Tuesday, October 2, 2007


----- Original Message -----
From: "Terry S. Singeltary Sr." <flounder9@VERIZON.NET>
Sent: Tuesday, October 02, 2007 10:43 AM
Subject: [BSE-L] Monthly Creutzfeldt Jakob Disease statistics 2 October 2007

Subject: Monthly Creutzfeldt Jakob Disease statistics 2 October 2007Date: October 2, 2007 at 8:10 am PST

Monthly Creutzfeldt Jakob Disease statistics

DEPARTMENT OF HEALTH News Release issued by The Government News Network on 2October 2007The Department of Health is today issuing the latest information about thenumbers of known cases of Creutzfeldt Jakob disease. This includes cases ofvariant Creutzfeldt Jakob disease (vCJD) - the form of the disease thoughtto be linked to BSE. The position is as follows:Definite and probable CJD cases in the UK:

As at 28 September 2007Summary of vCJD cases


Deaths from definite vCJD (confirmed): 114

Deaths from probable vCJD (without neuropathological confirmation): 47

Deaths from probable vCJD (neuropathological confirmation pending): 0

Number of deaths from definite or probable vCJD (as above): 161Alive

Number of definite/probable vCJD cases still alive: 5

Total number of definite or probable vCJD (dead and alive): 166Following this press notice the Department of Health will stop issuingmonthly CJD press notices because the same data is also published by theNational CJD Surveillance Unit in Edinburgh. Up to date figures for thenumber of vCJD cases in the UK can be found on the website of the NationalCJD Surveillance Unit at: http://www.cjd.ed.ac.uk/figures.htm.


see chart of steady increase of sporadic CJD cases ...tss


* As at 28th September 2007Referrals: a simple count of all the cases which have been referred to theNational CJD Surveillance Unit for further investigation in the year inquestion. CJD may be no more than suspected; about half the cases referredin the past have turned out not to be CJD. Cases are notified to the Unitfrom a variety of sources including neurologists, neuropathologists,neurophysiologists, general physicians, psychiatrists, electroencephalogram(EEG) departments etc. As a safety net, death certificates coded under thespecific rubrics 046.1 and 331.9 in the 9th ICD Revisions are obtained fromthe Office for National Statistics in England and Wales, the GeneralRegister Office for Scotland and the General Register Office for NorthernIreland.

Deaths: All columns show the number of deaths that have occurred in definiteand probable cases of all types of CJD and GSS in the year shown. Thefigures include both cases referred to the Unit for investigation while thepatient was still alive and those where CJD was only discovered post mortem(including a few cases picked up by the Unit from death certificates). Thereis therefore no read across from these columns to the referrals column. Thefigures will be subject to retrospective adjustment as diagnoses areconfirmed.

Definite cases: this refers to the diagnostic status of cases. In definitecases the diagnosis will have been pathologically confirmed, in most casesby post mortem examination of brain tissue (rarely it may be possible toestablish a definite diagnosis by brain biopsy while the patient is stillalive).

Probable vCJD cases: are those who fulfil the 'probable' criteria set out inthe Annex and are either still alive, or have died and await post mortempathological confirmation. Those still alive will always be shown within thecurrent year's figures.

Sporadic: Classic CJD cases with typical EEG and brain pathology. Sporadiccases appear to occur spontaneously with no identifiable cause and accountfor 85% of all cases.

Probable sporadic: Cases with a history of rapidly progressive dementia,typical EEG and at least two of the following clinical features; myoclonus,visual or cerebellar signs, pyramidal/extrapyramidalsigns or akineticmutism.

Iatrogenic: where infection with classic CJD has occurred accidentally asthe result of a medical procedure. All UK cases have resulted from treatmentwith human derived pituitary growth hormones or from grafts using dura mater(a membrane lining the skull).

Familial: cases occurring in families associated with mutations in the PrPgene (10 - 15% of cases).

GSS: Gerstmann-Straussler-Scheinker syndrome - an exceedingly rare inheritedautosomal dominant disease, typified by chronic progressive ataxia andterminal dementia. The clinical duration is from 2 to 10 years, much longerthan for CJD.

vCJD: Variant CJD, the hitherto unrecognised variant of CJD discovered bythe National CJD Surveillance Unit and reported in The Lancet on 6 April1996. This is characterised clinically by a progressive neuropsychiatricdisorder leading to ataxia, dementia and myoclonus (or chorea) without thetypical EEG appearance of CJD. Neuropathology shows marked spongiform changeand extensive florid plaques throughout the brain.

Definite vCJD cases still alive: These will be cases where the diagnosis hasbeen pathologically confirmed (by brain biopsy).




Beyond the PrPres Type1/ Type2 dichotomy in Creutzfeldt-Jakob Disease

Cassard, H1; Uro-Coste, E2; Simon, S3; Bilheude, JM4; Perret-Liaudet, A5;Ironside, J6; Haik, S7; Basset-Leobon, C2; Lacroux, C1; Peoch’, K8;Stressenberger, N9;Langeveld, J10; Head, M11; Hauw, JJ12; Schecher, F1; Delisle, MB13;Andreoletti, O11Ecole Natinale Vétérinaire de Toulouse, France; 22Service d’AnatomiePathologiqueand INSERM U466 R, France; 3DRM, CEA/Saclay, France; 4 Bio-Rad, R&D, France;5 Hôpital Neurologique Service de Neurochimie, France; 6School of Molecular& Clinical Medicine (Pathology),, National Creutzfeldt-Jakob DiseaseSurveillance Un,UK; 7Pitié Salpetriere Universitary Hospital, France; 8Hôpital Lariboisière,Service deBiochimie et Biologie Moléculaire,, France; 9Hôpital Neurologique -ServicedeNeurochimie, France; 10CIDC-Lelystad, Netherlands; 11University ofEdinburgh, Western GeneralHospital, UK; 12Pitié Salpetriere Universitary Hospital,, Laboratoire deNeuropathologie, France;13Rangueil Universitary Hospital, Service d’Anatomie Pathologique, France

Creutzfeldt-Jakob disease (CJD) cases are currently classified according toestablished diagnostic criteria and by the genotype at codon 129 of the PRNPgene and the Western blotting of the proteinase K digested abnormal prionprotein that distinguishes a type 1 and a type 2 profile. Thesebiochemicallydistinct PrPres types have been proposed to represent distinct prionstrains.However, since the cooccurence of type 1 and type 2 PrPres in the samepatientis common, the rationale of this classification and strain concept asapplied toCJD are currently under discussion.

Five different brain areas from of 40 sporadic CJD and 11 iatrogenic CJD(both dura matter-, and growth hormone-associated) cases, originating fromUK and France, were systematically investigated, using Western blottingtyping,and by two others biochemical assays that depend on the behaviour of PrPScinvariable PK digestion conditions.

As described previously, co-occurrence of type 1 and type 2 PrPres wasfound in 30% of the CJD patients examined. However, our novel PKconcentrationdependent assays identified a single uniform PrP type in cases where bothtype 1 andtype 2 were present. Moreover, in sCJD four distinct biochemical PrPScsignatures were identified by the PK concentration dependent assays andthesecorrelated to the current genotype/clinico-pathological sCJD groups. In iCJDthe foursimilar biochemical signatures were observed, but were not correlated toparticularPRNP 129 polymorphism or Western Blot PrPres patterns. Moreover notabledifferenceswere observed between PrPSc biochemical properties of French and UK GH-CJDcases,which could reflect, as already suspected, differences in the causativeagents.

Identification, in sCJD and iCJD, of four different PrPSc phenotypesirrespective of patients PRNP polymorphism at codon 129 and Western blotprofile provides new insights into human prion disease aetiology and couldreflects anunsuspected diversity of TSE agents in human disease. Further investigationsarecurrently underway using animal transmission to correlate agent strain withour newdiscriminant biochemical assays.


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

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


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


Clinical diagnoses are made through review of medical records, clinicalevaluation, andin many cases pathology. Data is stored in a secure clinical relationaldatabase, which wasqueried for various CSF findings, including cell count, protein, IgG index,oligoclonal bands(OCBs), 14-3-3, NSE, T-Tau in patients with probable or definite sporadicCJD andnon-prion rapidly progressive dementias (RPD), most of whom were referred toour centerwith a potential diagnosis of CJD. For probable sCJD diagnosis, we used UCSFcriteria thatare modified from WHO to substitute MRI for 14-3-3. T-Tau and NSE wereconsideredpositive if > 1300 pg/ml and > 35 ng/ml, respectively. For this analysis,ambiguous 14-3-3results were considered as negative.


14-3-3 protein (n=149) sensitivity was only 48% (47% for definite; 50% forprobable sCJD). NSE (n=49) sensitivity was 63% (66% for definite; 59% forprobablesCJD). T-Tau (n=28) was the most sensitive at 68% (69% for definite; 67% forprobable sCJD). The specificity of these biomarkers among our CJD and RPDcontrols(n=72) was 66% for 14-3-3 (n=47), 81% for NSE (n=21), and 100% for T-Tau(n=7). The14-3-3 had the lowest sensitivity and specificity. Mildly elevated CSFprotein(<100>20, is uncommon in sCJD.


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


see full text 143 pages ;



P02.35Molecular Features of the Protease-resistant Prion Protein (PrPres) inH-type BSE

Biacabe, A-G1; Jacobs, JG2; Gavier-Widén, D3; Vulin, J1; Langeveld, JPM2;Baron, TGM1 1AFSSA, France; 2CIDC-Lelystad, Netherlands; 3SVA, Sweden

Western blot analyses of PrPres accumulating in the brain of BSE-infectedcattle havedemonstrated 3 different molecular phenotypes regarding to the apparentmolecularmasses and glycoform ratios of PrPres bands. We initially described isolates(H-typeBSE) essentially characterized by higher PrPres molecular mass and decreasedlevels of the diglycosylated PrPres band, in contrast to the classical typeof BSE.This type is also distinct from another BSE phenotype named L-type BSE, oralso BASE (for Bovine Amyloid Spongiform Encephalopathy), mainlycharacterized by alow representation of the diglycosylated PrPres band as well as a lowerPrPresmolecular mass. Retrospective molecular studies in France of all availableBSE casesolder than 8 years old and of part of the other cases identified since thebeginning of theexhaustive surveillance of the disease in 20001 allowed to identify 7 H-typeBSE cases, among 594 BSE cases that could be classified as classical, L- orH-type BSE.By Western blot analysis of H-type PrPres, we described a remarkablespecific feature with antibodies raised against the C-terminal region of PrPthatdemonstrated the existence of a more C-terminal cleaved form of PrPres(named PrPres#2 ),in addition to the usual PrPres form (PrPres #1). In the unglycosylatedform,PrPres #2 migrates at about 14 kDa, compared to 20 kDa for PrPres #1. Theproportionof the PrPres#2 in cattle seems to by higher compared to the PrPres#1.Furthermoreanother PK–resistant fragment at about 7 kDa was detected by some moreN-terminalantibodies and presumed to be the result of cleavages of both N- andC-terminal partsof PrP. These singular features were maintained after transmission of thedisease toC57Bl/6 mice. The identification of these two additional PrPres fragments(PrPres #2 and7kDa band) reminds features reported respectively in sporadicCreutzfeldt-Jakob diseaseand in Gerstmann-Sträussler-Scheinker (GSS) syndrome in humans.

FC5.5.1BASE Transmitted to Primates and MV2 sCJD Subtype Share PrP27-30 and PrPScC-terminal Truncated Fragments

Zanusso, G1; Commoy, E2; Fasoli, E3; Fiorini, M3; Lescoutra, N4; Ruchoux,MM4; Casalone, C5; Caramelli, M5; Ferrari, S3; Lasmezas, C6; Deslys, J-P4;Monaco, S3 1University of Verona, of Neurological and Visual Sciences,Italy; 2CEA, IMETI/SEPIA, France; 3University of Verona, Neurological andVisual Sciences, Italy; 4IMETI/SEPIA, France; 5IZSPLVA, Italy; 6The ScrippsResearch Insitute, USA

The etiology of sporadic Creutzfeldt-Jakob disease (sCJD), the most frequenthumanprion disease, remains still unknown. The marked disease phenotypeheterogeneityobserved in sCJD is thought to be influenced by the type of proteinaseK-resistantprion protein, or PrPSc (type 1 or type 2 according to the electrophoreticmobility ofthe unglycosylated backbone), and by the host polymorphic Methionine/Valine(M/V) codon 129 of the PRNP. By using a two-dimensional gel electrophoresis(2D-PAGE) and imunoblotting we previously showed that in sCJD, in additionto thePrPSc type, distinct PrPSc C-terminal truncated fragments (CTFs) correlatedwithdifferent sCJD subtypes. Based on the combination of CTFs and PrPSc type, wedistinguishedthree PrPSc patterns: (i) the first was observed in sCJD with PrPSc type 1of allgenotypes,;

(ii) the second was found in M/M-2 (cortical form); (iii) the third inamyloidogenic M/V-2 and V/V-2 subtypes (Zanusso et al., JBC 2004) . Recently, we showed thatsCJDsubtype M/V-2 shared molecular and pathological features with an atypicalform ofBSE, named BASE, thus suggesting a potential link between the twoconditions. Thisconnection was further confirmed after 2D-PAGE analysis, which showed anidentical PrPSc signature, including the biochemical pattern of CTFs. Topursue thisissue, we obtained brain homogenates from Cynomolgus macaquesintracerebrallyinoculated with brain homogenates from BASE. Samples were separated by usinga twodimensional electrophoresis (2D-PAGE) followed by immunoblotting. Wehere show that the PrPSc pattern obtained in infected primates is identicaltoBASE and sCJD MV-2 subtype. These data strongly support the link, or atleast acommon ancestry, between a sCJD subtype and BASE. This work was supported byNeuroprion(FOOD-CT-2004-506579)




USA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling ittoday), please note that both the ALABAMA COW, AND THE TEXAS COW, both were''H-TYPE'', personal communication Detwiler et al Wednesday, August 22, 200711:52 PM. ...TSS



FC5.5.2 Transmission of Italian BSE and BASE Isolates in Cattle Results intoa Typical BSE Phenotype and a Muscle Wasting Disease

Zanusso, G1; Lombardi, G2; Casalone, C3; D’Angelo, A4; Gelmetti, D2;Torcoli, G2;Barbieri, I2; Corona, C3; Fasoli, E1; Farinazzo, A1; Fiorini, M1; Gelati,M1; Iulini, B3;Tagliavini, F5; Ferrari, S1; Monaco, S1; Caramelli, M3; Capucci, L21University of Verona, Neurological and Visual Sciences, Italy; 2IZSLER,Italy; 3IZSPLVA,Italy; 4University of Turin, Animal Pathology, Italy; 5Isituto Carlo Besta,Italy

The clinical phenotype of bovine spongiform encephalopathy has beenextensivelyreported in early accounts of the disorder. Following the introduction ofstatutory activesurveillance, almost all BSE cases have been diagnosed on apathological/molecularbasis, in a pre-symptomatic clinical stage. In recent years, the activesurveillancesystem has uncovered atypical BSE cases, which are characterized by distinctconformers of the PrPSc, named high-type (BSE-H) and low-type (BSE-L), whoseclinicopathological phenotypes remain unknown. We recently reported twoItalian atypical cases with a PrPSc type similar to BSE-L, pathologicallycharacterized by PrP amyloid plaques. Experimental transmission to TgBovmice hasrecently disclosed that BASE is caused by a distinct prion strain which isextremelyvirulent. A major limitation of transmission studies to mice is the lack ofreliableinformation on clinical phenotype of BASE in its natural host. In thepresent study, weexperimentally infected Fresian/Holstein and Alpine/Brown cattle withItalian BSE andBASE isolates by i.c. route. BASE infected cattle showed survival timessignificantlyshorter than BSE, a finding more readily evident in Fresian/Holstein, and inkeeping withprevious observations in TgBov mice. Clinically, BSE-infected cattledeveloped adisease phenotype highly comparable with that described in field BSE casesand in experimentally challenged cattle. On the contrary, BASE-inoculatedcattledeveloped an amyotrophic disorder accompanied by mental dullness.The molecular and neuropathological profiles, including PrP depositionpattern, closely matched those observed in the original cases. This studyfurther confirmsthat BASE is caused by a distinct prion isolate and discloses a noveldiseasephenotype in cattle, closely resembling the phenotype previous reported inscrapie-inoculatedcattle and in some subtypes of inherited and sporadic Creutzfeldt-Jakobdisease.Oral Abstracts14

FC5.1.1Transmission Results in Squirrel Monkeys Inoculated with Human sCJD, vCJD,and GSS Blood Specimens: the Baxter Study

Brown, P1; Gibson, S2; Williams, L3; Ironside, J4; Will, R4; Kreil, T5;Abee, C3 1Fondation Alliance BioSecure, France; 2University of SouthAlabama, USA;3University of Texas MD Anderson Cancer Center, USA; 4Western GeneralHospital, UK; 5Baxter BioSience, Austria

Background: Rodent and sheep models of Transmissible SpongiformEncephalopathy(TSE) have documented blood infectivity in both the pre-clinical andclinical phases ofdisease. Results in a (presumably more appropriate) non-human primate modelhave not been reported.

Objective: To determine if blood components (red cells, white cells,platelets, andplasma) from various forms of human TSE are infectious.

Methods: Blood components were inoculated intra-cerebrally (0.1 ml) andintravenously (0.5 ml) into squirrel monkeys from 2 patients with sporadicCreutzfeldt- Jakob disease (sCJD) and 3 patients with variantCreutzfeldt-Jakob disease(vCJD). Additional monkeys were inoculated with buffy coat or plasma samplesfromchimpanzees infected with either sCJD or Gerstmann-Sträussler-Scheinkerdisease (GSS). Animals were monitored for a period of 5 years, and all dyingor sacrificed animals had post-mortem neuropathological examinations andWestern blots to determine the presence or absence of the misfolded ‘prion’protein (PrPTSE).

Results: No transmissions occurred in any of the animals inoculated withblood components from patients with sporadic or variant CJD. All donorchimpanzees(sCJD and GSS) became symptomatic within 6 weeks of their pre-clinical phaseplasmapheresis, several months earlier than the expected onset of illness.One monkey inoculated with purified leukocytes from a pre-clinical GSSchimpanzee developed disease after 36 months.

Conclusion: No infectivity was found in small volumes of blood componentsfrom 4 patients with sporadic CJD and 3 patients with variant CJD.

***However, a single transmission from a chimpanzee-passaged strain of GSSshows that infectivity may be present in leukocytes, and the ‘shock’ ofgeneral anaesthesia and plasmspheresis appears to have triggered the onsetof illness in pre-clinical donor chimpanzees.

FC5.1.2Interim Transmission Results in Cynomolgus Macaques Inoculated with BSE and

vCJD Blood Specimens

Lasmezas, C1; Lescoutra, N2; Comoy, E2; Holznagel, E3; Loewer, J3; Motzkus,D4; Hunsmann, G4; Ingrosso, L5; Bierke, P6; Pocchiari, M5; Ironside, J7;Will,R7; Deslys, JP2 1Scripps Florida, Infectology, USA; 2CEA, France; 3PEI,Germany; 4DPZ, Germany; 5Istituto Superiore di Sanita, Italy; 6SMI, Sweden;7CJD Surveillance Unit, UK

BSE and vCJD transmitted to cynomolgus macaques reproduce many features ofhuman vCJD, including clinical symptoms, neuropathological hallmarks ofvCJD,PrPres electrophoretical pattern and, most importantly, the widedistribution ofinfectivity in peripheral organs. The latter characteristic distinguishesvCJD from sCJDin both humans and cynomolgus macaques, and prompted us to use thisnon-humanprimate model for further investigations of vCJD and its risk for humanhealth. Theoccurrence of four vCJD infections in humans transfused with blood frompatients wholater developed vCJD has raised concern about blood transfusion safety incountries with vCJD.In this collaborative European study, we investigated the infectivity ofblood components and whole blood administered by intracerebral (ic) andintravenous (iv) routes. Buffy-coat and whole blood was inoculated by ic andiv route, respectively, from two vCJD patients and from two clinicalvCJD-inoculatedmacaques. Transfusions were also performed from whole blood and bloodleucodepletedaccording to hospital practice standards from two clinical BSE inoculatedmacaques. Blood infectivity during the preclinical phase is being examinedin orallyinfected macaques. Whole blood was collected and transfused from one suchanimaltwo years after oral challenge, whereas buffy-coat and plasma from twoanimalsat 2 and 4.5 years post-challenge, respectively, have been inoculated by theic route.This is an ongoing study in which recipient animals continue to be observedat various times post-inoculation. So far, we have had one positivetransmission in oneanimal transfused 65 months earlier with 40 ml of whole blood from a vCJDmacaque(the characteristics of the disease in this animal will be shown in aseparate poster by E.Comoy). This positive transmission reproduces transfusion transmission ofvCJD inhumans, with an incubation of 5.5 years compatible with incubation periodsobserved in humans.

FC5.3Assessing the Risk of vCJD Transmission by Dentistry; Distribution ofInfectivity in Oral Tissues of VM Mice after Simulated Oral Feeding ofBSE-301V

Sutton, JM1; Kirby, E1; Dickinson, J1; Dennis, M1; Cornwall, M1; Vassey,MJ1; Smith, A2; Marsh, PD3; Walker, JT1; Raven, NDH11Health Protection Agency, Centre for Emergency Preparedness and Response,,TSE Research group, UK; 2University of Glasgow, Dental School, UK; 3HealthProtection Agency, Centre for Emergency Preparedness and Response,, UK

Background: Ongoing concerns about the prevalence of variant CreutzfeldtJakobDisease (vCJD) in the UK population has heightened concerns about the risksof iatrogenic transmission of the disease. Although there have been no casesto date of transmission by surgery there have been 4 cases involving bloodtransfusion. This study aims to assess the potential of transmission of thedisease bydental procedures. Whilst the risks are undoubtably low the very largenumbers ofprocedures carried out annually have the potential to amplify the risksconsiderablyand there is very little data in this area to form the basis for accurateriskassessments. Aim(s)/Objective(s): To assess the relative levels ofinfectivity in oraltissues from a murine model following exposure to BSE-301V through the smallintestine.

Methods. The study uses a BSE-301V, VM mouse model as a clinically relevantmodel for assessing iatrogenic vCJD transmission between humans. Infectiousmousebrain homogenate was prepared and inoculated into a loop of the duodenum, toprevent direct contamination of the oral tissues. Mice were sacrificed at3-weeklyintervals and at appearance of clinical symptoms. A range of oral tissues,including dental pulp, gingival margin, salivary gland, saliva, lingualtonsil andtrigeminal ganglia, together with brain and spleen tissues were removed,processed ashomogenates and reinoculated intracranially (ic.) into indicator mice.

Results: The primary challenge proved to be a very efficient route ofinfection with a 100% attack rate and a mean incubation to clinical diseaseof 157 ± 17 days (compared to 120 days for the same titre inoculum ic.).Infectivity was observed in all oral and control tissues with varyingtime-coursesand titres estimated from incubation period.

Discussion: The results throw new light on the potential routes ofdissemination and spread of infectivity from the small intestine to the oralcavity and its implications for possible iatrogenic transmission of vCJD viadental,endoscopic or other forms of surgery.

Conclusion: The data generated from the study provides support for ongoingrisk assessments to look at the potential for vCJD transmission via dentalprocedures alongside other elements of studies looking at effectiveness ofdecontamination and re-use of dental instruments.

From: "Terry S. Singeltary Sr."Subject: CWD UPDATE 88 AUGUST 31, 2007


Date: Wed, 29 Aug 2007 21:13:08 -0500From: "Terry S. Singeltary Sr."Subject: CWD NEW MEXICO RECORDS IT'S 19 CASE (near Texas border again)


Monitoring the Potential Transmission of Chronic Wasting Disease to HumansUsing a Hunter Registry Database in Wyoming (405 lines)From: Terry S. Singeltary Sr. <[log in to unmask]>Date: Thu, 30 Aug 2007 21:23:42 -0500



Quantifying the Species Barrier in Chronic Wasting Disease by a Novel invitro Conversion Assay

Li, L1; Coulthart, MB2; Balachandran, A3; Chakrabartty, A4; Cashman, NR11University of British Columbia, Brain Research Centre, Canada; 2PublicHealth Agencyof Canada, National Microbiology Laboratory, Canada; 3Animal DiseasesResearchInstitute, Canada Food Inspection Agency, National Reference Laboratory forScrapieand CWD, Canada; 4Ontario Cancer Institute and Department of MedicalBiophysics, University of Toronto, Canada

Background: Chronic wasting disease (CWD) is a transmissible spongiformencephalopathy that can affect North American cervids (deer, elk, andmoose).Although the risk of CWD crossing the species barrier and causing humandisease isstill unknown, however, definite bovine spongiform encephalopathy (BSE)transmissionto humans as variant CJD (vCJD), it would seem prudent to limit the exposureofhumans to CWD.

Aim: In view of the fact that BSE can be readily transmitted to non-bovidspecies, it isimportant to establish the species susceptibility range of CWD.

Methods: In vitro conversion system was performed by incubation of prionswithnormal brain homogenates as described before, and protease K (PK) resistantPrP was determined by immunoblotting with 6H4 monoclonal prion antibody.

Results: Our results demonstrate that PrPC from cervids (including moose)can beefficiently converted to a protease-resistant form by incubation with elkCWD prions,presumably due to sequence and structural similarities between thesespecies.Interestingly, hamster shows a high conversion ratio by PrPCWD. Moreover,partialdenaturation of substrate PrPC can apparently overcome the structuralbarriersbetween more distant species.

Conclusions: Our work correctly predicted the transmission of CWD to a wildmoose. We find a species barrier for prion protein conversion betweencervids andother species, however, this barrier might be overcome if the PrPC substratehasbeen partially denatured in a cellular environment. Such an environmentmightalso promote CWD transmission to non-cervid species, *** including humans.Acid/GdnHCl-treated brain PrPC was a superior substrate for the in vitroconversionthan PrPC treated at physiological pH. This has implications for the processby whichthe prion protein is converted in disease.


Subject: Cross-sequence transmission of sporadic Creutzfeldt-Jakob diseasecreates a new prion strain

Date: August 25, 2007 at 12:42 pm PST

Subject: Cross-sequence transmission of sporadic Creutzfeldt-Jakob diseasecreates a new prion strainDate: August 25, 2007 at 12:42 pm PST

J Biol Chem. 2007 Aug 20; : 17709374

Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease creates anew prion strain.

[My paper] Atsushi Kobayashi , Masahiro Asano , Shirou Mohri , TetsuyukiKitamoto

The genotype (methionine or valine) at polymorphic codon 129 of the humanprion protein (PrP) gene and the type (type 1 or type 2) of abnormal isoformof PrP (PrP(Sc)) are major determinants of the clinicopathologicalphenotypes of sporadic Creutzfeldt-Jakob disease (sCJD). Here we found thattransmission of sCJD prions from a patient with valine homozygosity (129V/V)and type 2 PrP(Sc) (sCJD-VV2 prions) to mice expressing human PrP withmethionine homozygosity (129M/M) generated unusual PrP(Sc) intermediate insize between type 1 and type 2. The intermediate type PrP(Sc) was seen inall examined dura mater graft-associated CJD cases with 129M/M andplaque-type PrP deposits (p-dCJD). p-dCJD prions and sCJD-VV2 prionsexhibited similar transmissibility and neuropathology, and the identicaltype of PrP(Sc) when inoculated into PrP-humanized mice with 129M/M or129V/V. These findings suggest that p-dCJD could be caused by cross-sequencetransmission of sCJD-VV2 prions.


In this study, the strain-dependent traits of sCJDMM1prions were inherited through cross-sequencetransmission without any modification. Thehumanized mice with 129V/V produced type 1 PrPresafter inoculation with sCJD-MM1 prions. BecausesCJD-VV1 cases are extremely rare (at most 1-2%of the total number of sCJD cases) and characterizedby early onset (mean age at onset: 39.3 years) (5),


our results raise the possibility that CJD casesclassified as VV1 may include cases caused byiatrogenic transmission of sCJD-MM1 prions orfood-borne infection by type 1 prions from animals,e.g., chronic wasting disease prions in cervid. In fact,two CJD-VV1 patients who hunted deer orconsumed venison have been reported (40, 41). Theresults of the present study emphasize the need fortraceback studies and careful re-examination of thebiochemical properties of sCJD-VV1 prions.


In conclusion, cross-sequence transmission ofsCJD-VV2 prions generates a new prion strain withaltered conformational properties and diseasephenotypes as p-dCJD prions. Furthermore, thenewly generated prions have unique transmissibilityincluding the traceback phenomenon. In the future, ifatypical prion strains emerge through cross-sequencetransmission, especially from animals, tracebackstudies will enable us to identify the origin of theprions.





Re: Colorado Surveillance Program for Chronic Wasting DiseaseTransmission to Humans (TWO SUSPECT CASES)


Subject: Aspects of the Cerebellar Neuropathology in Nor98Date: September 26, 2007 at 4:06 pm PST


Aspects of the Cerebellar Neuropathology in Nor98

Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E11National Veterinary Insitute, Sweden; 2National Veterinary Institute,Norway

Nor98 is a prion disease of old sheep and goats. This atypical form ofscrapie was first described in Norway in 1998. Several features of Nor98were shown to be different from classical scrapie including the distributionof disease associated prion protein (PrPd) accumulation in the brain. Thecerebellum is generally the most affected brain area in Nor98. The studyherepresented aimed at adding information on the neuropathology in thecerebellumof Nor98 naturally affected sheep of various genotypes in Sweden and Norway.A panel of histochemical and immunohistochemical (IHC) stainings such as IHCfor PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cellmarkersfor phagocytic cells were conducted. The type of histological lesions andtissuereactions were evaluated. The types of PrPd deposition were characterized.Thecerebellar cortex was regularly affected, even though there was a variationin the severity of the lesions from case to case.Neuropil vacuolation was more marked in the molecular layer, but affectedalso the granular cell layer. There was a loss of granule cells. Punctatedeposition of PrPd was characteristic. It was morphologically and indistributionidentical with that of synaptophysin, suggesting that PrPd accumulates inthe synaptic structures. PrPd was also observed in the granule cell layerand in thewhite matter.*** The pathology features of Nor98 in the cerebellum of the affected sheepshowed similarities with those of sporadic Creutzfeldt-Jakob disease inhumans.


From: "Terry S. Singeltary Sr."Sent: Tuesday, August 21, 2007 9:50 AMSubject: TWO MORE Nor98 atypical Scrapie cases detected in USA bringingtotal to 3 cases to date

Infected and Source Flocks

As of June 30, 2007, there were .....


One field case and one validation case were consistent with Nor-98 scrapie.


IN the February 2007 Scrapie report it only mentions ;

''One case was consistent with Nor98 scrapie.''


(please note flocks of origin were in WY, CO, AND CA. PERSONAL COMMUNCATIONSUSDA, APHIS, VS ET AL. ...TSS)



An evaluation of scrapie surveillance in the United States




Subject: FSIS NOTICE SAMPLE COLLECTION FROM CATTLE UNDER THE BOVINESPONGIFORM ENCEPHALOPATHY (BSE)ONGOING SURVEILLANCE PROGRAMFrom: "Terry S. Singeltary Sr."Reply-To: Sustainable Agriculture Network Discussion GroupDate: Fri, 2 Feb 2007 17:32:58 -0600




There is a growing number of human CJD cases, and they were presented lastweek in San Francisco by Luigi Gambatti(?) from his CJD surveillancecollection.

He estimates that it may be up to 14 or 15 persons which display selectivelySPRPSC and practically no detected RPRPSC proteins.



Diagnosis and Reporting of Creutzfeldt-Jakob Disease

Singeltary, Sr et al. JAMA.2001; 285: 733-734.



MARCH 26, 2003

RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob

disease in the United States

Email Terry S. Singeltary:


I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to

comment on the CDC's attempts to monitor the occurrence of emerging

forms of CJD. Asante, Collinge et al [1] have reported that BSE

transmission to the 129-methionine genotype can lead to an alternate

phenotype that is indistinguishable from type 2 PrPSc, the commonest

sporadic CJD. However, CJD and all human TSEs are not reportable

nationally. CJD and all human TSEs must be made reportable in every

state and internationally. I hope that the CDC does not continue to

expect us to still believe that the 85%+ of all CJD cases which are

sporadic are all spontaneous, without route/source. We have many TSEs in

the USA in both animal and man. CWD in deer/elk is spreading rapidly and

CWD does transmit to mink, ferret, cattle, and squirrel monkey by

intracerebral inoculation. With the known incubation periods in other

TSEs, oral transmission studies of CWD may take much longer. Every

victim/family of CJD/TSEs should be asked about route and source of this

agent. To prolong this will only spread the agent and needlessly expose

others. In light of the findings of Asante and Collinge et al, there

should be drastic measures to safeguard the medical and surgical arena

from sporadic CJDs and all human TSEs. I only ponder how many sporadic

CJDs in the USA are type 2 PrPSc?


doi:10.1016/S1473-3099(03)00715-1Copyright © 2003 Published by Elsevier Ltd.Newsdesk

Tracking spongiform encephalopathies in North America

Xavier Bosch

Available online 29 July 2003.

Volume 3, Issue 8, August 2003, Page 463

“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost mymom to hvCJD (Heidenhain variant CJD)and have been searching for answers ever since. What I have found is that wehave not been told the truth. CWDin deer and elk is a small portion of a much bigger problem.”............................



see history of cjd questionnaire


Sent: Monday May 28, 2007



Subject: HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and theUKBSEnvCJD only theoryDate: January 29, 2006 at 9:03 am PST

Comments sent via JAMA Feedback Page------------------------------------------------------------NAME: Terry S. Singeltary Sr.E-MAIL: flounder9@verizon.netIP ADDRESS: xxxxxxxxHOSTNAME: xxxxxxxxPREVIOUS PAGE: http://jama.ama-assn.org/misc/authors.dtlBROWSER: Mozilla/5.0 (Windows; U; Win98; en-US; rv:1.0.2) Gecko/20030208Netscape/7.02PROMOTIONAL USE: (not answered)

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

TSEs have been rampant in the USA for decades in many species, and they allhave been rendered and fed back to animals for human/animal consumption.propose that the current diagnostic criteria for human TSEs only enhancesand helps the spreading of human TSE from the continued belief of theUKBSEnvCJD only theory in 2007. With all the science to date refuting it, tocontinue to validate this myth, will only spread this TSE agent through amultitude of potential routes and sources i.e. consumption, surgical, blood,medical, cosmetics etc. I propose as with Aguzzi, Asante, Collinge, Caughey,Deslys, Dormont, Gibbs, Ironside, Manuelidis, Marsh, et al and many more,that the world of TSE Transmissible Spongiform Encephalopathy is far from anexact science, but there is enough provenscience to date that this myth should be put to rest once and for all, andthat we move forward with a new classification for human and animal TSE thatwould properly identify the infected species, the source species, and thenthe route.

This would further have to be broken down to strain of species and then theroute of transmission would further have to be broken down. Accumulation andTransmission are key to the threshold from sub-clinical to clinical disease,and key to all this, is to stop the amplification and transmission of thisagent, the spreading of, no matter what strain. In my opinion, to continuewith this myth that the U.K. strain of BSE (one strain TSE in cows), and thenv/v CJD (one strain TSE humans) and that all the rest of human TSE are justone single strain i.e. sporadic CJD (when to date there are 6 differentphenotypes of sCJD, and growing per Gambetti et al), and that no otheranimal TSE transmits to humans, to continue with this masquerade will onlycontinue to spread, expose, and kill, who knows how many more in the yearsand decades to come. ONE was enough for me, My Mom, hvCJD i.e. HeidenhainVariant CJD, DOD 12/14/97 confirmed, which is nothing more than another mansname added to CJD, like CJD itself, Jakob and Creutzfeldt, orGerstmann-Straussler-Scheinker syndrome, just another CJD or human TSE,named after another human.

WE are only kidding ourselves with the current diagnostic criteria for humanand animal TSE, especially differentiating between the nvCJD vs the sporadicCJDstrains and then the GSS strains and also the FFI fatal familial insomniastrains or the ones that mimics one or the other of those TSE? Tissueinfectivity and strain typing of the many variants of the human and animalTSEs are paramount in all variants of all TSE. There must be a properclassification that will differentiate between all these human TSE in orderto do this. With the CDI and other more sensitive testing coming about, Ionly hope that my proposal will some day be taken seriously. ...

Terry S. Singeltary Sr.P.O. Box 42Bacliff, Texas USA 77518flounder9@verizon.net



CJD VOICE (voice for _all_ victims of human TSE)



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