfeld-Jakob Disease in Michigan

http://creutzfeldt-jakob-disease.blogspot.com/2009/08/cases-of-early-onset-sporadic.html



2006


From: TSS
Subject: HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory
Date: January 29, 2006 at 9:03 am PST
In Reply to: Tracking Spongiform Encephalopathies in North America (Lancet Infectious Disease Volume 3, Number 8 01 August 2003)
posted by TSS on August 14, 2003 at 6:56 pm:
------------------------------------------------------------
Comments sent via JAMA Feedback Page
------------------------------------------------------------
NAME: Terry S. Singeltary Sr.E-MAIL: flounder9@verizon.
http://jama.ama-assn.org/


Comments sent via JAMA Feedback Page

NAME: Terry S. Singeltary Sr. E-MAIL: flounder9@verizon.net




COMMENTS: I wish to submit the following ;

HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory

TSEs have been rampant in the USA for decades in many species, and they all have been rendered and fed back to animals for human/animal consumption. I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2005. With all the science to date refuting it, to continue to validate this myth, will only spread this TSE agent through a multitude of potential routes and sources...snip...end...TSS



Monday, April 20, 2009

National Prion Disease Pathology Surveillance Center Cases Examined1 (December 31, 2008)

http://prionunitusaupdate2008.blogspot.com/2009/04/national-prion-disease-pathology.html




CJD TEXAS (cjd clusters)

http://cjdtexas.blogspot.com/



USA WRITTEN CJD QUESTIONNAIRE ???

http://cjdquestionnaire.blogspot.com/



The statistical incidence of CJD cases in the United States has been revised to reflect that there is one case per 9000 in adults age 55 and older. Eighty-five percent of the cases are sporadic, meaning there is no known cause at present.

http://www.cjdfoundation.org/fact.html



Attending Dr.: Date / Time Admitted : 12/14/97 1228

UTMB University of Texas Medical Branch Galveston, Texas 77555-0543 (409) 772-1238 Fax (409) 772-5683 Pathology Report

FINAL AUTOPSY DIAGNOSIS Autopsy' Office (409)772-2858

FINAL AUTOPSY DIAGNOSIS

I. Brain: Creutzfeldt-Jakob disease, Heidenhain variant.

http://creutzfeldt-jakob-disease.blogspot.com/2008/07/heidenhain-variant-creutzfeldt-jakob.html








Tuesday, July 14, 2009

U.S. Emergency Bovine Spongiform Encephalopathy Response Plan Summary and BSE Red Book Date: February 14, 2000 at 8:56 am PST

WHERE did we go wrong $$$

http://madcowtesting.blogspot.com/2009/07/us-emergency-bovine-spongiform.html


Transgenic mice expressing porcine prion protein resistant to classical scrapie but susceptible to sheep bovine spongiform encephalopathy and atypical scrapie. Emerg Infect Dis. 2009 Aug; [Epub ahead of print]

http://nor-98.blogspot.com/2009/07/transgenic-mice-expressing-porcine.html


Transmissible mink encephalopathy - review of the etiology

http://transmissible-mink-encephalopathy.blogspot.com/2009/07/transmissible-mink-encephalopathy.html


Wednesday, July 1, 2009

Nor98 scrapie identified in the United States J Vet Diagn Invest 21:454-463 (2009)

http://nor-98.blogspot.com/2009/07/nor98-scrapie-identified-in-united.html


Monday, June 01, 2009 Biochemical typing of pathological prion protein in aging cattle with BSE

SOMETHING TO PONDER ???

O.K. confusious asks, IF all these new atypical BSEs i.e. new strains of mad cow disease is just an 'OLD COW PRION DISEASE', why then can not the 'old human prion disease' such as the sporadic CJD, be from an 'old cow prion disease', same as the nvCJD 'young people mad cow disease' (which also happens in 74 year old), but why cannot the 'old cow prion diseases', i.e. l-BSE, h-BSE, and ibncBSE, cause the 'old people prion disease', which looks like sporadic CJD. seems that is what some of the pathology is showing ???

OH, that probably makes too much sense, and that the only answer could be that it's all just a happenstance of bad luck and or a spontaneous event, that just happens out of the clear blue sky $$$

IF this is the case, then where are all the SPONTANEOUS BSE CASES OF MAD COW DISEASE IN THE U.S.A., AND WHERE HAVE THEY BEEN BURIED IN THE USA OVER THE LAST 25 YEARS ???

http://bse-atypical.blogspot.com/2009/06/biochemical-typing-of-pathological.html


Tuesday, August 04, 2009

Susceptibilities of Nonhuman Primates to Chronic Wasting Disease

http://chronic-wasting-disease.blogspot.com/2009/08/susceptibilities-of-nonhuman-primates.html


Thursday, July 23, 2009

UW Hospital warning 53 patients about possible exposure to rare brain disease

http://creutzfeldt-jakob-disease.blogspot.com/2009/07/uw-hospital-warning-53-patients-about.html


Wednesday, August 05, 2009 Rate of CWD infection increases in core area WISCONSIN

http://chronic-wasting-disease.blogspot.com/2009/08/rate-of-cwd-infection-increases-in-core.html


Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518

Revision to pre-surgical assessment of risk for vCJD in neurosurgery and eye surgery units Volume 3 No 28; 17 July 2009

Volume 3 No 28; 17 July 2009

HPR Home Archives 2009 news

Revision to pre-surgical assessment of risk for vCJD in neurosurgery and eye surgery units

Pandemic flu: UK situation at 16 July 2009

Revision to pre-surgical assessment of risk for vCJD in neurosurgery and eye surgery units

Patients are routinely assessed prior to undergoing surgical or neuro-endoscopy procedures to determine whether they may have an increased risk of CJD infection. If this is the case, special infection control precautions should be followed [1].

This pre-surgical assessment process has been revised to fully take account of the latest knowledge of variant CJD (vCJD). Now patients undergoing high risk surgery [2] or neuro-endoscopy should be assessed to identify those who have received transfusions from 80 or more donors since 1980. Any patients so identified have an increased risk of vCJD, and special infection control procedures should be followed. It is estimated that around 50 patients will be identified in this way in the UK each year.

Hospitals are being asked to collate blood transfusion histories for these patients, and conduct risk assessments for patients with uncertain or incomplete transfusion histories. Patients who are found to have an increased risk of vCJD will need to be informed via the HPA Centre for Infections CJD section, which is coordinating the implementation of the revised guidance, and their GP.

The vCJD risk to these patients is uncertain, and depends on the prevalence of subclinical vCJD infection among blood donors, the infectivity in the blood of infected donors, and the number of donors the patients have received blood from.

The HPA's CfI-CJD section should be informed of any patients who are identified prior to high risk surgery or neuro-endoscopy as having received blood from 80 or more donors. Health Protection Units have been asked to ensure that infection control teams are aware of the revised guidance.

Information for healthcare workers and patients is available at:


http://www.hpa.org.uk/vCJDpresurgicalassessment



References/notes

1. Department of Health. "Assessment to be carried out before surgery and/or endoscopy to identify patients with, or at increased risk of, CJD or vCJD" (Annex J of ACDP TSE Working Group guidance).

2. High risk surgery is defined as surgery involving any of the following organs or tissues (high risk tissues): brain, spinal cord, dura mater, cranial nerves (specifically the entire optic nerve and only the intracranial components of the other cranial nerves), cranial nerve ganglia, posterior eye (specifically the posterior hyaloid face, retina, retinal pigment epithelium, choroid, subretinal fluid, optic nerve) and pituitary gland.

Pandemic flu: UK situation at 16 July 2009

The latest HPA Weekly Pandemic Flu Update [1] notes the following developments as at 16 July:

GP consultation rates in England for individuals presenting with flu-like illness showed increased rates, well above the threshold level for normal seasonal flu activity; the under-fives and 5-14 year olds are the age groups predominantly affected; the majority of cases continue to be mild, but there had been 26 deaths in England as at 16 July; and HPA estimated that there were 55,000 new cases of swine flu during the previous week (within a possible range of 30,000 to 85,000). Following the move away from laboratory testing for confirmation of swine flu cases to clinical diagnosis [2], the level of influenza in the community is being monitored using a range of surveillance mechanisms. One of these is the collaborative project between the HPA and the University of Nottingham Division of Primary Care known as QSurveillance®. This is a not-for-profit network over 3,300 general practices covering a total population of almost 22 million patients (more than 25% of the UK population). In the week-ending 12 July, the flu-like illness weekly consultation rate recorded by QSurveillance® reached 86.8 per 100,000, higher than the peak activity in winter 08/09 (see figure 2 in the HPA Weekly Pandemic Flu Update for 16 July [1]).

Given that laboratory testing is no longer routinely recommended, figure 1 (below) graphically illustrates how primary care surveillance such as QSurveillance® is providing a good comparator to laboratory confirmation, showing daily reporting of laboratory confirmed cases alongside daily primary care surveillance reports for flu-like illness.

Figure 1: Comparison of daily laboratory confirmed H1N1v case reports and daily QSurveillance® reports of influenza-like illness, UK*

* Data source: QSurveillance (daily data). Database version 1. Copyright QRESEARCH 2009.

Department of Health guidance: the National Pandemic Flu Service

In view of the very high demand for primary care, NHS Direct and A and E services in many areas, the Department of Health announced plans to activate, subject to rigorous testing, the National Pandemic Flu Service before the end of July [3].

References

1. "Weekly pandemic flu update (16 July 2009)", (HPA press release of 16 July 2009). HPA website: National Press Releases.

2. “Treatment approach announced for pandemic flu”, Health Protection Report [serial online] 2009; 3 (26): news. Available at:


http://www.hpa.org.uk/hpr/archives/2009/news2609.htm#h1n1



3. Department of Health. “National Pandemic Flu Service”, 17 July 2009



http://www.hpa.org.uk/hpr/archives/2009/news2809.htm



Pre-surgical risk assessment for variant Creutzfeldt-Jakob disease (vCJD) risk in neurosurgery and eye surgery units


Hospitals should already be using a questionnaire in Annex J of the ACDP TSE Working Group Infection Control guidance to find out whether any patients who are about to undergo any surgery or endoscopy may be at increased risk of being infected with CJD. If a patient is found to have an increased risk of CJD prior to their surgery or endoscopy then special infection control precautions may need to be taken.

Annex J of the TSE Infection Control guidance has recently been revised, and now advises that patients who are due to have high risk surgery [1] or neuro-endoscopy should be asked an additional question: whether they have received transfusions of blood or blood components from 80 or more donors since 1980. This is because these patients may have an increased risk of being infected with variant CJD (vCJD).

On 16 July 2009 the HPA wrote to the chief executives of NHS trusts asking them to ensure that the guidance is implemented. Detailed information and tools for implementing the guidance can be downloaded from the links below.

If you have any queries about the implementation of the guidance, please contact the HPA Centre for Infections CJD Section at mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000391/!x-usc:mailto:cjd@hpa.org.uk or on 020 8327 6074/6411.

Background information on this new pre-surgical assessment is contained in this Letter to chief executives - July 2009 (PDF, 73 KB) written to all hospitals in England.

The new version of Annex J of the TSE Infection Control Guidance contains new question for patients undergoing high risk surgery and neuro-endoscopy. These questions should be used to assess patients' CJD risk factors.

Clinicians carrying out the new pre-surgical assessment should read Pre-surgical assessment Information for healthcare staff - July 2009 (PDF, 163 KB) This vCJD Algorithm for per-surgical roles - July 2009 (PDF, 28 KB) shows suggested roles and responsibilities for infection control teams, surgical teams and blood transfusion specialists.

Information on patients' transfusion histories should be collected using the Highly transfused vCJD risk assessment form - July 2009 (Word Document, 328 KB) This form is also available as a vCJD risk assessment spreadsheet - July 2009 (Excel Spreadsheet, 2.7 MB). This may help calculate the number of blood donors to a patient. The form may be posted or emailed to the HPA Centre for Infections CJD Section mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000391/!x-usc:mailto:cjd@hpa.org.uk.

Blood transfusion laboratories may wish to use this draft Letter to other blood laboratories - July 2009 (Word Document, 31 KB) when collecting transfusion information from other hospitals.

Pre-surgical assessment teams and patients may wish to read this vCJD Information for presurgical patients - July 2009 (PDF, 29 KB) about this new pre-surgical assessment.

[1] High risk surgery is defined as surgery involving any of the following organs or tissues (high risk tissues): brain, spinal cord, cranial nerves (specifically the entire optic nerve and only the intercranial components of the other cranial nerves), cranial nerve ganglia, posterior eye (specifically the posterior hyaloid face, retina, retinal pigment epithelium, choroid, subretinal fluid, optic nerve) and pituitary gland.

Letter to chief executives - July 2009 (PDF, 73 KB) Added/updated: 16 July 2009



http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1247469060207



Pre-surgical assessment Information for healthcare staff - July 2009 (PDF, 163 KB) Added/updated: 16 July 2009



http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1247469061870



vCJD Algorithm for per-surgical roles - July 2009 (PDF, 28 KB) Added/updated: 16 July 2009



http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1247469062057



Highly transfused vCJD risk assessment form - July 2009 (Word Document, 328 KB) Added/updated: 16 July 2009



http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1247469062225



Letter to other blood laboratories - July 2009 (Word Document, 31 KB) Added/updated: 16 July 2009



http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1247469062420



vCJD Information for presurgical patients - July 2009 (PDF, 29 KB) Added/updated: 16 July 2009



http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1247469062586



vCJD risk assessment spreadsheet - July 2009 (Excel Spreadsheet, 2.7 MB) Added/updated: 16 July 2009



http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1247728926790



full text ;



http://www.hpa.org.uk/webw/HPAweb&Page&HPAwebAutoListName/Page/1247469069188



http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1247728926790




Saturday, May 23, 2009

Latest results of HPA study on vCJD-related abnormal prion proteins in extracted tonsil



http://creutzfeldt-jakob-disease.blogspot.com/2009/05/latest-results-of-hpa-study-on-vcjd.html




Wednesday, August 20, 2008

Tonometer disinfection practice in the United Kingdom: A national survey



http://creutzfeldt-jakob-disease.blogspot.com/2008/08/tonometer-disinfection-practice-in.html



Wednesday, January 02, 2008

Risk factors for sporadic Creutzfeldt-Jakob disease



http://creutzfeldt-jakob-disease.blogspot.com/2008/01/risk-factors-for-sporadic-creutzfeldt.html



Sunday, December 16, 2007

Risk factors for sporadic Creutzfeldt-Jakob disease



http://creutzfeldt-jakob-disease.blogspot.com/2007/12/risk-factors-for-sporadic-creutzfeldt.html



Monday, December 31, 2007

Risk Assessment of Transmission of Sporadic Creutzfeldt-Jakob Disease in Endodontic Practice in Absence of Adequate Prion Inactivation



http://creutzfeldt-jakob-disease.blogspot.com/2007/12/risk-assessment-of-transmission-of.html



Eye procedure raises CJD concerns November 19, 2004 United Press International by STEVE MITCHELL

A New York man who died from a rare brain disorder similar to mad cow disease in May underwent an eye procedure prior to his death that raises concerns about the possibility of transmitting the fatal disease to others, United Press International has learned. The development comes on the heels of the announcement Thursday by U.S. Department of Agriculture officials of a possible second case of mad cow disease in U.S. herds.

Richard Da Silva, 58, of Orange County, N.Y., died from Creutzfeldt Jakob disease, an incurable brain-wasting illness that strikes about one person per million.

Richard's wife Ann Marie Da Silva told UPI he underwent a check for the eye disease glaucoma in 2003, approximately a year before his death. The procedure involves the use of a tonometer, which contacts the cornea -- an eye tissue that can contain prions, the infectious agent thought to cause CJD.

Ann Marie's concern is that others who had the tonometer used on them could have gotten infected.

A 2003 study by British researchers suggests her concerns may be justified. A team led by J.W. Ironside from the National Creutzfeldt-Jakob Disease Surveillance Unit at the University of Edinburgh examined tonometer heads and found they can retain cornea tissue that could infect other people -- even after cleaning and decontaminating the instrument.

"Retained corneal epithelial cells, following the standard decontamination routine of tonometer prisms, may represent potential prion infectivity," the researchers wrote in the British Journal of Ophthalmology last year. "Once the infectious agent is on the cornea, it could theoretically infect the brain."

Prions, misfolded proteins thought to be the cause of mad cow, CJD and similar diseases, are notoriously difficult to destroy and are capable of withstanding most sterilization procedures.

Laura Manuelidis, an expert on these diseases and section chief of surgery in the neuropathology department at Yale University, agreed with the British researchers that tonometers represent a potential risk of passing CJD to other people.

Manuelidis told UPI she has been voicing her concern about the risks of corneas since 1977 when her own study, published in the New England Journal of Medicine, showed the eye tissue, if infected, could transmit CJD.

At the time the procedure was done on Richard Da Silva, about a year before he died, she said it was "absolutely" possible he was infectious.

The CJD Incidents Panel, a body of experts set up by the U.K. Department of Health, noted in a 2001 report that procedures involving the cornea are considered medium risk for transmitting CJD. The first two patients who have a contaminated eye instrument used on them have the highest risk of contracting the disease, the panel said.

In 1999, the U.K. Department of Health banned opticians from reusing equipment that came in contact with patients' eyes out of concern it could result in the transmission of variant CJD, the form of the disease humans can contract from consuming infected beef products.

Richard Da Silva was associated with a cluster of five other cases of CJD in southern New York that raised concerns about vCJD.

None of the cases have been determined to stem from mad cow disease, but concerns about the cattle illness in the United States could increase in light of the USDA announcement Thursday that a cow tested positive on initial tests for the disease. If confirmed, this would be the second U.S. case of the illness; the first was detected in a Washington cow last December. The USDA said the suspect animal disclosed Thursday did not enter the food chain. The USDA did not release further details about the cow, but said results from further lab tests to confirm the initial tests were expected within seven days.

Ann Marie Da Silva said she informed the New York Health Department and later the eye doctor who performed the procedure about her husband's illness and her concerns about the risk of transmitting CJD via the tonometer.

The optometrist -- whom she declined to name because she did not want to jeopardize his career -- "didn't even know what this disease was," she said.

"He said the health department never called him and I called them (the health department) back and they didn't seem concerned about it," she added. "I just kept getting angrier and angrier when I felt I was being dismissed."

She said the state health department "seems to have an attitude of don't ask, don't tell" about CJD.

"There's a stigma attached to it," she said. "Is it because they're so afraid the public will panic? I don't know, but I don't think that the answer is to push things under the rug."

New York State Department of Health spokeswoman Claire Pospisil told UPI she would look into whether the agency was concerned about the possibility of transmitting CJD via tonometers, but she had not called back prior to story publication.

Disposable tonometers are readily available and could avoid the risk of transmitting the disease, Ironside and colleagues noted in their study. Ann Marie Da Silva said she asked the optometrist whether he used disposable tonometers and "he said 'No, it's a reusable one.'"

Ironside's team also noted other ophthalmic instruments come into contact with the cornea and could represent a source of infection as they are either difficult to decontaminate or cannot withstand the harsh procedures necessary to inactivate prions. These include corneal burrs, diagnostic and therapeutic contact lenses and other coated lenses.

Terry Singletary, whose mother died from a type of CJD called Heidenhain Variant, told UPI health officials were not doing enough to prevent people from being infected by contaminated medical equipment.

"They've got to start taking this disease seriously and they simply aren't doing it," said Singletary, who is a member of CJD Watch and CJD Voice -- advocacy groups for CJD patients and their families.

U.S. Centers for Disease Control and Prevention spokeswoman Christine Pearson did not return a phone call from UPI seeking comment. The agency's Web site states the eye is one of three tissues, along with the brain and spinal cord, that are considered to have "high infectivity."

The Web site said more than 250 people worldwide have contracted CJD through contaminated surgical instruments and tissue transplants. This includes as many as four who were infected by corneal grafts. The agency noted no such cases have been reported since 1976, when sterilization procedures were instituted in healthcare facilities.

Ironside and colleagues noted in their study, however, many disinfection procedures used on optical instruments, such as tonometers, fail. They wrote their finding of cornea tissue on tonometers indicates that "no current cleaning and disinfection strategy is fully effective."

Singletary said CDC's assertion that no CJD cases from infected equipment or tissues have been detected since 1976 is misleading.

"They have absolutely no idea" whether any cases have occurred in this manner, he said, because CJD cases often aren't investigated and the agency has not required physicians nationwide report all casesof CJD.

"There's no national surveillance unit for CJD in the United States; people are dying who aren't autopsied, the CDC has no way of knowing" whether people have been infected via infected equipment or tissues, he said.

Ann Marie Da Silva said she has contacted several members of her state's congressional delegation about her concerns, including Rep. Sue Kelly, R-N.Y., and Sen. Charles Schumer, D-N.Y.

"Basically, what I want is to be a positive force in this, but I also want more of a dialogue going on with the public and the health department," she said.



http://www.upi.com/NewsTrack/Science/2004/11/18/eye_procedure_raises_cjd_concerns/2974/




Cadaver corneal transplants -- without family permission Houston, Texas channel 11 news 28 Nov 99 Reported by Terry S. Singeltary Sr.son of CJD victim



http://www.mad-cow.org/dec99_news.html#bbb




Wednesday, July 8, 2009

Transgenic mice expressing porcine prion protein resistant to classical scrapie but susceptible to sheep bovine spongiform encephalopathy and atypical scrapie. Emerg Infect Dis. 2009 Aug; [Epub ahead of print]



http://nor-98.blogspot.com/2009/07/transgenic-mice-expressing-porcine.html



Wednesday, July 1, 2009

Nor98 scrapie identified in the United States J Vet Diagn Invest 21:454-463 (2009)



http://nor-98.blogspot.com/2009/07/nor98-scrapie-identified-in-united.html




Monday, July 06, 2009

Prion infectivity in fat of deer with Chronic Wasting Disease



http://chronic-wasting-disease.blogspot.com/2009/07/prion-infectivity-in-fat-of-deer-with.html




Saturday, June 13, 2009

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009



http://cjdusa.blogspot.com/2009/06/monitoring-occurrence-of-emerging-forms.html





Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (TRANSCRIPT)



http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/UCM171810.pdf



Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (Singeltary submission)



http://tseac.blogspot.com/2009/05/meeting-of-transmissible-spongiform.html





TSS