A case-control study of sporadic Creutzfeldt-Jakob disease in Switzerland: analysis of potential risk factors with regard to an increased CJD incidence in the years 2001–2004
Jessica Ruegger†1, Katharina Stoeck†2,3, Lorenz Amsler4,5, Thomas Blaettler2,6, Marcel Zwahlen7, Adriano Aguzzi2, Markus Glatzel2,8, Klaus Hess1 and Tobias Eckert*4,9 Address: 1Department of Neurology, University Hospital Zurich, Zurich, Switzerland, 2Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland, 3Department of Neurology, University Hospital Hamburg-Eppendorf, Hamburg-Eppendorf, Hamburg, Germany, 4Federal Office of Public Health, Bern, Switzerland, 5CSL Behring, Bern, Switzerland, 6Bristol-Myers Squibb, Wallingford, CT, USA, 7Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland, 8Institute of Neuropathology, University Hospital Hamburg-Eppendorf, Hamburg- Eppendorf, Hamburg, Germany and 9Swiss Tropical Institute, Basel, Switzerland Email: Jessica Ruegger - mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000046/!x-usc:mailto:jessica.ruegger@gmail.com; Katharina Stoeck - mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000046/!x-usc:mailto:kstoeck@uke.uni-hamburg.de; Lorenz Amsler - mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000046/!x-usc:mailto:Lorenz.Amsler@cslbehring.com; Thomas Blaettler - mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000046/!x-usc:mailto:thomas.blaettler@bms.com; Marcel Zwahlen - mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000046/!x-usc:mailto:zwahlen@ispm.unibe.ch; Adriano Aguzzi - mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000046/!x-usc:mailto:adriano.aguzzi@usz.ch; Markus Glatzel - mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000046/!x-usc:mailto:m.glatzel@uke.uni-hamburg.de; Klaus Hess - mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000046/!x-usc:mailto:k_h@bluewin.ch; Tobias Eckert* - mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000046/!x-usc:mailto:tobias.eckert@bag.admin.ch * Corresponding author †Equal contributors
Published: 14 January 2009 BMC Public Health 2009, 9:18 doi:10.1186/1471-2458-9-18 Received: 11 July 2008 Accepted: 14 January 2009 This article is available from: http://www.biomedcentral.com/1471-2458/9/18 © 2009 Ruegger et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background: In 2001, the observed annual mortality from Creutzfeldt-Jakob disease (CJD) in Switzerland increased from less than 1.5 to 2.6 per million inhabitants. An underlying cause could not be identified.
Methods: To analyse potential risk factors for sCJD in Switzerland, close relatives of 69 sCJD-patients and 224 frequency age-matched controls were interviewed in a case-control study using a standardised questionnaire. 135 potential risk factors including socio-demographics, medical history, occupation and diet were analysed by logistic regression adjusting for age, sex and education.
Results: sCJD patients were more likely to have travelled abroad, worked at an animal laboratory, undergone invasive dental treatment, orthopaedic surgery, ophthalmologic surgery after 1980, regular GP visits, taken medication regularly, and consumed kidney. No differences between patients and controls were found for residency, family history, and exposure to environmental and other dietary factors.
Conclusion: Although some factors were significantly more frequent among sCJD-cases, this study did not reveal specific explanations for the increased incidence of deaths due to sporadic CJD observed in Switzerland since 2001. Results have to be interpreted with caution due to multiple testing and possible recall bias in association with a long incubation period. The most plausible reason for the increase in Swiss sCJD cases after 2000 is an improved case ascertainment. Therefore, underreporting of cases might well have occurred before the year 2001, and the "real" yearly incidence of sCJD might not be lower than, but rather above 2 per million inhabitants.
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Discussion
This study evaluated a wide range of possible risk factors as risk factors for sCJD-cases observed in Switzerland between 2001 and 2004. If some of the positively associated risk factors were truly causal and would have become more frequent in recent years and decades, then they might have contributed to the increase in sCJD-cases in Switzerland. Although some analysed factors were significantly more frequent in the group of sCJD patients, the results of this case-control study have not produced unequivocal evidence for specific environmental or iatrogenic risk factors for sCJD, and thus could not reveal a specific explanation for the increased incidence. In interpreting the results, one has to bear in mind that with a significance level set at 5%, on average one in twenty results will be significant, by chance alone.
Starting with the hypothesis of a zoonotic cause similar to the development of vCJD by consumption of BSE-contaminated material, the present study does not demonstrate a clearly increased risk for sCJD with respect to dietary habits. Although previous studies revealed that consumption of several meat products was increased in sCJD cases compared to controls,[26,27] no such clear differences for any of the twenty diet-related exposures were found in our as well as in earlier studies. [28-30] Consistent with previous studies, no significant differences between sCJD patients and controls was found with respect to occupational exposures, including work in animal farming or in the meat industry in the present study. One exception was work in an animal laboratory. [27-31] Some findings of earlier studies which revealed higher frequencies of sCJD among butchers,[32] among those exposed to leather products, to fertiliser consisting of hoofs and horns,[27] and to farm-stays for any length of time,[31] could not be reproduced in this study. Contrary to the hypothesis of a zoonotic cause, earlier studies did not link pet animals possession to increased risk. [27-30] Patients in this study even less often owned cats or pet rodents.
Travelling abroad was significantly more frequent in sCJD patients. Controls, however, travelled more frequently to the United Kingdom where risk for vCJD was elevated and to tropical destinations where some infectious diseases are more prevalent than in Switzerland. No differences in age, sex, place of birth and living or family history of dementia were found. These results are consistent with data from previous studies.[26,28,29] In contrast to earlier studies, sCJD-patients in our study had completed less years of education.[26,28] Only 45% of the cases had ten or more school years, whereas this figure was at 71% among the controls. These findings might be due to recall bias which can occur when interviewing proxy persons. However, another neurodegenerative disease, Alzheimer's disease has been shown to be observed more frequently in persons with lower levels of education.[ 33]
Concerning the hypothesis of an iatrogenic cause, sCJD cases in this study significantly more often had undergone orthopaedic and ophthalmologic surgery, invasive dental treatment as well as regular medical treatment. In previous studies, physical injuries and stressful life events such as surgical procedures,[23,28,30,31,34,35] and work in a medical profession[32] have been found to constitute a risk factor for sCJD. In particular, head surgery and trauma to other body parts were identified.[36] In contrast to the present study, however, orthopaedic surgery and invasive dental treatments per se were not associated with an elevated risk for sCJD before.[27,28,31,36] One could speculate that the use of surgical instruments as well as a potentially higher rate of blood transfusions in orthopaedic surgery may explain these findings. Receiving blood transfusions has been demonstrated to be a potential route of vCJD transmission.[20] The development of vCJD involves a peripheral route of prion transmission to the CNS. In sCJD, however, the disease most likely starts in the brain, even though recently, prions have been detected in peripheral organs such as the spleen and skeletal muscles of sCJD patients.[37] Blood transfusions, however, were not associated with sCJD in the present study. Interestingly, blood donation was less frequently observed in sCJD patients than in controls. Correspondingly, neither receiving blood transfusions nor blood donation was identified as a risk factor for sCJD in previous studies.[23,26,38,39] Cigarette smoking was more frequent in controls (29%) than in sCJD patients (13%) or in the general population, a finding which points to some bias in the selection of controls. A previous analysis did not find any association with smoking.[26]
Recently, the heightened incidence of sCJD in Switzerland was found to be associated with a shift in clinicopathological profiles, in that sporadic CJD patients from the cohort with elevated sporadic CJD incidence presented with a higher frequency of rare sporadic CJD-subtypes (MV2, VV2). Patients of these subtypes were significantly older and showed a skewed male/female ratio when compared to patients of identical sporadic CJD-types or to patients from the 1996–2000 cohort.[22] The third hypothesis to explain the increase in annual mortality rates from sCJD in Switzerland between 2001 and 2004 is a better case ascertainment. Over recent years in Europe, as a general tendency incidences have been rising, however not to such extent as in Switzerland. Given that our results do not support strong evidence for the hypotheses of a zoonotic or iatrogenic cause, ascertainment bias due to a heightened perception and awareness of the disease in physicians must be regarded as the most likely cause for the observed increase.
One factor that might be jointly responsible for this increase might be altered reporting requirements in 1999. Since that year all suspected cases in Switzerland had to be reported. In this respect, also the role of chance must be considered, as it is possible that the observed increase of Swiss sCJD-deaths was due to random fluctuation. The rise in annual mortality rate from the years before 2000 to the period 2001– 2004, however, was statistically significant, and therefore, chance must be considered a less likely explanation.
In the most recent years, the observed incidence in sCJD deaths (2005: 10; 2006: 13, 2007: 15) dropped to levels just slightly above those before 2000. When recent incidence data until 2007 are included, however, the rise in the annual mortality rate after 2001 was still significant. The sudden increase in 2001 and the slow decrease afterwards are well in line with the media coverage of the CJD topic in the respective years. Strengths and limitations This study was initiated to clarify whether cases of sCJD from 2001 to 2004 were associated with a specific environmental risk factor in Switzerland. A well defined group of patients was examined. The 69 sCJD cases consisted of all but three known cases in Switzerland during the study period. The participation rate of relatives and friends of cases was high, and for cases and controls there were only few missing data points in the data sets. The study used a standardised questionnaire with a wide range of potential risk factors reported in previous studies. However a subtype analysis in correlation with risk factors was not performed in this analysis because of the small number of cases. Due to Switzerland's small population size, the rarity of the disease, and the fact that sCJD invariably leads to death within less than 2 years, the number of cases in the study was relatively small. Other case-control studies conducted in Europe were somewhat larger. However, of these studies, just four recent studies also included data of cases from the year 2001 or later,[32,40-42] and none was performed within Switzerland. Consequently, they could not contribute to an explanation for the increased incidence of reported sCJD deaths in Switzerland. Two different control groups were chosen to limit selection bias. The interviews of controls by telephone yield potential for self-selection bias in that ownership of a fixed telephone line or willingness to participate might be unevenly distributed among the general population. On the other hand, the control-group of patients from GP offices were matched more closely but certain illnesses and other factors may be overrepresented in this group. The interviewed control persons answered the questions directly – either by a face-to-face interview or by telephone, whereas for the cases a close relative or friend of the patient answered the questions as a proxy. Furthermore, interviewed persons were conscious about the aims of the study, all of which could have resulted in the introduction of recall bias. Interviewing a proxy person for sCJD cases could imply that responses were less accurate, with fewer positive responses with respect to potential risk factors, potentially masking differences between the cases and controls. Conversely, a face-to-face interview could have resulted in more accurate data than a telephone interview. For instance, in the subgroup analysis comparing ophthalmologic surgery after 1980 in patients and telephone controls, the finding of an odds ratio of 18.31 with a very wide 95% C.I. of 3.65–91.97 has to be interpreted with care. Only 2 of 155 telephone controls (1.3%) recalled having undergone ophthalmologic surgery after 1980, while in the face-to-face interviews this proportion was 15.4% among proxy persons for patients and 24.6% among the GP controls. In the present study, we renounced interviewing proxy persons for controls, since we hypothesised that proxy-persons for cases would be more disposed to answer such questions correctly than proxy-persons for controls would do, and that such an effort would not have excluded recall bias. Unanswered questions, future research To identify environmental or other causes of sCJD, further research is necessary. The questionnaire of our study has been used in other CJD case-control studies,[23,24] which will allow to combine our results with those from other studies. As a potential risk factor for prion infection, ear, nose and throat (ENT) – surgery was not included as an item in this study. Other than recall bias, we could not find an explanation, why some of the examined factors, such as the number of school years differed between sCJD cases and controls. In this study, no genetic markers were analysed. For practical and ethical reasons, this information was only available for patients and not for controls. However, such information could have given additional clues, in that the development of sporadic CJD due to environmental factors might be linked to some so far unknown genetic factors. More recent research indicates that there are different subtypes of sCJD. Patients have a wide range of genetic backgrounds, which results in different clinical and histopathological presentations and diverse PrPSc distribution patterns in the brain.[43] Conclusion This study did not reveal a specific explanation for the increased annual death rates for sCJD observed in Switzerland between 2001 and 2004 with respect to external – and potentially avoidable – risk factors. Although some factors were significantly more frequent in the group of sCJD cases, the results have to be interpreted with caution due to fact of having tested multiple hypotheses and due to the possibility of bias in the selection of controls and of recall bias in association with the potentially long incubation period as seen in other prion diseases. The most plausible reason for the observed increase in 2001 in Swiss sCJD cases is an improved case ascertainment. The improved reporting of cases was in temporal correlation with the rise in variant CJD cases in the United Kingdom and the resulting high media coverage. Therefore, underreporting of cases might well have occurred before the year 2001, and the "real" yearly incidence of sCJD might not be lower than, but rather above 2 per million inhabitants.
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=2637857&blobtype=pdf
>>>The rise in annual mortality rate from the years before 2000 to the period 2001– 2004, however, was statistically significant, and therefore, chance must be considered a less likely explanation.<<<
I REPEAT QUOTE ''chance must be considered A LESS LIKELY EXPLANATION ! '' AMEN TO THAT!!!
Case Report Creutzfeldt-Jacob disease presenting as severe depression: a case report
Ethan U Cumbler , Kristin Furfari and Jeannette Guerrasio Cases Journal 2009, 2:122doi:10.1186/1757-1626-2-122 Published: 4 February 2009 Abstract (provisional) Background An 81 year old female presented with altered mental status after new onset of severe depression and suicidal ideation with recent psychiatric hospitalization. Case presentation Key clinical features included muscle rigidity, prominent startle reflex, and rapidly progressing cognitive decline. Initial working hypothesis was serotonin syndrome or neuroleptic malignant syndrome but continued deterioration after medication removal prompted evaluation for alternative etiology. Work-up revealed elevated 14-3-3 CSF protein which suggested the prion disorder which was confirmed on post-mortem examination of brain tissue. Conclusion While the degree of depression was unusually severe, the case highlights the behavioral and psychiatric manifestations which frequently accompany Creutzfeldt-Jacob disease. The complete article is available as a provisional PDF.
http://www.casesjournal.com/content/pdf/1757-1626-2-122.pdf
Wednesday, February 04, 2009 Creutzfeldt-Jacob disease presenting as severe depression: a case report
http://creutzfeldt-jakob-disease.blogspot.com/2009/02/creutzfeldt-jacob-disease-presenting-as.html
HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory JUNE 2008
snip...
Tissue infectivity and strain typing of the many variants Manuscript 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. ...
snip...
http://cjdmadcowbaseoct2007.blogspot.com/2008/06/human-and-animal-tse-classifications-ie.html
Wednesday, February 11, 2009
Atypical BSE North America Update February 2009
Greetings,
Considering that Mad Cow disease of all documented phenotypes, either the c-BSE, or the atypical h-BSE and or the l-BSE, ALL of which have been documented in North America, how many more, who knows, but they seem to be throwing all there marbles in the pot now by calling the h-type BSE 'familial'. what happens if we come up with another strain ? kinda like the sporadic FFI, that's not familial, what's that all about ? considering the many different strains of the typical scrapie 20+, and then the atypical Nor-98 Scrapie, which the USA has documented 6 cases the last i heard, and the thought of more than one strain of CWD in deer and elk, where will the next year, 4 years, 8 years, and beyond take us in the world of human and animal Transmissible Spongiform Encephalopathy and 'sound science' in the USA ? WILL the New Administration see the enfamous enhanced bse surveillance program of 2004 for what it was, a fraud, and have a 'redo' ? WE can hope i suppose. ...TSS
Both of the BSE cases ascertained in the US native-born cattle were atypical cases (H-type), which contributed to the initial ambiguity of the diagnosis. 174, 185 In Canada, there have been 2 atypical BSE cases in addition to the 14 cases of the classic UK strain of BSE2: one was the H-type, and the other was of the L-type.198
snip...end
source :
Enhanced Abstract Journal of the American Veterinary Medical Association January 1, 2009, Vol. 234, No. 1, Pages 59-72
Bovine spongiform encephalopathy
Jane L. Harman, DVM, PhD; Christopher J. Silva, PhD
http://avmajournals.avma.org/doi/ref/10.2460/javma.234.1.59
Thursday, December 04, 2008 2:37 PM
"we have found that H-BSE can infect humans."
personal communication with Professor Kong. ...TSS
see full text ;
http://bse-atypical.blogspot.com/2009/02/atypical-bse-north-america-update.html
Sunday, December 28, 2008
MAD COW DISEASE USA DECEMBER 28, 2008 an 8 year review of a failed and flawed policy
http://bse-atypical.blogspot.com/2008/12/mad-cow-disease-usa-december-28-2008-8.html
Monday, December 1, 2008
When Atypical Scrapie cross species barriers
http://nor-98.blogspot.com/2008/12/when-atypical-scrapie-cross-species.html
Monday, December 08, 2008
vCJD & dental treatment
http://creutzfeldt-jakob-disease.blogspot.com/2008/12/vcjd-dental-treatment.html
Tuesday, July 29, 2008
Docket No. 2005N-0373 and RIN number 0910-AF54 Use of Materials Derived From Cattle in Medical Products March 30, 2007 at 11:37 am PST
http://madcowfeed.blogspot.com/2008/07/docket-no-2005n-0373-and-rin-number.html
Subject: CJD: update for dental staff
Date: November 12, 2006 at 3:25 pm PST
http://neurotalk.psychcentral.com/showthread.php?t=13173
Archive Number 20061208.3468 Published Date 08-DEC-2006 Subject PRO/AH/EDR> CJD (new var.), blood transfusion risk
http://apex.oracle.com/pls/otn/f?p=2400:1202:5490148654931058710::NO::F2400_P1202_CHECK_DISPLAY,F2400_P1202_PUB_MAIL_ID:X,35445
4th CASE VCJD VIA BLOOD TRANSFUSION, BSE, BASE, AND SPORADIC CJD By Terry S Singeltary
http://www.bloodindex.org/view_news_zone.php?id=206
(Adopted by the International Committee of the OIE on 23 May 2006)
11. Information published by the OIE is derived from appropriate declarations made by the official Veterinary Services of Member Countries.The OIE is not responsible for inaccurate publication of country disease status based on inaccurate information or changes in epidemiological status or other significant events that were not promptly reported to then Central Bureau............
http://www.oie.int/eng/Session2007/RF2006.pdf
full text ;
http://madcowtesting.blogspot.com/2007/10/bse-base-mad-cow-testing-texas-usa-and.html
http://madcowtesting.blogspot.com/
bought and paid for by your local cattle dealer $$$
IN my opinion the WOAH/OIE is nothing more than a organized bunch of lobbyist for the members Countries in support of there INDUSTRY, bound together as one, with the only purpose of open trade for there precious commodities and futures. Speaking only of BSE, they failed at every corner, and then just said to hell with it, well just trade all strains of TSE globally.
snip...
NOW, ask yourself why not one single mad cow has been documented in the USA since the Honorable Phyllis Fong of the OIG did the end around Johanns, Dehaven et al ??? found two atypical BSE or BASE cases and they flat shut it down i tell you. IF the OIE gives a favorable rating, IF the OIE gives any other rating but the lowest, poorest possible BSE/TSE rating, the OIE will have sealed there fate once and for all, because most of the world knows the truth about the USA and there mad cows. THE OIE will then be able to stand side by side with the USA, and proudly claim to have sold there soul to the devil, all for a buck, commodities and futures, to hell with human health. A 'CONTROLLED' RATING IS EXACTLY what the OIE will get if that is what they classify the USA as a 'CONTROLLED RATING'. IT will be controlled by Johanns, Dehaven, and GW. IT WILL BE RIGGED in other words. but that is nothing new, it's been rigged for years. ...
snip...
SEE FULL TEXT with facts and sources @ ;Wednesday, June 11, 2008
OIE Recognition of the BSE Status of Members RESOLUTION No. XXI (Adopted by the International Committee of the OIE on 27 May 2008)
Attachment to Singeltary comment January 28, 2007 Greetings APHIS, I would kindly like to submit the following to ; BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01 [Federal Register: January 9, 2007 (Volume 72, Number 5)] [Proposed Rules] [Page 1101-1129] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr09ja07-21]
BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01 Date: January 9, 2007 at 9:08 am PST
snip...
MY personal belief, since you ask, is that not only the Canadian border, but the USA border, and the Mexican border should be sealed up tighter than a drum for exporting there TSE tainted products, until a validated, 100% sensitive test is available, and all animals for human and animal consumption are tested. all we are doing is the exact same thing the UK did with there mad cow poisoning when they exported it all over the globe, all the while knowing what they were doing. this BSE MRR policy is nothing more than a legal tool to do just exactly what the UK did, thanks to the OIE and GW, it's legal now. and they executed Saddam for poisoning ???
go figure....
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=09000064801f3412
http://www.regulations.gov/fdmspublic/ContentViewer?objectId=09000064801f3413&disposition=attachment&contentType=msw8
January 28, 2007
Greetings APHIS,
I would kindly like to submit the following to ;
BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01
[Federal Register: January 9, 2007 (Volume 72, Number 5)] [Proposed Rules] [Page 1101-1129] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr09ja07-21]
[[Page 1101]]
http://docket-aphis-2006-0041.blogspot.com/2008/06/bovine-spongiform-encephalopathy.html
Docket APHIS-2007-0033 Docket Title Agricultural Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select Agent and Toxin List Docket Type Rulemaking Document APHIS-2007-0033-0001 Document Title Agricultural Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select Agent and Toxin List Public Submission APHIS-2007-0033-0002.1 Public Submission Title Attachment to Singeltary comment
http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=090000648027c28e
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
OIE amending the Annex to Decision 2007/453/EC establishing the BSE status of Member States or third countries or regions thereof according to their BSE risk
http://docket-aphis-2006-0041.blogspot.com/2009/01/oie-amending-annex-to-decision.html
Wednesday, February 11, 2009
Atypical scrapie in sheep from a UK research flock which is free from classical scrapie
Research article
http://nor-98.blogspot.com/2009/02/atypical-scrapie-in-sheep-from-uk.html
Monday, February 09, 2009
Exotic Meats USA Announces Urgent Statewide Recall of Elk Tenderloin Because It May Contain Meat Derived From An Elk Confirmed To Have CWD
http://chronic-wasting-disease.blogspot.com/2009/02/exotic-meats-usa-announces-urgent.html
In short, a great deal of further work will need to be done before the phenotypic features and prevalence of atypical BSE are understood. More than a single strain may have been present from the beginning of the epidemic, but this possibility has been overlooked by virtue of the absence of widespread Western blot confirmatory testing of positive screening test results; or these new phenotypes may be found, at least in part, to result from infections at an older age by a typical BSE agent, rather than neonatal infections with new "strains" of BSE. Neither alternative has yet been investigated.
http://www.cdc.gov/ncidod/EID/vol12no12/06-0965.htm
A New Prionopathy OR more of the same old BSe and sporadic CJD
http://creutzfeldt-jakob-disease.blogspot.com/2008/08/new-prionopathy-or-more-of-same-old-bse.html
Communicated by: Terry S. Singeltary Sr.
[In submitting these data, Terry S. Singeltary Sr. draws attention to the steady increase in the "type unknown" category, which, according to their definition, comprises cases in which vCJD could be excluded. The total of 26 cases for the current year (2007) is disturbing, possibly symptomatic of the circulation of novel agents. Characterization of these agents should be given a high priority. - Mod.CP]
http://pro-med.blogspot.com/2007/11/proahedr-prion-disease-update-2007-07.html
http://www.promedmail.org/pls/askus/f?p=2400:1001:6833194127530602005::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1010,39963
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
sporadic Fatal Familial Insomnia
http://sporadicffi.blogspot.com/
JOURNAL OF NEUROLOGY
MARCH 26, 2003
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob
disease in the United States
Email Terry S. Singeltary:
mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000046/!x-usc:mailto:flounder@wt.net
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/cgi/eletters/60/2/176#535
Subject: Re: Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States [FULL TEXT] Date: September 10, 2003 at 1:43 pm PST
In Reply to: Re: Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States [FULL TEXT] posted by TSS on March 27, 2003 at 7:15 am:
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States
IN the reply from Dr. Maddox to Terry S. Singeltary Sr., he states;
snip...
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)...
snip...
http://www.neurology.org/cgi/eletters/60/2/176#535
THERE seems to be some difference of opinion;
Mouse model sheds new light on human prion disease
snip...
Professor John Collinge said “We are not saying that all or even most cases of sporadic CJD are as a result of BSE exposure, but some more recent cases may be – the incidence of sporadic CJD has shown an upward trend in the UK over the last decade. While most of this apparent increase may be because doctors are now more aware of CJD and better at diagnosing it, serious consideration should be given to a proportion of this rise being BSE-related. Switzerland, which has had a substantial BSE epidemic, has noted a sharp recent increase in sporadic CJD.
snip...
http://www.mrc.ac.uk/txt/index/public-interest/public-news-4/public-news_archive/public-news-archive_nov_dec_02/public-bse_and_sporadic_cjd.htm
ALSO, Dr. Maddox states;
make routine mortality surveillance a useful surrogate for ongoing CJD surveillance...
THIS has proven not 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 bu 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://www.bseinquiry.gov.uk/files/mb/m26/tab01.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://www.bseinquiry.gov.uk/files/yb/1991/01/04004001.pdf
DR. Maddox states here;
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.
HOWEVER in a recent article in the UPI out of Washington;
CJD screening may miss thousands of cases
By Steve Mitchell UPI Medical Correspondent Published 7/21/2003 3:00 PM
snip...
In addition, the NPDPSC sees less than half of all the CJD cases each year, so the CDC's investigational system not only is missing many of the misdiagnosed CJD cases, it also is not conducting autopsies on most of the detected cases.
snip...
http://www.upi.com/view.cfm?StoryID=20030721-102924-4786r
ALSO in Philip Yams book 'The Pathological Protein';
''Answering critics like Terry Singeltary, who feels that the US undercounts CJD, Schonberger _conceded_ that the current surveillance system has errors but stated that most of the errors will be confined to the older population''....
http://www.thepathologicalprotein.com/
THERE has been a _documented_ case of nv/v CJD in a 74 year old, so the errors Schonberger speaks of (above) would be of significant importance, if one believes in the nv/v CJD 'only' theory.
NOW we have _documented_ cases of very young CJD victims in the USA continuing to appear in several different states.
HOW does Dr. Maddox explain this, and does he still believe that a National CJD surveillance program with a CJD questionnaire to every victims family is still not warranted?
WITH CWD and Scrapie running rampant in the USA, with BSE now _documented_ in North America, with the feeding of ruminant-to-ruminant animal protein still happening in the USA in 2003 even though there has been a partial voluntary ban on ruminant feeding since 8/4/97, with only 48,000 BSE/TSE tests done on USA cattle in some 14 years of surveillance, when in any given year there are 100 million cattle in the USA, with all this, i think refusing to make CJD/TSEs reportable Nationally in the USA is not ONLY a grave mistake, but in my opinion, should be looked at with great suspicion...
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, TEXAS USA 77518
USA WRITTEN CJD QUESTIONNAIRE ???
http://cjdquestionnaire.blogspot.com/
Subject: Re: Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States [FULL TEXT] Date: November 13, 2004 at 2:35 pm PST
In Reply to: Re: Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States [FULL TEXT] posted by TSS on September 10, 2003 at 1:43 pm:
Re: Reply to Singletary Terry S. Singeltary Sr., CJD WATCH P.O. Box 42, none
Send Correspondence to journal: Re: Re: Reply to Singletary
Email Terry S. Singeltary Sr., et al.
Singeltary Reply to Dr. Maddox, Belay, Schonberger et al 11/13/04;
Greetings Dr. Maddox, Belay, Schonberger et al;
IN your reply to me on 26 March 2003, Dr. Maddox, Belay, Schonberger et al write;
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]
I kindly wish to submit the following to dispute this;
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://www.bseinquiry.gov.uk/files/yb/1989/05/00005001.pdf
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 bu 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://www.bseinquiry.gov.uk/files/mb/m26/tab01.pdf
IN your reply to me on 26 March 2003, Dr. Maddox, Belay, Schonberger et al write;
[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.
I kindly wish to submit the following to dispute this;
11 November 2004
Genetic make-up may determine what type of CJD occurs when humans are infected with BSE
New research published by a team from the Medical Research Council (MRC) Prion Unit offers an explanation about why only people with a particular genetic make-up have so far developed vCJD. It also provides evidence that other types of BSE-derived prion infection with a different pattern of symptoms might occur in humans. The findings are published in the journal Science.
Variant CJD (vCJD) is the human disease thought to be caused by eating food contaminated with the infectious agent, known as a prion, responsible for the epidemic of BSE or “mad cow disease” in cattle. So far, everyone known to have developed vCJD has been of a particular genetic type – known as MM. Until now it has been a mystery why everyone that has developed vCJD is of the MM type and one possibility is that they are simply the first to develop the disease when infected with BSE, and that people with the other genetic types1 (known as VV and MV*) infected with BSE prions will also develop vCJD, but some years later.
In a series of experiments spanning more than ten years, the MRC team has been studying mice genetically modified so that they make human prion proteins – which are used to model human susceptibility to BSE. The team has now shown that mice with the human VV genetic type do become infected when given BSE or vCJD prions, but manifest a different form of the disease which looks quite different to vCJD and has a novel prion “strain” type.
Remarkably, when these novel prions were used to infect mice of the MM genetic type, the mice either developed a disease very like vCJD, or else a pattern of disease that looks like so-called sporadic CJD – the “classical” form of CJD. This form has been known about for many years, is seen all over the world and has not hitherto been associated with BSE. However, the new strain identified in the mice, being called ‘type 5’, has not been seen yet in people and we do not know what pattern of disease it would cause. It could look like one of the forms of classical or sporadic CJD or perhaps be yet another different “variant” form.
The work from the MRC team suggests that type 4 prions, the type associated with vCJD, can only propagate themselves in people that make the M form of the protein. It seems the V form of the protein just cannot adopt the particular molecular shape that characterises type 4.
The studies in mice also suggest that if these prions were to pass from person to person (for example by blood transfusion) then, depending on the genetic type of the person becoming infected, at least three different patterns of disease might result: type 2 (which is seen in sporadic CJD); type 4 (which causes vCJD) or type 5 (which may cause a new pattern of disease).
Professor John Collinge, Director of the MRC Prion Unit, which is based at University College London, said: “These mouse studies give us vital clues about the behaviour of prions and how they appear to modify and adapt depending on the genetic makeup of the individual they are infecting.
“We always have to be cautious about making direct comparison to the human condition, but our work strongly suggests that we can not assume only those with one genetic profile are vulnerable to BSE infection.
“At this stage it is not possible to say how this should alter estimates of those likely to become ill, but our findings do suggest we should be taking steps to draw up a more sophisticated system of categorizing the disease so that we don’t mistake BSE related infection for a version of sporadic CJD.”
For more information call the MRC press office on 020 7 637 6011
Notes to Editors
*The human prion protein comes in two common forms, known as M and V. Because everyone has two copies of this gene, there are three possible genetic types: MM, MV and VV.
Paper - Human Prion protein v129 prevent expression of vCJD phenotype – Science On line 11.11.04
Prions are rogue forms of one of the body’s own proteins – known as the prion protein – which are misshapen. There are several different rogue or misshapen forms that can infect humans, and these different types of prions are known as “strains”. This is analogous to different strains of other germs such ‘flu virus causing influenza or strains of salmonella causing different forms of food poisoning for example.
The strain of prion causing vCJD is known as type 4, types 1-3 cause the different forms of sporadic or classical CJD. Each strain causes a different pattern or type of disease. It is known that prion strains can change or “mutate” when they pass between different animals.
The Medical Research Council (MRC) is a national organisation funded by the UK tax-payer. Its business is medical research aimed at improving human health; everyone stands to benefit from the outputs. The research it supports and the scientists it trains meet the needs of the health services, the pharmaceutical and other health-related industries and the academic world. MRC has funded work which has led to some of the most significant discoveries and achievements in medicine in the UK. About half of the MRC’s expenditure of £430 million is invested in its 40 Institutes, Units and Centres. The remaining half goes in the form of grant support and training awards to individuals and teams in universities and medical schools.
©2004 Medical Research Council
http://www.mrc.ac.uk/public-11_november_2004
BSE prions propagate as either variant CJD-like or sporadic CJD-like
prion strains in transgenic mice expressing human prion protein
Emmanuel A. Asante, Jacqueline M. Linehan, Melanie Desbruslais, Susan Joiner, Ian Gowland, Andrew L. Wood, Julie Welch, Andrew F. Hill, Sarah E. Lloyd, Jonathan D.F. Wadsworth and John Collinge1
MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK 1 Corresponding author e-mail: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000046/!x-usc:mailto:j.collinge@prion.ucl.ac.uk
Received August 1, 2002; revised September 24, 2002; accepted October 17, 2002
Abstract
Variant CreutzfeldtJakob disease (vCJD) has been recognized to date only in individuals homozygous for methionine at PRNP codon 129. Here we show that transgenic mice expressing human PrP methionine 129, inoculated with either bovine spongiform encephalopathy (BSE) or variant CJD prions, may develop the neuropathological and molecular phenotype of vCJD, consistent with these diseases being caused by the same prion strain. Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrPSc type 2. These data suggest that more than one BSE-derived prion strain might infect humans; it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure...
http://embojournal.npgjournals.com/cgi/content/full/21/23/6358
THE new findings of BASE in cattle in Italy of Identification of a second bovine amyloidotic spongiform encephalopathy: Molecular similarities with sporadic Creutzfeldt-Jakob disease
http://www.pnas.org/cgi/content/abstract/0305777101v1
Adaptation of the bovine spongiform encephalopathy agent to primates
and comparison with Creutzfeldt- Jakob disease: Implications for
human health
THE findings from Corinne Ida Lasmézas*, [dagger] , Jean-Guy Fournier*, Virginie Nouvel*,
Hermann Boe*, DomÃnÃque Marcé*, François Lamoury*, Nicolas Kopp [Dagger
] , Jean-Jacques Hauw§, James Ironside¶, Moira Bruce [] , Dominique
Dormont*, and Jean-Philippe Deslys* et al, that The agent responsible for French iatrogenic growth hormone-linked CJD taken as a control is very different from vCJD but is similar to that found in one case of sporadic CJD and one sheep scrapie isolate;
http://www.pnas.org/cgi/content/full/041490898v1
Characterization of two distinct prion strains derived from bovine spongiform encephalopathy transmissions to inbred mice
Sarah E. Lloyd, Jacqueline M. Linehan, Melanie Desbruslais, Susan Joiner, Jennifer Buckell, Sebastian Brandner, Jonathan D. F. Wadsworth and John Collinge
Correspondence John Collinge mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000046/!x-usc:mailto:j.collinge@prion.ucl.ac.uk
MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, London WC1N 3BG, UK Received 9 December 2003 Accepted 27 April 2004
Distinct prion strains can be distinguished by differences in incubation period, neuropathology and biochemical properties of disease-associated prion protein (PrPSc) in inoculated mice. Reliable comparisons of mouse prion strain properties can only be achieved after passage in genetically identical mice, as host prion protein sequence and genetic background are known to modulate prion disease phenotypes. While multiple prion strains have been identified in sheep scrapie and CreutzfeldtJakob disease, bovine spongiform encephalopathy (BSE) is thought to be caused by a single prion strain. Primary passage of BSE prions to different lines of inbred mice resulted in the propagation of two distinct PrPSc types, suggesting that two prion strains may have been isolated. To investigate this further, these isolates were subpassaged in a single line of inbred mice (SJL) and it was confirmed that two distinct prion strains had been identified. MRC1 was characterized by a short incubation time (110±3 days), a mono-glycosylated-dominant PrPSc type and a generalized diffuse pattern of PrP-immunoreactive deposits, while MRC2 displayed a much longer incubation time (155±1 days), a di-glycosylated-dominant PrPSc type and a distinct pattern of PrP- immunoreactive deposits and neuronal loss. These data indicate a crucial involvement of the host genome in modulating prion strain selection and propagation in mice. It is possible that multiple disease phenotypes may also be possible in BSE prion infection in humans and other animals.
http://vir.sgmjournals.org/cgi/content/abstract/85/8/2471
THE recent discoveries of previously unidentified strains of Scrapie such as 221C44 and the Nor9845;
FULL TEXT APPRX. 91 PAGES
UK Strategy for Research and Development on Human and Animal Health Aspects of Transmissible Spongiform Encephalopathies
2004-2007
http://www.mrc.ac.uk/pdf-uk_strategy_v5.2.pdf
IP/04/1324
Brussels, 28 October 2004
Commission submits French Research Findings on TSE in a goat to Expert
Panel
Following the findings by a research group in France that they suspect the presence of a TSE infection in a goats brain which tests cannot distinguish from BSE, the European Commission has submitted data received from the French authorities to the Community Reference Laboratory (CRL) for TSEs based in Weybridge, England, for an evaluation by an expert panel. TSEs are transmissible spongiform encephalopathies, namely BSE affecting cattle, and scrapie affecting goats and sheep. The expert panel will evaluate, over the next two weeks or so, the scientific evidence to see if it indicates the presence of BSE in the goat. This isolated incident does not present a risk to public health as the goat and its herd did not enter the food and feed chain.
snip...
http://europa.eu.int/rapid/pressReleasesAction.do?reference=IP/04/1324&format=HTML&aged=0&language=EN&guiLanguage=en
According to Nov. 2 Yomiuri Newspaper, researchers of the Prion Disease Research Center, the National Institute of Animal Health of Japan reported in the International Symposium of Prion Diseases held in Sendai from October 31 to November 2., 2004, that they detected prion in the adrenal gland and peripheral (sciatic and peroneal) nerves of the 11th BSE case of Japan (a 94-months old cow found dead on the farm on March 4 this year).
http://www.maff.go.jp/www/press/cont2/20041101press_7.htm
(only in Japanese)
Sendai and the International Symposium of Prion Diseases held here from October 31 to November 2.,2004
Abstract
ORAL 8
Bovine spongiform encephalopathy (BSE) in Japan
Takashi Yokoyama, Kumiko M. Kimura, Morikazu Shinagawa Prion Disease Research Center, National Institute of Animal Health, Japan
Bovine spongiform encephalopathy (BSE) has become an important problem not only for animal industry, but also for public health. In Japan, BSE was first recognized in September 2001 by fallen stock surveillance. Since October 2001, BSE examination for all cattle slaughtered at abattoirs has started. In April 2004, all dead cattle examination (over 24 months) has been conducted at livestock hygiene service center. Samples positive in enzyme linked immunosorbent assay (ELISA) are further subjected to western blot (WB) and immunohistochemistry (IHC). Thirteen BSE cases have been reported by September 2004. Twelve cases were classified as typical BSE, and the remained one was an atypical BSE. Variant forms of BSE with atypical histopathological and/or biochemical phenotype were reported in Italy and France. Further study is required for BSE prion characteristics. To characterize BSE prion properties, brain homogenates of Japanese BSE cases were intracerebrally inoculated into wild-type mice. The first case (BSE/Chiba) was successfully transmitted to rodents. The mean incubation periods (409.0 days) in this experiment was preferably longer than that of previously reported. PrPSc distribution, prion titer, mice susceptibility and/or storage condition of sample might be influenced the result. Recently, we introduced transgenic mice that overexpress a bovine PrP gene to overcome the species barrier problem. These mice are expected to accelerate the transmission experiment of BSE prion. Transmission of atypical BSE case is undergoing by using these transgenic mice.
http://www.knt.co.jp/ec/2004/prion/E2.htm
Docket No. 2003N-0312 Animal Feed Safety System [TSS SUBMISSION]
From: Terry S. Singeltary Sr. [flounder@wt.net] Sent: Tuesday, July 29, 2003 1:03 PM To: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000046/!x-usc:mailto:fdadockets@oc.fda.gov Cc: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000046/!x-usc:mailto:ggraber@cvm.fda.gov; mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000046/!x-usc:mailto:Linda.Grassie@fda.gov; BSE-L Subject: Docket No. 2003N-0312 Animal Feed Safety System [TSS SUBMISSION TO DOCKET 2003N-0312]
snip...
Greetings FDA,
PLUS, if the USA continues to flagrantly ignore the _documented_ science to date about the known TSEs in the USA (let alone the undocumented TSEs in cattle), it is my opinion, every other Country that is dealing with BSE/TSE should boycott the USA and demand that the SSC reclassify the USA BSE GBR II risk assessment to BSE/TSE GBR III 'IMMEDIATELY'. for the SSC to _flounder_ any longer on this issue, should also be regarded with great suspicion as well. NOT to leave out the OIE and it's terribly flawed system of disease surveillance. the OIE should make a move on CWD in the USA, and make a risk assessment on this as a threat to human health...
snip...full text;
http://www.fda.gov/ohrms/dockets/dockets/03n0312/03N-0312_emc-000001.txt
EFSA Scientific Report on the Assessment of the Geographical BSE-Risk (GBR) of the United States of America (USA) Publication date: 20 August 2004
Adopted July 2004 (Question N° EFSA-Q-2003-083)
* 167 kB Report
* 105 kB Summary
Summary of the Scientific Report
The European Food Safety Authority and its Scientific Expert Working Group on the Assessment of the Geographical Bovine Spongiform Encephalopathy (BSE) Risk (GBR) were asked by the European Commission (EC) to provide an up-to-date scientific report on the GBR in the United States of America, i.e. the likelihood of the presence of one or more cattle being infected with BSE, pre-clinically as well as clinically, in USA. This scientific report addresses the GBR of USA as assessed in 2004 based on data covering the period 1980-2003.
The BSE agent was probably imported into USA and could have reached domestic cattle in the middle of the eighties. These cattle imported in the mid eighties could have been rendered in the late eighties and therefore led to an internal challenge in the early nineties. It is possible that imported meat and bone meal (MBM) into the USA reached domestic cattle and leads to an internal challenge in the early nineties.
A processing risk developed in the late 80s/early 90s when cattle imports from BSE risk countries were slaughtered or died and were processed (partly) into feed, together with some imports of MBM. This risk continued to exist, and grew significantly in the mid 90’s when domestic cattle, infected by imported MBM, reached processing. Given the low stability of the system, the risk increased over the years with continued imports of cattle and MBM from BSE risk countries.
EFSA concludes that the current GBR level of USA is III, i.e. it is likely but not confirmed that domestic cattle are (clinically or pre- clinically) infected with the BSE-agent. As long as there are no significant changes in rendering or feeding, the stability remains extremely/very unstable. Thus, the probability of cattle to be (pre- clinically or clinically) infected with the BSE-agent persistently increases.
http://www.efsa.eu.int/science/efsa_scientific_reports/gbr_assessments/573_en.html
IN your reply to me on 26 March 2003, Dr. Maddox, Belay, Schonberger et al write;
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).
I kindly wish to submit the following to dispute this;
Mouse model sheds new light on human prion disease
snip...
Professor John Collinge said We are not saying that all or even most cases of sporadic CJD are as a result of BSE exposure, but some more recent cases may be the incidence of sporadic CJD has shown an upward trend in the UK over the last decade. While most of this apparent increase may be because doctors are now more aware of CJD and better at diagnosing it, serious consideration should be given to a proportion of this rise being BSE-related. Switzerland, which has had a substantial BSE epidemic, has noted a sharp recent increase in sporadic CJD.
snip...
http://www.mrc.ac.uk/index/public-interest/public-bse_and_sporadic_cjd.htm
http://www.mrc.ac.uk/txt/index/public-interest/public-news-4/public-news_archive/public-news-archive_nov_dec_02/public-bse_and_sporadic_cjd.htm
A simple look at sporadic CJD statistics in EU countries with BSE will reveal this;
CANADA 2 IN 94 COMPARED TO 30 IN 2002
FRANCE 35 IN 93 COMPARED TO 102 IN 2003
GERMANY 21 IN 93 COMPARED TO 112 IN 2003
ITALY 27 IN 93 TO COMPARED TO 75 IN 2003
UK 37 IN 93 COMPARED TO 74 IN 2003
USA (UNKNOWN...TSS)
http://www.eurocjd.ed.ac.uk/sporadic.htm
EVEN SEAC admits a rise in sporadic CJD in UK;
SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE Draft minutes of the open session of the 84th meeting held on 28th September 2004
snip...
In contrast, the number of deaths in the UK from sCJD per annum had increased but this may reflect improved case ascertainment. A similar increase in sCJD had been observed in other countries... snip..
HOWEVER, I do not agree with this _assumption_!
I believe there are multiple routes and sources for this agent and they are going ignored, while being called 'sporadic' and or 'spontaneous' or 'classic' CJD.
TO continue to ignore Professor Collinge/Asanta et al's advice;
“We always have to be cautious about making direct comparison to the human condition, but our work strongly suggests that we can not assume only those with one genetic profile are vulnerable to BSE infection.
“At this stage it is not possible to say how this should alter estimates of those likely to become ill, but our findings do suggest we should be taking steps to draw up a more sophisticated system of categorizing the disease so that we don’t mistake BSE related infection for a version of sporadic CJD.”
TO continue to ingore this and the other evidence that is and has been mounting about sporadic CJD not being as sporadic and or spontaneos as once thought, to continue this ignorance and blantantly let this agent continue to spread via the proven routes to date and continue to infect and kill, should warrant a TSE Inquiry in the USA by a Congressional Investigation followed by International Council of some kind. WE are not only infecting US citizens by this ignorance, but also the International community that visits our Country. With the recent findings of nv/v CJD transmitting via blood, we must not flounder any longer;
Summary of SEACs discussion on the second presumed case of blood transfusion-associated infection with vCJD
7. SEAC agreed that the western blot results and glycotype profile suggested it was unlikely that the infection was preclinical sporadic CJD (sCJD). The committee noted that a single study by Glatzel et al (2003) had reported PrPres in the spleen of sCJD clinical cases. However, the levels of PrPres present in sCJD cases were low and detected in patients with a lengthy clinical illness from sporadic CJD.
http://www.seac.gov.uk/statements/state070804.htm
vCJD: Blood Transfusion Incident
http://www.publications.parliament.uk/pa/ld199697/ldhansrd/pdvn/lds03/text/31217-09.htm
CJD (all human TSEs) should be made reportable Nationally and Internationally immediately, with a follow up investigation and questionnaire of each victim (family) asking questions pertaining to route and source of agent. ALL ages must be included in this. Anything less will only allow the agent to continue to spread and kill...
Thank You,
with kindest regards, I am sincerely,
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA CJD WATCH
http://www.neurology.org/cgi/eletter-submit
Date: March 16, 2005 at 1:17 pm PST
In Reply to: Re: Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States [FULL TEXT] posted by TSS on March 13, 2005 at 6:58 pm:
-------- Original Message -------- Subject: Re: The public health impact of prion diseases (1) Date: Mon, 14 Mar 2005 16:57:46 -0600 From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy To: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000046/!x-usc:mailto:BSE-L@KALIV.UNI-KARLSRUHE.DE References: <mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000046/!x-usc:mailto:4234FD63.5040302@wt.net>
##################### Bovine Spongiform Encephalopathy #####################
Greetings List Members,
can someone please explain this phenomenal statement to me ;
However, in the period following the first published description of vCJD in 1996, there was no increasing trend in the reported annual number of U.K. sporadic CJD deaths (52).
the UK went from 40 cases in 1996 to 77 cases in 2003, almost double. this is an increase.
IN this full text article (some 25 pages) it states ;
Multiple BSE Strains Unlike scrapie or classic CJD, BSE is likely caused by a single strain of an infectious agent that has a strikingly stable molecular property after natural or experimental transmission to other species. In 2004, however, researchers in Italy reported that the brain lesions of two of eight cattle they studied were distinguished from BSE by the presence of amyloid plaques and distribution of protease-resistant prion protein in the brain (16). OnWestern blot analysis, the prion fragment in the two cases had a lower molecular mass than that of the classic form of BSE. The researchers suggested that the difference in neuropathology and molecular mass indicates the existence of a second strain of BSE. To distinguish the disease in the two cows from the classic form of BSE, the researchers coined the name bovine amyloidotic spongiform encephalopathy (BASE). Three BSE cases with distinct molecular phenotype among cattle routinely diagnosed in a BSE surveillance system were independently reported in France also (9). Whether the findings from Italy and France do or do not represent new strains of widely circulating BSE should be confirmed through identification of more cases and additional laboratory studies. No scientific evidence exists to causally link any form of BSE with a sporadic CJD-like illness in humans. Concerns about BSE causing a sporadic CJD-like illness have persisted after BSE-infected transgenic mice expressed prions with a molecular phenotype consistent with a subtype of sporadic CJD (2). The transgenic mice were designed to produce the human prion protein, which is homozygous for methionine at codon 129. If BSE causes a sporadic CJD-like illness in humans, an increase in sporadic CJD cases would be expected to occur in the United Kingdom first, where the vast majority of vCJD cases have been reported. However, in the period following the first published description of vCJD in 1996, there was no increasing trend in the reported annual number of U.K. sporadic CJD deaths (52). Furthermore, surveillance in the United Kingdom has shown no increase in the proportion of sporadic CJD cases that are homozygous for methionine.
No scientific evidence exists to causally link any form of BSE with a sporadic CJD-like illness in humans. Concerns about BSE causing a sporadic CJD-like illness have persisted after BSE-infected transgenic mice expressed prions with a molecular phenotype consistent with a subtype of sporadic CJD (2). The transgenic mice were designed to produce the human prion protein, which is homozygous for methionine at codon 129. If BSE causes a sporadic CJD-like illness in humans, an increase in sporadic CJD cases would be expected to occur in the United Kingdom first, where the vast majority of vCJD cases have been reported. However, in the period following the first published description of vCJD in 1996, there was no increasing trend in the reported annual number of U.K. sporadic CJD deaths (52). Furthermore, surveillance in the United Kingdom has shown no increase in the proportion of sporadic CJD cases that are homozygous for methionine.
IF we look at sporadic incidence of CJD in UK from 1993 to 2003, the incidence rose from 37 in 1993 to 77 in 2003. THIS seems to show an increase to me? I do not understand the statement ;
However, in the period following the first published description of vCJD in 1996, there was no increasing trend in the reported annual number of U.K. sporadic CJD deaths (52).
IF we go further and look at some of the other documented BSE countries, you will the increase of sporadic CJD there as well ;
Canada from 2 to 25
France from 35 to 108
Germany 21+ to 96
Italy 27 to 76
http://www.eurocjd.ed.ac.uk/sporadic.htm
and Switzerland sporadic CJD ;
Swiss rise in CJD raises concerns over possible BSE link [LONDON] THE LANCET
Plaque attack: Swiss patients have spongiform patterns in the brain typical of sporadic CJD. The number of people dying from Creutzfeldt-Jakob disease (CJD) has risen sharply in Switzerland -- sparking fears of a possible link with bovine spongiform encephalopathy (BSE).
BSE is thought to be the cause of a distinctive form of the brain-wasting disease known as variant CJD. The Swiss cases, in contrast, are standard 'sporadic' CJD. Each year between 1997 and 2000, no more than 11 Swiss people developed CJD. But 19 cases were reported in 2001, and seven were recorded in the first quarter of this year. This is some four times higher than the incidence elsewhere, reports a team led by Adriano Aguzzi of the University Hospital Zurich (M. Glatzel et al. Lancet 360, 139-141; 2002).
The increase could be a mere statistical blip, or it may be due to increased awareness of the disease leading to more diagnoses. More disturbing is the possibility that the cases are linked to the consumption of BSE-infected meat products -- which would mean that the BSE agent can cause two distinct forms of CJD.
Possible links between the Swiss CJD cases and BSE will now be explored by strain-typing experiments in which the disease is transmitted to mice. These tests will take at least a year to complete. "It's the best way to establish or exclude any suspected link," says Moira Bruce of the UK Institute for Animal Health's Neuropathogenesis Unit in Edinburgh.
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Experiences in England and Switzerland -- two countries that discovered mad cow disease in their cattle -- have heightened concerns about the possibility some cases of sporadic CJD are due to consuming mad-cow-tainted beef. Both countries have reported increases in sporadic CJD since mad cow was first detected in British herds in 1986.
Switzerland discovered last year its CJD rate was twice that of any other country in the world. Switzerland had been seeing about eight to 11 cases per year from 1997 to 2000. Then the incidence more than doubled, to 19 cases in 2001 and 18 cases in 2002.
http://www.upi.com/view.cfm?StoryID=20030721-102924-4786r
Mouse model sheds new light on human prion disease
snip...
Professor John Collinge said We are not saying that all or even most
cases of sporadic CJD are as a result of BSE exposure, but some more
recent cases may be the incidence of sporadic CJD has shown an upward
trend in the UK over the last decade. While most of this apparent
increase may be because doctors are now more aware of CJD and better at
diagnosing it, serious consideration should be given to a proportion of
this rise being BSE-related. Switzerland, which has had a substantial
BSE epidemic, has noted a sharp recent increase in sporadic CJD.
snip...
http://www.mrc.ac.uk/txt/index/public-interest/public-news-4/public-news_archive/public-news-archive_nov_dec_02/public-bse_and_sporadic_cjd.htm
snip...END...TSS
I still strongly disagree with the statement. THE figures do NOT support this statement;
However, in the period following the first published description of vCJD in 1996, there was no increasing trend in the reported annual number of U.K. sporadic CJD deaths (52).
BACK TO ARTICLE;
CHRONICWASTING DISEASE Distribution CWD (chronic wasting disease), a prion disease of North American deer and elk, was first identified as a fatal wasting syndrome of captive mule deer in the late 1960s in research facilities in Colorado (76). It was first recognized as a TSE in 1978. The occurrence of CWD among wild cervids was first identified in 1981 when a free-ranging elk from Colorado was diagnosed with the disease. Subsequent surveillance studies demonstrated the endemic occurrence of CWD among free-ranging deer and elk in a contiguous area in northeastern Colorado, southeastern Wyoming, and, most recently, in western Nebraska (76). Epidemic modeling suggested thatCWDmight have been present among free-ranging animals in some portions of the endemic area several decades before itwas initially recognized (55). PRION DISEASES 207 After 2000, new foci of CWD have increasingly been identified in Illinois, New Mexico, South Dakota, Utah, Wisconsin, and non-CWD-endemic areas of Colorado and Wyoming (6, 76). The identification of CWD in these new areas seems to be related to increased surveillance and spread of the disease as a result of natural migration of deer and elk or translocation of infected cervids by humans. Currently, two largely independent outbreaks, one in free-ranging deer and elk and another in the captive elk and deer industry, are occurring in Canada and the United States (6). Risk to Humans The increasing spread of CWD in the United States and the zoonotic transmission of BSE raised concerns about the possible transmission of CWD to humans (6). Several CJD cases or apparent CJD clusters with suspect CWD transmission have been reported in the United States (4, 6, 23). Epidemiologic and laboratory investigations of these isolated cases and clusters did not provide convincing evidence for a link between CWD and the patients illnesses. However, the studies seeking evidence for a possible link between CWD and human illness have been limited. Additional epidemiologic and laboratory studies should be conducted before the CWD agent can be exonerated as a possible human pathogen. Because persons who hunted deer and elk in the known CWD-endemic areas of Colorado andWyoming are more likely to have been exposed to the CWD agent over many years, a follow-up study of these hunters has been initiated to monitor the possible zoonotic transmission of CWD. A transgenic mice study, involving humanized and cervidized mice, is also in progress to determine the susceptibility of these mice to the CWD agent (6). CONCLUSION Three distinct prion diseaserelated human health risks from environmental sources of infection can be identified in the United States. These include the iatrogenic transmission of CJD, occurrence of vCJD from exposure to BSE-contaminated cattle products in the United States or other countries with BSE, and possible transmission of CWD to humans. The iatrogenic transmission of CJD appears to be on the decline following appropriate preventive measures that were instituted as the different iatrogenic modes of spread were identified. Additional iatrogenic CJD cases, however, can be anticipated primarily because of the long incubation period associated with prion diseases. To date, only one vCJD patient has been identified as a resident of the United States (25). This patient is believed to have contracted the disease while growing up in her native country of Britain during the height of human exposure to the BSE outbreak. Although the public health preventive measures recently instituted by the USDA should further reduce the risk of BSE exposure to the U.S. population, the possibility that domestically acquired vCJD may appear in the Annu. Rev. Public. Health. 2005.26:191-212. Downloaded from arjournals.annualreviews.org by IRMO/Information Center on 03/14/05. For personal use only. 208 BELAY SCHONBERGER United States cannot be totally dismissed. However, this possibility is probably much smaller than the risk of contracting vCJD as a result of BSE exposure during any previous travel or residence in countri s where a much higher rate of BSE has been documented. Recent reports of vCJD transmission via blood products obtained from donors who were incubating the disease are of concern because of a potentially large number of blood donors who might have been exposed to BSE and are incubating the disease. Theoretically, these persons might transmit the vCJD agent if they donate blood while they are clinically asymptomatic. The blood donor deferral policy instituted by the FDA is expected to greatly minimize this possible risk of bloodborne transmission of vCJD in the United States. The findings of vCJD transmission in a patient who was heterozygous at codon 129 may have implications for the eventual size of the vCJD outbreak. Heterozygous patients may develop vCJD after a longer incubation period and at an older age than methionine homozygous patients, potentially resulting in a more protracted course for the vCJD outbreak. To date, no convincing evidence of CWD transmission to humans has been reported. Because the decade-long occurrence ofCWDhad been relatively limited to a small geographic area, it is possible that not enough human exposure with the appropriate latency period has occurred for the agent to overcome the species barrier and cause disease in humans. There is a concern that the level of human exposure to CWD might increase over time with the increasing spread of CWD to new areas. Continued surveillance for possible human CWD among high-risk populations (e.g., persons hunting for many years in the CWD-endemic areas of Colorado and Wyoming) and evaluation of the zoonotic potential of the CWD agent in transgenic animal models should be conducted to monitor the possibility that the CWD agent can cause disease in humans. Suspected cases of iatrogenic CJD, vCJD, or human CWD cases should be reported to the CDC through local and state health departments. To facilitate surveillance for emerging forms of prion diseases such as vCJD and human CWD, the CDC, in collaboration with the American Association of Neuropathologists, established a National Prion Disease Pathology Surveillance Center. This pathology center is located at CaseWestern Reserve University, in Cleveland, Ohio, and provides state-of-the-art diagnostic support free of charge to U.S. physicians and develops laboratory methods to detect emerging human prion diseases. Autopsies should be sought in all clinically suspected and diagnosed human prion disease cases. Brain tissues from these cases should be sent to the National Prion Disease Pathology Surveillance Center to confirm the diagnosis of CJD and determine the CJD subtype. Increased testing of brain tissues from suspected case-patientswould facilitate detection of the emergence of any new prion diseases, such as vCJD or possible human CWD, in the United States. Annu. Rev. Public. Health. 2005.26:191-212. Downloaded from arjournals.annualreviews.org by IRMO/Information Center on 03/14/05. For personal use only.
snip...END
Autopsies should be sought in all clinically suspected and diagnosed human prion disease cases.
SADLY, in the elderly, i think only about 1 in 25 deaths get autopsied...
kind regards,
Terry S. Singeltary Sr.
Terry S. Singeltary Sr. wrote:
##################### Bovine Spongiform Encephalopathy #####################
Annu Rev Public Health. 2005;26:191-212.
The public health impact of prion diseases (1).
Belay ED, Schonberger LB.
Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333; email: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000046/!x-usc:mailto:EBelay@cdc.gov.
Several prion disease-related human health risks from an exogenous source can be identified in the United States, including the iatrogenic transmission of Creutzfeldt-Jakob disease (CJD), the possible occurrence of variant CJD (vCJD), and potential zoonotic transmission of chronic wasting disease (CWD). Although cross-species transmission of prion diseases seems to be limited by an apparent "species barrier," the occurrence of bovine spongiform encephalopathy (BSE) and its transmission to humans indicate that animal prion diseases can pose a significant public health risk. Recent reports of secondary person-to-person spread of vCJD via blood products and detection of vCJD transmission in a patient heterozygous at codon 129 further illustrate the potential public health impacts of BSE.
PMID: 15760286 [PubMed - in process]
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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15760286
Reply to Singletary 26 March 2003
Previous Correspondence Top
Ryan A. Maddox, MPH Centers for Disease Control and Prevention Atlanta GA, Ermias D. Belay, MD, Lawrence B. Schonberger, MD
Send Correspondence to journal: Re: Reply to Singletary
Email Ryan A. Maddox, MPH, et al.
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.
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 26 March 2003
Next Correspondence Top
Terry S. Singeltary, retired (medically) CJD WATCH
Send Correspondence to journal: Re: RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States
Email
Terry S. Singeltary
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?
http://www.neurology.org/cgi/eletters/60/2/176#535
TSS
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Subject: Re: Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States [FULL TEXT] Date: October 25, 2007 at 6:50 am PST
In Reply to: Re: Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States [FULL TEXT] posted by TSS on March 27, 2003 at 3:46 pm:
Dear Dr. Singeltary,
According to our Information for Authors and Correspondence policy, we can only consider Correspondence written about articles published within the last six weeks. Please consider Neurology again in the future.
Sincerely,
Morgan Serry
Neurology Editorial Office
Thursday, July 10, 2008
A New Prionopathy OR more of the same old BSe
http://cjdmadcowbaseoct2007.blogspot.com/2008/07/new-prionopathy-update-july-10-2008.html
THE PATHOLOGICAL PROTEIN
Hardcover, 304 pages plus photos and illustrations. ISBN 0-387-95508-9
June 2003
BY Philip Yam
CHAPTER 14 LAYING ODDS
Answering critics like Terry Singeltary, who feels that the U.S. under- counts CJD, Schonberger conceded that the current surveillance system has errors but stated that most of the errors will be confined to the older population.
http://www.thepathologicalprotein.com/
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
Creutzfeldt Jakob Disease
http://creutzfeldt-jakob-disease.blogspot.com/
USA PRION UNIT BLOG
http://prionunitusaupdate2008.blogspot.com/
Sunday, April 20, 2008
Progress Report from the National Prion Disease Pathology Surveillance Center April 3, 2008
Atypical forms of BSE have emerged which, although rare, appear to be more virulent than the classical BSE that causes vCJD.
see full text ;
http://prionunitusaupdate2008.blogspot.com/2008/04/progress-report-from-national-prion.html
CJD TEXAS (cjd clusters)
http://cjdtexas.blogspot.com/
Thursday, January 29, 2009
Medical Procedures and Risk for Sporadic Creutzfeldt-Jakob Disease, Japan, 1999-2008 (WARNING TO Neurosurgeons and Ophthalmologists) Volume 15, Number 2-February 2009 Research
http://creutzfeldt-jakob-disease.blogspot.com/2009/01/medical-procedures-and-risk-for.html
Nature 420, 450 (5 December 2002) doi:10.1038/420450a
Prion data suggest BSE link to sporadic CJD Declan Butler
Predicting the number of cases of Creutzfeldt–Jakob disease (CJD) in people as a result of transmission of bovine spongiform encephalopathy (BSE) has just got more difficult.Whereas it was thought that BSE only caused a new form of the disease called variant CJD (vCJD), a study in mice from a team led by John Collinge at University College London suggests that it may also cause a disease indistinguishable from the commonest form of classical, or 'sporadic', CJD
http://www.nature.com/nature/journal/v420/n6915/full/420450a.html
EMBO J. 2002 December 2; 21(23): 6358–6366. doi: 10.1093/emboj/cdf653. PMCID: PMC136957
Copyright © 2002 European Molecular Biology Organization BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein Emmanuel A. Asante, Jacqueline M. Linehan, Melanie Desbruslais, Susan Joiner, Ian Gowland, Andrew L. Wood, Julie Welch, Andrew F. Hill, Sarah E. Lloyd, Jonathan D.F. Wadsworth, and John Collinge1 MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK 1Corresponding author e-mail: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000046/!x-usc:mailto:j.collinge@prion.ucl.ac.uk Received August 1, 2002; Revised September 24, 2002; Accepted October 17, 2002. This article has been cited by other articles in PMC.
Abstract
Variant Creutzfeldt–Jakob disease (vCJD) has been recognized to date only in individuals homozygous for methionine at PRNP codon 129. Here we show that transgenic mice expressing human PrP methionine 129, inoculated with either bovine spongiform encephalopathy (BSE) or variant CJD prions, may develop the neuropathological and molecular phenotype of vCJD, consistent with these diseases being caused by the same prion strain. Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrPSc type 2. These data suggest that more than one BSE-derived prion strain might infect humans; it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=136957
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
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
UPDATE 2009
Monday, May 11, 2009
Rare BSE mutation raises concerns over risks to public health
http://bse-atypical.blogspot.com/2009/05/rare-bse-mutation-raises-concerns-over.html