Warning over second wave of CJD cases
Scientists say that threat of brain illness returning will persist for decades
Robin McKie, science editor The Observer,
Sunday August 3 2008 Article history
Doctors and scientists have warned that a second wave of CJD cases could sweep Britain over the next two to three decades. The initial outbreak of the fatal brain illness peaked several years ago but could break out again, they argue.
The prediction comes as officials consider ending some of the research projects that were set up to improve understanding of CJD - Creutzfeldt-Jakob disease - and the closely related illness in cows, BSE.
The Department for Environment, Food and Rural Affairs confirmed last week that some experiments aimed at providing detailed data on ways in which cattle could be struck by infectious particles, or prions, would soon be wound up. 'Where cattle are approaching 10 years old, we will probably need to end the experiments in the next year or so,' said a spokesman.
It is estimated that cases of BSE - bovine spongiform encephalopathy - have cost the European Union €80bn (£65bn). However, the condition has since been eliminated in UK cattle and numbers of human cases have declined dramatically. Health officials are now examining expenditure on the screening of blood, beef and surgical instruments.
Neurobiologist Professor Colin Blakemore of Oxford University, former head of the Medical Research Council (MRC), said: 'We have to ask just how much effort and money we should be putting into dealing with BSE and its human counterpart, variant CJD. Either the epidemic is all over and we have nothing to worry about, or we may be facing a second wave among humans. We are going to have to work out the risks very carefully.'
BSE first appeared in cattle in Britain in 1986 and was found to infect humans - in the form of variant CJD - 10 years later. Nineteen-year-old Stephen Churchill, of Devizes, Wiltshire, was identified as its first victim, triggering widespread alarm. It was claimed that tens of thousands of people could be killed. In fact, vCJD has killed only 164 people over the past 13 years in Britain, with the number of cases peaking at 28 in 2000. Only one new case has been recorded so far this year.
But scientists warn that the worst may not yet be over. 'We must not forget that almost every person in the UK was exposed to the agent that causes variant CJD,' said Professor John Collinge, head of the MRC's prion unit in London. 'It went through the entire food chain, not just in burgers but in cakes containing gelatins made from meat products. Even cosmetics contained beef-derived chemicals then.'
In fact, the extent to which people were brought into contact with a deadly human pathogen was unprecedented. Hence the insistence that while some relaxation of BSE monitoring was now acceptable, there should be no reduction in efforts to understand CJD. Certainly it is far too early to assume that Britain - the country most affected by BSE and vCJD - is in the clear, say researchers. They believe a second wave of cases will probably occur, based on studies of a closely related disease, kuru, which affected tribes in New Guinea.
Researchers have found that a key gene shapes the body's defences against kuru and this exists in two forms: version-m and version-v. These gene versions produce different responses to kuru. Individuals who have two m-versions (one from each parent) are the first to succumb to kuru, while those with one or two v-genes have a delayed onset.
Crucially, scientists have now found a similar picture among vCJD patients. Every victim to date has possessed two m-versions, a point stressed by Professor Chris Higgins, chair of the government's Spongiform Encephalopathy Advisory Committee (SEAC).
'About 40 per cent of the population is double-m,' he said. 'We have seen 160 cases develop. That suggests the remaining 60 per cent of the population will throw up about 250 cases some time in the next couple of decades. In other words, we face at least one more wave of variant CJD in Britain. That suggests we need to maintain our research efforts into finding treatments for the condition.'
'So far, UK funding has remained strong in its support for CJD work, though researchers in France and Germany have already noted grants for CJD work are drying up,' Collinge told The Observer. 'That would be a mistake if it were repeated here. We have the chance not just to find treatments for future CJD cases but to make progress in understanding conditions such as Alzheimer's and Parkinson's, which - although not caused by the same agent that triggers CJD - progress in very similar ways once the disease begins to take effect. We still have a lot to learn from this epidemic, in other words.'
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Jan 29 2005 BSE found in French goat Printable version Send to a friend Share Clip Contact us Article history About this articleClose This article appeared in the Observer on Sunday August 03 2008 on p11 of the News section. It was last updated at 00:02 on August 03 2008. ShareClose Digg reddit Google Bookmarks Yahoo! My Web del.icio.us StumbleUpon Newsvine livejournal Facebook BlinkList EmailClose Recipient's email address Your name Add a note (optional)
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http://www.guardian.co.uk/uk/2008/aug/03/bse.medicalresearch/print
10 people killed by new CJD-like disease
Public release date: 9-Jul-2008
Since Gambetti's team wrote a paper describing an initial 11 cases referred to his centre between 2002 and 2006 (Annals of Neurology, vol 63, p 697), another five have come to light. "So it is possible that it could be just the tip of the iceberg," Gambetti says.
snip...end
http://www.eurekalert.org/pub_releases/2008-07/ns-tpk070908.php
sporadic CJD, the big lie
Thursday, July 10, 2008 A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease update July 10, 2008
http://cjdmadcowbaseoct2007.blogspot.com/2008/07/novel-human-disease-with-abnormal-prion.html
Thursday, July 10, 2008 A New Prionopathy update July 10, 2008
http://cjdmadcowbaseoct2007.blogspot.com/2008/07/new-prionopathy-update-july-10-2008.html
CANADA
Creutzfeldt-Jakob Disease Surveillance System (CJD-SS)
Referrals of Suspected CJD Reported by CJD-SS(1), 1997-2007(2)
Year of Reporting Numbers of Referrals
1997 4 1998 43 1999 63 2000 82 2001 101 2002 103 2003 75 2004 89 2005 97 2006 78 2007 88
Total 823
1CJD-SS began in April 1998 2Data before April 1998 are retrospective and partial, data from 1999 to 2005 are complete, and data for 2006 and 2007 are provisional As of December 1, 2007
http://www.phac-aspc.gc.ca/hcai-iamss/cjd-mcj/cjdss-ssmcj/pdf/refs0408_e.pdf
http://www.phac-aspc.gc.ca/hcai-iamss/cjd-mcj/cjdss-ssmcj/stats_e.html
Neuropathology Volume 27 Issue 5 Page 419-428, October 2007
To cite this article: Leora Velásquez-Pérez, Daniel Rembao-Bojorquez, Jorge Guevara, Rosa María Guadarrama-Torres, Araceli Trejo-Contreras (2007) Creutzfeldt-Jakob disease in Mexico
Neuropathology 27 (5), 419-428. doi:10.1111/j.1440-1789.2007.00807.x
Abstract
Original Article
Creutzfeldt-Jakob disease in Mexico
Leora Velásquez-Pérez,1Departments of 1Epidemiology and Leora Velásquez-Pérez, MD, MSc, Department of Epidemiology, National Institute of Neurology and Neurosurgery, Insurgentes Sur 3877 Col. La Fama Tlalpan 14269, México, DF, Mexico. Email: leoravelasquez@hotmail.com Daniel Rembao-Bojorquez,22Pathology, and Jorge Guevara,33Neurodegenerative Diseases Laboratory, National Institute of Neurology and Neurosurgery, Mexico DF, Mexico Rosa María Guadarrama-Torres1Departments of 1Epidemiology and and Araceli Trejo-Contreras1Departments of 1Epidemiology and Departments of 1Epidemiology and 2Pathology, and 3Neurodegenerative Diseases Laboratory, National Institute of Neurology and Neurosurgery, Mexico DF, Mexico Leora Velásquez-Pérez, MD, MSc, Department of Epidemiology, National Institute of Neurology and Neurosurgery, Insurgentes Sur 3877 Col. La Fama Tlalpan 14269, México, DF, Mexico. Email: leoravelasquez@hotmail.com
Abstract
Creutzfeldt-Jakob disease (CJD) is classified within the group of transmissible spongiform encephalopathies (TSE). It is a rapidly progressive illness that affects mental functions. The average age of onset is 50 years. Various tests can help orient the clinical diagnosis, but the confirmatory test is still the post mortem analysis. The aim of this study was to describe the epidemiological, clinical and histopathological characteristics of patients diagnosed as suffering from CJD, at the National Institute of Neurology and Neurosurgery of Mexico (NINN). An observational, descriptive and transversal study was conducted. We collected information concerning these cases from the Departments of Epidemiology and Pathology, as well as the clinical charts of the patients with a diagnosis of CJD. Fifteen cases were registered of which three CJD cases were definite, five probable cases were identified, and seven were possible. The average age of the patients was 49 years. Two definite cases were female and one was male. It is important to improve the systems for surveillance of this type of disease and, furthermore, to permit greater accessibility to laboratories where the procedures necessary for supporting diagnosis can be followed.
snip...
In Mexico there are some deficiencies in the surveillance system, among other reasons due to limited knowledge concerning this disease on the part of administrative and medical staff, which causes a lack of notification of cases and an under-registration of these diseases. On the other hand, the National System of Epidemiological Surveillance has not rigorously integrated and made obligatory the notification and control of TSE, and there are no centers or laboratories of microbiology and genetics where tests to support the diagnosis of the disease can be conducted. Another problem in Mexico is the fact that many of the suspected or probable cases are never confirmed because of the refusal of relatives to allow deceased patients to undergo autopsies.
The aim of this study was to describe and present the epidemiological, clinical, and histopathological characteristics of CJD cases, detected between January 1, 2000 and May 31, 2005 in our institution; this being one of the world's main neurological institutions.
snip...
RESULTS
Between January 1, 2000 and May 31, 2005, three definite CJD cases were identified (20%), five probable cases were identified (33%), and seven were classified as possible (47%). The laboratory investigations used for the patients are presented in Table 1. The year of diagnosis of these patients is shown in Table 2. By the end of May 2005, eight patients were still alive (53%), and seven had died (47%). Of the seven deceased patients, the neurohistophatological study was performed in three patients. Of these, autopsy was carried out in two and stereotactic biopsy was performed in one. Histopathological images of definite cases of CJD are presented in Figure 1. Of these 15 cases,47% were male and 53% were female. The youngest patient was 23 years old, while the oldest was 75 (average: 49 years). The clinical manifestations observed most frequently at the beginning of the disease included cognitive symptoms, behavioral changes, cephalalgia and depression.The rest of the symptoms are shown in Table 2. The elapsed time between the beginning of symptoms and the patient's arrival at the NINN for medical attention consisted of a mean of 71 days (range: 10-210).The elapsed time from the beginning of clinical manifestations until the date of death and that between their arrival at the NINN and date of death are shown in Table 2. When analyzing their family history with respect to the presence of CJD and any type of dementia, all patients denied having this kind of antecedent. The past medical history of each patient is shown in Table 3. Ten patients (66.6%) were married or lived as couples, four (26.7%) were single, and only one (6.7%) was a widower. Regarding their educational level, nine (60%) had completed elementary education or had taken the first 3 years of courses and knew how to read and write; two (13%) had completed secondary education; three (20%) had completed high school or had at least a technical degree; and one (7%) had a bachelor degree. Concerning their residential locations, it was found that seven patients (47%) lived in Mexico City, five (33%) in the state of Mexico or suburban zones of the City, and three (20%) in other states of the Mexican Republic. The distribution of the cases in Mexico City, according to political divisions of the city, is shown in Figure 2. Regarding patients living in the state of Mexico, two (40%) were from Chalco, one (20%) was from Cuautitlan, one (20%) was from Ecatepec, and one (20%) from San JuanTeotihuacan. The three states of the Mexican Republic from where the other patients came were Guerrero, Hidalgo, and Sonora, each with one case. Regarding the occupational activities of the seven female patients, six (86%) were housewives and one (14%) was a secretary.With respect to the occupational activities of the male patients, two (25%) were retailers, two (25%) were office employees, and the remaining 50% was made up of farmers, drivers, bricklayers, and students, each with one case.
DISCUSSION
The average age in this study was 49 years, with an age range of 23-75 years. The age range reported by Bateman et al.13 is 45-75 years, and they mentioned that sCJD is extremely rare under age 30. However, in our study we had patients younger than this latter age. Nevertheless, gender frequency was similar, with 53% of female patients and 47% of male patients. Our results are more consistent with the work of Olov et al.32 who reported cases of CJD in younger patients, ranging from 34 to 84 years of age. Of the three definite cases, two were female, an interesting fact, as in 1995, in Mexico, Martínez et al.33 reported three cases, all of them female patients, but only one of them had a brain biopsy result. We are aware that PrP genotyping is important to classify prion diseases. However, in Mexico this technique is not available, a limitation of this study. However, we consider that this study reveals important information about CJD in Mexico. In the future, it would be interesting to perform a retrospective study with genetic analysis. Although seven cases died over a 5-year period, only 43% of them had a confirmed diagnosis. Despite the clinical profile, the laboratory, and the imaging studies that
could be made due to the refusal by the patients' relatives. Unfortunately, Mexican culture is not oriented towards organ donation and post mortem studies. Besides this fact, specialized centers or laboratories where 14.3.3 protein determinations can be carried out are scarce. In Mexico, only one National Institute of Health conducts this type of analysis, which means blood samples have to be analyzed in foreign countries, making studies more expensive for patients, most of whom have low economic resources.This makes it impossible for them to obtain studies that support the CJD diagnosis. A tendency therefore exists to underestimate the real frequency of the disease, thus it may be more common in Mexico than it appears. In effect, the lack of knowledge among the population and among the medical staff of some institutions, as well as different levels of medical attention provided countrywide, may cause this disease not to be consistently diagnosed. This contrasts greatly with what happens in many European countries, where prompt post mortem studies for BSE have been carried out since January 1, 2001.
Fig. 2 Geographical areas of the Mexican Republic where the studied cases were located.
DELEGATIONS OF FEDERAL DISTRICT
GUSTAVO A MADERO 2 CASES
VENUSTIANO CARRANZA 1 CASE
IZTACALCO 1 CASE
COYOACAN 2 CASES
XOCHIMILCO 1 CASE
Table 2 indicates that most of the reported cases applied for medical attention 1-2 months after the appearance of symptoms, due to the limited importance patients give to behavioral and psycho-affective disorders. Early identification of the first symptoms in sporadic CJD, like depression, agitation, irritability, and memory loss, is important for public health reasons and potential timely interventions when treatments become available.34 No similarities were observed among the occupational activities of the studied male patients. Besides this, the fact that most of the female patients were housewives is most probably a reflection of the usual occupation of lowincome Mexican women. Forty-seven percent of the cases died, and the available information indicates that the elapsed time from the initiation of symptoms and the patient's death is short - less than a year - indicating the damaging and aggressive impact of this disease. In spite of the fact that CJD is sporadic and its frequency of appearance is relatively low, it is necessary to make patients and their relatives aware of the importance of brain donation, to be able to reach more precise diagnoses and avoid many of these cases being classified either as probable or possible. Information about TSE must be widespread, particularly that concerning CJD; epidemiological surveillance and diagnostic systems must be established, so that more precise data concerning the incidence of these diseases are available, allowing for stricter control and prevention to be imposed. The training process should be enriched by increasing the number of autopsies performed in the NINN. From 1998 onwards, an institutional autopsy program has been established; however, proven cases of dementia including prion diseases are still low.35 It is necessary to increase the study of prion diseases by including autopsies as an integral part of medical education programs, along with a participating academic committee that should promote, assess, and evaluate the results obtained.
REFERENCES
snip...end...TSS
2007 Japanese Society of Neuropathology
http://www.blackwell-synergy.com/doi/abs/10.1111/j.1440-1789.2007.00807.x
PLEASE NOTE ABOVE CJD MEXICO ''The youngest patient was 23 years old,''... TSS
Cases of atypical BSE have only been found in countries having implemented large active surveillance programs. As of 1st September 2007, 36 cases (16 H, 20 L) have been described all over the world in cattle: Belgium (1 L) [23], Canada (1 H)15, Denmark (1 L)16, France (8 H, 6 L)17, Germany (1 H, 1 L) [13], Italy (3 L)18, Japan (1 L) [71], Netherlands (1 H, 2 L)19, Poland (1 H, 6 L)20, Sweden (1 H)21, United Kingdom (1 H)22, and USA (2 H)23. Another H-type case has been found in a 19 year old miniature zebu in a zoological park in Switzerland [56]. It is noteworthy that atypical cases have been found in countries that did not experience classical BSE so far, like Sweden, or in which only few cases of classical BSE have been found, like Canada or the USA.
And last but not least, similarities of PrPres between Htype BSE and human prion diseases like CJD or GSS have been put forward [10], as well as between L-type BSE and CJD [17]. These findings raise questions about the origin and inter species transmission of these prion diseases that were discovered through the BSE active surveillance.
full text 18 pages ;
http://www.vetres.org/index.php?option=article&access=standard&Itemid=129&url=/articles/vetres/pdf/2008/04/v07232.pdf
USDA Food Safety & Inspection Service
Freedom of Information Act Requests received: February 1, 2008 to February 29, 2008
http://www.fsis.usda.gov/PDF/FOIA_Requests_0208.pdf
Thursday, April 24, 2008 RE-FOIA OF DECLARATION OF EXTRAORDINARY EMERGENCY BECAUSE OF AN ATYPICAL T.S.E. OF FOREIGN ORIGIN IN THE UNITED STATES [Docket No. 00-072-1]
http://foiamadsheepmadrivervalley.blogspot.com/2008/04/re-foia-of-declaration-of-extraordinary.html
SEAC Draft minutes of the 100th meeting held on 25th April 2008
http://seac992007.blogspot.com/2008/07/seac-draft-minutes-of-100th-meeting.html
Friday, July 18, 2008 TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from TSE infected flocks intended for human consumption
http://nor-98.blogspot.com/2008/07/tse-risk-assessment-from-carcasses-of.html
Tuesday, June 3, 2008
SCRAPIE USA UPDATE JUNE 2008 NOR-98 REPORTED PA
http://nor-98.blogspot.com/2008/06/scrapie-usa-update-june-2008-nor-98.html
Tuesday, June 3, 2008 SCRAPIE USA UPDATE JUNE 2008 NOR-98 REPORTED PA
http://nor-98.blogspot.com/2008/06/scrapie-usa-update-june-2008-nor-98.html
Thursday, April 03, 2008 A prion disease of cervids: Chronic wasting disease 2008
1: Vet Res. 2008 Apr 3;39(4):41
http://chronic-wasting-disease.blogspot.com/2008/04/prion-disease-of-cervids-chronic.html
Transmissible Mink Encephalopathy TME
http://transmissible-mink-encephalopathy.blogspot.com/
Published online before print January 2, 2008, 10.1073/pnas.0710824105 PNAS January 8, 2008 vol. 105 no. 1 11-12
COMMENTARY
Unraveling prion strains with cell biology and organic chemistry
Adriano Aguzzi*
Institute of Neuropathology, UniversitätsSpital Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland
Prions are the infectious agents causing transmissible spongiform encephalopathies (TSEs), which comprise human Creutzfeldt-Jakob disease (CJD), scrapie of sheep, bovine spongiform encephalopathy (BSE), and several other rare ailments of various species. According to the protein-only hypothesis (1), prions are composed solely of PrPSc, a misfolded form of the cellular protein PrPC. PrPSc typically forms highly ordered fibrillary aggregates, also termed "amyloid." The term "prion strain" denotes individual prion isolates sharing the same PrP sequence but giving rise to distinct, stable disease traits with different incubation periods and lesion profiles upon serial transmission in congenic hosts. The propagation of different strains in mice congenic with respect to their Prnp allelotypes is difficult to explain by the protein-only hypothesis because the epigenetic strain characteristics of prions appear to dominate over the primary prion protein sequence of the infected host (2, 3).
Circumstantial evidence suggests that strain phenotypes are encoded by distinct conformations of PrPSc (Fig. 1). This was first implied by experiments showing that distinct strains of transmissible mink encephalopathy went along with different protease-exposed sites within PrPSc (4). Great strides have been made since then, yet the final proof that conformational variants of PrPSc represent the biological basis of mammalian prion strains is still elusive. Distinct prion strains may bear highly divergent risks of transmission to humans: Sheep scrapie-derived strains may be mostly innocuous, whereas BSE-derived strains appear to induce variant CJD (vCJD) in humans. Also, two subtypes . . .see full text ;
http://www.pnas.org/cgi/content/extract/105/1/11?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=prion&searchid=1&FIRSTINDEX=0&volume=105&issue=1&resourcetype=HWCIT
MAD COW DISEASE terminology UK c-BSE (typical), atypical BSE H or L, and or Italian L-BASE
http://bse-atypical.blogspot.com/2008/03/mad-cow-disease-terminology-uk-c-bse.html
Manuscript Draft Manuscript Number: Title: HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory Article Type: Personal View Corresponding Author: Mr. Terry S. Singeltary, Corresponding Author's Institution: na First Author: Terry S Singeltary, none Order of Authors: Terry S Singeltary, none; Terry S. Singeltary Abstract: TSEs have been rampant in the USA for decades in many species, and they all have been rendered and fed back to animals for human/animal consumption. I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2007.
http://www.regulations.gov/fdmspublic/ContentViewer?objectId=090000648027c28e&disposition=attachment&contentType=pdf
http://cjdmadcowbaseoct2007.blogspot.com/2008/06/human-and-animal-tse-classifications-ie.html
REPORT ON THE INVESTIGATION OF THE TWELFTH CASE OF BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) IN CANADA Thursday, July 31, 2008
http://madcowtesting.blogspot.com/2008/07/report-on-investigation-of-twelfth-case.html
Please remember, the last two mad cows documented in the USA i.e. Alabama and Texas, both were of the 'atypical' BSE strain, and immediately after that, the USDA shut down the testing from 470,000 to 40,000 in the U.S. in 2007 out of about 35 million cattle slaughtered. also, science is showing that some of these atypical cases are more virulent to humans than the typical UK BSE strain ;
***Atypical forms of BSE have emerged which, although rare, appear to be more virulent than the classical BSE that causes vCJD.***
Progress Report from the National Prion Disease Pathology Surveillance Center
An Update from Stephen M. Sergay, MB, BCh & Pierluigi Gambetti, MD
April 3, 2008
http://www.aan.com/news/?event=read&article_id=4397&page=72.45.45
In this context, a word is in order about the US testing program. After the discovery of the first (imported) cow in 2003, the magnitude of testing was much increased, reaching a level of >400,000 tests in 2005 (Figure 4). Neither of the 2 more recently indigenously infected older animals with nonspecific clinical features would have been detected without such testing, and neither would have been identified as atypical without confirmatory Western blots. Despite these facts, surveillance has now been decimated to 40,000 annual tests (USDA news release no. 0255.06, July 20, 2006) and invites the accusation that the United States will never know the true status of its involvement with BSE.
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
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518