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Can Mortality Data Provide Reliable Indicators for Creutzfeldt-Jakob Disease Surveillance? A Study in France from 2000 to 2008

Posted Nov 08 2011 10:01pm
Vol. 37, No. 3-4, 2011

Original Paper

Can Mortality Data Provide Reliable Indicators for Creutzfeldt-Jakob Disease Surveillance? A Study in France from 2000 to 2008

Jean-Philippe Brandela–e, Arlette Welaratnea, Dominique Salomonf, g, Isabelle Capekh, Véronique Vaillanth, Albertine Aouabai, Stéphane Haïka–e, Annick Alpérovitchf, g

aAP-HP, Cellule Nationale de Référence des Maladies de Creutzfeldt-Jakob, Groupe Hospitalier Pitié-Salpêtrière, bINSERM, UMR-S 975, Equipe Maladie d’Alzheimer – Maladies à prions, cCNRS, UMR 7225, dUniversité Pierre et Marie Curie Paris 06, UMR 7225, S-975, Centre de Recherche de l’Institut Cerveau-Moelle (CRICM), eCNR des ATNC, fINSERM, U708, Neuroépidémiologie, gUPMC Université Paris 06, UMR S708, Paris, hInstitut de Veille Sanitaire, Saint-Maurice, et iINSERM-CépiDc, Le Vésinet, France

Address of Corresponding Author

Neuroepidemiology 2011;37:188-192 (DOI: 10.1159/000332764)

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Key Words

Creutzfeldt-Jakob disease Mortality register Active surveillance Evaluation of surveillance systems

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Abstract

Background: Surveillance of Creutzfeldt-Jakob disease (CJD) is still an important issue because of the variant CJD epidemic, which is in decline and also because of the emergence of novel forms of animal transmissible spongiform encephalopathy with zoonotic potential and the risk of nosocomial and blood transfusion-related transmission. Active surveillance has been implemented in most European countries and requires important human resources and funding. Here, we studied whether national mortality and morbidity statistics can be used as reliable indicators. Methods: CJD data collected by the French national CJD surveillance centre were compared with data registered in the national mortality statistics. Results: From 2000 to 2008, the two sources reported fairly similar numbers of CJD deaths. However, analysis of individual data showed important between-sources disagreement. Nearly 24% of CJD reported by the mortality register were false-positive diagnoses and 21.6% of the CJD cases diagnosed by the surveillance centre were not registered as CJD in the national mortality statistics. One out of 22 variant CJD cases was not reported as having any type of CJD in the mortality statistics. Conclusions:These findings raise doubt about the possibility of a reliable CJD surveillance only based on mortality data.

Copyright © 2011 S. Karger AG, Basel

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Author Contacts

Jean-Philippe Brandel Cellule Nationale de Référence des Maladies de Creutzfeldt-Jakob Groupe Hospitalier Pitié-Salpêtrière, 47–83 boulevard de l’Hôpital FR–75013 Paris (France) Tel. +33 14 216 2626, E-Mail jean-philippe.brandel@psl.aphp.fr

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© 2011 S. Karger AG, Basel

http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=332764&Ausgabe=255660&ProduktNr=224263



"Conclusions:These findings raise doubt about the possibility of a reliable CJD surveillance only based on mortality data."


i been saying it for a decade. however, as with the USDA et al BSE aka mad cow surveillance and testing there from, the CJD surveillance program was set up the same way, NOT TO FIND CASES OF HUMAN TSE AKA CJD from any source of livestock in the USA $$$



Views & Reviews



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

Ermias D. Belay, MD, Ryan A. Maddox, MPH, Pierluigi Gambetti, MD and Lawrence B. Schonberger, MD

+ Author Affiliations

From the Division of Viral and Rickettsial Diseases (Drs. Belay and Schonberger and R.A. Maddox), National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA; and National Prion Disease Pathology Surveillance Center (Dr. Gambetti), Division of Neuropathology, Institute of Pathology, Case Western Reserve University, Cleveland, OH.

Address correspondence and reprint requests to Dr. Ermias D. Belay, 1600 Clifton Road, Mailstop A-39, Atlanta, GA 30333.

http://www.neurology.org/content/60/2/176


26 March 2003

Terry S. Singeltary, retired (medically) CJD WATCH

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?

http://www.neurology.org/content/60/2/176/reply#neurology_el_535


Reply to Singletary

Ryan A. Maddox, MPH Ermias D. Belay, MD, Lawrence B. Schonberger, MD Centers for Disease Control and Prevention Atlanta GA

Mr. Singletary raises several issues related to current Creutzfeldt- Jakob disease (CJD) surveillance activities. Although CJD is not a notifiable disease in most states, its unique characteristics, particularly its invariably fatal outcome within usually a year of onset, make routine mortality surveillance a useful surrogate for ongoing CJD surveillance.[1] In addition, because CJD is least accurately diagnosed early in the course of illness, notifiable-disease surveillance could be less accurate than, if not duplicative of, current mortality surveillance.[1] However, in states where making CJD officially notifiable would meaningfully facilitate the collection of data to monitor for variant CJD (vCJD) or other emerging prion diseases, CDC encourages the designation of CJD as a notifiable disease.[1] Moreover, CDC encourages physicians to report any diagnosed or suspected CJD cases that may be of special public health importance (e.g., vCJD, iatrogenic CJD, unusual CJD clusters).

As noted in our article, strong evidence is lacking for a causal link between chronic wasting disease (CWD) of deer and elk and human disease,[2] but only limited data seeking such evidence exist. Overall, the previously published case-control studies that have evaluated environmental sources of infection for sporadic CJD have not consistently identified strong evidence for a common risk factor.[3] However, the power of a case-control study to detect a rare cause of CJD is limited, particularly given the relatively small number of subjects generally involved and its long incubation period, which may last for decades. Because only a very small proportion of the US population has been exposed to CWD, a targeted surveillance and investigation of unusual cases or case clusters of prion diseases among persons at increased risk of exposure to CWD is a more efficient approach to detecting the possible transmission of CWD to humans. In collaboration with appropriate local and state health departments and the National Prion Disease Pathology Surveillance Center, CDC is facilitating or conducting such surveillance and case- investigations, including related laboratory studies to characterize CJD and CWD prions.

Mr. Singletary also expresses concern over a recent publication by Asante and colleagues indicating the possibility that some sporadic CJD cases may be attributable to bovine spongiform encephalopathy (BSE).[4] The authors reported that transgenic mice expressing human prion protein homozygous for methionine at codon 129, when inoculated with BSE prions, developed a molecular phenotype consistent with a subtype of sporadic CJD. Although the authors implied that BSE might cause a sporadic CJD-like illness among persons homozygous for methionine, the results of their research with mice do not necessarily directly apply to the transmission of BSE to humans. If BSE causes a sporadic CJD-like illness in humans, an increase in sporadic CJD cases would be expected to first occur in the United Kingdom, where the vast majority of vCJD cases have been reported. In the United Kingdom during 1997 through 2002, however, the overall average annual mortality rate for sporadic CJD was not elevated; it was about 1 case per million population per year. In addition, during this most recent 6-year period following the first published description of vCJD in 1996, there was no increasing trend in the reported annual number of UK sporadic CJD deaths.[3, 5] Furthermore, surveillance in the UK has shown no increase in the proportion of sporadic CJD cases that are homozygous for methionine (Will RG, National CJD Surveillance Unit, United Kingdom, 2003; personal communication).

References

1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Diagnosis and reporting of Creutzfeldt-Jakob disease. JAMA 2001;285:733-734.

2. Belay ED, Maddox RA, Gambetti P, Schonberger LB. Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States. Neurology 2003;60:176-181.

3. Belay ED. Transmissible spongiform encephalopathies in humans. Annu Rev Microbiol 1999;53:283-314.

4. Asante EA, Linehan JM, Desbruslais M, et al. BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein. EMBO J 2002;21:6358-6366.

5. The UK Creutzfeldt-Jakob Disease Surveillance Unit. CJD statistics. Available at: http://www.cjd.ed.ac.uk/figures.htm. Accessed February 18, 2003.

http://www.neurology.org/content/60/2/176/reply#neurology_el_582


Human Prion Diseases in the United States

Robert C. Holman1*, Ermias D. Belay1, Krista Y. Christensen1, Ryan A. Maddox1, Arialdi M. Minino2, Arianne M. Folkema1, Dana L. Haberling1, Teresa A. Hammett1, Kenneth D. Kochanek2, James J. Sejvar1, Lawrence B. Schonberger1

1 Division of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-borne and Enteric Diseases, Centers for Disease Control and Prevention (CDC), U.S. Department of Health and Human Services (USDHHS), Atlanta, Georgia, United States of America, 2 Division of Vital Statistics, National Center for Health Statistics, Centers for Disease Control and Prevention (CDC), U.S. Department of Health and Human Services (USDHHS), Hyattsville, Maryland, United States of America

Abstract Top

Background

Prion diseases are a family of rare, progressive, neurodegenerative disorders that affect humans and animals. The most common form of human prion disease, Creutzfeldt-Jakob disease (CJD), occurs worldwide. Variant CJD (vCJD), a recently emerged human prion disease, is a zoonotic foodborne disorder that occurs almost exclusively in countries with outbreaks of bovine spongiform encephalopathy.

This study describes the occurrence and epidemiology of CJD and vCJD in the United States.

Methodology/Principal Findings

Analysis of CJD and vCJD deaths using death certificates of US residents for 1979–2006, and those identified through other surveillance mechanisms during 1996–2008. Since CJD is invariably fatal and illness duration is usually less than one year, the CJD incidence is estimated as the death rate. During 1979 through 2006, an estimated 6,917 deaths with CJD as a cause of death were reported in the United States, an annual average of approximately 247 deaths (range 172–304 deaths). The average annual age-adjusted incidence for CJD was 0.97 per 1,000,000 persons. Most (61.8%) of the CJD deaths occurred among persons =65 years of age for an average annual incidence of 4.8 per 1,000,000 persons in this population. Most deaths were among whites (94.6%); the age-adjusted incidence for whites was 2.7 times higher than that for blacks (1.04 and 0.40, respectively). Three patients who died since 2004 were reported with vCJD; epidemiologic evidence indicated that their infection was acquired outside of the United States.

Conclusion/Significance

Surveillance continues to show an annual CJD incidence rate of about 1 case per 1,000,000 persons and marked differences in CJD rates by age and race in the United States. Ongoing surveillance remains important for monitoring the stability of the CJD incidence rates, and detecting occurrences of vCJD and possibly other novel prion diseases in the United States.

Citation: Holman RC, Belay ED, Christensen KY, Maddox RA, Minino AM, et al. (2010) Human Prion Diseases in the United States. PLoS ONE 5(1): e8521. doi:10.1371/journal.pone.0008521

Editor: Mick F. Tuite, University of Kent, United Kingdom

Received: July 21, 2009; Accepted: October 30, 2009; Published: January 1, 2010

Holman et al. This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.

Funding: The authors have no support or funding to report.

Competing interests: The authors have declared that no competing interests exist.

* E-mail: rholman@cdc.gov



http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0008521&annotationId=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd;jsessionid=42A8AB7D8AE8305E793259D57C0F5DCF.ambra02



2 responses

re-Human Prion Diseases in the United States

Posted by flounder on 01 Jan 2010 at 18:11 GMT

Most recent response on 02 Jan 2011 at 20:00 GMT


http://www.plosone.org/article/fetchArticleComments.action?annotationId=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd&articleURI=info%3Adoi%2F10.1371%2Fjournal.pone.0008521




my comments to PLosone here ;



re-Human Prion Diseases in the United States Posted by flounder on 01 Jan 2010 at 18:11 GMT


I kindly disagree with your synopsis for the following reasons ;



No competing interests declared.



RE: re-Human Prion Diseases in the United States part 2



flounder replied to flounder on 02 Jan 2010 at 21:26 GMT


I would kindly like to add to my initial concerns, something I brought up years ago, and I believe that still hold true today, more so even than when I first stated these concerns in 2003 ;


routine passive mortality CJD surveillance USA ?


THIS has been proven not to be very useful in the U.K.;


THE EPIDEMIOLOGY OF CJD RG WILL 1984 (182 PAGES)

snip...

One reason for this was the _inaccuracy_ in coding of cases correctly certified as CJD Coding is carried out by staff who are not medically qualified and it is not surprising that coding errors occur in the processing of large numbers of certificates. In 1982, 12,000 certificates per week were processed at the office of population censuses and surveys by 15 coders and 6 checkers (Alderson et al., 1983). The occurrence of both inter- and intra-observer coding errors has been described (Curb et al., 1983) and the _inaccuracies_ of BOTH certification and coding discovered in this study _support_ the introduction of a more accurate system of death certificates and a more detailed and specific coding system...

snip...

http://web.archive.org/web/20040521215716/http://www.bseinquiry.gov.uk/files/mb/m26/tab01.pdf



Draft Proposal For The Monitoring of Creutzfeldt-Kakob Disease 1989 Dr. R. Will

snip...

IDENTIFICATION OF CASES

Cases of CJD may be identified from death certificates, but this alone is unlikely to provide adequate monitoring. ERRORS are made in certification and diagnosis; in the Oxford study death certificates were obtained on a series of known confirmed cases and CJD was mentioned in only 66% of certificates. In another series of 175 certified cases, 42 patients were judged not to have suffered from CJD after examination of case notes (7)...

full text;

http://web.archive.org/web/20050526035006/http://www.bseinquiry.gov.uk/files/yb/1989/05/00005001.pdf



AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease.

snip...

http://web.archive.org/web/20060307063542/http://www.bseinquiry.gov.uk/files/yb/1991/01/04004001.pdf



Confucius is confused again? how in 1996 and earlier can the 28 sporadic CJD victims and the one-in-a-million there from, how can it still be one in a million in 2008, with the sporadic CJD count rising to 205, still be one-in-a-million? and the years in-between, steady rise just about every year, and it still be only one-in-a-million, year after year after years? I suppose just more of that fuzzy math, which you can see here;


http://www.cjdsurveillance.com/pdf/case-table.pdf


Please see my complete comment to this synopsis here ;



Saturday, January 2, 2010

Human Prion Diseases in the United States January 1, 2010

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


No competing interests declared.

RE: RE: re-Human Prion Diseases in the United States part 2

flounder replied to flounder on 02 Jan 2011 at 20:00 GMT

Wednesday, December 29, 2010

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY PRION END OF YEAR REPORT DECEMBER 29, 2010

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/transmissible-spongiform-encephalopathy.html


Wednesday, December 29, 2010

CWD Update 99 December 13, 2010

http://chronic-wasting-disease.blogspot.com/2010/12/cwd-update-99-december-13-2010.html



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


No competing interests declared.



Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: an updated classification

Piero Parchi Æ Rosaria Strammiello Æ Silvio Notari Æ Armin Giese Æ Jan P. M. Langeveld Æ Anna Ladogana Æ Inga Zerr Æ Federico Roncaroli Æ Patrich Cras Æ Bernardino Ghetti Æ Maurizio Pocchiari Æ Hans Kretzschmar Æ Sabina Capellari

Received: 30 June 2009 / Revised: 16 August 2009 / Accepted: 17 August 2009 / Published online: 29 August 2009

The Author(s) 2009. This article is published with open access at Springerlink.com

Abstract

Six subtypes of sporadic Creutzfeldt-Jakob disease with distinctive clinico-pathological features have been identified largely based on two types of the abnormal prion protein, PrPSc, and the methionine (M)/valine (V) polymorphic codon 129 of the prion protein. The existence of affected subjects showing mixed phenotypic features and concurrent PrPSc types has been reported but with inconsistencies among studies in both results and their interpretation. The issue currently complicates diagnosis and classification of cases and also has implications for disease pathogenesis. To explore the issue in depth, we carried out a systematic regional study in a large series of 225 cases. PrPSc types 1 and 2 concurrence was detected in 35% of cases and was higher in MM than in MV or VV subjects. The deposition of either type 1 or 2, when concurrent, was not random and always characterized by the coexistence of phenotypic features previously described in the pure subtypes. PrPSc type 1 accumulation and related pathology predominated in MM and MV cases, while the type 2 phenotype prevailed in VVs. Neuropathological examination best identified the mixed types 1 and 2 features in MMs and most MVs, and also uniquely revealed the cooccurrence of pathological variants sharing PrPSc type 2. In contrast, molecular typing best detected the concurrent PrPSc types in VV subjects and MV cases with kuru plaques. The present data provide an updated disease classification and are of importance for future epidemiologic and transmission studies aimed to identify etiology and extent of strain variation in sporadic Creutzfeldt-Jakob disease.

snip...

Discussion

Previous studies have addressed the issue of PrPSc types 1 and 2 co-occurrence in sCJD. Most of them raised the question of the influence of the number of cases and brain areas analyzed and emphasized the possibility that the cooccurrence of PrPSc types 1 and 2 is underestimated [13, 18, 20, 30, 37, 40, 43]. On the other hand, the use of a novel, potentially very sensitive approach, later shown to have pitfalls related to the detection of unspecific bands generated by partially digested PrPSc fragments [25], likely led other investigators to overestimate the incidence of the concurrent PrPSc types [35, 45]. Thus, the overall results on the phenomenon of the coexistence of molecular and clinico-pathological sCJD subtypes are at present inconclusive with respect to incidence, effect on disease phenotype and criteria for disease classification. To contribute to the full understanding of these issues, in the present study, we combined a systematic analysis of several brain regions in a large series of case including all codon 129 genotypes and the rarest phenotypes with the use of a refined methodology for the detection of the PrPSc type concurrence, which provides good sensitivity combined with high specificity [25].

After screening about 4,200 samples from a largely consecutive series of 200 cases, we estimated that PrPSc types 1 and 2 coexist in about 35% of sCJD cases, which is overall consistent with figures from some of the previous studies [13, 37, 43] in which the number of cases and areas analyzed were significantly lower. This finding supports the idea that PrPSc types co-occurrence involves a relevant but limited group of sCJD subjects and indicates that the incidence of the phenomenon had not been significantly underestimated.

As far as the characteristics of the CJD population with mixed phenotypes are concerned, our data show that the PrPSc types 1 and 2 co-occur more frequently in the MM than in the MV and VV genotypes. More specifically, the large majority of sCJD cases with concurrent PrPSc types combines features of the MM and MM 2C sCJD subtypes, in variable proportions. Most commonly, in such cases, the MM1 phenotype is predominant over the MM 2C phenotype, but the opposite situation also rarely occurs. The latter results significantly differ from those obtained in most previous studies. Indeed, Head et al. [13] mainly found a focal type 1 co-occurrence in MM and MV subjects with dominant type 2, Schoch et al. [40] detected the mixed protein types mostly in MV2 cases showing the type 1 only focally in subcortical areas, and Uro-Coste et al. [43] mainly detected a random co-occurrence of type 1 in MV or VV cases with dominant type 2. Given that only our study was based on a large series of consecutive cases, we attribute such heterogeneity of previous results to case selection biases, although methodological differences may also have contributed [43].

snip...

Taken together, our data indicate that a protocol including the neuropathologic assessment of the eight brain regions mentioned above and PrPSc typing in four critical regions such as the temporal, parietal and occipital neocortices, and medial thalamus is strongly recommended for a reliable sCJD group classification addressing the issue of mixed phenotypes. Indeed, by applying this protocol instead of examining all 21 brain regions, we would have reached the same classification of cases in the present series.

We also wish to underline the importance of identifying correctly the sCJD cases with mixed features for transmission purposes. Indeed, the question of whether the concurrence of PrPSc types 1 and 2 in CJD reflects a coinfection by two prion strains related to specific undiscovered human genotypes, or determined by epigenetic factors remains unanswered and will largely rely on transmission studies in which the careful selection of samples will be of critical importance. Concerning this critical question, we find intriguing that the large, confluent vacuoles and the perivacuolar pattern of PrPSc deposition, we originally linked to sCJD MM 2C are also found in a subgroup of MV 2K subjects in addition to MM/MV 1?2C. In addition, we have described here the same morphological features in one case of fatal insomnia (i.e. the MM2-thalamic subtype or MM 2T) which adds to two previously reported cases [19, 30, 31]. Thus, it seems that large confluent vacuoles and the perivacuolar pattern of PrPSc deposition may be found in sCJD associated with all phenotypes linked to MM or MV at codon 129. Although this observation remains difficult to interpret at present, it appears relevant for our future understanding of the molecular basis and the extent of strain variation in sCJD. In any case, our observation strongly suggests that the phenomenon of mixed phenotypes in sCJD goes beyond PrPSc types 1 and 2 coexistence and also involves subtypes which shares the same PrPSc type. This, in turn, further underlines the importance of combining histopathological assessment and biochemical PrPSc typing for sCJD subtype characterization.

The present data also show that the association of two PrP27-30 fragments, which does not represent a bona-fide type 1 and 2 concurrence, may also be a feature of some sCJD cases. Thus, the PrP27-30 profile in VV2 cases in the cerebellum, thalamus and midbrain is sometime characterized by a doublet comprising a 18.5 kDa in addition to the typical 19 kDa band, while the western blot profile of PrP27-30 in the MV 2K cases appears almost invariably characterized by the association of two PrPSc core fragments including a classic 19 kDa type 2 band and a slower migrating band of about 20 kDa. Although these profiles truly represent concurrent PrPSc fragments, and the 20 and 18.5 kDa fragments likely reflect specific PK cleavage sites, the 20 and 18.5 kDa bands are distinguished from the type 1 and type 2 fragments because, at least to date, they were never detected independently from types 1 and 2, and are not markers of specific clinico-pathological phenotypes. Knowledge of these regional variations is nonetheless important to avoid misinterpreting a PrPSc profile as novel when only one brain region is analyzed [21].

Finally, the results obtained from the analyses of lesion profiles and clinical features in the subgroups of sCJD cases with mixed features deserve further comment. By showing that the relative load of each of the two PrPSc types significantly correlates with disease duration, the relative frequency of certain symptoms, and the ratio between cortical and cerebellar pathology, our study provides further strong evidence for the PrPSc type being a major biological determinant in human prion disease. In conclusion, the present data add to our knowledge of the prevalence and phenotypic spectrum of the sCJD variants with mixed molecular and pathological features, provide an updated molecular classification of the disease subtypes and will serve for future epidemiologic and transmission studies aimed at disclosing the etiology and extent of strain variation in sCJD.

Acknowledgments We wish to thank Barbara Polischi and Sabrina Boninsegna for her technical assistance. We also thank all the physicians who provided clinical data and helped in the collection of tissues and all family members who consented to the use of tissue for research. This study was funded in the frame of the bilateral Italy (ISS)-USA (NIH, Office for Rare Diseases) agreement on joint research on rare diseases, by the European Commission (FOOD-CT- 2004-506579), the Italian Ministry of University, Research and Technology (FIRB-2003-RBNE03FMCJ_006), the Federal Ministry of Health (ZV2-1369-340): grant PHS P30 AG010133, and the Gino Galletti Foundation.

Keywords Prion protein Brain mapping Molecular typing Neurodegeneration Classification

P. Parchi R. Strammiello S. Notari S. Capellari Dipartimento di Scienze Neurologiche, Universita` di Bologna, Bologna, Italy A. Giese H. Kretzschmar Institut fu¨r Neuropathologie, Ludwig-Maximilians-Universita¨t Mu¨nchen, Munich, Germany J. P. M. Langeveld Central Veterinary Institute of Wageningen UR, Lelystad, The Netherlands A. Ladogana M. Pocchiari Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita`, Rome, Italy I. Zerr Department of Neurology, National Reference Center for TSE Surveillance, Georg-August University, Go¨ttingen, Germany F. Roncaroli Division of Neuroscience and Mental Health, Department of Clinical Neuroscience, Imperial College, London, UK P. Cras Born-Bunge Institute (BBI), University of Antwerp (UA), Antwerp, Belgium B. Ghetti Department of Pathology, Indiana University, Indianapolis, IN, USA P. Parchi (&) Department of Neurological Sciences, Universtity of Bologna, Via Foscolo 7, 40123 Bologna, Italy e-mail: piero.parchi@unibo.it

http://www.springerlink.com/content/21552482u6761291/fulltext.pdf


MANY, MANY THANKS TO Parchi et al for this study, AND for the public access to full text. ...TSS


Tuesday, August 11, 2009

Characteristics of Established and Proposed Sporadic Creutzfeldt-Jakob Disease Variants

Brian S. Appleby, MD; Kristin K. Appleby, MD; Barbara J. Crain, MD, PhD; Chiadi U. Onyike, MD, MHS; Mitchell T. Wallin, MD, MPH; Peter V. Rabins, MD, MPH

Background: The classic Creutzfeldt-Jakob disease (CJD), Heidenhain, and Oppenheimer-Brownell variants are sporadic CJD (sCJD) phenotypes frequently described in the literature, but many cases present with neuropsychiatric symptoms, suggesting that there may be additional sCJD phenotypes.

Objective: To characterize clinical, diagnostic, and molecular features of 5 sCJD variants.

Design: Retrospective analysis.

Setting: The Johns Hopkins and Veterans Administration health care systems.

Participants: Eighty-eight patients with definite or probable sCJD.

Main Outcome Measures: Differences in age at onset, illness progression, diagnostic test results, and molecular subtype.

Results: The age at onset differed among sCJD variants (P=.03); the affective variant had the youngest mean age at onset (59.7 years). Survival time (P .001) and the time to clinical presentation (P=.003) differed among groups. Patients with the classic CJD phenotype had the shortest median survival time from symptom onset (66 days) and those who met criteria for the affective sCJD variant had the longest (421 days) and presented to clinicians significantly later (median time from onset to presentation, 92 days; P=.004). Cerebrospinal fluid analyses were positive for 14-3-3 protein in all of the affective variants, regardless of illness duration. Periodic sharp-wave complexes were not detected on any of the electroencephalography tracings in the Oppenheimer-Brownell group; basal ganglia hyperintensity was not detected on brain magnetic resonance imaging in this group either. All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.

Conclusions: The classic CJD phenotype and the Heidenhain, Oppenheimer-Brownell, cognitive, and affective sCJD variants differ by age at disease onset, survival time, and diagnostic test results. Characteristics of these 5 phenotypes are provided to facilitate further clinicopathologic investigation that may lead to more reliable and timely diagnoses of sCJD.

Arch Neurol. 2009;66(2):208-215

snip...

COMMENT

snip...see full text ;

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


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

August 10, 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



WHO WILL WATCH THE CHILDREN for CJD over the next 5 decades ?


SCHOOL LUNCH PROGRAM FROM DOWNER CATTLE UPDATE

http://downercattle.blogspot.com/2009/05/who-will-watch-children.html


http://downercattle.blogspot.com/



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


Sunday, September 6, 2009

MAD COW USA 1997 SECRET VIDEO

http://madcowusda.blogspot.com/2009/09/mad-cow-usa-1997-video.html



U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ? see video at bottom

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



DAMNING TESTIMONY FROM STANLEY PRUSINER THE NOBEL PEACE PRIZE WINNER ON PRIONS SPEAKING ABOUT ANN VENEMAN see video

http://maddeer.org/

CVM Annual Report Fiscal Year 2008: October 1, 2007-September 30, 2008

PUTTING LIPSTICK ON A PIG AND TAKING HER TO A DANCE...TSS

BSE Feed Rule Enforcement: A Decade of Success OFF TO A FAST START

http://madcowfeed.blogspot.com/2008/06/texas-firm-recalls-cattle-heads-that.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


Sent: Tuesday, November 03, 2009 9:07 PM

Subject: [BSE-L] re-FOIA REQUEST ON FEED RECALL PRODUCT contaminated with prohibited material Recall # V-258-2009 and Recall # V-256-2009 (CONFIRMED BSE RELATED, BOTH INCIDENCES)

http://madcowfeed.blogspot.com/2009/11/re-foia-request-on-feed-recall-product.html


Thursday, November 05, 2009

Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: an updated classification

http://creutzfeldt-jakob-disease.blogspot.com/2009/11/incidence-and-spectrum-of-sporadic.html


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



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, 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


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


(American Journal of Pathology. 2009;175:2566-2573.) © 2009 American Society for Investigative Pathology DOI: 10.2353/ajpath.2009.090623

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

Wiebke M. Wemheuer*, Sylvie L. Benestad, Arne Wrede*, Ulf Schulze-Sturm*, Wilhelm E. Wemheuer, Uwe Hahmann*, Joanna Gawinecka, Ekkehard Schütz, Inga Zerr, Bertram Brenig, Bjørn Bratberg, Olivier Andréoletti¶ and Walter J. Schulz-Schaeffer* From the Prion and Dementia Research Unit,* Department of Neuropathology, and the National Transmissible Spongiform Encephalopathies Reference Center, Department of Neurology, University Medical Center Goettingen, Goettingen, Germany; the Department of Pathology, National Veterinary Institute, Oslo, Norway; the Institute of Veterinary Medicine, Faculty for Agricultural Sciences, University of Goettingen, Goettingen, Germany; and Animal Health,¶ Interactions Hôte Agent Pathogène, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France

Transmissible spongiform encephalopathies such as scrapie in sheep, Creutzfeldt-Jakob disease (CJD) in humans, and bovine sporadic encephalopathy in cattle are characterized by the accumulation of a misfolded protein: the pathological prion protein. Ever since bovine sporadic encephalopathy was discovered as the likely cause of the new variant of CJD in humans, parallels between human and animal transmissible spongiform encephalopathies must be viewed under the aspect of a disease risk for humans. In our study we have compared prion characteristics of different forms of sheep scrapie with those of different phenotypes of sporadic CJD. The disease characteristics of sporadic CJD depend considerably on the prion type 1 or 2. Our results show that there are obvious parallels between sporadic CJD type 1 and the so-called atypical/Nor98 scrapie. These parelleles apply to the deposition form of pathological prion protein in the brain, detected by the paraffin-embedded-tissue blot and the prion aggregate stability with regard to denaturation by the chaotropic salt guanidine hydrochloride. The same applies to sporadic CJD type 2 and classical scrapie. The observed parallels between types of sporadic CJD and types of sheep scrapie demonstrate that distinct groups of prion disease exist in different species. This should be taken into consideration when discussing interspecies transmission.

snip...

UPDATE ON THIS STUDY, further into this study ;

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

snip...

Different Scrapie Prion Types Show Similarities to Human Prion Types: PrPsc Deposition Pattern and Western Blot Results

After proteinase K-digestion and Western blot analysis, two different prion protein types were detectable in clinically distinct human Creutzfeldt-Jakob diseases.30 Depending on the PrPSc types 1 or 2 (Figure 1C) a difference in the form of PrPSc aggregates and the neuroanatomical distribution in the brain could be observed similar to differences identified in sheep scrapie. In patients with CJD that accumulate PrPSc type 1, reticular/synaptic were detected in cortical structures (Figure 3F), subcortical nuclei, and the cerebellar cortex (Figure 4D). By contrast, prion aggregates in patients accumulating PrPSc type 2 appeared to be complex as they displayed in particular perivacuolar, intra- and perineuronal, and/or plaque-like forms (Figures 3C and 5B). These differences concerning the deposition form of PrPSc aggregates were independent of the methionine/valine polymorphism at codon 129 of the PRNP. The topographical pattern of PrPSc distribution between these two prion types differed as follows: type 1 deposits were typically restricted to gray matter structures, while all type 2 patients showed deposits in the white matter. In patients with type 1 PrPSc the midbrain and brain stem structures were relatively spared, but in patients with type 2 PrPSc brain stem and midbrain were heavily affected. Although these prion type-related topographical differences are not completely identical to those in sheep scrapie, a comparable connection between prion type and deposition pattern is evident.

Aggregate Stability Regarding Denaturation

Similar to scrapie in sheep, the stability of PrPSc aggregates of human sporadic CJD against denaturation with GdnHCl showed two groups: denaturation-resistant and denaturation-sensitive PrPSc aggregates. This property correlated with the prion protein type according to Parchi et al8 and is independent from the physiologically occurring methionine/valine polymorphism at codon 129 of the PRNP. By membrane adsorption after GdnHCl denaturation and proteinase K-digestion, human PrPSc type 1 proved to be less stable than human PrPSc type 2. While human PrPSc type 2 was detectable up to GdnHCl concentrations between 3M and 4M, human PrPSc type 1 was stable up to 2M GdnHCl. Neither methionine nor valine at codon 129 in type 1 or type 2 seemed to alter the stability of the prion protein aggregates (Figure 5).

Summarizing the results, striking parallels between human PrPSc type 1 and atypical/Nor98 scrapie as well as human PrPSc type 2 and classical scrapie are observed with regard to PrPSc deposition and stability of the prion aggregates.

Discussion

In humans, different prion types are linked with clinically and neuropathologically distinct prion diseases.8 The present work emphasizes that the differences in deposition characteristics and stability with regard to denaturation between atypical/Nor98 and classical scrapie also account for different prion types. Moreover, the two scrapie types that have been characterized show a number of striking similarities with human PrPSc types in sporadic CJD. Hence, we propose that the existence of different PrPSc types might be a common denominator of prion diseases in humans and animals. Since these two prion types show an across-the-species comparability with similar biochemical and pathological characteristics, it is most likely that they exist due to a different conformational pattern of the disease-related prion protein.

Prion Types Depend on Conformation

The interpretation that the conformation of PrPSc accounts for prion types is supported by different proteinase K-cleavage sites of human prion types9 and the propagation of mutation-associated prion characteristics in human transgenic mice without PRNP-point mutation. 31 However, differences in protein stability as they have been found in this study, provide direct evidence for a conformational distinction between these molecules.32 Further support for the relation between type and conformation is also given by experiments focusing on the size of prion protein aggregates. Using virus removal filters, Kobayashi et al33 were able to show differences in the size of CJD type 1 and type 2 aggregates: PrPSc type 2 forms larger aggregates than PrPSc type 1, independent of whether the disease was sporadic, iatrogenic or acquired. This difference is clearly reflected by the morphology of the PrPSc depositions we have found in sheep scrapie and human CJD. Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine (reticular) deposits, whereas CJD type 2 and classical scrapie display a complex aggregate pattern, regardless of the respective genotypes at the polymorphic positions of the PRNP that were investigated.

Prion Type Characteristics Versus Prion Strain Characteristics

Structural differences of the disease-associated protein have also been proposed as an explanation for the existence of strains. Partial digestion of the disease-associated protein with proteinase K as well as differences in antibody binding after the protein was partially denatured were used to identify structural characteristics in correlation with strain properties and different clinical TSE forms.23,34,35 It needs to be considered that the kinetics of proteinase K-digestion of PrPSc are markedly influenced by detergent effects in the buffer, demonstrating that the accessibility of the cleavage sites are variable.35 In contrast, differences in the stability against total unfolding of PrPSc seem to be a usable criterion to identify conformational differences or conformational motives. Whereas detergents affect the tertiary structure of a protein by interacting with hydrophilic and hydrophobic areas of protein molecules, chaotropic salts like GdnHCl destroy the hydrogen bonds in -helices and -sheets leading to an irregular coiled polypeptide chain.36 This is in line with the observation that detergents remove prion infectivity only partially, whereas chemicals that destroy secondary structures like chaotropic salts are highly effective. 37 However, detectable differences regarding the stability against denaturation with GdnHCl shown for various prion strains in hamsters seem to be very small compared with the ones that can be shown here for the prion types of human and ovine prion diseases. Strains could thus correspond to structural differences that are less marked than those defining types and are probably constant only under defined conditions. Influences of polymorphisms or interactions with other genetic factors like the promotor region, species-specific factors like the recently detected incorporation of polyanionic molecules into prions,38 glycosaminoglycans or other yet unknown factors of the original host may also lead to different strains in a new host within the prion types of the original species.5,39 The existence of prion types does not exclude the existence of strains. The same variations that account for strains might be the reason for differences in the clinical disease course of the natural host.

Two Different Prion Types also in BSE?

Parallel to human sporadic CJD and our results in sheep scrapie, there is increasing evidence that two prion types also exist in cattle BSE. Two presumably sporadic forms of BSE known as H-type BSE14 and bovine amyloidotic spongiform encephalopathy, also called L-type BSE,15 have been described in cattle in addition to typical/classical BSE.40 The small variation in the apparent molecular weight of the unglycosylated band of bovine amyloidotic spongiform encephalopathy is considered to be well within the range of classical BSE,41,42 which would leave H-type BSE with a considerably larger unglycosylated fragment in Western blot analysis than the second BSE type. Interestingly, bovine amyloidotic spongiform encephalopathy converts into classical BSE after serial passages in bovine-transgenic mice,43 although displaying clinically different diseases in cattle.44 From the latter experiment the authors concluded that different strains were responsible for different phenotypes. Obviously the different clinical diseases were generated by agents that belong to a single prion type. These results together with our observations emphasize the need to differentiate strictly between prion types and prion strains and demonstrate that even in cattle BSE, one prion type may contain different prion strains.

Prion Type Displays Parallels in the Pathophysiology of Disease between Species

Biochemical and morphological similarities have been used to draw parallels between forms of BSE and human prion diseases.15 Parallels between species can also be observed with regard to the route of prion infection: in classical BSE, variant CJD, and classical scrapie, all of which presumably belong to one class of prion type (type 2 in humans) according to the observations made above, the oral route of infection has been identified. These TSEs use the dorsal motor nucleus of the vagus nerve as an entry site into the brain.29,45,46 This observation suggests that distinct prion types in human and animal TSEs possibly have an impact on the pathogenesis of prion diseases.

Conclusion

As the prion protein is a highly conserved protein in terms of evolution, parallels between characteristics of prion types in TSEs of different species are of interest. In the present study, we report previously unknown similarities between sheep scrapie forms and human sporadic CJD types. We propose that the observed similarities between sheep scrapie and sporadic CJD in humans justify new interspecies groups of prion diseases in which prion types, not prion strains, are the major determinant for prion disease forms. While epidemiology implies that classical scrapie is not related to human TSEs,47 the atypical/Nor98 scrapie risk for human transmission has not yet been elucidated. Currently there is no compelling evidence that sCJD has a different origin than sporadic genesis. However, the finding of prion types with an across-the-species comparability might provide further understanding of the pathogenesis in prion diseases.

Acknowledgments We thank Tatjana Pfander, Nadine Rupprecht, and Kerstin Brekerbohm for their skillful technical assistance.

http://ajp.amjpathol.org/cgi/content/abstract/175/6/2566



hmmm, this is getting interesting now...


Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine (reticular) deposits,

see also ;

All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.



http://cjdusa.blogspot.com/2009/09/co-existence-of-scrapie-prion-protein.html


Tuesday, July 29, 2008

Heidenhain Variant Creutzfeldt Jakob Disease Case Report

snip...

Heidenhain Variant Creutzfeldt Jakob Disease autopsy case report 'MOM'

DIVISION OF NEUROPATHOLOGY University of Texas Medical Branch 114 McCullough Bldg. Galveston, Texas 77555-0785

FAX COVER SHEET

DATE: 4-23-98

TO: Mr. Terry Singeltary @ -------

FROM: Gerald Campbell

FAX: (409) 772-5315 PHONE: (409) 772-2881

Number of Pages (including cover sheet)
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*CONFIDENTIALITY NOTICE*

This document accompanying this transmission contains confidential information belonging to the sender that is legally privileged. This information is intended only for the use of the individual or entry names above. If you are not the intended recipient, you are hereby notified that any disclosure, copying distribution, or the taking of any action in reliances on the contents of this telefaxed information is strictly prohibited. If you received this telefax in error, please notify us by telephone immediately to arrange for return of the original documents. -------------------------- Patient Account: 90000014-518 Med. Rec. No.: (0160)118511Q Patient Name: POULTER, BARBARA Age: 63 YRS DOB: 10/17/34 Sex: F Admitting Race: C

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

Autopsy NO.: AU-97-00435

AUTOPSY INFORMATION: Occupation: Unknown Birthplace: Unknown Residence: Crystal Beach Date/Time of Death: 12/14/97 13:30 Date/Time of Autopsy: 12/15/97 15:00 Pathologist/Resident: Pencil/Fernandez Service: Private Restriction: Brain only

FINAL AUTOPSY DIAGNOSIS

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

snip...see full text ;

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


P.5.21

Parallels between different forms of sheep scrapie and types of Creutzfeldt-Jakob disease (CJD)

Wiebke M. Wemheuer1, Sylvie L. Benestad2, Arne Wrede1, Wilhelm E. Wemheuer3, Tatjana Pfander1, Bjørn Bratberg2, Bertram Brenig3,Walter J. Schulz-Schaeffer1 1University Medical Center Goettingen, Germany; 2Institute of Veterinary Medicine Oslo, Norway; 3Institute of Veterinary Medicine Goettingen, Germany

Background: Scrapie in sheep and goats is often regarded as the archetype of prion diseases. In 1998, a new form of scrapie - atypical/Nor98 scrapie - was described that differed from classical scrapie in terms of epidemiology, Western blot profile, the distribution of pathological prion protein (PrPSc) in the body and its stability against proteinase K. In a similar way, distinct disease types exist in sporadic Creutzfeldt-Jakob disease (CJD). They differ with regard to their clinical outcome, Western blot profile and PrPSc deposition pattern in the central nervous system (CNS).

Objectives: The comparison of PrPSc deposits in sheep scrapie and human sporadic CJD.

Methods: Tissues of the CNS of sheep with classical scrapie, sheep with atypical/Nor98 scrapie and 20 patients with sporadic CJD were examined using the sensitive Paraffin Embedded Tissue (PET) blot method. The results were compared with those obtained by immunohistochemistry. With the objective of gaining information on the protein conformation, the PrPSc of classical and atypical/Nor98 sheep scrapie and sporadic CJD was tested for its stability against denaturation with guanidine hydrochloride (GdnHCl) using a Membrane Adsorption Assay.

Results: The PrPSc of atypical/Nor98 scrapie cases and of CJD prion type 1 patients exhibits a mainly reticular/synaptic deposition pattern in the brain and is relatively sensitive to denaturation with GdnHCl. In contrast classical scrapie cases and CJD prion type 2 patients have a more complex PrPSc deposition pattern in common that consists of larger PrPSc aggregates and the PrPSc itself is comparatively stable against denaturation.

Discussion: The similarity between CJD types and scrapie types indicates that at least two comparable forms of the misfolded prion protein exist beyond species barriers and can elicit prion diseases. It seems therefore reasonable to classify classical and atypical/Nor98 scrapie - in analogy to the existing CJD types - as different scrapie types.

http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf


Monday, November 30, 2009

USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE

http://nor-98.blogspot.com/2009/11/usda-and-oie-collaborate-to-exclude.html


Monday, December 1, 2008

When Atypical Scrapie cross species barriers

http://nor-98.blogspot.com/2008/12/when-atypical-scrapie-cross-species.html


EVIDENCE OF SCRAPIE IN SHEEP AS A RESULT OF FOOD BORNE EXPOSURE

This is provided by the statistically significant increase in the incidence of sheep scrape from 1985, as determined from analyses of the submissions made to VI Centres, and from individual case and flock incident studies. ........

http://web.archive.org/web/20010305222246/www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf


1: J Infect Dis 1980 Aug;142(2):205-8

Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.

snip...

The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.

PMID: 6997404

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract


12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY

snip...

A The Present Position with respect to Scrapie A] The Problem

Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries.

The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep.

It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible.

Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"

Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.

snip...

76/10.12/4.6

http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf


Nature. 1972 Mar 10;236(5341):73-4.

Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis). Gibbs CJ Jr, Gajdusek DC.

Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)

C. J. GIBBS jun. & D. C. GAJDUSEK

National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland

SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).

http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.html


Epidemiology of Scrapie in the United States 1977

http://web.archive.org/web/20030513212324/http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf


Tuesday, April 28, 2009

Nor98-like Scrapie in the United States of America

http://nor-98.blogspot.com/2009/04/nor98-like-scrapie-in-united-states-of.html


Scrapie USA

http://scrapie-usa.blogspot.com/



Like lambs to the slaughter 31 March 2001 by Debora MacKenzie Magazine issue 2284

FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.

Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.

Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in ...

http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.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


Tuesday, August 18, 2009

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

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


Wednesday, December 30, 2009

Is there evidence of vertical transmission of variant CJD ?

http://creutzfeldt-jakob-disease.blogspot.com/2009/12/is-there-evidence-of-vertical.html


Alzheimer's and CJD

http://betaamyloidcjd.blogspot.com/


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


Friday, January 01, 2010

Human Prion Diseases in the United States

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


-------------------- BSE-L@LISTS.AEGEE.ORG --------------------



No competing interests declared.



see full text ;


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



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




Diagnosis and Reporting of Creutzfeldt-Jakob Disease Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.

Terry S. Singeltary, Sr Bacliff, Tex

1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323. FREE FULL TEXT



http://jama.ama-assn.org/cgi/content/extract/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT



http://jama.ama-assn.org/cgi/content/full/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT




2 January 2000

British Medical Journal

U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well

http://www.bmj.com/cgi/eletters/320/7226/8/b#6117



15 November 1999

British Medical Journal

vCJD in the USA * BSE in U.S.

http://www.bmj.com/cgi/eletters/319/7220/1312/b#5406



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



Manuscript Draft Manuscript Number: Title: HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory Article Type: Personal View Corresponding Author: Mr. Terry S. Singeltary, Corresponding Author's Institution: na First Author: Terry S Singeltary, none Order of Authors: Terry S Singeltary, none; Terry S. Singeltary Abstract: 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 2007.

http://www.regulations.gov/fdmspublic/ContentViewer?objectId=090000648027c28e&disposition=attachment&contentType=pdf



2011 NOVEMBER

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION AKA MAD COW, BSE, CJD, CWD, SCRAPIE UPDATE

P.9.21

Molecular characterization of BSE in Canada

Jianmin Yang1, Sandor Dudas2, Catherine Graham2, Markus Czub3, Tim McAllister1, Stefanie Czub1 1Agriculture and Agri-Food Canada Research Centre, Canada; 2National and OIE BSE Reference Laboratory, Canada; 3University of Calgary, Canada

Background: Three BSE types (classical and two atypical) have been identified on the basis of molecular characteristics of the misfolded protein associated with the disease. To date, each of these three types have been detected in Canadian cattle.

Objectives: This study was conducted to further characterize the 16 Canadian BSE cases based on the biochemical properties of there associated PrPres. Methods: Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases was determined using modified Western blot analysis.

Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and changes in glycosylation similar to other atypical BSE cases. PK digestion under mild and stringent conditions revealed a reduced protease resistance of the atypical cases compared to the C-type cases. N terminal- specific antibodies bound to PrPres from H type but not from C or L type. The C-terminal-specific antibodies resulted in a shift in the glycoform profile and detected a fourth band in the Canadian H-type BSE.

Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada.

*** It also suggests a similar cause or source for atypical BSE in these countries.

http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf



STRICTLY PRIVATE AND CONFIDENTIAL 25, AUGUST 1995

snip...

To minimise the risk of farmers' claims for compensation from feed compounders.

To minimise the potential damage to compound feed markets through adverse publicity.

To maximise freedom of action for feed compounders, notably by maintaining the availability of meat and bone meal as a raw material in animal feeds, and ensuring time is available to make any changes which may be required.

snip...

THE FUTURE

4..........

MAFF remains under pressure in Brussels and is not skilled at handling potentially explosive issues.

5. Tests _may_ show that ruminant feeds have been sold which contain illegal traces of ruminant protein. More likely, a few positive test results will turn up but proof that a particular feed mill knowingly supplied it to a particular farm will be difficult if not impossible.

6. The threat remains real and it will be some years before feed compounders are free of it. The longer we can avoid any direct linkage between feed milling _practices_ and actual BSE cases, the more likely it is that serious damage can be avoided. ...

SEE full text ;

http://web.archive.org/web/20060517074958/http://www.bseinquiry.gov.uk/files/yb/1995/08/24002001.pdf




Saturday, August 14, 2010

BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY

(see mad cow feed in COMMERCE IN ALABAMA...TSS)

http://prionpathy.blogspot.com/2010/08/bse-case-associated-with-prion-protein.html



10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN COMMERCE USA 2007

Date: March 21, 2007 at 2:27 pm PST

RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II

___________________________________

PRODUCT

Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007

CODE

Cattle feed delivered between 01/12/2007 and 01/26/2007

RECALLING FIRM/MANUFACTURER

Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.

Firm initiated recall is ongoing.

REASON

Blood meal used to make cattle feed was recalled because it was cross- contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement.

VOLUME OF PRODUCT IN COMMERCE

42,090 lbs.

DISTRIBUTION

WI

___________________________________

PRODUCT

Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007

CODE

The firm does not utilize a code - only shipping documentation with commodity and weights identified.

RECALLING FIRM/MANUFACTURER

Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete.

REASON

Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement.

VOLUME OF PRODUCT IN COMMERCE

9,997,976 lbs.

DISTRIBUTION

ID and NV

END OF ENFORCEMENT REPORT FOR MARCH 21, 2007

http://www.fda.gov/Safety/Recalls/EnforcementReports/2007/ucm120446.htm



Monday, September 12, 2011

BSE PRION Agriculture Animal Feed Question House of Lords Thursday, 8 September 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/09/bse-prion-agriculture-animal-feed.html




Saturday, July 23, 2011

CATTLE HEADS WITH TONSILS, BEEF TONGUES, SPINAL CORD, SPECIFIED RISK MATERIALS (SRM's) AND PRIONS, AKA MAD COW DISEASE

http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/cattle-heads-with-tonsils-beef-tongues.html



Saturday, November 6, 2010

TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU Berne, 2010 TAFS

INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation

http://madcowfeed.blogspot.com/2010/11/tafs1-position-paper-on-position-paper.html



Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject PRO/AH/EDR; Prion disease update 2010 (11)

PRION DISEASE UPDATE 2010 (11)

http://www.promedmail.org/direct.php?id=20101206.4364



Saturday, June 25, 2011

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque


"BSE-L in North America may have existed for decades"


http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html




Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.

snip...

The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...

http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf



Sunday, June 26, 2011

Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/risk-analysis-of-low-dose-prion.html




MAD COW DISEASE, TEXAS STYLE

http://www.organicconsumers.org/articles/article_23850.cfm




Wednesday, June 15, 2011

Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor

http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html



Sunday, May 01, 2011

STUDY OF ATYPICAL BSE 2010 Annual Report May 2011

http://bse-atypical.blogspot.com/2011/05/study-of-atypical-bse-2010-annual.html




Thursday, February 10, 2011

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY REPORT UPDATE CANADA FEBRUARY 2011 and how to hide mad cow disease in Canada Current as of: 2011-01-31

http://madcowtesting.blogspot.com/2011/02/transmissible-spongiform-encephalopathy.html



Friday, February 18, 2011

UNITED STATES OF AMERICA VS GALEN J. NIEHUES FAKED MAD COW FEED TEST ON 92 BSE INSPECTION REPORTS FOR APPROXIMATELY 100 CATTLE OPERATIONS ''PLEADS GUILTY"

http://bse-atypical.blogspot.com/2011/02/united-states-of-america-vs-galen-j.html



Wednesday, November 17, 2010

MAD COW TESTING FAKED IN USA BY Nebraska INSPECTOR Senator Mike Johanns STATE

http://madcowtesting.blogspot.com/2010/11/mad-cow-testing-faked-in-usa-by.html



Wednesday, February 16, 2011

IN CONFIDENCE

SCRAPIE TRANSMISSION TO CHIMPANZEES

IN CONFIDENCE

http://scrapie-usa.blogspot.com/2011/02/in-confidence-scrapie-transmission-to.html



Sunday, April 18, 2010

SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010

http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html



Monday, April 25, 2011

Experimental Oral Transmission of Atypical Scrapie to Sheep

Volume 17, Number 5-May 2011

http://nor-98.blogspot.com/2011/04/experimental-oral-transmission-of.html



Monday, November 30, 2009

USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE

http://nor-98.blogspot.com/2009/11/usda-and-oie-collaborate-to-exclude.html



Monday, June 27, 2011

Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates

http://chronic-wasting-disease.blogspot.com/2011/06/zoonotic-potential-of-cwd-experimental.html



Wednesday, September 21, 2011

Evidence for distinct CWD strains in experimental CWD in ferrets

http://chronic-wasting-disease.blogspot.com/2011/09/evidence-for-distinct-cwd-strains-in.html




UPDATED DATA ON 2ND CWD STRAIN

Wednesday, September 08, 2010

CWD PRION CONGRESS SEPTEMBER 8-11 2010

http://chronic-wasting-disease.blogspot.com/2010/09/cwd-prion-2010.html



Wednesday, January 5, 2011

ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011

Prions

David W. Colby1,* and Stanley B. Prusiner1,2

http://betaamyloidcjd.blogspot.com/2011/01/enlarging-spectrum-of-prion-like.html



Wednesday, July 06, 2011

Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation

http://chronic-wasting-disease.blogspot.com/2011/07/swine-are-susceptible-to-chronic.html



Thursday, April 03, 2008

A prion disease of cervids: Chronic wasting disease

2008 1: Vet Res. 2008 Apr 3;39(4):41

A prion disease of cervids: Chronic wasting disease

Sigurdson CJ.

snip...

*** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,

snip...

full text ;

http://chronic-wasting-disease.blogspot.com/2008/04/prion-disease-of-cervids-chronic.html



1989

IN CONFIDENCE

Perceptions of unconventional slow virus diseases of animals in the USA

Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or about that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep. Whether they were scrapie infected sheep or not is unclear.

http://collections.europarchive.org/tna/20080102193705/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf




http://wildlife.state.co.us/NR/rdonlyres/C82EB818-90C6-4D85-897E-9CE279546CCB/0/JWDEpiCWD.pdf



CJD9/10022

October 1994

Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane BerksWell Coventry CV7 7BZ

Dear Mr Elmhirst,

CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT

Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published.

The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication.

The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department.

The statistical results reqarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme.

I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all.

http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf




14th ICID International Scientific Exchange Brochure -

Final Abstract Number: ISE.114

Session: International Scientific Exchange

Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America update October 2009

T. Singeltary

Bacliff, TX, USA

Background
An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.

Methods
12 years independent research of available data

Results
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.

Conclusion
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. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. 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.

http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf




Monday, May 23, 2011

Atypical Prion Diseases in Humans and Animals 2011

Top Curr Chem (2011)

DOI: 10.1007/128_2011_161

# Springer-Verlag Berlin Heidelberg 2011

Michael A. Tranulis, Sylvie L. Benestad, Thierry Baron, and Hans Kretzschmar

Abstract

Although prion diseases, such as Creutzfeldt-Jakob disease (CJD) in humans and scrapie in sheep, have long been recognized, our understanding of their epidemiology and pathogenesis is still in its early stages. Progress is hampered by the lengthy incubation periods and the lack of effective ways of monitoring and characterizing these agents. Protease-resistant conformers of the prion protein (PrP), known as the "scrapie form" (PrPSc), are used as disease markers, and for taxonomic purposes, in correlation with clinical, pathological, and genetic data. In humans, prion diseases can arise sporadically (sCJD) or genetically (gCJD and others), caused by mutations in the PrP-gene (PRNP), or as a foodborne infection, with the agent of bovine spongiform encephalopathy (BSE) causing variant CJD (vCJD). Person-to-person spread of human prion disease has only been known to occur following cannibalism (kuru disease in Papua New Guinea) or through medical or surgical treatment (iatrogenic CJD, iCJD). In contrast, scrapie in small ruminants and chronic wasting disease (CWD) in cervids behave as infectious diseases within these species. Recently, however, so-called atypical forms of prion diseases have been discovered in sheep (atypical/Nor98 scrapie) and in cattle, BSE-H and BSE-L. These maladies resemble sporadic or genetic human prion diseases and might be their animal equivalents. This hypothesis also raises the significant public health question of possible epidemiological links between these diseases and their counterparts in humans.

M.A. Tranulis (*)

Norwegian School of Veterinary Science, Oslo, Norway

e-mail: Michael.Tranulis@nvh.no

S.L. Benestad

Norwegian Veterinary Institute, Oslo, Norway

T. Baron

Agence Nationale de Se´curite´ Sanitaire, ANSES, Lyon, France

H. Kretzschmar

Ludwig-Maximilians University of Munich, Munich, Germany

Keywords Animal Atypical Atypical/Nor98 scrapie BSE-H BSE-L Human Prion disease Prion strain Prion type

http://resources.metapress.com/pdf-preview.axd?code=f433r34h34ugg617&size=largest



Wednesday, March 31, 2010

Atypical BSE in Cattle

To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE.

In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2



Thursday, August 12, 2010

Seven main threats for the future linked to prions

First threat

The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.

***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.

Second threat

snip...

http://www.neuroprion.org/en/np-neuroprion.html



Rural and Regional Affairs and Transport References Committee

The possible impacts and consequences for public health, trade and agriculture of the Government’s decision to relax import restrictions on beef Final report June 2010

2.66 Dr Fahey also told the committee that in the last two years a link has been established between forms of atypical CJD and atypical BSE. Dr Fahey said that: They now believe that those atypical BSEs overseas are in fact causing sporadic Creutzfeldt-Jakob disease. They were not sure if it was due to mad sheep disease or a different form. If you look in the textbooks it looks like this is just arising by itself. But in my research I have a summary of a document which states that there has never been any proof that sporadic Creutzfeldt-Jakob disease has arisen de novo—has arisen of itself. There is no proof of that. The recent research is that in fact it is due to atypical forms of mad cow disease which have been found across Europe, have been found in America and have been found in Asia. These atypical forms of mad cow disease typically have even longer incubation periods than the classical mad cow disease.50

http://www.aph.gov.au/senate/committee/rrat_ctte/mad_cows/report/report.pdf



Terry S. Singeltary Sr. has added the following comment
"According to the World Health Organisation, the future public health threat of vCJD in the UK and Europe and potentially the rest of the world is of concern and currently unquantifiable. However, the possibility of a significant and geographically diverse vCJD epidemic occurring over the next few decades cannot be dismissed.

The key word here is diverse. What does diverse mean? If USA scrapie transmitted to USA bovine does not produce pathology as the UK c-BSE, then why would CJD from there look like UK vCJD?"

http://www.promedmail.org/direct.php?id=20100405.1091




When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2



The conclusions state that, at present, the only TSE agent demonstrated to be zoonotic is the classical BSE agent. Active screening has allowed the identification of 3 new forms of animal TSEs (H-type atypical BSE, L-type atypical BSE, and atypical scrapie), but the information obtained has major limitations due to the unknown sensitivity of the current monitoring system for these TSEs. There is no epidemiological evidence to suggest that classical scrapie is zoonotic. The epidemiological data are too limited to conclude whether the atypical scrapie agent has a zoonotic potential. Transmission experiments to human PrP transgenic mice or primates suggest that some TSE agents other than the classical BSE agent in cattle (namely L-type atypical BSE, classical BSE in sheep, TME, CWD agents) might have zoonotic potential and indicate that that of the L-type atypical BSE agent appears similar or even higher than that of the classical BSE agent. A single study reported efficient transmission of a natural sheep classical scrapie isolate to primates.

Commentary ---------- Following to a request from the European Commission, the Panel on Biological Hazards (BIOHAZ) and the European Centre for Disease Prevention and Control (ECDC) were asked to deliver a scientific opinion on any possible epidemiological or molecular association between transmissible spongiform encephalopathies (TSEs) in animals and humans. The opinion reviews and discusses the existing scientific evidence that links animal and human TSEs currently known.

The opinion first considers the definition of zoonoses and the principles for the identification of zoonotic diseases, which can be based on evidence gathered from both epidemiological and laboratory studies. The opinion describes the challenges involved in identifying TSEs as zoonoses, due to the specific characteristics of TSE infections/diseases, such as the nature of TSE agents, the occurrence of animal and human TSEs, and the type of monitoring applied, the long incubation period of TSEs etc. The example of the process that led to establishing a link between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) is reviewed. The epidemiological and laboratory criteria that can be used to investigate such a link are described in detail, since those criteria might be useful for the identification of links between other animal and human TSEs.

The opinion discusses the strain diversity of the TSE agents described in sheep, goats, cattle, cervids, and humans, based on the current knowledge, which highlights that multiple TSE agents exist in each species. The factors influencing the capacity of TSE agents to cross the species transmission barrier are then considered in detail, including the variability in host and donor PrP gene and protein, the TSE strain type involved and its interaction with the host PrP, and the route of infection.

The opinion critically assesses the tools and methodologies currently available to study and evaluate the possible association between animal and human TSEs. The use of epidemiology is discussed for TSEs in both animals and humans, and the possibility to compare the 2 sources of information is presented as a possible method to study the possible links.

Both in vivo and in vitro laboratory methods are considered and discussed, including neuropathology, transmission experiments involving different animal models (wild type and transgenic mice, primates and other species), biochemical methods, cell-free conversion assays, protein misfolding cyclic amplification (PMCA), and cell culture assays. Characteristics, advantages, and disadvantages of the different methods are reviewed, including the opportunity to collate data from different types of experiments for the study of potential associations between animal and human TSEs.

The opinion then reviews the scientific evidence currently available for the different animal and human TSEs, including classical BSE, atypical BSE (H-type and L-type), classical scrapie, atypical scrapie, chronic wasting disease (CWD), transmissible mink encephalopathy (TME), and human TSEs. In particular, the following aspects are systematically discussed for each TSE agent: epidemiology, pathogenesis, and in vivo and in vitro transmission experiments.

The opinion concludes that, at present, the only TSE agent demonstrated to be zoonotic is the classical BSE agent. With regard to human TSEs, detected cases of sporadic CJD are randomly distributed in time and geographical location. These observations have been interpreted as a supportive argument that sporadic CJD is not environmentally acquired. However, the epidemiological evidence in relation to sporadic CJD cannot be regarded as definitive, and the possibility that a small proportion of cases are zoonotic cannot be excluded.

It also concludes that a series of uncertainties in relation to the epidemiological patterns of animal and human TSEs indicate that even a rough comparison of the present epidemiological patterns of human and animal TSEs other than classical BSE is unlikely to be informative. Because of these uncertainties, it is an imperative to continue to carry out systematic surveillance of human TSE diseases, and to continue and improve the surveillance of animal TSE diseases.

The opinion highlights that the active screening has allowed the identification of 3 new forms of animal TSEs (L-type atypical BSE, H-type atypical BSE, and atypical scrapie), but that the information obtained has major limitations due to the unknown sensitivity of the current monitoring system for these TSEs.

There is no epidemiological evidence to suggest that classical scrapie is zoonotic. The epidemiological data are too limited to conclude whether the atypical scrapie agent has a zoonotic potential.

Transmission experiments to human PrP transgenic mice suggest that some TSE agents other than the classical BSE agent in cattle (namely L-type atypical BSE and classical BSE in sheep agents) might have zoonotic potential, whereas for other agents there is no evidence provided of a zoonotic potential (H-type atypical BSE and CWD), or no published studies are available (classical and atypical scrapie). In addition, transmission experiments to primates suggest that some TSE agents other than the classical BSE agent in cattle (namely L-type atypical BSE, classical BSE in sheep, TME, CWD agents) might have zoonotic potential. In particular, primates are highly permissive to L-type atypical BSE, even by the oral route.

The opinion emphasizes that laboratory transmission experiments indicate that the L-type atypical BSE agent has a significant zoonotic potential, which appears similar or even higher than that of the classical BSE agent. While transmission data for evaluating the zoonotic potential of classical scrapie in primates and human PrP transgenic mice are extremely limited or not yet available, a single study reported efficient transmission of a natural sheep classical scrapie isolate to primates.

The opinion concludes that human PrP transgenic mice and primates are currently the most relevant models for investigating the human transmission barrier, but the extent to which such models are informative for measuring the zoonotic potential of an animal TSE under field exposure conditions is unknown. It is unpredictable whether a TSE agent will transmit to a new host, and if the transmission principally occurs, what the transmission rate will be.

Based on the results obtained with in vitro conversion assays, the opinion concludes that there is probably no absolute molecular barrier to transmission of TSE agents between mammalian species. Results also suggest that these assays may be developed as a tool for quantifying the transmission barriers between species for different TSE agent strains; however, there is no means at the moment to transpose in vitro results into the likelihood of in vivo interspecies transmission.

-- Communicated by: Terry S Singeltary Sr

[ProMED-mail thanks Terry S Singeltary Sr for drawing attention to this comprehensive document which provides a current evaluation of experimental work designed to explore the zoonotic potential of the various recently recognised TSEs of domestic and other animals.

It is concluded that at present the only TSE agent demonstrated to be zoonotic is the classical BSE agent. Nor can it be entirely excluded at the present time that a small proportion of cases of sporadic CJD may be environmentally acquired. - Mod.CP]

******

http://www.promedmail.org/direct.php?id=20110607.1736




U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ? (see video at bottom)

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



2006

USA sporadic CJD cases rising ;

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

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

http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm


http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf


2008

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


CJD USA RISING, with UNKNOWN PHENOTYPE ;

5 Includes 41 cases in which the diagnosis is pending, and 17 inconclusive cases;

*** 6 Includes 46 cases with type determination pending in which the diagnosis of vCJD has been excluded.

http://www.cjdsurveillance.com/pdf/case-table.pdf


Thursday, August 4, 2011

Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011 (SEE VIDEO)

http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html



Sunday, August 21, 2011

The British disease, or a disease gone global, The TSE Prion Disease (SEE VIDEO)

http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/british-disease-or-disease-gone-global.html


Saturday, March 5, 2011

MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA

http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html


Friday, November 04, 2011

Diagnostic accuracy of cerebrospinal fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada: a 6-year prospective study Research article

http://creutzfeldt-jakob-disease.blogspot.com/2011/11/diagnostic-accuracy-of-cerebrospinal.html



WHO WILL FOLLOW THE CHILDREN FOR CJD SYMPTOMS ??

Saturday, May 2, 2009

U.S. GOVERNMENT SUES WESTLAND/HALLMARK MEAT OVER USDA CERTIFIED DEADSTOCK DOWNER COW SCHOOL LUNCH PROGRAM

http://downercattle.blogspot.com/2009/05/us-government-sues-westlandhallmark.html



http://downercattle.blogspot.com/



Tuesday, October 4, 2011

De novo induction of amyloid-ß deposition in vivo

Molecular Psychiatry advance online publication 4 October 2011; doi: 10.1038/mp.2011.120

Molecular Psychiatry advance online publication 4 October 2011; doi: 10.1038/mp.2011.120

De novo induction of amyloid-ß deposition in vivo

R Morales1,2, C Duran-Aniotz1,3, J Castilla2,4, L D Estrada2,5 and C Soto1,2

1Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, TX, USA 2University of Texas Medical Branch at Galveston, Galveston, TX, USA 3Universidad de Los Andes, Facultad de Medicina. Av. San Carlos de Apoquindo 2200, Las Condes, Santiago, Chile 4CIC bioGUNE, Parque Tecnologico de Biskaia, Ed 800, 48160 Derio and IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain

Correspondence: Dr C Soto, Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, 6431 Fannin St, Houston, TX 77030, USA. E-mail: Claudio.Soto@uth.tmc.edu

5Current address: Laboratorio de Señalización Celular, Centro de Envejecimiento y Regeneración. P. Universidad Catolica de Chile, Santiago, Chile.

Received 8 March 2011; Revised 15 August 2011; Accepted 25 August 2011; Published online 4 October 2011.

Abstract

Alzheimer's disease (AD), the most common type of senile dementia, is associated to the build-up of misfolded amyloid-ß (Aß) in the brain. Although compelling evidences indicate that the misfolding and oligomerization of Aß is the triggering event in AD, the mechanisms responsible for the initiation of Aß accumulation are unknown. In this study, we show that Aß deposition can be induced by injection of AD brain extracts into animals, which, without exposure to this material, will never develop these alterations. The accumulation of Aß deposits increased progressively with the time after inoculation, and the Aß lesions were observed in brain areas far from the injection site. Our results suggest that some of the typical brain abnormalities associated with AD can be induced by a prion-like mechanism of disease transmission through propagation of protein misfolding. These findings may have broad implications for understanding the molecular mechanisms responsible for the initiation of AD, and may contribute to the development of new strategies for disease prevention and intervention.

Keywords
amyloid; prion; protein misfolding; disease transmission

http://www.nature.com/mp/journal/vaop/ncurrent/abs/mp2011120a.html


see more here ;

http://betaamyloidcjd.blogspot.com/2011/10/de-novo-induction-of-amyloid-deposition.html



http://transmissiblespongiformencephalopathy.blogspot.com/2011/10/alzheimers-disease-is-transmissible.html


Wednesday, September 21, 2011

PrioNet Canada researchers in Vancouver confirm prion-like properties in Amyotrophic Lateral Sclerosis (ALS)

http://transmissiblespongiformencephalopathy.blogspot.com/2011/09/prionet-canada-researchers-in-vancouver.html


POLITICAL BSe and CJD and THE WOW FACTOR $$$

Monday, September 26, 2011

Variably Protease-Sensitive Prionopathy, Prionpathy, Prionopathy, FFI, GSS, gCJD, hvCJD, sCJD, TSE, PRION, update 2011

http://prionopathy.blogspot.com/2011/09/variably-protease-sensitive-prionopathy.html


Mad Cow Scaremongers

Mad Cow Scaremongers by Terry S. Singeltary Sr. a review of the TSE prion agent 2003-2011

re-2003

"he also blindly insists upon a mad-cow with Alzheimer’s, Parkinson’s, and Lou Gehrig’s disease."


http://www.seac.gov.uk/pdf/hol-response091008.pdf



http://bse-atypical.blogspot.com/2009/10/seac-science-and-technology-committees.html



SNIP...SEE FULL TEXT ;



http://transmissiblespongiformencephalopathy.blogspot.com/2011/09/mad-cow-scaremongers.html




EFSA Journal 2011 The European Response to BSE: A Success Story

This is an interesting editorial about the Mad Cow Disease debacle, and it's ramifications that will continue to play out for decades to come ;

Monday, October 10, 2011

EFSA Journal 2011 The European Response to BSE: A Success Story

snip...

EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.

snip...

http://www.efsa.europa.eu/en/efsajournal/pub/e991.htm?emt=1


http://www.efsa.europa.eu/en/efsajournal/doc/e991.pdf


see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;

http://transmissiblespongiformencephalopathy.blogspot.com/2011/10/efsa-journal-2011-european-response-to.html




layperson

TSS

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