UK infected blood inquiry releases compensation report
Compensation for thousands of people given contaminated blood and blood products must be widened, the inquiry has said.
Jacqui Thornton reports. Before the start of the UK’s Infected Blood Inquiry in 2018, the Chair, Sir Brian Langstaff, held a welcoming event for the main participants at Church House, Westminster, in central London, UK. Most were completely unfamiliar with the formality of a public inquiry and were likely to be overwhelmed by what was to come. It was an early sign of Langstaff’s humanity and compassion, which has continued in his 4·5-year stewardship.
During the luncheon, Langstaff, a former High Court judge, mingled with the guests and met Perry Evans, then aged 57 years, who had contracted HIV and hepatitis C after receiving infected factor VIII for his moderate haemophilia while he was a teenager. Evans shook his hand and, with trademark dry humour, told Langstaff: “Thank you for taking this on. Please stay alive.”
This statement was a tragicomic remark from Evans, who was, in reality, concerned that a number of witnesses might die during the course of the lengthy investigation, before giving evidence. In fact, The Haemophilia Society now believes that more than 500 people have died since the inquiry was announced.
The scandal, which has been called the biggest treatment disaster in the UK National Health Service history, involves men, women, and children who were given contaminated blood and blood products in the 1970s–80s; these products were imported from the USA from high-risk paid donors such as people in prison and drug users. Tens of thousands of individuals were infected, and more than 3000 people are believed to have died after acquiring HIV or hepatitis C, with five people dying from variant Creutzfeldt-Jakob disease.
Now, 6 years on from the announcement of the inquiry, and 2 months after the last evidence was submitted, Langstaff has, unusually, issued recommendations to the UK Government on compensation, ahead of his final report, which is due to be published in the autumn. He has done so because he considers speed is of the essence. In a video statement, played at the announcement of his recommendations at the Infected Blood Inquiry headquarters in London on April 5 he said: “I could not in conscience add to the decades-long delays many of you have already experienced due to failures to recognise the depth of your losses.” In an earlier report on compensation (released July, 2022), Langstaff had recommended giving an interim payment of £100000 to 4000 infected people and bereaved partners, which was then actioned in October.
Now, Langstaff has said that interim compensation should be extended to previously unrecognised deaths—to parents who lost their children, and to children who were orphaned when their parents died—to immediately alleviate their suffering too. He said around 380 children with bleeding disorders were infected with HIV and more than half have died.
Langstaff said that a longer term compensation scheme with “appropriate redress for all who have been wronged” should be set up as soon as possible, and definitely before the publication of his final report in the autumn, suggesting that it should be run by a body independent of government. Everyone infected and affected should be eligible, including siblings and carers, with five awards considering five areas: injury impact, social impact, autonomy, care, and financial loss.
Langstaff said: “It will clearly take political will to act quickly, but the circumstances here warrant it.” He also called for a bespoke psychological service in England for survivors and relatives, which does not currently exist, unlike in Northern Ireland, Scotland, and Wales. His new report goes further than the framework for compensation produced by Sir Robert Francis. The new report says that people with chronic hepatitis B infection from contaminated blood should be included, and that there should be no fixed and definitive rule to exclude hepatitis C infections after September, 1991, when screening of blood for hepatitis C virus was introduced.
Langstaff said wrongs were done at the “individual, collective, and systemic levels” and that in his judgement “not only do the infections themselves and their consequences merit compensation, but so too do the wrongs done by authority, whose response served to compound people’s suffering”.
The recommendations have been welcomed by witnesses, campaigners, and specialist medical groups. Jefferson Courtney, Policy and Public Affairs Manager at the Haemophilia Society said it was a “clear blueprint” for the Government to pay compensation, which should happen as soon as possible. Samantha May, Information and Support Service Manager at the Hepatitis C Trust, was “really delighted” that the bulk of the recommendations by Sir Robert Francis have been accepted and expanded. Josh Wright, President of the British Society for Haematology, welcomed Langstaff’s latest report, which acknowledged the severe harms caused. He said: “We expect the full report of the inquiry to detail all the lessons that we can learn…This will be important reading for all health-care professionals.”
Rosemary Calder, whose son died in 1999, aged 25 years, after he was infected with HIV, will not receive an interim payment because his widow has already received an interim £100000 payment. However, she says the extension of compensation in the longer-term scheme is significant. “Compensation is the only way of getting some form of contrition from the Government, which let them down so badly.”
Adam Jones, a Physiologist and Senior Lecturer in Bioscience at the University of Sunderland was inspired to pursue his career after his personal experience. He was infected with hepatitis B when he was aged 2 years and hepatitis C when he was 3 or 4, but did not find out until he was 23 years. Although his head was “spinning” from the detailed report, he said he was encouraged by the fact that Langstaff accepted that there are more people affected and infected than the Government has ever been willing to admit or acknowledge. It was made clear right from the start that people were at the heart of the inquiry—the witness positioned at the centre of the hearing room, the public at the front, and the lawyers and Chair to the side.
The evidence was staged in order: first were the infected and affected people, who were divided into two groups—people with bleeding disorders who received infected blood clotting factor, and people who received blood transfusions for conditions such as anaemia and haemorrhaging during surgery or childbirth.
Medical professionals gave evidence next, followed by civil servants, and politicians. The public hearing covered five decades and all four countries of the UK. Expert groups on medical ethics, health economics, psychosocial impact, statistics, fractionation, public health, and administration were convened, including a clinical group with 28 clinicians of varying specialties. As many as 100000 documents have been reviewed, comprising 750000 pages of material, including 4000 statements from infected and affected people, and a further 1200 statements from other witnesses, including doctors, politicians, civil servants, and employees of pharmaceutical companies. Oral testimony was heard from 370 witnesses. The work involved in the 4·5-year public hearing was not a marathon, but “a series of ultramarathons” for the inquiry legal team, one barrister said.
Allyson Pollock, Clinical Professor of Public Health at Newcastle University, Honorary Professor at University College London, and a member of the public health and administration expert group, told The Lancet that a no-fault compensation scheme (which has also been considered by the inquiry) along the lines of New Zealand would have been a better and swifter system for the UK. She said: “This infected blood inquiry has demonstrated just how incredibly expensive it is when the public health system fails and also how long it takes for the wheels of justice to turn. It should not have taken decades for the victims and their families to have their say—let alone compensation. A nofault compensation scheme…would not require enormously expensive judge-led inquiries and prevent huge legal costs and lengthy delays.”
However, for many of the infected and affected people, being able to hear the evidence, although shocking at times, was helpful, as was the camaraderie of meeting other people with similar experiences. Susan Wathen, a former primary school teacher, who was infected with hepatitis C after transfusions for anaemia, said she came to the inquiry as much as she could; she made lifelong friends, as previously she knew no one else in her position.
When examining the allegations in 2023, it sounds quite unbelievable: some doctors gave blood and blood products to people with haemophilia and other conditions allegedly knowing they might be infected with HIV and hepatitis C virus; patients were tested for these conditions without knowing; and, most amazingly, some doctors did not tell patients or their parents, often for years, that they were positive.
One of the UK’s leading haematologists at the time, Arthur Bloom, who died aged 62 years in 1992, was Director of the Cardiff Haemophilia Centre. He has been named by a number of families giving evidence to the inquiry, some of whom have alleged that he failed to tell patients about the risks of the treatments they were given. During the inquiry, a bust of Bloom was removed from the haemophilia centre at University Hospital of Wales in Cardiff by the Cardiff and Vale University health board.
In her closing speech to the inquiry the Haemophilia Society’s barrister Katie Gollop highlighted evidence that Bloom, who was Chair of The United Kingdom Haemophilia Centre Doctors’ Organisation and an adviser to the Government, had downplayed warnings from US specialists on the risk of HIV/AIDS for patients with haemophilia. She said perhaps because he was Chair, he was asked to “sit on almost every other committee and had a finger in almost every other blood products pie, and we see the damage that that over-reliance on one single individual caused”.
In “truly shocking evidence”, according to the inquiry barrister, 72 boys aged 8–18 years at a specialist boarding school for people with haemophilia (Lord Mayor Treloar College in Hampshire, UK) died after receiving infected pooled factor VIII. The Headmaster accepted the doctors were “experimenting”. One former pupil told the inquiry: “We were ill because of a treatment which was supposed to enhance our lives, but it was killing us.” Other evidence described previously untreated patients as ideal individuals on whom to carry out research and as cheaper than chimpanzees. Heather Evans, wife of Perry Evans, listened to much of the evidence and, after the closing speeches, she felt she had been “groomed”. “I believed the lies. I believed that factor VIII was a great product, the best product. We’d been told that cryoprecipitate was out of date, expensive, and cumbersome. And that was not the truth”, she said.
In the interim report, Langstaff singled out four former UK Health Ministers, who he indicated had understood the ramifications of what had happened, and the personal consequences. Other politicians have caused some eye-opening moments as witnesses to the inquiry. Sir John Major, the former UK Prime Minister from 1990 to 1997, attracted strong criticism when he described what had happened to infected people as “incredibly bad luck”. Lord Kenneth Clarke, former UK Health Minister from 1982 to 1985, was widely derided for his irritation at the detailed questioning.
There have been previous inquiries into the scandal, notably The Archer Inquiry in 2009, which was not statutory and therefore could not compel witnesses to give evidence, and The Penrose Inquiry in 2015, which regarded Scotland, but was considered a whitewash. Langstaff’s inquiry was the first UK-wide inquiry to compel witnesses, although the Government has the final say on what actions to take, which is the next hurdle for campaigners. One campaigner said: “As we have seen over the last 40 years, they could do nothing, as they are not compelled to. Whatever happens could be 1–2 years from now.” Responding to the report on April 5, a Government spokesperson accepted the scandal should never have happened, and said the Government was continuing preparations for responding to the final report when published.
As with all campaigns involving different groups and perspectives, the range of opinions on the subject and desired outcome is wide— some are extremely angry, others more moderate. Some people are already pursuing civil legal action, and believe there should be criminal prosecutions as happened in France, where the former Prime Minister Laurent Fabius went on trial but was acquitted of manslaughter in 1999. Michel Garretta, the Director of the National Blood Centre, was jailed for fraud in a separate trial in 1992. Other people believe that being listened to and really heard, with everything documented and written down, and establishing legislation to prevent these events from happening again are more important.
Jones said the report will go a long way to help the community feel that they have been listened to and taken seriously. He believes that money is a side issue: “For some people, no amount is ever enough, not because they want to be rich but they view the amount that they get as a gesture of punishment towards the perpetrators. For others the compensation is a symbol of acceptance of guilt and reparation. For a third group, it’s for the simple replacement of things, helping them to get back onto an even keel. The most important thing for them all is justice.”
The Hepatitis C Trust believes education is also key, with increased awareness needed in the medical world of undiagnosed cases of hepatitis C from transfusions. May said that just last week a woman rang the charity’s helpline to seek help after discovering that she had been infected with hepatitis C in the 1970s, but has only just been diagnosed. She now has liver cirrhosis. “How many people are still out there? Now’s the time to find them. There’s huge ignorance about how hep C is transmitted, even amongst GPs”, May said.
Wathen, who had multiple blood transfusions in the 1990s, but was only diagnosed in 2014, agrees: “My GP never joined the dots. I was finally diagnosed by a young locum doctor. When I asked for a second test to confirm, my consultant exclaimed ‘you won’t have that’. But I did. Those words will live with me. My message to doctors is this: ‘If someone has symptoms that don’t add up, ask if they have had a blood transfusion and do a blood test.’”
What all the participants agree is needed is a meaningful apology, drawing a line in the sand, thus ending their feeling of persecution. Evans, who, after that meeting with Langstaff, turned out to be a key witness giving evidence on day 1, says the final inquiry report should do that job. This interim report, he thinks, is very thorough, typical of Langstaff’s forensic, but human, way of working. “People will remember these recommendations.” Until a meaningful apology comes, Evans says he is getting on with his life. “I’m not sitting around waiting. I’ve seen it too often, that it just takes over your life. I’ve got life to live. Yes, I’m infected, but then lots of people are infected with lots of other things, like cancer. I’ve been given a heads up. I shouldn’t be here. But I am here. So, carry on.”
Jacqui Thornton
In my opinion, i believe it is incredibly blind to ignore the many different variants, of the many different TSE Prion disease, in the many different species to date, and the list is still growing, especially with chronic wasting disease of cervid, all of which have been exposed to humans, that continue to give blood. This is extremely concerning to me. By the time science and politics makes the call that CWD in cervid is transmissible to humans (when the science today is so convincing), so many humans that give blood will have been exposed to CWD in cervid needlessly, either by consumption, or friendly fire i.e. iatrogenic, it will be futile by then to issue any kind of blood ban. imo, it's only by the Grace of God that blood tainted with nvCJD has only been documented to be transmitted to so few, to date. sporadic CJD, 85%+ of all human TSE Prion disease, no known/documented cause to date, but remember, all iatrogenic cjd is, is sporadic cjd, before the iatrogenic event is discovered, traced back, proven, documented, put into the academic domain, and then finally the public domain, this very seldom happens, thus problem solved, it's all sporadic cjd. what might CWD zoonosis from an iatrogenic event via blood, what if? IT's just so foolish to continue to repeat the same mistakes over and over again with Transmissible Spongiform Encephalopathy TSE prion disease, imo...terry
PLoS One. 2020; 15(8): e0237410.
Published online 2020 Aug 20. doi: 10.1371/journal.pone.0237410
PMCID: PMC7446902
PMID: 32817706
Very low oral exposure to prions of brain or saliva origin can transmit chronic wasting disease
Nathaniel D. Denkers, Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing – review & editing,#1 Clare E. Hoover, Conceptualization, Data curation, Investigation, Writing – original draft, Writing – review & editing,#2 Kristen A. Davenport, Conceptualization, Data curation, Investigation, Writing – review & editing,3 Davin M. Henderson, Conceptualization, Data curation, Investigation, Methodology,1 Erin E. McNulty, Data curation, Investigation, Methodology, Writing – review & editing,1 Amy V. Nalls, Conceptualization, Investigation, Methodology, Writing – review & editing,1 Candace K. Mathiason, Conceptualization, Funding acquisition, Investigation, Supervision, Writing – review & editing,1 and Edward A. Hoover, Conceptualization, Data curation, Funding acquisition, Supervision, Writing – review & editing1,* Byron Caughey, Editor
Author information Article notes Copyright and License information Disclaimer
This article has been corrected. See PLoS One. 2021 June 10; 16(6): e0253356.
Associated Data
Abstract
The minimum infectious dose required to induce CWD infection in cervids remains unknown, as does whether peripherally shed prions and/or multiple low dose exposures are important factors in CWD transmission. With the goal of better understand CWD infection in nature, we studied oral exposures of deer to very low doses of CWD prions and also examined whether the frequency of exposure or prion source may influence infection and pathogenesis. We orally inoculated white-tailed deer with either single or multiple divided doses of prions of brain or saliva origin and monitored infection by serial longitudinal tissue biopsies spanning over two years. We report that oral exposure to as little as 300 nanograms (ng) of CWD-positive brain or to saliva containing seeding activity equivalent to 300 ng of CWD-positive brain, were sufficient to transmit CWD disease. This was true whether the inoculum was administered as a single bolus or divided as three weekly 100 ng exposures. However, when the 300 ng total dose was apportioned as 10, 30 ng doses delivered over 12 weeks, no infection occurred. While low-dose exposures to prions of brain or saliva origin prolonged the time from inoculation to first detection of infection, once infection was established, we observed no differences in disease pathogenesis. These studies suggest that the CWD minimum infectious dose approximates 100 to 300 ng CWD-positive brain (or saliva equivalent), and that CWD infection appears to conform more with a threshold than a cumulative dose dynamic.
snip...
Discussion As CWD expands across North America and Scandinavia, how this disease is transmitted so efficiently remains unclear, given the low concentrations of prions shed in secretions and excretions [13, 14]. The present studies demonstrated that a single oral exposure to as little as 300nmg of CWD-positive brain or equivalent saliva can initiate infection in 100% of exposed white-tailed deer. However, distributing this dose as 10, 30 ng exposures failed to induce infection. Overall, these results suggest that the minimum oral infectious exposure approaches 100 to 300 ng of CWD-positive brain equivalent. These dynamics also invite speculation as to whether potential infection co-factors, such as particle binding [46, 47] or compromises in mucosal integrity may influence infection susceptibility, as suggested from two studies in rodent models [48, 49].
Few studies in rodent models have explored oral infection with murine or hamster adapted scrapie by assessing the same total dose administered as a single bolus vs. the same bolus divided into fractional, sequential exposures [50–52]. The results reported by Diringer et al. [50] and Jacquemot et al. [52] have indicated that divided-dose exposures were as effective as a single bolus only if the interval between doses was short (1–2 days). In deer, we likewise found that when a total dose of 300 ng of brain was administered as 10 doses divided doses over 12 weeks this exposure failed to induce CWD infection, whereas three weekly 100 ng doses (300 ng total) induced infection. While this latter outcome may have involved an additive dynamic, we cannot exclude that a dose 100 ng alone also may have been sufficient to establish infection. Our conclusions here are unfortunately limited by the absence of a single 100 ng dose group. Additional experiments are needed to further directly compare single vs. divided exposures to strengthen the tenet that establishment of CWD infection is more a threshold than cumulative dose phenomenon.
We also sought to examine a relatively unexamined possibility that prions emanating from different tissues and/or cells may possess different capacities to establish infections by mucosal routes. Our results indicated that brain and saliva inocula containing similar levels of prion seeding activity, also had similar infectivity, which did not support our hypothesis that saliva prions may be more infectious by mucosal routes. There are of course, several caveats bearing on this conclusion. These could include: the inherent limits in using an in vitro seeding assay as a surrogate to equate in vivo infectivity, the likelihood that small differences in prion susceptibility among deer may be more significant at very low exposure doses, and the greater variation of inoculum uptake and routing through mucosal surfaces associated with the oral route of exposure.
The chief correlate we observed between magnitude of infectious dose and disease course was in time from exposure to first detected amplification of prions in tonsil, an event which is closely followed by or concurrent with detection in pharyngeal lymph nodes [41]. Once a threshold dose was established, the subsequent pathogenesis of infection and disease appeared to vary little.
In addition to potential cofactors that could influence CWD infectivity, such as particle binding [47] and compromised mucosal integrity [48, 53], there is PRNP genotype, in which polymorphisms at codon 96 of the white-tailed deer are known to affect the temporal dynamics of CWD infections [23, 41, 45]. In the present studies, most cohorts of 96GG deer became CWD-positive before 96GS animals in the same exposure group [cohorts 1, 2, 4, 6]. Thus, the low dose studies are consistent with the current concept of delayed conversion rate in PRNP 96GS vs. 96GG white-tailed deer [44].
In conclusion, we have attempted to model and better understand CWD infection relative to natural exposure. The results demonstrate: (a) that the minimum CWD oral infectious dose is vastly lower than historical studies used to establish infection; (b) that a direct relationship exists between dose and incubation time to first prion replication detection in tonsils, irrespective of genotype; (c) that a difference was not discernible between brain vs. saliva source prions in ability to establish infection or in resultant disease course; and (d) that the CWD infection process appears to conform more to a threshold dose than an accumulative dose dynamic.
Document (FDA-2012-D-0307-0011)
Recommendations to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Components; Draft Guidance for Industry Draft Guidance for Industry.
Comment from Terry Singeltary
Posted by the Food and Drug Administration on Feb 2, 2020
Greetings FDA et al,
I would again kindly like to comment on Docket Number: FDA-2012-D-0307, Docket Number: FDA-2012-D-0307 Recommendations to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Components; Draft Guidance for Industry Draft Guidance for Industry.
I still believe, that it is extremely dangerous to continue to base the safety of blood from the TSE Prion, by only believing the nvcjd only theory.
TSE Prion disease have expanded to other species i.e. the camel, and we now know that cwd and scrapie will transmit to pigs by oral routes.
Chronic Wasting Disease CWD TSE Prion in cervid has exploded across the USA, Canada, Mexico has now clue, Norway, Sweden, Finland, S. Korea, and we know that cwd is detected in the blood of cervid. CWD TSE Prion is highly infectious, and the risk factors from blood there from are very real.
we also know that all iatrogenic CJD is, is sporadic CJD, until the iatrogenic event is discovered, traced back, proven, documented in the academic domain, and finally the public domain, which very seldom happens due to lack of trace back efforts, thus, all iatrogeic events stay as sporadic cjd.
with the blood of cervid and cwd tse prion being detected there from, the science showing that cwd zoonotic potential is now real, the many different strains of cwd to date, with no real factor of how many different strains there are, with science now showing that indeed BSE, Scrapie, and CWD, both typical and atypical strains, showing scientific links to sporadic cjd, and that cwd in humans would would NOT look like nvcjd, but science shows that it would look like sporadic cjd, therefore, iatrogenic cjd from human cwd exposure is very real threat, i find these weakening of rules for blood risk factors from all the different strains of sporadic cjd very worrisome, especially now that officials are classifying vpspr, sgss, sffi, as sporadic cjd cases. we have no clue whether or not these are from iatrogenic events or not. this will be a foolish move if we put once again, corporate interest over human and animal health, but does not surprise me.
THIS will be very dangerous, and a foolish move for people who need blood, and for the medical and surgical theaters, and humans there from, and simply are not based on sound science imo, but are based on corporate greed.
WE KNOW now that the real statistics on human TSE Prion IS NOT one in a million, but data now shows that sporadic CJD, 85%+ of all human TSE Prion, the read statistics now show that those figures are one in 5,000. and sporadic cjd is NOT a single strain, but many, many, different strains, and the routes and sources are simply unknown.
NO WHERE IN SCIENCE LITERATURE HAS THE SPONTANEOUS CJD EVER BEEN PROVEN, without route and source, a happenstance of bad luck, this is simply wishful thinking$
TO weaken, instead of enhance and strengthen the risk of sporadic CJD tse prion from blood products by this Docket Number FDA-2012-D-0307 Recommendations, will only enhance the risk of TSE Prion to hemophiliacs, the medical and surgical arenas around the globe
yes, human tse prion are now 1 in 5,000. let that sink in.
Thursday, June 3, 2021
CWD TSE PRION ZOONOSIS TRANSMISSION TO HUMANS BY BLOOD TRANSFUSION, iatrogenic CJD, WHAT IF?
some history of my concerns of blood and TSE PrP...terry
The Lancet 2006; 368:2061-2067
DOI:10.1016/S0140-6736(06)69835-8
Articles
Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt-Jakob disease associated with blood transfusion: a case report
Stephen J Wroe FRCP a b, Suvankar Pal MRCP a b, Durrenajaf Siddique MRCP a b, Harpreet Hyare FRCR a b, Rebecca Macfarlane MRCS a b, Susan Joiner MSc b, Jacqueline M Linehan BSc b, Sebastian Brandner MRCPath b, Jonathan DF Wadsworth PhD b, Patricia Hewitt FRCPath c and Prof John Collinge FRS a b
Concerns have been raised that variant Creutzfeldt-Jakob disease (vCJD) might be transmissible by blood transfusion. Two cases of prion infection in a group of known recipients of transfusion from donors who subsequently developed vCJD were identified post-mortem and reported in 2004. Another patient from this at-risk group developed neurological signs and was referred to the National Prion Clinic.
Methods
The patient was admitted for investigation and details of blood transfusion history were obtained from the National Blood Service and Health Protection Agency; after diagnosis of vCJD, the patient was enrolled into the MRC PRION-1 trial. When the patient died, brain and tonsil tissue were obtained at autopsy and assessed for the presence of disease-related PrP by immunoblotting and immunohistochemistry.
Findings
A clinical diagnosis of probable vCJD was made; tonsil biopsy was not done. The patient received experimental therapy with quinacrine, but deteriorated and died after a clinical course typical of vCJD. Autopsy confirmed the diagnosis and showed prion infection of the tonsils.
Interpretation
This case of transfusion-associated vCJD infection, identified ante-mortem, is the third instance from a group of 23 known recipients who survived at least 5 years after receiving a transfusion from donors who subsequently developed vCJD. The risk to the remaining recipients of such transfusions is probably high, and these patients should be offered specialist follow-up and investigation. Tonsil biopsy will allow early and pre-symptomatic diagnosis in other iatrogenically exposed individuals at high risk, as in those with primary infection with bovine spongiform encephalopathy prions.
Affiliations
a. National Prion Clinic, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK b. MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK c. National Blood Service, London, UK
Correspondence to: Prof John Collinge
TSS
#################### https://lists.aegee.org/bse-l.html ####################
MEDICAL IMPLANTS CONTAINING BOVINE MATERIAL
see new url link;
----- Original Message -----
From: Terry S. Singeltary Sr.
To: FREAS@CBER.FDA.GOV
Cc: william.freas@fda.hhs.gov ; rosanna.harvey@fda.hhs.gov
Sent: Friday, December 01, 2006 2:59 PM Subject: Re: TSE advisory committee for the meeting December 15, 2006 [TSS SUBMISSION PART III]
Lancet Neurology DOI:10.1016/S1474-4422(06)70413-6
Predicting susceptibility and incubation time of human-to-human transmission of vCJD
MT Bishop a, P Hart b, L Aitchison b, HN Baybutt b, C Plinston b, V Thomson b, NL Tuzi b, MW Head a, JW Ironside a, RG Will a and JC Manson b
Summary Background Identification of possible transmission of variant Creutzfeldt-Jakob disease (vCJD) via blood transfusion has caused concern over spread of the disease within the human population. We aimed to model iatrogenic spread to enable a comparison of transmission efficiencies of vCJD and bovine spongiform encephalopathy (BSE) and an assessment of the effect of the codon-129 polymorphism on human susceptibility.
Methods Mice were produced to express human or bovine prion protein (PrP) by direct replacement of the mouse PrP gene. Since the human PrP gene has variation at codon 129, with MM, VV, and MV genotypes, three inbred lines with an identical genetic background were produced to express human PrP with the codon-129 MM, MV, and VV genotypes. Mice were inoculated with BSE or vCJD and assessed for clinical and pathological signs of disease.
Findings BSE was transmitted to the bovine line but did not transmit to the human lines. By contrast, vCJD was transmitted to all three human lines with different pathological characteristics for each genotype and a gradation of transmission efficiency from MM to MV to VV.
Interpretation Transmission of BSE to human beings is probably restricted by the presence of a significant species barrier. However, there seems to be a substantially reduced barrier for human-to-human transmission of vCJD. Moreover, all individuals, irrespective of codon-129 genotype, could be susceptible to secondary transmission of vCJD through routes such as blood transfusion. A lengthy preclinical disease is predicted by these models, which may represent a risk for further disease transmission and thus a significant public-health issue.
Affiliations
a. National CJD Surveillance Unit, Bryan Matthews Building, Western General Hospital, Edinburgh, UK b. Institute for Animal Health, Neuropathogenesis Unit, King's Buildings, Edinburgh, UK
Correspondence to: Prof J C Manson, Institute for Animal Health, Neuropathogenesis Unit, Ogston Building, King's Buildings, West Mains Road, Edinburgh EH9 3JF, UK
snip...
Discussion
Although the cattle BSE epidemic in the UK has amounted to more than 180 000 cases since the 1980s, the extent of the human vCJD epidemic has so far remained limited with the total number of cases worldwide currently at 190. One explanation for this apparent discrepancy is that there exists a significant species barrier between cattle and human beings, which limits the susceptibility of the human population to BSE. The data shown here suggest that this could indeed be the case since BSE was readily transmissible to the bovine transgenic mice but not to the human transgenic mice. However, once BSE has passed through human beings in the form of vCJD, the transmissibility of this TSE strain is altered for the human population.
All the human transgenic lines inoculated with BSE were negative for TSE transmission, which suggests that either the human transgenic lines are relatively resistant to transmission of BSE or the incubation time is longer than the length of the experiment (approximately 700 days). BSE transmission previously observed by others, in human transgenic lines overexpressing the human prion protein, could be due to overexpression of the PrP gene and may not therefore give a true reflection of the species barrier between BSE and human beings.15,25,26 This apparent resistance of human transgenic mice to BSE could be explained by a large species barrier and this in turn could explain the low number of vCJD cases in the human population.
vCJD was transmitted to all three human lines with different pathological characteristics for each genotype, and a gradation of transmission efficiency from MM to MV to VV. The greater transmission efficiency in HuMM mice suggests that homozygosity for methionine at codon 129 leads to earlier onset of TSE-related pathological features and clinical disease than for the other two genotypes. The differences in PrPSc deposition in the HuMM and HuMV lines suggest that the codon- 129 polymorphism in human beings is likely to affect the distribution of PrPSc deposition in the brain. Moreover, the similar numbers that scored positive for PrP deposition in each of the MM and MV groups (11/15 and 11/13 respectively) suggest that the two genotypes might be equally susceptible to vCJD, but with different incubation periods. Titration experiments are needed to fully compare the susceptibility of each line. The single HuVV mouse positive for PrPSc shows that VV individuals may be susceptible to vCJD with very long incubation times, including a lengthy subclinical phase. Transmission studies from all three genotype mice are now underway to examine the infectious nature of the disease and determine any alterations in the strain characteristics on passage through human transgenic mice. By contrast with published data suggesting that VV individuals cannot propagate the vCJD biochemical phenotype,15 the data presented here suggest that the
PrPSc type will remain a useful diagnostic feature of secondary vCJD infection irrespective of codon-129 genotype, as has been observed for the two extant cases of transfusion-associated vCJD infection. 5,27
Transmission of vCJD to the three lines of human transgenic mice indicates that the human population could be at significantly heightened risk of developing disease after iatrogenic exposure to vCJD. Secondary transmission of vCJD has partly removed the cattle-to- human species barrier and has resulted in an agent that can be transmitted from human to human with relative efficiency. Transmission studies in cynomolgus macaques provide further evidence for this agent adaptation as they show reduction in incubation times after serial passage of BSE.28 Our BSE inoculation at 10-1 dilution was compared with vCJD inoculation at 10-2 because the latter inoculum was found to be toxic to the mice at 10-1. Use of a higher dose ofvCJD inoculum would have maintained or increased the transmission efficiency of vCJD and enhanced the current findings.
Our findings raise concerns relevant to the possibility of secondary transmission of vCJD through blood transfusion, fractionated blood products, or contaminated surgical instruments. For this study mice were injected intracerebrally, whereas the probable human exposure to these agents is by peripheral routes (eg, oral or intravenous), and thus human-to-human exposures might be significantly less efficient. However, it is difficult to know for sure what the practical implications might be in human beings. Peripheral route challenge is in progress; however, BSE transmission studies in primates have shown the intravenous route to be as efficient as the intracerebral route, with an extension of the incubation time.28
Although all cases of vC]D up to now have been observed in the MM genotype, this model of human-to- human vCJD transmission suggests that other genotypes are also susceptible. In our experimental setting, all PRNP codon-129 genotypes are susceptible to vCJD infection; however, progressive development of pathological TSE features (vacuolation and PrP deposition) is more rapid in the MM-genotype mice. An explanation for this finding might be provided by in-vitro conversion of recombinant human PrP by BSE and vCJD agents, which has shown that PrP with methionine at position 129 is more efficiently converted than PrP with valine, and that conversion by vCJD is significantly more efficient than by BSE.29 Long incubation periods during which PrPSc is deposited predicts that, in human beings, infection could be present in all genotypes for a significant period before clinical onset. Incubation periods of more than 30 years have been reported in the human TSE disease kuru.30
The possibility that an MV or VV genotype could result in a phenotype distinct from that recognised in vCJD draws attention to the importance of systematic assessment of the clinical, genetic, pathological, and
biochemical features of all human prion diseases. Our findings indicate that for human-to-human vCJD infection
it should be assumed that all codon-129 genotype individuals (not just MM) can be infected, that long incubation times can occur, and that a significant level of subclinical disease might be present in the population.
Contributors
MTB, PH, and CP did immunocytochemical and western blot analysis;
JCM, NT, HNB, and LA produced the transgenic mouse lines; JWI supplied vCJD case material and reviewed the neuropathology; VT did the mouse inoculations; and MTB, PH, MWH, RGW, JWI, and JCM prepared the manuscript.
Conflicts of interest
We have no conflicts of interest.
Acknowledgments
snip... end
http://www.thelancet.com/journals/laneur/article/PIIS1474442206704136/abstract?isEOP=true
TSS
----- Original Message -----
From: Terry S. Singeltary Sr.
To: FREAS@CBER.FDA.GOV
Cc: william.freas@fda.hhs.gov ; rosanna.harvey@fda.hhs.gov Sent:
Wednesday, November 29, 2006 1:24 PM
Subject: TSE advisory committee for the meeting December 15, 2006 [TSS SUBMISSION]
November 29, 2006
Greetings FDA, DHH, Dr. Freas, and Dr. Harvey et al,
a kind and warm Holiday Greetings to you all.
i kindly wish to submit the following to the TSE advisory committee for the meeting December 15, 2006, about the assessment for potential exposure to vCJD in human plasma-derived antihemophilic factor (FVIII) products manufactured from U.S. plasma donors and related communication material ;
i see the media picked up on this as a 'low risk', from what the gov. agency perceived to be to them;
however, i seem to disagree. from my primitive ciphering, i see it another way. this is a huge catastrophic risk. 3 in 160 is 1.9%. so call that 2% which is 1 in 50 or twenty per thousand or 20,000 per million. also, what about the mixed genotypes/mixed susceptibility? what about the silent carriers that donated tainted blood? what about the sporadic CJDs of UNKNOWN strain or phenotype? this risk assessment is just more BSe to me. just another in a long line of industry fed crap. i pray that my assessment is the one that is wrong. but it is THEY who roll the dice with your life. it is THEY who refuse to regulate an industry that has run amok. just from a recall aspect of potentially tainted blood, and these are just recent recalls ;
PRODUCT Source Plasma, Recall # B-0054-7 CODE Units: 03MMNC5465, 03MMNC6361, 03MMNC6801, 03MMNC7510, 03MMNC7891, 03MMNC8252, 03MMNC8801, 03MMNC9144, 03MMND1122, 03MMND1478, 03MMND1969, 03MMND2350, 03MMND2825, 03MMND3211, 03MMND3708, 03MMND4072, 03MMND4588, 03MMND4831, 03MMND5320, 03MMND5719, 03MMND6268, 03MMND6683, 03MMND7228, 03MMND7656, 03MMND8211, 03MMND8652, 03MMND9195, 03MMND9618, 03MMNE0628, 03MMNE0884, 03MMNE1597, 03MMNE1979, 03MMNE2644, 03MMNE3064, 03MMNE3707, 03MMNE4122, 03MMNE4750, 03MMNE5080, 03MMNE5876, 03MMNE6218, 03MMNE7189, 03MMNE7587, 03MMNE8027, 03MMNE8645, 03MMNE9029, 03MMNE9641, 03MMNE9979, 03MMNF0491, 03MMNF0685, 03MMNF0937, 03MMNF1260, 04MMNA0351, 04MMNA0707, 04MMNA1241, 04MMNA1650, 04MMNA2291, 04MMNA2646, 04MMNA3340, 04MMNA3719, 04MMNA4312, 04MMNA4683, 04MMNA5298, 04MMNA5750, 04MMNA6407, 04MMNA6816, 04MMNA7482, 04MMNA7915, 04MMNA8632, 04MMNA9076, 04MMNA9723, 04MMNB0063, 04MMNB0696, 04MMNB1100, 04MMNB1845, 04MMNB2285, 04MMNB3035, 04MMNB3485, 04MMNB4213, 04MMNB4672, 04MMNB5841, 04MMNB6652, 04MMNB7162, 04MMNB7930, 04MMNB8453, 04MMNB9239, 04MMNB9747, 04MMNC0456, 04MMNC0931, 04MMNC1578 RECALLING FIRM/MANUFACTURER BioLife Plasma Services, L.P., Mankato, MN, by facsimile on June 4, 2004. Firm initiated recall is complete. REASON Blood products, collected from a donor who was at increased risk for new variant Creutzfeldt-Jakob Disease (nvCJD), were distributed. VOLUME OF PRODUCT IN COMMERCE 89 units DISTRIBUTION CA and Austria
END OF ENFORCEMENT REPORT FOR October 25, 2006
###
http://www.fda.gov/bbs/topics/enforce/2006/ENF00975.html
USA FDA MAD COW BLOOD HUMANS RECALL (these are dime a dozen)
RECALLS AND FIELD CORRECTIONS: BIOLOGICS -- CLASS II
______________________________
PRODUCT Source Plasma, Recall # B-1708-6 CODE Units: MI180733, MI180927, MI181625, MI181780, MI182337, MI182519, MI183140, MI183311, MI183955, MI185006, MI185278, MI185822, MI186081, MI186855, MI187183, MI187903, MI188273, MI188695, MI189257, MI189553, MI190136, MI190473, MI191073, MI191395, MI191972, MI192303, MI193473, MI194343, 04MINA0377, 04MINA0801, 05MINA7147, 05MINA7451, 05MINA8094, 05MINA8504, 05MINA9548, 05MINA9883, 05MINB0489, 05MINB0875, 05MINB1469, 05MINB1874, 05MINB3116, 05MINB7192, 05MINB7529, 05MINB8246, 05MINB8612, 05MINB9236, 05MINB9366, 05MINB9475, 05MINB9641, 05MINC0031, 05MINC0237, 05MINC0336, 05MINC0894, 05MINC0964, 05MINC1138, 05MINC1619, 05MINC1750, 05MINC1907, 05MINC1977, 05MINC2375, 05MINC2774, 05MINC3113, 05MINC3484, 05MINC4277, 05MINC4623, 05MINC5623, 05MINC5914, 05MINC7545, 05MINC7870, 05MINC8355, 05MINC8689, 05MINC9437, 05MINC9775, 05MIND0067, 05MIND0393, 05MIND0892, 05MIND0951, 05MIND1836, 05MIND2183 and 05MIND2962 RECALLING
FIRM/MANUFACTURER BioLife Plasma Services L.P., Muncie, IN, by facsimile on November 22, 2005. Firm initiated recall is complete.
REASON Blood products, collected from unsuitable donors based on risk factors for Creutzfeldt-Jakob Disease (CJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE 80 units DISTRIBUTION CA, NC, and MD
______________________________
PRODUCT a) Red Blood Cells, Leukocytes Reduced, Recall # B-1714-6; b) Fresh Frozen Plasma, Recall # B-1715-6; c) Platelets, Recall # B-1716-6 CODE a), b), and c) Unit: 2443732 RECALLING FIRM/MANUFACTURER South Texas Blood and Tissue Center, San Antonio, TX, by letters dated November 11, 2003 and December 18, 2003. Firm initiated recall is complete.
REASON Blood products, collected from a donor who was at increased risk for new variant Creutzfeldt-Jakob Disease (nvCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE 3 units DISTRIBUTION TX and WI
END OF ENFORCEMENT REPORT FOR SEPTEMBER 13, 2006
###
http://www.fda.gov/bbs/topics/enforce/2006/ENF00969.html
PRODUCT Fresh Frozen Plasma, Recall # B-1751-6 CODE Unit: 4936623 RECALLING FIRM/MANUFACTURER Gulf Coast Regional Blood Center, Houston, TX, by facsimile dated September 16, 2005. Firm initiated recall is complete.
REASON Blood product, which was collected from an unsuitable donor based on risk factors for variant Creutzfeldt-Jakob Disease (vCJD), was distributed.
VOLUME OF PRODUCT IN COMMERCE 1 unit DISTRIBUTION TX
END OF ENFORCEMENT REPORT FOR SEPTEMBER 6, 2006
snip...just for grins, i am going to post mad cow feed ban warnings with this one link, not going through all of them, and to think .05 grams of BSE tainted feed is enough to taint several cows with BSE...tss
PRODUCT
a) EVSRC Custom dairy feed, Recall # V-130-6;
b) Performance Chick Starter, Recall # V-131-6;
c) Performance Quail Grower, Recall # V-132-6;
d) Performance Pheasant Finisher, Recall # V-133-6.
CODE
None
RECALLING FIRM/MANUFACTURER Donaldson & Hasenbein/dba J&R Feed Service, Inc., Cullman, AL, by telephone on June 23, 2006 and by letter dated July 19, 2006. Firm initiated recall is complete.
REASON Dairy and poultry feeds were possibly contaminated with ruminant based protein.
VOLUME OF PRODUCT IN COMMERCE 477.72 tons
DISTRIBUTION AL
______________________________
PRODUCT
a) Dairy feed, custom, Recall # V-134-6;
b) Custom Dairy Feed with Monensin, Recall # V-135-6.
CODE
None. Bulk product
RECALLING FIRM/MANUFACTURER
Recalling Firm: Burkmann Feed, Greeneville, TN, by Telephone beginning on June 28, 2006. Manufacturer: H. J. Baker & Bro., Inc., Albertville, AL. Firm initiated recall is complete.
REASON
Possible contamination of dairy feeds with ruminant derived meat and bone meal.
VOLUME OF PRODUCT IN COMMERCE 1,484 tons
DISTRIBUTION TN and WV
###
http://www.fda.gov/bbs/topics/enforce/2006/ENF00968.html
Mon Aug 7, 2006 10:24 71.248.132.189
PRODUCT a) Red Blood Cells, Recall # B-1587-6; b) Cryoprecipitated AHF, Recall # B-1588-6; c) Recovered Plasma, Recal # B-1589-6 CODE a), b) and c) Unit: 2016719 RECALLING FIRM/MANUFACTURER Walter Shepeard Community Blood Center, Inc., Augusta, GA, by facsimile on March 13, 2003. Firm initiated recall is complete. REASON Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed. VOLUME OF PRODUCT IN COMMERCE 3 units DISTRIBUTION GA and Germany
______________________________
PRODUCT a) Red Blood Cells Leukocytes Reduced, Recall # B-1590-6; b) Fresh Frozen Plasma, Recall # B-1591-6 CODE a) and b) Unit: 2443595 RECALLING FIRM/MANUFACTURER South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on June 30, 2004. Firm initiated recall is complete.
REASON Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE 2 units DISTRIBUTION TX
______________________________
PRODUCT a) Red Blood Cells Leukocytes Reduced, Recall # B-1592-6; b) Fresh Frozen Plasma, Recall # B-1593-6 CODE a) and b) Unit: 2545596 RECALLING FIRM/MANUFACTURER South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on December 14, 2004 and January 3, 2005. Firm initiated recall is complete.
REASON Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE 2 units DISTRIBUTION TX
______________________________
http://www.fda.gov/bbs/topics/enforce/2006/ENF00963.html
PRODUCT a) Red Blood Cells Leukocytes Reduced, Recall # B-1550-6; b) Fresh Frozen Plasma, Recall # B-1551-6 CODE a) and b) Unit 2395371 RECALLING FIRM/MANUFACTURER South Texas Blood and Tissue Center, San Antonio, TX, by fax on August 20, 2003. Firm initiated recall is complete.
REASON Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE 2 units DISTRIBUTION TX
______________________________
PRODUCT a) Red Blood Cells Leukocytes Reduced, Recall # B-1552-6; b) Platelets, Recall # B-1553-6; c) Fresh Frozen Plasma, Recall # B-1554-6 CODE a), b) and c) Unit 2438702 RECALLING FIRM/MANUFACTURER South Texas Blood and Tissue Center, San Antonio, TX, by fax on May 29, 2003. Firm initiated recall is complete.
REASON Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE 3 units DISTRIBUTION TX
______________________________
PRODUCT a) Red Blood Cells Leukocytes Reduced, Recall # B-1555-6; b) Fresh Frozen Plasma, Recall # B-1556-6 CODE a) and b) Unit 2454970 RECALLING FIRM/MANUFACTURER South Texas Blood and Tissue Center, San Antonio, TX, by fax on July 23 and December 11. 2003. Firm initiated recall is complete.
REASON Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE 2 units DISTRIBUTION TX
______________________________
PRODUCT a) Red Blood Cells, Recall # B-1494-6 b) Cryoprecipitated AHF, Recall # B-1495-6 CODE a) and b) Unit 5013100 RECALLING FIRM/MANUFACTURER Walter L. Shepeard Community Blood Center, Inc., Augusta, GA, by fax on May 17, 2005. Firm initiated recall is complete.
REASON Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE 2 units DISTRIBUTION GA
______________________________
PRODUCT Source Plasma, Recall # B-1450-6 CODE Unit numbers ST0824313 and ST0824764 RECALLING FIRM/MANUFACTURER Stillwater Plasma Center LLC, Stillwater, OK, by fax on November 21, 2003. Firm initiated recall is complete.
REASON Blood products, which were collected from a donor whose suitability pertaining to risk factors for Creutzfeldt-Jakob Disease (vCJD) was not adequately determined, were distributed.
VOLUME OF PRODUCT IN COMMERCE 2 units DISTRIBUTION UK
______________________________
PRODUCT Plasma Frozen, Recall # B-1422-6; Recovered Plasma, Recall # B-1423-6 CODE a) Unit 03E42218; b) Unit 03E38153 RECALLING FIRM/MANUFACTURER American Red Cross Blood Services, Atlanta, GA, by telephone, e-mail or letter on February 20 or 21, 2004. Firm initiated recall is complete.
REASON Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE 2 units DISTRIBUTION GA and Switzerland
______________________________
PRODUCT a) Red Blood Cells Leukocytes Reduced, Recall # B-1374-6; b) Recovered Plasma, Recall # B-1375-6 CODE a) and b) unit 2453906 RECALLING FIRM/MANUFACTURER South Texas Blood and Tissue Center, San Antonio, TX, by fax on October 31 and November 5, 2003. Firm initiated recall is complete.
REASON Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE 2 units DISTRIBUTION TX and Austria
______________________________
PRODUCT Source Plasma. Recall # B-1295-6 CODE Units: NG0046551, NG0045950 RECALLING FIRM/MANUFACTURER DCI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax on December 20, 2002, Firm initiated recall is complete.
REASON Blood products, collected from a donor who did not answer the questions on the new variant Creutzfeldt-Jacob disease (nvCJD) questionnaire appropriately, were distributed.
VOLUME OF PRODUCT IN COMMERCE 2 units DISTRIBUTION KY
______________________________
PRODUCT Source Plasma. Recall # B-1296-6 CODE Unit: NG 0044520 RECALLING FIRM/MANUFACTURER DCI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax on December 12, 2002. Firm initiated recall is complete.
REASON Blood product, collected from a donor who did not answer the questions on the new variant Creutzfeldt-Jacob disease (nvCJD) questionnaire, was distributed.
VOLUME OF PRODUCT IN COMMERCE 1 unit DISTRIBUTION KY
______________________________
PRODUCT Source Plasma. Recall # B-1297-6 CODE Units: NG0042874, NG0043139, NG0043312, NG0043618, NG0043797, NG0044020, NG0044209, NG0044507, NG0044718, NG0044977, NG0045161, NG0045412, NG0045555 RECALLING FIRM/MANUFACTURER DCI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax on December 20, 2002. Firm initiated recall is complete.
REASON Blood products, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE 13 units DISTRIBUTION KY
______________________________
PRODUCT Source Plasma, Recall # B-1298-6 CODE Units: NG 0046823, NG 0046671, NG 0045205, NG 0044635, NG 0043095, NG 0042525, NG 0042341 RECALLING FIRM/MANUFACTURER DCI Biologicals Nacogdoches LLC, Nacogdoches, TX, by telephone and fax on December 20, 2002. Firm initiated recall is complete.
REASON Blood products, collected from a donor who answered questions on the variant Creutzfeldt-Jacob disease (vCJD) questionnaire inappropriately, were distributed.
VOLUME OF PRODUCT IN COMMERCE 7 units DISTRIBUTION KY
______________________________
PRODUCT Recovered Plasma, Recall # B-1299-6 CODE Unit: 4357117 RECALLING FIRM/MANUFACTURER Department of the Navy, Naval Medical Center, San Diego, CA, by fax and letter on September 25, 2003. Firm initiated recall is complete.
REASON Blood product, collected from a donor considered to be at risk of exposure to Creutzfeldt-Jacob Disease (CJD), was distributed.
VOLUME OF PRODUCT IN COMMERCE 1 unit DISTRIBUTION Germany
END OF ENFORCEMENT REPORT FOR July 12, 2006
###
http://www.fda.gov/bbs/topics/enforce/2006/ENF00960.html
CJD WATCH MESSAGE BOARD TSS FDA mad cow nvCJD 'only' blood recalls 1ST WEEK JULY Fri Jul 7, 2006 09:37 70.110.83.160
FDA mad cow nvCJD 'only' blood recalls 1ST WEEK JULY
PRODUCT a) Red Blood Cells Leukocytes Reduced, Recall # B-1379-6; b) Platelets, Recall # B-1380-6; c) Fresh Frozen Plasma, Recall # 1381-6; d) Recovered Plasma, Recall # B-1382-6 CODE a) Unit numbers: 2343106, 2377779, and 2403533; b) and c) Unit numbers: 2377779; d) Unit numbers: 2343106 and 2403533 RECALLING FIRM/MANUFACTURER South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on June 12, 2003. Firm initiated recall is complete.
REASON Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE 7 units DISTRIBUTION TX and Austria
______________________________
PRODUCT a) Red Blood Cells Leukocytes Reduced, Recall # B-1467-6; b) Recovered Plasma, Recall # B-1468-6 CODE a) and b) Unit numbers: 2329380 RECALLING FIRM/MANUFACTURER South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on May 8, 2003. Firm initiated recall is complete.
REASON Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE 2 units DISTRIBUTION TX and Switzerland
______________________________
PRODUCT a) Red Blood Cells Leukocytes Reduced, Recall # B-1479-6; b) Cryoprecipitated AHF, Recall # B-1480-6; c) Recovered Plasma, Recall # B-1481-6 CODE a), b), and c) Unit numbers: 2383280 RECALLING FIRM/MANUFACTURER South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on July 23 and 29, 2004. Firm initiated recall is complete.
REASON Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE 3 units DISTRIBUTION TX and Switzerland
______________________________
PRODUCT a) Red Blood Cells Leukocytes Reduced, Recall # B-1482-6; b) Fresh Frozen Plasma, Recall # B-1483-6 CODE a) and b) Unit number: 2501452 RECALLING FIRM/MANUFACTURER South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on October 5, 2004. Firm initiated recall is complete.
REASON Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE 2 units DISTRIBUTION TX and NY
______________________________
PRODUCT a) Red Blood Cells Leukocytes Reduced, Recall # B-1484-6; b) Plasma Cryoprecipitated Reduced, Recall # B-1485-6; c) Recovered Plasma, Recall # B-1486-6 CODE a) and c) Unit number: 2554077; b) Unit number: 2415708 RECALLING FIRM/MANUFACTURER South Texas Blood and Tissue Center, San Antonio, TX, by facsimile on August 13, 2004. Firm initiated recall is complete.
REASON Blood products, which were collected from a donor who may be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), were distributed.
VOLUME OF PRODUCT IN COMMERCE 3 units DISTRIBUTION TX and Austria
_____________________________________
END OF ENFORCEMENT REPORT FOR July 5, 2006
###
http://www.fda.gov/bbs/topics/enforce/2006/ENF00959.html
Greetings again Dr. Freas et al at FDA,
WITH new atypical TSE in the bovine, in the sheep, goat, and humans, and the fact that the new BASE TSE in cattle being very very similar to sporadic CJD, rather than the nvCJD, the fact that now science showing the TSE agent of the atypical cattle in Japan showing infectivity other than CNS tissue, the fact that the latest Texas mad cow and the recent Alabama mad cow both being of the atypical strain, it would seem prudent to include all human TSE in the blood ban, in my opinion. with sporadic CJD, you have many strains and or phenotypes, some of which are 'UNKNOWN', so we do not know how this will transmit, what tissues are infectious and or if blood transmits. that's the bottom line, however it has been reported that the BASE is more virulent to humans. With this, and the fact that sporadic CJD has tripled in the past few years or so, i see it as being prudent to take serious and immediate action ;
PERSPECTIVE
On the Question of Sporadic or Atypical Bovine Spongiform Encephalopathy and Creutzfeldt-Jakob Disease
Paul Brown,* Lisa M. McShane,† Gianluigi Zanusso,‡ and Linda Detwiler§
Strategies to investigate the possible existence of sporadic
bovine spongiform encephalopathy (BSE) require
systematic testing programs to identify cases in countries
considered to have little or no risk for orally acquired disease,
or to detect a stable occurrence of atypical cases in
countries in which orally acquired disease is disappearing.
To achieve 95% statistical confidence that the prevalence
of sporadic BSE is no greater than 1 per million (i.e., the
annual incidence of sporadic Creutzfeldt-Jakob disease
[CJD] in humans) would require negative tests in 3 million
randomly selected older cattle. A link between BSE and
sporadic CJD has been suggested on the basis of laboratory
studies but is unsupported by epidemiologic observation.
Such a link might yet be established by the discovery
of a specific molecular marker or of particular combinations
of trends over time of typical and atypical BSE and various
subtypes of sporadic CJD, as their numbers are influenced
by a continuation of current public health measures that
exclude high-risk bovine tissues from the animal and
human food chains. ......
PLEASE READ FULL TEXT ;
CDC DR. PAUL BROWN TSE EXPERT COMMENTS 2006
The U.S. Department of Agriculture was quick to assure the public earlier this week that the third case of mad cow disease did not pose a risk to them, but what federal officials have not acknowledged is that this latest case indicates the deadly disease has been circulating in U.S. herds for at least a decade.
The second case, which was detected last year in a Texas cow and which USDA officials were reluctant to verify, was approximately 12 years old.
These two cases (the latest was detected in an Alabama cow) present a picture of the disease having been here for 10 years or so, since it is thought that cows usually contract the disease from contaminated feed they consume as calves. The concern is that humans can contract a fatal, incurable, brain-wasting illness from consuming beef products contaminated with the mad cow pathogen.
"The fact the Texas cow showed up fairly clearly implied the existence of other undetected cases," Dr. Paul Brown, former medical director of the National Institutes of Health's Laboratory for Central Nervous System Studies and an expert on mad cow-like diseases, told United Press International. "The question was, 'How many?' and we still can't answer that."
Brown, who is preparing a scientific paper based on the latest two mad cow cases to estimate the maximum number of infected cows that occurred in the United States, said he has "absolutely no confidence in USDA tests before one year ago" because of the agency's reluctance to retest the Texas cow that initially tested positive.
USDA officials finally retested the cow and confirmed it was infected seven months later, but only at the insistence of the agency's inspector general.
"Everything they did on the Texas cow makes everything USDA did before 2005 suspect," Brown said. ...snip...end
http://www.upi.com/
*** Inherent Challenges in Identifying and Testing High-Risk Cattle Still Remain
3:00 Afternoon Refreshment Break, Poster and Exhibit Viewing in the Exhibit Hall
3:30 Transmission of the Italian Atypical BSE (BASE) in Humanized Mouse Models
Qingzhong Kong, Ph.D., Assistant Professor, Pathology, Case Western Reserve University
Bovine Amyloid Spongiform Encephalopathy (BASE) is an atypical BSE strain discovered recently in Italy, and similar or different atypical BSE cases were also reported in other countries. The infectivity and phenotypes of these atypical BSE strains in humans are unknown. In collaboration with Pierluigi Gambetti, as well as Maria Caramelli and her co-workers, we have inoculated transgenic mice expressing human prion protein with brain homogenates from BASE or BSE infected cattle. Our data shows that about half of the BASE-inoculated mice became infected with an average incubation time of about 19 months; in contrast, none of the BSE-inoculated mice appear to be infected after more than 2 years. ***These results indicate that BASE is transmissible to humans and suggest that BASE is more virulent than classical BSE in humans***.
6:30 Close of Day One
SUNDAY, FEBRUARY 11
5:00 - 6:00 pm Early Registration
MONDAY, FEBRUARY 12
7:30 am Registration, Morning Coffee
Emerging Concerns
8:30 Welcome by Session Chairperson
Paul W. Brown, M.D.
8:45 Variant CJD: The End of the Beginning or the Beginning of the End?
Robert G. Will, M.D., National CJD Surveillance Unit, University of Edinburgh
Variant CJD incidence has been in decline in the UK since 1999 and the feared epidemic of this zoonotic disease has not yet materialized. A number of other countries have identified cases of vCJD, notably in France, but the overall non-UK incidence of vCJD is not increasing markedly. There is good evidence indicating that vCJD can be iatrogenically transmitted through blood transfusion but it is unlikely that this route of transmission will lead to a self-sustaining outbreak. Public health concerns are therefore in decline, but because of the potentially extended incubation periods, it will be many years before further outbreaks of vCJD can be excluded, for example through alternative mechanisms of transmission.
9:15 Sporadic CJD: Does Transmission through Blood Occur?
Maurizio Pocchiari, Ph.D., Director of Research-Virology, Istituto Superiore Di Sanita (Italy)
9:45 The 'Spontaneous' BSE Issue: Pros, Cons, and Strategies to Test the Hypothesis
Paul W. Brown, M.D.
Strategies to investigate the possible existence of sporadic BSE require systematic testing programs to identify cases in countries considered to have little or no risk of orally-acquired disease, or to detect a stable occurrence of atypical cases in countries in which orally-acquired disease is disappearing. To achieve 95% statistical confidence that the prevalence of sporadic BSE is no greater than one per million (i.e., the annual incidence of sporadic Creutzfeldt-Jakob disease in humans) would require negative tests in three million randomly selected older cattle. A link between atypical BSE and sporadic CJD, suggested by some laboratory studies but unsupported by epidemiological observation, might yet be established by the discovery of a specific molecular marker, or by trends in the incidence of atypical BSE and sporadic CJD.
10:15 Coffee Break, Poster and Exhibit Viewing in the Exhibit Hall
10:45 Discrimination between CWD, BSE and Scrapie Strains: An Evaluation of Tests
Michael Stack, Senior Researcher, TSE Molecular Biology, Veterinary Laboratories Agency
Bovine spongiform encephalopathy (BSE) has been implicated as the cause of the appearance in humans of new variant In Great Britain, during the 1980s, it is possible that BSE-contaminated meat and bone meal may have been fed to sheep, raising the possibility that BSE could have been transmitted to the national sheep flock, and could therefore be a potential secondary threat to public health. Molecular and immunohistochemical techniques which can discriminate between experimental BSE in sheep, and natural scrapie cases have been developed and evaluated in blinded ring trials. Increased surveillance for Transmissible Spongiform Encephalopathies (TSEs) in cervid populations across Europe is planned to start in 2007, and if a disease such as Chronic Wasting Disease (CWD) is discovered, one of the first questions would be whether the molecular profile is similar to that found for North American CWD cases, or could there have been contact with the agents of BSE or scrapie resulting in a change of disease profile? The tests evaluated in the blinded ring trials in Europe also offer potential discrimination between CWD and other animal TSEs, and could therefore be used to rule out BSE in cervids as another possible secondary threat to public health. This presentation will describe the principles of discrimination and the evaluation results obtained so far.
New Research Directions
Session Chairperson:
Suzette A. Priola, Ph.D., Senior Investigator, Chief, TSE/Prion Molecular Biology Section, National Institutes of Health, NIAID, Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories
11:15 Developing Cell Cultures for Prion Studies
Sylvain Lehmann, Professor, Institut de Génétique Humaine du CNRS Cell cultures susceptible to TSE agents represent relevant and useful experimental models for Prion studies. They have been used in particular to study TSE molecular events and to develop and validate innovative therapeutic approaches. More recently, prion infected cell culture models have been considered as an alternative to animal bioassays to detect the presence of infectivity. In fact, it was possible to obtain in specific cell culture paradigms a reliable and highly sensitive detection of prions that was much faster and at a lesser cost than in animals. Nevertheless, many problems persist with the use of these cell culture models including their standardization or the range of prion species and strains that they can detect.
11:45 Retroviral Infection Strongly Enhances the Release of Scrapie Infectivity in Cell Culture
Pascal LeBlanc, Ph.D., LaboRetro unité de virologie humaine, INSERM
Although there is much evidence to suggest that PrPSc, a misfolded form of the cellular prion protein PrPC, is the infectious agent of prion diseases, the mechanism of PrPSc transmission and the factors that affect its spread remain unknown. Here we show that the release of PrPSc from scrapie-infected cells is markedly enhanced by retroviral infection, implicating retroviruses in the spread of prion diseases and providing mechanistic insights into prion transmission.
12:15 Lunch on Your Own (Luncheon Technology Workshops Available)
Infectivity and Transmission
1:20 Comments by Session Chairpersons
Kiki B. Hellman, Ph.D., President & Founder, The Hellman Group, LLC
Suzette A. Priola, Ph.D., Senior Investigator, Chief, TSE/Prion Molecular Biology Section, National Institutes of Health, NIAID, Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories
1:30 Infectivity in Urine of Hamsters Infected with Scrapie
Luisa Gregori, Ph.D., Assistant Director and Assistant Professor, VA Research Services and University of Maryland, BREF
Horizontal transmission from animal to animal of Transmissible Spongiform Encephalopathies (TSE) has been documented in the wild and in laboratory animals. The cause(s) of this transmission is not fully understood, although bodily excretions such as urine and feces are often proposed as potential sources of secondary exposure leading to horizontal transmissions. We report here on our investigation on infectivity in urine of TSE infected animals. Urine from hamsters infected with the 263K strain of scrapie was collected using metabolic cages and titered by intracerebral inoculation in the same animal species with the limiting dilution method. Five-ml equivalents of urine (diluted 1:3) were inoculated. After 357 days post inoculation, 11 animals developed scrapie with a titer of 2.3 +/- 0.4 ID/ml. No infectious have been observed in the cohort of animals inoculated with urine from control animals. Ten percent bladder and kidney tissue homogenates from infected hamsters were also titered using the end point titration method. At 343 days, the titers are 10(5.5) and 10(4.8) ID50/g for bladder and kidney, respectively. These results propose a new pathway of infection of the natural environment. The implications are far reaching from environmental contamination of pastures in the wild to risk management of domestic livestock and the safety of urine-derived therapeutic products.
2:00 Soil Minerals Enhance Prion Infectivity
Judd M. Aiken, DVM, Professor, Animal Health & Biomedical Sciences, University of Wisconsin-Madison, School of Veterinary Medicine
We have recently demonstrated that prions bind clay and silica. The binding of PrPSc to a common soil clay (montmorillonite) is avid and this interaction enhances infectivity. The implications of this enhancement of transmission are far-reaching and include how scrapie and CWD are environmentally transmitted. The ramifications of these findings with regard to food safely will also be discussed.
2:30 Transmission of BSE-301v Following Infection from the Small Intestine: A New Model for Investigating Iatrogenic Transmission Risks for vCJD
James Walker, Ph.D., Senior Project Manager, TSE Research Group, Health Protection Agency
The study explores the use of a novel challenge model designed to provide information on the levels of infectivity of tissues following infection from the small intestine. The model uses direct challenge via the small intestine to prevent the contamination of the oral cavity by the primary inoculum. Groups of VM mice (n=10) were inoculated with 100ul of 2% w/v BSE-301v infected brain homogenate directly into the small intestine and sacrificed at 3, 6, 9, 12, 15, 18, 21 weeks post-inoculation. Tissues including spleen, saliva, salivary gland, trigeminal ganglia, gingival margin, alveolar bone, dental pulp, posterior tongue, anterior tongue, and brain were removed at the appropriate time points and re-inoculated (intra-cranially) into groups of mice (n=6) which were sacrificed at a clinical end point. Results to date indicate that brain and spleen from mice inoculated via this route became infectious very early in the course of disease progression and achieved maximum infectious titers well before clinical symptoms became apparent. Western blot analysis for the presence of PrPSc in the brain samples does not correlate well with the levels of infectivity and this is currently being investigated further. These results will be discussed in connection with our understanding of the iatrogenic transmission.
3:00 Afternoon Refreshment Break, Poster and Exhibit Viewing in the Exhibit Hall
3:30 Transmission of the Italian Atypical BSE (BASE) in Humanized Mouse Models
Qingzhong Kong, Ph.D., Assistant Professor, Pathology, Case Western Reserve University
Bovine Amyloid Spongiform Encephalopathy (BASE) is an atypical BSE strain discovered recently in Italy, and similar or different atypical BSE cases were also reported in other countries. The infectivity and phenotypes of these atypical BSE strains in humans are unknown. In collaboration with Pierluigi Gambetti, as well as Maria Caramelli and her co-workers, we have inoculated transgenic mice expressing human prion protein with brain homogenates from BASE or BSE infected cattle. Our data shows that about half of the BASE-inoculated mice became infected with an average incubation time of about 19 months; in contrast, none of the BSE-inoculated mice appear to be infected after more than 2 years. These results indicate that BASE is transmissible to humans and suggest that BASE is more virulent than classical BSE in humans.
4:00 Production of Cattle Lacking Prion Protein Sponsored by
Jerry Pommer, MS, Senior Director of Quality Systems/Regulatory Affairs, Hematech, Inc.
Disruption of PrPC expression in mice, a species that does not naturally contract prion diseases, results in no apparent development abnormalities. However, the impact of ablating PrPC function in natural host species of prion diseases is unknown. Here we report the generation and characterization of PrPC-deficient cattle produced by a sequential gene-targeting system. At 2 years of age, the cattle are clinically, physiologically, histopathologically, immunologically and reproductively, normal. Brain tissue homogenates are resistant to prion propagation in vitro, as assessed by a protein misfolding cyclic amplification assay. PrPC-deficient cattle may be a useful model for prion research and could provide industrial bovine products free of prion proteins. 4:15 Regulatory Panel Discussion:
Answers to the Regulatory Questions Regarding TSEs
David M. Asher, M.D., Laboratory Chief, Laboratory of Methods Development, FDA
Daniel Engeljohn, Ph.D., Deputy Assistant Administrator, USDA FSIS OPPED, USDA
Morris Potter, DVM, HHS CFSAN OSCI, FDA
Richard Wiggins, Ph.D., Senior Science Advisor, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. EPA
5:30 Networking Reception in Exhibit Hall
6:30 Close of Day One
SEE STEADY INCREASE IN SPORADIC CJD IN THE USA FROM 1997 TO 2006. SPORADIC CJD CASES TRIPLED, with phenotype of 'UNKNOWN' strain growing. ...
http://www.cjdsurveillance.com/resources-casereport.html
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
Prion infections, blood and transfusions
Adriano Aguzzi* and Markus Glatzel
Prion infections lead to invariably fatal diseases of the CNS, including
Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform
encephalopathy (BSE), and scrapie in sheep. There have been hundreds
of instances in which prions have been transmitted iatrogenically among
humans, usually through neurosurgical procedures or administration of
pituitary tissue extracts. Prions have not generally been regarded as bloodborne
infectious agents, and case-control studies have failed to identify
CJD in transfusion recipients. Previous understanding was, however,
questioned by reports of prion infections in three recipients of blood
donated by individuals who subsequently developed variant CJD. On
reflection, hematogenic prion transmission does not come as a surprise, as
involvement of extracerebral compartments such as lymphoid organs and
skeletal muscle is common in most prion infections, and prions have been
recovered from the blood of rodents and sheep. Novel diagnostic strategies,
which might include the use of surrogate markers of prion infection, along
with prion removal strategies, might help to control the risk of iatrogenic
prion spread through blood transfusions. ...
snip...
Last, despite all epidemiological evidence to
the contrary, patients who are methionine/valine
heterozygous at codon 129 of the PRNP gene are
susceptible to infection with vCJD prions, which
raises several important questions. Is the virulence
of BSE prions enhanced when passaged
from human to human, as opposed to the
original bovine to human situation? Passaging
experiments of scrapie infectivity between mice
and hamsters indicate that this scenario is highly
plausible.6 Even more importantly, can vCJD
infection of heterozygous individuals establish
a permanent subclinical carrier state? Although
this situation might constitute a best-case
scenario for the infected individuals, it could be
disastrous from an epidemiological viewpoint,
as it might lead to an unrecognized and possibly
self-sustaining epidemic. ...
snip... full text ;
JUNE 2006 VOL 2 NO 6 AGUZZI AND GLATZEL NATURE CLINICAL PRACTICE NEUROLOGY 329
FDA Fines American Red Cross $4.2 Million (BLOOD CJD) Fri Sep 8, 2006 20:01 71.248.154.242
FDA Statement FOR IMMEDIATE RELEASE Statement September 8, 2006 Media Inquiries: 301-827-6242 Consumer Inquiries: 888-INFO-FDA
FDA Fines American Red Cross $4.2 Million for Failure to Meet Established Blood Safety Laws
http://www.fda.gov/cber/talkpapers.htm#arc
snip...
One way the Red Cross erred was by failing to ask donors about travel history that could increase the chances of having malaria or the human version of mad cow disease, FDA officials said.
snip...
Greetings again Dr. Freas et al at FDA,
THIS was like closing the barn door after the mad cows got loose. not only the red cross, but the FDA has failed the public in protecting them from the TSE aka mad cow agent. TSE agent i.e. bse, base, cwd, scrapie, tme, and any sub strains thereof. we do not know if these strains will or have transmitted to humans as subclinical TSE or clinical disease, and we do not know if they have or will transmit second, third, forth passage via friendly fire i.e. multiple potential routes via medical, surgical, pharmaceutical etc.
IF you remember correctly Dr. Freas et al, i called this long ago, almost 6 years ago ;
PDF]Freas, William TSS SUBMISSION
File Format: PDF/Adobe Acrobat -
Page 1. J Freas, William From: Sent: To: Subject: Terry S. Singeltary
Sr. [flounder@wt.net] Monday, January 08,200l 3:03 PM freas ...
Freas, William
From: Terry S. Singeltary Sr. [flounder@wt.net]
Sent: Monday, January 08,200l 3:03 PM
To: freas@CBS5055530.CBER.FDA.GOV
Subject: CJDIBSE (aka madcow) Human/Animal TSE’s--U.S.--Submission To Scientific Advisors and
Consultants Staff January 2001 Meeting (short version)
Greetings again Dr. Freas and Committee Members,
I wish to submit the following information to the
Scientific Advisors and Consultants Staff
2001 Advisory Committee (short version).
I understand the reason of having to shorten my submission,
but only hope that you add it to a copy of the long version,
for members to take and read at their pleasure,
(if cost is problem, bill me, address below).
So when they realize some time in the near future
of the 'real' risks i speak of from human/animal TSEs and
blood/surgical products. I cannot explain the 'real' risk
of this in 5 or 10 minutes at some meeting,
but will attempt here:
remember AIDS/HIV, 'no problem to heterosexuals in the U.S.?
no need to go into that, you know of this blunder:
DO NOT make these same stupid mistakes again with
human/animal TSE's aka MADCOW DISEASE. I lost my Mom to hvCJD,
and my neighbor lost his Mother to sCJD as well (both cases
confirmed). I have seen many deaths, from many diseases.
I have never seen anything as CJD, I still see my Mom laying helpless,
jerking tremendously, and screaming "God, what's wrong
with me, why can't I stop this". I still see this, and will
never forget. Approximately 10 weeks from 1st of symptoms to death.
This is what drives me. I have learned more in 3 years about not only
human/animal TSE's but the cattle/rendering/feeding industry/government
than i ever wished to.
I think you are all aware of CJD vs vCJD, but i don't think
you all know the facts of human/animal TSE's as a whole,
they are all very very similar, and are all tied to the
same thing, GREED and MAN.
I am beginning to think that the endless attempt to track
down and ban, potential victims from known BSE Countries
from giving blood will be futile. You would have to ban
everyone on the Globe eventually? AS well, I think we
MUST ACT SWIFTLY to find blood test for TSE's,
whether it be blood test, urine test, eyelid test,
anything at whatever cost, we need a test FAST.
DO NOT let the incubation time period of these TSEs fool you.
To think of Scrapie as the prime agent to compare CJD,
but yet overlook the Louping-ill vaccine event in 1930's
of which 1000's of sheep where infected by scrapie
from a vaccine made of scrapie infected sheep brains,
would be foolish. I acquired this full text version of the
event which was recorded in the Annual Congress of 1946
National Vet. Med. Ass. of Great Britain and Ireland.
From the BVA and the URL is posted in my (long version).
U.S.A. should make all human/animal TSE's notifiable at all ages,
with requirements for a thorough surveillance and post-mortem
examinations free of charge, if you are serious about eradicating
this horrible disease in man and animal.
There is histopathology reports describing "florid plaques"
in CJD victims in the USA and some of these victims are getting
younger. I have copies of such autopsies, there has to
be more. PLUS, sub-clinical human TSE's will most definitely
be a problem.
THEN think of vaccineCJD in children and the bovine tissues
used in the manufacturing process, think of the FACT that
this agent surviving 6OO*C.
PNAS -- Brown et al. 97 (7): 3418 scrapie agent live at 600*C
Then think of the CONFIDENTIAL documents of what was known of
human/animal TSE and vaccines in the mid to late 8Os, it was all about
depletion of stock, to hell with the kids, BUT yet they knew.
To think of the recall and worry of TSE's from the polio vaccine,
(one taken orally i think?), but yet neglect to act on the
other potential TSE vaccines (inoculations, the most effective mode to
transmit TSEs) of which thousands of doses were kept and used,
to deplete stockpile, again would be foolish.
--Oral polio; up to 1988, foetal calf serum was used from UK and
New Zealand (pooled); since 1988 foetal calf serum only from New
Zealand. Large stocks are held.
--Rubella; bulk was made before 1979 from foetal calf serum from UK
and New Zealand. None has been made as there are some 15 years stock.
--Diphtheria; UK bovine beef muscle and ox heart is used but since the
end of 1988 this has been sourced from Eire. There are 1,250 litres of
stock.
--Tetanus; this involves bovine material from the UK mainly Scottish.
There are 21,000 litres of stock.
--Pertussis; uses bovine material from the UK. There are 63,000 litres
of stock.
--They consider that to switch to a non-UK source will take a minimum of
6-18 months and to switch to a non-bovine source will take a minimum of
five years.
3. XXXXXXXXXXX have measles, mumps, MMR, rubella vaccines. These
are sourced from the USA and the company believes that US material only
is used.
89/2.14/2.1
============
BSE3/1 0251
4. XXXXXXXXXXX have a measles vaccine using bovine serum from the UK.
there are 440,000 units of stock. They have also got MMR using bovine
serum from the UK.
5. XXXXXXXXXXX have influenza, rubella, measles,' MMR vaccines
likely to be used in children. Of those they think that only MMR
contains bovine material which is probably a French origin.
6. XXXXXXXXXXX have diphtheria/tetanus and potasses on clinical trial.
hese use veal material, some of which has come from the UK and has been
ade by XXXXXXXXXXX (see above).
I have documents of imports from known BSE Countries,
of ferments, whole blood, antiallergenic preparations,
2
human blood plasma, normal human blood sera, human immune
blood sera, fetal bovine serum, and other blood fractions
not elsewhere specified or included, imported glands,
catgut, vaccines for both human/animal, as late as 1998.
Let us not forget about PITUITARY EXTRACT. This was used to help COWS
super ovulate. This tissue was considered to be of greatest risk of
containing BSE and consequently transmitting the disease.
ANNEX 6
MEETING HELD ON 8 JUNE 1988 TO DISCUSS THE IMPLICATIONS OF BSE TO
BIOLOGICAL PRODUCTS CONTAINING BOVINE - EXTRACTED MATERIAL
How much of this was used in the U.S.?
Please do not keep making the same mistakes.
'Absence of evidence is not evidence of absence'.
What are the U.S. rules for importing and manufacturing vaccines,
medicines and medical devices?
Does the U.S.A. allow sourcing of raw material of ruminants from
the U.S.A.?
U.S. cattle, what kind of guarantee can you give for serum or
tissue donor herds.?
The U.S. rendering system would easily amplify T.S.E.'s:
Have we increased the stability of the system (improved heat treatments)
since the EU SSC report on the U.S.A. was published
in july 2000?
What is done to avoid cross-contaminations in the U.S.A.?
How can the U.S. control absence of cross-contaminations of animal
TSE's when pig and horse MBM and even deer and elk are allowed in
ruminant feed, as well as bovine blood? I sadly think of the rendering
and feeding policy before the Aug. 4, 1997 'partial'
feed ban, where anything went, from the city police horse, to the circus
elephant, i will not mention all the scrapie infected sheep.
I am surprised that we have not included man 'aka soyent green'.
It is a disgusting industry and nothing more than greed fuels it.
When will the U.S.. start real surveillance of the U.S. bovine
population (not passive, this will not work)?
When will U.S. start removing SRMs?
Have they stopped the use of pneumatic stunners in the U.S.?
If so, will we stop it in all U.S. abattoirs or only in those
abattoirs exporting to Europe?
If not, WHY NOT?
same questions for removal of SRM in the U.S.A.,
or just for export?
If not, WHY NOT?
How do we now sterilize surgical/dental instruments in the U.S.A.?
Where have we been sourcing surgical catgut?
(i have copies of imports to U.S., and it would floor you)
When will re-usable surgical instruments be banned?
'Unregulated "foods" such as 'nutritional supplements' containing various
extracts from ruminants, whether imported or derived from
US cattle/sheep/cervids ("antler velvet" extracts!) should be
forbidden or at least very seriously regulated.
(neighbors Mom, whom also died from CJD, had been taking
bovine based supplement, which contained brain, eye, and many
other bovine/ovine tissues for years, 'IPLEX').
What is the use of banning blood or tissue donors from Germany, France,
etc... when the U.S.A. continues exposing cattle, sheep and people to
SRM, refuses to have a serious feed ban, refuses
to do systematic BSE-surveillance?
The FDA should feel responsible for the safety of what people eat.
prohibit the most dangerous foods, not only prohibit a few more donors,
the FDA should be responsible for the safe sourcing of medical devices,
not only rely on banning donors "from Europe",
The 'real' risks are here in the U.S. as well, and have been for some
time.
We must not forget the studies that have proven
infectivity in blood from TSE's.
The Lancet, November 9, 1985
" Sir, --Professor Manuelidis and his colleagues (Ott 19, p896) report
transmission to animals of Creutzfeldt-Jakob disease (CJD) from the
buffy coat from two patients. We also transmitted the disease from ,
whole blood samples of a patient (and of mice) infected with CJD.l
Brain, Cornea, and urine from this patient were also infectious,
and the clinicopathological findings2 are summarised as follows.
snip...
full text ;
http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf
Greetings again Dr. Freas et al at FDA,
NOW, here we are in 2006, worried and still fumbling around with what should have been done long, long ago ;
Subject: 91ST MEETING OF THE SEAC MEETING LONDON 24TH FEB 2006 Date: March 10, 2006 at 7:36 am PST 1
© SEAC 2006
NINETY FIRST MEETING OF THE SPONGIFORM
ENCEPHALOPATHY ADVISORY COMMITTEE
The Spongiform Encephalopathy Advisory Committee held its 91st
meeting in London on 24th February 2006.
snip...
MEDICAL IMPLANTS CONTAINING BOVINE MATERIAL
SEAC considered the risk to human health from medical implants
that include bovine material sourced from the USA. This material
was used for a wide range of medical devices, some of which are
life saving and for which there are no alternative products.
SEAC considered that the source of the animal was crucial to
manage the risk. The committee suggested that other
precautionary steps be taken where practicable, such as using
material from young animals, sourcing material from countries with
good surveillance procedures and a low prevalence of disease. ......
snip...
http://www.seac.gov.uk/minutes/final90.pdf
A BIT OF HISTORY ON THIS TOPIC
TWA LITTLE minute
http://www.bseinquiry.gov.uk/files/yb/1988/06/10001001.pdf
http://web.archive.org/web/20090718143101/http://www.bseinquiry.gov.uk/files/yb/1988/06/10001001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/06/13010001.pdf
http://web.archive.org/web/20090718143112/http://www.bseinquiry.gov.uk/files/yb/1988/06/13010001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/06/14006001.pdf
http://web.archive.org/web/20090718143117/http://www.bseinquiry.gov.uk/files/yb/1988/06/14006001.pdf
COMMERCIAL IN CONFIDENCE
http://www.bseinquiry.gov.uk/files/yb/1988/09/06005001.pdf
http://web.archive.org/web/20090718143134/http://www.bseinquiry.gov.uk/files/yb/1988/09/06005001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/10/06005001.pdf
http://web.archive.org/web/20090718143144/http://www.bseinquiry.gov.uk/files/yb/1988/10/06005001.pdf
NOT FOR PUBLICATION
http://www.bseinquiry.gov.uk/files/yb/1988/11/01012001.pdf
http://web.archive.org/web/20090718143149/http://www.bseinquiry.gov.uk/files/yb/1988/11/01012001.pdf
http://www.bseinquiry.gov.uk/yb/1988/11/04003001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/04/00007001.pdf
http://web.archive.org/web/20090718143048/http://www.bseinquiry.gov.uk/files/yb/1988/04/00007001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/07/00007001.pdf
http://web.archive.org/web/20090718143123/http://www.bseinquiry.gov.uk/files/yb/1988/07/00007001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/09/00004001.pdf
http://web.archive.org/web/20090718143129/http://www.bseinquiry.gov.uk/files/yb/1988/09/00004001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/10/00003001.pdf
http://web.archive.org/web/20090718143137/http://www.bseinquiry.gov.uk/files/yb/1988/10/00003001.pdf
http://www.bseinquiry.gov.uk/files/yb/1989/01/04001001.pdf
http://web.archive.org/web/20090718143157/http://www.bseinquiry.gov.uk/files/yb/1989/01/04001001.pdf
http://www.bseinquiry.gov.uk/files/yb/1989/01/26007001.pdf
http://web.archive.org/web/20090718143205/http://www.bseinquiry.gov.uk/files/yb/1989/01/26007001.pdf
http://www.bseinquiry.gov.uk/files/yb/1989/01/30001001.pdf
http://web.archive.org/web/20090718143213/http://www.bseinquiry.gov.uk/files/yb/1989/01/30001001.pdf
http://www.bseinquiry.gov.uk/files/yb/1989/09/06011001.pdf
http://web.archive.org/web/20090718143231/http://www.bseinquiry.gov.uk/files/yb/1989/09/06011001.pdf
NON-LICENSED HUMAN TISSUE DEVICES WERE NOT COMMERCIALLY AVAILABLE
snip...
I was quite prepared to believe in unofficial pituitary hormones, also in the 1970's, whether as described by Dr. Little, or in other circumstances, for animal use.
snip...
The fact that there were jars of pituitaries (or extract) around on shelves is attested by the still potent 1943 pituitaries, described in Stockell Hartree et al. (J/RF/17/291) which had come from the lab. at Mill Hill. Having taken the trouble to collect them, they were not lightly thrown out...
http://www.bseinquiry.gov.uk/files/ws/s467bx.pdf
more on the 1968 medicine act, they forgot to follow
http://www.bseinquiry.gov.uk/files/yb/1989/01/30008001.pdf
http://web.archive.org/web/20090718143216/http://www.bseinquiry.gov.uk/files/yb/1989/01/30008001.pdf
8. The Secretary of State has a number of licences. We understand that the inactivated polio vaccine is no longer being used. There is a stock of smallpox vaccine. We have not been able to determine the source material. (Made in sheep very unlikely to contain bovine ingredients).
http://www.bseinquiry.gov.uk/files/yb/1989/02/14010001.pdf
http://web.archive.org/web/20090505223918/http://www.bseinquiry.gov.uk/files/yb/1989/02/14010001.pdf
http://www.bseinquiry.gov.uk/files/yb/1989/02/14011001.pdf
http://web.archive.org/web/20090506060303/http://www.bseinquiry.gov.uk/files/yb/1989/02/14011001.pdf
although 176 products do _not_ conform to the CSM/VPC guidelines.
http://www.bseinquiry.gov.uk/files/yb/1989/09/06011001.pdf
http://web.archive.org/web/20090718143231/http://www.bseinquiry.gov.uk/files/yb/1989/09/06011001.pdf
Draft cover letter to product licence holders (considered by Human and Vet Medicines including deer)
http://www.bseinquiry.gov.uk/files/yb/1989/02/22008001.pdf
http://web.archive.org/web/20090718143224/http://www.bseinquiry.gov.uk/files/yb/1989/02/22008001.pdf
http://www.bseinquiry.gov.uk/files/yb/1989/02/22011001.pdf
http://web.archive.org/web/20090718143228/http://www.bseinquiry.gov.uk/files/yb/1989/02/22011001.pdf
(It was noted with concern that hormone extracts could be manufactured by a veterinary surgeon for administration to animals under his care without any Medicines Act Control.)
http://www.bseinquiry.gov.uk/files/yb/1988/06/08011001.pdf
http://web.archive.org/web/20090718143059/http://www.bseinquiry.gov.uk/files/yb/1988/06/08011001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/06/08011001.pdf
http://web.archive.org/web/20090718143059/http://www.bseinquiry.gov.uk/files/yb/1988/06/08011001.pdf
http://www.bseinquiry.gov.uk/files/yb/1988/06/07010001.pdf
http://web.archive.org/web/20090718143053/http://www.bseinquiry.gov.uk/files/yb/1988/06/07010001.pdf
TWA LITTLE STATEMENT 331
http://www.bseinquiry.gov.uk/files/ws/s331.pdf
WE know about USA serum and tissue donor herds from the now infamous
Jan. 9, 2001 FDA emergency 50 state BSE conference call, that in fact, USA serum
and tissue donor herds were eating banned ruminant feed as well ;
Date: Sun, 7 Jan 2001 09:45:19 -0800
Reply-To: Sustainable Agriculture Network Discussion Group <[log in to unmask]>
Sender: Sustainable Agriculture Network Discussion Group <[log in to unmask]>
From: Beth von Gunten <[log in to unmask]>
Subject: [BSE] FDA/IMPORTANT NOTICE: 50 STATE CONFERENCE CALL
IMPORTANT NOTICE: 50 STATE CONFERENCE CALL - BSE
TUESDAY, JANUARY 9, 2001 1:00-2:00 PM EST CALL: 1-888-273-9887
A special "50 STATE CONFERENCE CALL" to discuss BSE (Bovine Spongiform Encephalopathy) issues for Food and Drug Administration (FDA) regulated animal feed products in the United States and imported animal feeds. The conference call will discuss the FDA proposed response to the current BSE issue and the assistance needed from state feed and agriculture programs. THIS ISSUE MAY IMPACT ALL STATES AND ALL ANIMAL FEED AND PRODUCTION INDUSTRIES.
The 50 State call is scheduled for Tuesday, January 9, 2001 from 1:00-2:00 pm EST. Any state agency responsible for animal feed issues wishing to participate should call 1-888-273-9887 and ask to be connected to the "50 State BSE Call". The conference host operator will explain how to participate, including asking questions during the call. If possible, please coordinate within your state to utilize only one phone line per state agency.
We request that you forward this message to your agency management and feed coordinators or other agencies or departments who may be responsible for any animal feed issues related to FDA regulated products.
The agenda will be as follows:
1. Center For Veterinary Medicine (FDA) - Discussion of the problem related to BSE events in Europe and the impact on US feed ingredients for animals and feed operations. Discussion of the proposed actions/inspections/compliance of licensed and unlicensed feed mills, commercial feed manufacturers, animal feed imports, renderer's, protein blenders, on-farm mixers, and ruminant feeders.
2. Office of Regional Operations (FDA) - Discussion of contracting/working with states to inspect the universe of feed mills/industry for "Animal Proteins Prohibited from Use in Animal Feed". Discussion of working with FDA field offices.
3. Questions and answers.
Richard H. Barnes, Director Division of Federal-State Relations (HFC-150) 5600 Fishers Lane Room 1207 Rockville, Md. 20857 ph: (301) 827-6906 FAX: (301) 443-2143 Email: [log in to unmask]
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0101&L;=sanet-mg&P;=13410
Subject: BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001
Date: Tue, 9 Jan 2001 16:49:00 -0800
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
######### Bovine Spongiform Encephalopathy #########
Greetings List Members,
I was lucky enough to sit in on this BSE conference call today and even managed to ask a question. that is when the trouble started. I submitted a version of my notes to Sandra Blakeslee of the New York Times, whom seemed very upset, and rightly so. "They tell me it is a closed meeting and they will release whatever information they deem fit. Rather infuriating." and i would have been doing just fine, until i asked my question. i was surprised my time to ask a question so quick. (understand, these are taken from my notes for now. the spelling of names and such could be off.)
[host Richard Barns] and now a question from Terry S. Singeltary of CJD Watch.
[TSS] yes, thank you, U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?
[no answer, you could hear in the back ground, mumbling and 'we can't. have him ask the question again.]
[host Richard] could you repeat the question?
[TSS] U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?
[not sure whom ask this] what group are you with?
[TSS] CJD Watch, my Mom died from hvCJD and we are tracking CJD world-wide.
[not sure who is speaking] could you please disconnect Mr. Singeltary
[TSS] you are not going to answer my question?
[not sure whom speaking] NO
from this point, i was still connected, got to listen and tape the whole conference. at one point someone came on, a woman, and ask again;
[unknown woman] what group are you with?
[TSS] CJD Watch and my Mom died from hvCJD we are trying to tract down CJD and other human TSE's world wide. i was invited to sit in on this from someone inside the USDA/APHIS and that is why i am here. do you intend on banning me from this conference now?
at this point the conference was turned back up, and i got to finish listening. They never answered or even addressed my one question, or even addressed the issue. BUT, i will try and give you a run-down for now, of the conference. IF i were another Country, I would take heed to my notes, BUT PLEASE do not depend on them. ask for transcript from;
RBARNS@ORA.FDA.GOV 301-827-6906 he would be glad to give you one ;-)
Rockville Maryland, Richard Barns Host BSE issues in the U.S., How they were labelling ruminant feed?
Revising issues.
The conference opened up with the explaining of the U.K. BSE epidemic winding down with about 30 cases a week.
although new cases in other countries were now appearing.
Look at Germany whom said NO BSE and now have BSE.
BSE increasing across Europe. Because of Temporary Ban on certain rendered product, heightened interest in U.S.
A recent statement in Washington Post, said the New Administration (old GW) has a list of issues.
BSE is one of the issues. BSE Risk is still low, minimal in U.S. with a greater interest in MBM not to enter U.S.
HOWEVER, if BSE were to enter the U.S. it would be economically disastrous to the render, feed, cattle, industries, and for human health. (human health-they just threw that in cause i was listening.
I will now jot down some figures in which they told you, 'no need to write them down'. just hope i have them correct. hmmm, maybe i hope i don't ???)
80% inspection of rendering *Problem-Complete coverage of rendering HAS NOT occurred. sizeable number of 1st time FAILED INITIAL INSPECTION, have not been reinspected (70% to 80%).
Compliance critical, Compliance poor in U.K. and other European Firms. Gloria Dunason Major Assignment 1998 goal TOTAL compliance. This _did not_ occur.
Mixed level of compliance, depending on firm.
Rendering FDA license and NON FDA license system in place for home rendering & feed
76% in compliance
79% cross contamination
21% DID NOT have system
92% record keeping less than
60% total compliance
279 inspectors
185 handling prohibited materials
Renderer at top of pyramid, significant part of compliance.
84% compliance failed to have caution statement render 72% compliance & cross contamination caution statement on feed, 'DO NOT FEED TO CATTLE'
56 FIRMS NEVER INSPECTED
1240 FDA license feed mills
846 inspected
"close to 400 feed mills have not been inspected"
80% compliance for feed.
10% don't have system.
NON-FDA licensed mills There is NO inventory on non licensed mills.
approximately 6000 to 8000 Firms ???
4,344 ever inspected.
"FDA does not have a lot of experience with"
40% do NOT have caution statement 'DO NOT FEED'.
74% Commingling compliance
"This industry needs a lot of work and only half gotten to"
"700 Firms that were falitive, and need to be re-inspected, in addition to the 8,000 Firms."
Quote to do BSE inspection in 19 states by end of January or 30 days, and other states 60 days.
to change feed status???
Contract check and ask questions and pass info.
At this time, we will take questions.
[I was about the third or fourth to ask question. then all B.S.eee broke loose, and i lost my train of thought for a few minutes. picked back up here] someone asking about nutritional supplements and sourcing, did not get name. something about inspectors not knowing of BSE risk??? the conference person assuring that Steve Follum? and the TSE advisory Committee were handling that. Some other Dr. Vet, whom were asking questions that did not know what to do???
[Dennis Wilson] California Food Agr. Imports, are they looking at imports?
[Conference person] they are looking at imports, FDA issued imports Bulletin.
[Linda Singeltary ??? this was a another phone in question, not related i don't think] Why do we have non-licensed facilities?
(conference person) other feed mills do not handle as potent drugs???
Dennis Blank, Ken Jackson licensed 400 non FDA 4400 inspected of a total of 6000 to 8000, (they really don't know how many non licensed Firms in U.S. they guess 6000 to 8000??? TSS)
Linda Detwiler asking everyone (me) not to use emergency BSE number, unless last resort. (i thought of calling them today, and reporting the whole damn U.S. cattle herd ;-) 'not' Warren-Maryland Dept. Agr. Prudent to re-inspect after 3 years. concerned of Firms that have changed owners. THE END TSS
############ http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############
FROM New York TIMES
Subject: Re: BSE 50 STATE CONFERENCE CALL thread from BSE List and FDA Posting of cut version...
Date: Thu, 11 Jan 2001 22:02:47 -0700
From: "Sandy Blakeslee"
To: "Terry S. Singeltary Sr." References: 1
Hi terry -- thanks for all your help. I know it made a difference with the FDA getting out that release.
----- Original Message -----
From: "Terry S. Singeltary Sr."
To: XXXXXXXX
Sent: Thursday, January 11, 2001 2:06 PM
Subject: BSE 50 STATE CONFERENCE CALL thread from BSE List and FDA
----- Original Message -----
From: "Terry S. Singeltary Sr."
To: XXXXXXXX
Sent: Thursday, January 11, 2001 2:06 PM
Subject: BSE 50 STATE CONFERENCE CALL thread from BSE List and FDA
> hi sandy,
>From the New York Times NYTimes.com,
January 11, 2001
Many Makers of Feed Fail to Heed Rules on Mad Cow Disease
By SANDRA BLAKESLEE
Large numbers of companies involved in manufacturing animal feed are not complying with regulations meant to prevent the emergence and spread of mad cow disease in the United States, the Food and Drug Administration said yesterday.
The widespread failure of companies to follow the regulations, adopted in August 1997, does not mean that the American food supply is unsafe, Dr. Stephen Sundlof, director of the Center for Veterinary Medicine at the F.D.A., said in an interview.
But much more needs to be done to ensure that mad cow disease does not arise in this country, Dr. Sundlof said.
The regulations state that feed manufacturers and companies that render slaughtered animals into useful products generally may not feed mammals to cud-chewing animals, or ruminants, which can carry mad cow disease.
All products that contain rendered cattle or sheep must have a label that says, "Do not feed to ruminants," Dr. Sundlof said.
Manufacturers must also have a system to prevent ruminant products from being commingled with other rendered material like that from chicken, fish or pork.
Finally, all companies must keep records of where their products originated and where they were sold.
Under the regulations, F.D.A. district offices and state veterinary offices were required to inspect all rendering plants and feed mills to make sure companies complied.
But results issued yesterday demonstrate that more than three years later, different segments of the feed industry show varying levels of compliance.
Among 180 large companies that render cattle and another ruminant, sheep, nearly a quarter were not properly labeling their products and did not have a system to prevent commingling, the F.D.A. said.
And among 347 F.D.A.-licensed feed mills that handle ruminant materials - these tend to be large operators that mix drugs into their products - 20 percent were not using labels with the required caution statement, and 25 percent did not have a system to prevent commingling.
Then there are some 6,000 to 8,000 feed mills so small they do not require F.D.A. licenses.
They are nonetheless subject to the regulations, and of 1,593 small feed producers that handle ruminant material and have been inspected, 40 percent were not using approved labels and 25 percent had no system in place to prevent commingling.
On the other hand, fewer than 10 percent of companies, big and small, were failing to comply with the record-keeping regulations.
The American Feed Industry Association in Arlington, Va., did not return phone calls seeking comment.
see archive url link;
Subject: USDA/APHIS response to BSE-L--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001
Date: Wed, 10 Jan 2001 14:04:21 -0500
From: "Gomez, Thomas M."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
######### Bovine Spongiform Encephalopathy #########
USDA/APHIS would like to provide clarification on the following point from Mr. Singeltary's 9 Jan posting regarding the 50 state conference call. [Linda Detwiler asking everyone (me) not to use emergency BSE number, unless last resort. (i thought of calling them today, and reporting the whole damn U.S. cattle herd ;-) 'not'] Dr. Detwiler was responding to an announcement made during the call to use the FDA emergency number if anyone wanted to report a cow with signs suspect for BSE. Mr. Singeltary is correct that Dr. Detwiler asked participants to use the FDA emergency number as a last resort to report cattle suspect for BSE. What Mr. Singeltary failed to do was provide the List with Dr. Detwiler's entire statement. Surveillance for BSE in the United States is a cooperative effort between states, producers, private veterinarians, veterinary hospitals and the USDA. The system has been in place for over 10 years. Each state has a system in place wherein cases are reported to either the State Veterinarian, the federal Veterinarian in Charge or through the veterinary diagnostic laboratory system. The states also have provisions with emergency numbers. Dr. Detwiler asked participants to use the systems currently in place to avoid the possibility of a BSE-suspect report falling through the cracks. Use of the FDA emergency number has not been established as a means to report diseased cattle of any nature.
############ http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############
Subject: Re: USDA/APHIS response to BSE-L--U.S. 50 STATE CONFERENCE CALL Jan.9, 2001
Date: Wed, 10 Jan 2001 13:44:49 -0800
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de References: 1
######### Bovine Spongiform Encephalopathy #########
Hello Mr. Thomas,
> What Mr. Singeltary failed to do was provide
> the List with Dr. Detwiler's entire statement.
would you and the USDA/APHIS be so kind as to supply this list with a full text version of the conference call and or post on your web-site? if so when, and thank you. if not, why not?
> The system has been in place for over 10 years.
that seems to be a very long time for a system to be in place, and only test 10,700 cattle from some 1.5 BILLION head (including calf crop). Especially since French are testing some 20,000 weekly and the E.U. as a whole, are testing many many more than the U.S., with less cattle, same risk of BSE/TSEs. Why does the U.S. insist on not doing massive testing with the tests which the E.U. are using? Why is this, please explain? Please tell me why my question was not answered?
> U.S. cattle, what kind of guarantee can you
> give for serum or tissue donor herds?
It was a very simple question, a very important question, one that pertained to the topic of BSE/feed, and asked in a very diplomatic way. why was it not answered? If all these years, we have been hearing that pharmaceutical grade bovines were raised for pharmaceuticals vaccines etc. But yet the USA cannot comply with feed regulations of the ruminant feed ban, PLUS cannot even comply with the proper labelling of the feed, cross contamination etc. Then how in the world can you Guarantee the feed fed to pharmaceutical grade bovine, were actually non ruminant feed? Before i was ask to be 'disconnected', i did hear someone in the background say 'we can't'-- have him ask the question again. could you please be so kind, as to answer these questions?
thank you,
Terry S. Singeltary Sr.
Bacliff, Texas USA
P.S. if you will also notice, i did not post that emergency phone number and do not intend on passing it on to anyone. I was joking when i said i should call and report the whole damn U.S. Herd. So please pass that on to Dr. Detwiler, so she can rest easily. BUT, they should be reported, some are infected with TSE. The U.S. is just acting as stupid as Germany and other Countries that insist they are free of BSE. TSS
Subject: Report on the assessment of the Geographical BSE-risk of the USA July 2000 (not good)
Date: Wed, 17 Jan 2001 21:23:51 -0800
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
######### Bovine Spongiform Encephalopathy #########
Greetings List Members and ALL EU Countries,
Because of this report, and the recent findings of the 50-state BSE Conference call, I respectfully seriously suggest that these Countries and the SSC re-evaluate the U.S.A. G.B.R. to a risk factor of #3. snip...
Terry S. Singeltary Sr., P.O. Box , Bacliff, Texas USA 77518
http://www.fda.gov/ohrms/dockets/dailys/03/Jan03/012403/8004be07.html
CVM Update
Bovine spongiform encephalopathy (BSE) is a type of “transmissible spongiform encephalopathy” disease that infects cattle.
After the first case in 1986 in the United Kingdom, BSE quickly became an epidemic in cattle herds there.
No cases of BSE have been found in U.S. cattle, despite active monitoring.
Rendered feed ingredients contaminated with an infectious agent are believed to be the source of BSE infection in cattle.
Some of the feed given to cattle includes remnants of the slaughtering process, such as the brain and spinal cord, which may harbor the agent that causes BSE.
Although the material is cooked during the rendering process, the BSE agent can survive.
To prevent the establishment and amplification of BSE through feed in the United States, FDA implemented a final rule that prohibits the feeding of mammalian protein to ruminant animals in most cases. T
his rule, Title 21 Part 589.2000 of the Code of Federal Regulations, became effective on August 4, 1997.
FDA developed an enforcement plan with the goal of 100% compliance with this rule.
For the first two years it was in effect, the enforcement plan included education as well as inspections with FDA taking compliance actions for egregious actions or repeated non-compliance.
As part of the enforcement plan, an assignment was issued to all FDA District Offices in 1998 to conduct inspections of 100% of all renderers and feed mills and some ruminant feeders to determine compliance.
FDA's Center for Veterinary Medicine (CVM) has assembled data from the inspections conducted thus far, and presented the following data in a conference call FDA held with Federal and State feed control officials on January 9, 2001.
To date, there have been a total of 9,947 inspections.
The majority of these inspections (around 80%) were conducted by State officials and the remainder by FDA.
Various segments of the feed industry had different levels of compliance.
For Renderers, who are at the "top of the pyramid" since they are the first to handle rendered protein, and who send materials to feed mills and other ruminant feeders:
Total number of inspections -- 239.
Firms handling prohibited material -- 180
Firms whose products were labeled with the required caution statement -- 84%
Had a system to prevent commingling -- 72%
Followed recordkeeping regulations -- 96-98%
For FDA Licensed Feed Mills -- 1,240 total -- Inspected -- 846.
Of those feed mills inspected, 347 were handling prohibited material:
Firms whose products were labeled with the required caution statement -- 80% Had a system to prevent commingling -- 91% Followed recordkeeping regulations -- 98
For Non-FDA Licensed Feed Mills -- 4,344 inspected (FDA does not know the total number since they are not required to be licensed by the Agency, but it could be 6,000 - 8,000.)
Of those feed mills inspected, 1,593 were handling prohibited material:
Firms whose products were labeled with the required caution statement -- 59% Had a system to prevent commingling -- 74% Followed recordkeeping regulations -- 91%
FDA is continuing its enforcement efforts to achieve the goals of 100% inspection of all renderers and feed mills and some ruminant feeders and 100% compliance with the ruminant feed regulations.
FDA Field offices have an assignment to re-inspect 700 firms that were not in full compliance with the rule but have committed to implementing the regulation.
In addition, FDA is seeking assistance from State feed control officials to identify non-FDA licensed feed mills and to conduct additional inspections in all categories.
FDA anticipates higher levels of compliance after completion of follow-up inspections.
--------------------------------------------------------------------------------
Issued by:FDA, Center for Veterinary Medicine, Office of Management and Communications, HFV-127519 Standish Place, Rockville, MD 20855Telephone: (301) 827-3800 FAX: (301) 827-4065Internet Web Site: http://www.fda.gov/cvm http://www.fda.gov/cvm/bseup.htm
From: Subject: confidential
To: flounder@wt.net
Sorry did not get back to you. (Ran out of time!!)
Of interest...don't repeat.
On Jan 9, was somewhere and not able to tie into conference call. Was around an official who should have been on conference call.. another person with me also remembered it and we both inquired as to how the call went. Was told (to both of us) that the call had been cancelled!! (Told us several times that the call was cancelled and they did not know why!!!) I will try to find out why this person said that... maybe they got off the call or they were told to tell everyone that the call was cancelled. You need to POST your interaction with the conference call on a web site.... let me know when you do...
snip...
There must be a reason for the lying....??? Surely people who are really interested will found out what went on? There are quite a few people who listened in and declined to identify or acknowledge that they listened in... why the big secrecy or this person may have been told to do this. Need to know!!! Something dirty is going on... some sort of treachery seems to be in the works... Not a good situation for me right now... wish I could tell you more as to what is going on... but too dangerous right now... got to sort it out. ***
Date: Sun, 21 Jan 2001 23:50:31 +0000 (GMT)
From: Subject: stuff
To: "Terry S. Singeltary Sr."
Confidential:
Budget:
let me know what you find out and the breakdown. There may be some stuff stuffed into it which is not legit... They may figure some salaries and such... the real gist of the matter is the shocking amount of $ that is actually used to "ferret" out the disease and the $ that are used to P.R. the whole affair and give appearance of being concerned and involved... again it was said years ago and it should be taken seriously.... BSE will NEVER be found in the US! As for the BSE conference call...
I think you did a great service to freedom of information and making some people feign integrity... I find it scary to see that most of the "experts" are employed by the federal government or are supported on the "teat" of federal funds. A scary picture!
snip...
The most frightening thing I have read all day is the report of Gambetti's finding of a new strain of sporadic cjd in young people.........
Dear God, what in the name of all that is holy is that!!! If the US has different strains of scrapie..... why???? than the UK... then would the same mechanisms that make different strains of scrapie here make different strains of BSE... if the patterns are different in sheep and mice for scrapie..... could not the BSE be different in the cattle, in the mink, in the humans.......
I really think the slides or tissues and everything from these young people with the new strain of sporadic cjd should be put up to be analyzed by many, many experts in cjd........ bse..... scrapie Scrape the damn slide and put it into mice..... wait..... chop up the mouse brain and and spinal cord........ put into some more mice..... dammit amplify the thing and start the damned research..... This is NOT rocket science...
we need to use what we know and get off our butts and move.... the whining about how long everything takes..... well it takes a whole lot longer if you whine for a year and then start the research!!!
Not sure where I read this but it was a recent press release or something like that: I thought I would fall out of my chair when I read about how there was no worry about infectivity from a histopath slide or tissues because they are preserved in formic acid, or formalin or formaldehyde..... for God's sake........ Ask any pathologist in the UK what the brain tissues in the formalin looks like after a year....... it is a big fat sponge... the agent continues to eat the brain ...... you can't make slides anymore because the agent has never stopped........ and the old slides that are stained with Hemolysin and Eosin...... they get holier and holier and degenerate and continue... what you looked at 6 months ago is not there........ Gambetti better be photographing every damned thing he is looking at.....
Okay, you need to know. You don't need to pass it on as nothing will come of it and there is not a damned thing anyone can do about it. Don't even hint at it as it will be denied and laughed at.......... USDA is gonna do as little as possible until there is actually a human case in the USA of the nvcjd........ if you want to move this thing along and shake the earth.... then we gotta get the victims families to make sure whoever is doing the autopsy is credible, trustworthy, and a saint with the courage of Joan of Arc........ I am not kidding!!!! so, unless we get a human death from EXACTLY the same form with EXACTLY the same histopath lesions as seen in the UK nvcjd........ forget any action........ it is ALL gonna be sporadic!!! And, if there is a case....... there is gonna be every effort to link it to international travel, international food, etc. etc. etc. etc. etc. They will go so far as to find out if a sex partner had ever traveled to the UK/europe, etc. etc. .... It is gonna be a long, lonely, dangerous twisted journey to the truth. They have all the cards, all the money, and are willing to threaten and carry out those threats.... and this may be their biggest downfall...
Thanks as always for your help. Recently had a very startling revelation from a rather senior person in government here.......... knocked me out of my chair........ you must keep pushing. If I was a power person.... I would be demanding that there be at least a million bovine tested as soon as possible and aggressively seeking this disease. The big players are coming out of the woodwork as there is money to be made!!! In short: "FIRE AT WILL"!!! for the very dumb.... who's "will"! "Will be the burden to bare if there is any coverup!"
snip...end
========================
[Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified RiskMaterials for Human Food and Requirement for the Disposition of Non-Ambulatory Disabled Cattle
[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of BovineSpongiform Encephalopathy (BSE)
THE SEVEN SCIENTIST REPORT ***
PAUL BROWN M.D.
9 December 2005Division of Dockets Management (RFA-305) SEROLOGICALS CORPORATIONJames J. Kramer, Ph.D.Vice President, Corporate Operations
Full Text
Diagnosis and Reporting of Creutzfeldt-Jakob Disease Singeltary, Sr et al. JAMA.2001; 285: 733-734.
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
Correspondence to:
VIEWS & REVIEWS:
Ermias D. Belay, Ryan A. Maddox, Pierluigi Gambetti, and Lawrence B. Schonberger
Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States
Neurology 2003; 60: 176-181 [Abstract] [Full text] [PDF]
*Correspondence:
Submit a response to this article
Correspondence published:
[Read Correspondence] Reply to Singletary
Ryan A. Maddox, MPH, Ermias D. Belay, MD, Lawrence B. Schonberger, MD (26 March 2003)
[Read Correspondence] RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States
Terry S. Singeltary (26 March 2003)
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
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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
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Terry S. Singeltary, retired (medically) CJD WATCH
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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?
Re: vCJD in the USA * BSE in U.S.
15 November 1999
Terry S Singeltary,
NA
medically retired
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Re: Re: vCJD in the USA * BSE in U.S.
In reading the recent article in the BMJ about the potential BSE tests being developed in the U.S. and Bart Van Everbroeck reply. It does not surprize me, that the U.S. has been concealing vCJD. There have been people dying from CJD, with all the symptoms and pathological findings that resemble U.K. vCJD for some time. It just seems that when there is one found, they seem to change the clarical classification of the disease, to fit their agenda. I have several autopsies, stating kuru type amyloid plaques, one of the victims was 41 years of age. Also, my Mom died a most hideous death, Heidenhain Variant Creutzfeldt Jakob disease. Her symptoms resemble that of all the U.K. vCJD victims. She would jerk so bad at times, it would take 3 of us to hold her down, while she screamed "God, what's wrong with me, why can't I stop this." 1st of symptoms to death, 10 weeks, she went blind in the first few weeks. But, then they told me that this was just another strain of sporadic CJD. They can call it what ever they want, but I know what I saw, and what she went through. Sporadic, simply means, they do not know. My neighbors Mom also died from CJD. She had been taking a nutritional supplement which contained the following; vacuum dried bovine BRAIN, bone meal, bovine EYE, veal bone, bovine liver powder, bovine adrenal, vacuum dried bovine kidney, and vacuum dried porcine stomach. As I said, this woman taking these nutritional supplements, died from CJD. The particular batch of pills that was located, in which she was taking, was tested. From what I have heard, they came up negative, for the prion protein. But, in the same breath, they said their testing, may not have been strong enough to pick up the infectivity. Plus, she had been taking these type pills for years, so, could it have come from another batch?
CWD is just a small piece of a very big puzzle. I have seen while deer hunting, deer, squirrels and birds, eating from cattle feed troughs where they feed cattle, the high protein cattle by products, at least up until Aug. 4, 1997. So why would it be so hard to believe that this is how they might become infected with a TSE. Or, even by potentially infected land. It's been well documented that it could be possible, from scrapie. Cats becoming infected with a TSE. Have you ever read the ingredients on the labels of cat and dog food? But, they do not put these tissues from these animals in pharmaceuticals, cosmetics, nutritional supplements, hGH, hPG, blood products, heart valves, and the many more products that come from bovine, ovine, or porcine tissues and organs. So, as I said, this CWD would be a small piece of a very big puzzle. But, it is here, and it most likely has killed. You see, greed is what caused this catastrophe, rendering and feeding practices. But, once Pandora's box was opened, the potential routes of infection became endless.
No BSE in the U.S.A.? I would not be so sure of that considering that since 1990;
Since 1990 the U.S. has raised 1,250,880,700 cattle;
Since 1990 the U.S. has ONLY checked 8,881 cattle brains for BSE, as of Oct. 4, 1999;
There are apprx. 100,000 DOWNER cattle annually in the U.S., that up until Aug. 4, 1997 went to the renders for feed;
Scrapie running rampant for years in the U.S., 950 infected FLOCKS, as of Aug. 1999;
Our feeding and rendering practices have mirrored that of the U.K. for years, some say it was worse. Everything from the downer cattle, to those scrapie infected sheep, to any roadkill, including the city police horse and the circus elephant went to the renders for feed and other products for consumption. Then they only implemented a partial feed ban on Aug. 4, 1997, but pigs, chickens, dogs, and cats, and humans were exempt from that ban. So they can still feed pigs and chickens those potentially TSE tainted by-products, and then they can still feed those by-products back to the cows. I believe it was Dr. Joe Gibbs, that said, the prion protein, can survive the digestinal track. So you have stopped nothing. It was proven in Oprah Winfrey's trial, that Cactus Cattle feeders, sent neurologically ill cattle, some with encephalopathy stamped on the dead slips, were picked up and sent to the renders, along with sheep carcasses. Speaking of autopsies, I have a stack of them, from CJD victims. You would be surprised of the number of them, who ate cow brains, elk brains, deer brains, or hog brains.
I believe all these TSE's are going to be related, and originally caused by the same greedy Industries, and they will be many. Not just the Renders, but you now see, that they are re-using medical devices that were meant for disposal. Some medical institutions do not follow proper auto- claving procedures (even Olympus has put out a medical warning on their endescopes about CJD, and the fact you cannot properly clean these instruments from TSE's), and this is just one product. Another route of infection.
Regardless what the Federal Government in the U.S. says. It's here, I have seen it, and the longer they keep sweeping it under the rug and denying the fact that we have a serious problem, one that could surpass aids (not now, but in the years to come, due to the incubation period), they will be responsible for the continued spreading of this deadly disease.
It's their move, it's CHECK, but once CHECKMATE has been called, how many thousands or millions, will be at risk or infected or even dead. You can't play around with these TSE's. I cannot stress that enough. They are only looking at body bags, and the fact the count is so low. But, then you have to look at the fact it is not a reportable disease in most states, mis-diagnosis, no autopsies performed. The fact that their one-in-a- million theory is a crude survey done about 5 years ago, that's a joke, under the above circumstances. A bad joke indeed........
The truth will come, but how many more have to die such a hideous death. It's the Government's call, and they need to make a serious move, soon. This problem, potential epidemic, is not going away, by itself.
Terry S. Singeltary Sr. P.O., Bacliff, Texas 77518 USA flounder@wt.net
BRITISH MEDICAL JOURNAL BMJ
BMJ
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well...
Terry S Singeltary (2 January 2000)
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well... 2 January 2000
Terry S Singeltary
retired
Re: U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well...
In reading your short article about 'Scientist warn of CJD epidemic' news in brief Jan. 1, 2000. I find the findings in the PNAS old news, made famous again. Why is the U.S. still sitting on their butts, ignoring the facts? We have the beginning of a CJD epidemic in the U.S., and the U.S. Gov. is doing everything in it's power to conceal it.
The exact same recipe for B.S.E. existed in the U.S. for years and years. In reading over the Qualitative Analysis of BSE Risk Factors-1, this is a 25 page report by the USDA:APHIS:VS. It could have been done in one page. The first page, fourth paragraph says it all;
"Similarities exist in the two countries usage of continuous rendering technology and the lack of usage of solvents, however, large differences still remain with other risk factors which greatly reduce the potential risk at the national level."
Then, the next 24 pages tries to down-play the high risks of B.S.E. in the U.S., with nothing more than the cattle to sheep ratio count, and the geographical locations of herds and flocks. That's all the evidence they can come up with, in the next 24 pages.
Something else I find odd, page 16;
"In the United Kingdom there is much concern for a specific continuous rendering technology which uses lower temperatures and accounts for 25 percent of total output. This technology was _originally_ designed and imported from the United States. However, the specific application in the production process is _believed_ to be different in the two countries."
A few more factors to consider, page 15;
"Figure 26 compares animal protein production for the two countries. The calculations are based on slaughter numbers, fallen stock estimates, and product yield coefficients. This approach is used due to variation of up to 80 percent from different reported sources. At 3.6 million tons, the United States produces 8 times more animal rendered product than the United Kingdom."
"The risk of introducing the BSE agent through sheep meat and bone meal is more acute in both relative and absolute terms in the United Kingdom (Figures 27 and 28). Note that sheep meat and bone meal accounts for 14 percent, or 61 thousand tons, in the United Kingdom versus 0.6 percent or 22 thousand tons in the United States. For sheep greater than 1 year, this is less than one-tenth of one percent of the United States supply."
"The potential risk of amplification of the BSE agent through cattle meat and bone meal is much greater in the United States where it accounts for 59 percent of total product or almost 5 times more than the total amount of rendered product in the United Kingdom."
Considering, it would only take _one_ scrapie infected sheep to contaminate the feed. Considering Scrapie has run rampant in the U.S. for years, as of Aug. 1999, 950 scrapie infected flocks. Also, Considering only one quarter spoonful of scrapie infected material is lethal to a cow. Considering all this, the sheep to cow ration is meaningless. As I said, it's 24 pages of B.S.e.
To be continued...
Terry S. Singeltary Sr., Bacliff, Texas USA
your only fooling yourselves with this stupid ukbsenvcjd only theory, and the BSE methology of the OIE. most any country that went by those OIE BSE guidelines all went down with BSE.
THE OIE has now shown they are nothing more than a National Trading Brokerage for all strains of animal TSE. AS i said before, OIE should hang up there jock strap now, since it appears they will buckle every time a country makes some political hay about trade protocol, commodities and futures. IF they are not going to be science based, they should do everyone a favor and dissolve there organization. ... Page 95 of 98 8/3/2006
O.K., let me get this straight. after the first documented case of BSE in the USA, the rest i.e (the next two documented TSE cows) became atypical, of which USDA now wants us to believe are of a spontaneous nature, that feed did not cause this?
r i g h t ............
IF typical BSE spread via feed, why can't atypical BSE or BASE spread the same way ???
STUDIES in Mission Texas of USA sheep scrapie to USA produced a TSE unlike BSE.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db;=PubMed&list;_uids=8133096&dopt;=Citation
http://www.bseinquiry.gov.uk/files/sc/seac17/tab03.pdf
Visit to USA ... info on BSE and Scrapie
http://www.bseinquiry.gov.uk/files/yb/1988/10/00001001.pdf
snip...
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf
http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf
http://www.usaha.org/committees/reports/2005/report-scr-2005.pdf
Title: Experimental Transmission of Transmissible Mink Encephalopathy (Tme) to Cattle by Intracerebral Inoculation
Subject: USA MINK FARMS AND TSE TESTING ???
Date: July 15, 2006 at 5:52 am PST Pelt Production Up 3 Percent Mink pelt production in the United States in 2005 totaled2.63 million pelts, up 3 percent from 2004. Wisconsin, the largest mink producing State, produced 778,000 pelts. Utah the second largest producing State, produced 600,000 pelts. The number of pelts by color class as a percent of the total U.S. production in 2005 is as follows: Black at 47.6 percent, Mahoganyat 20.9 percent, Blue Iris at 11.3 percent, Demi/Wild at6.3 percent, Sapphire at 4.0 percent, and White at 3.8 percent. The remaining color classes accounted for 6.1 percent. Value of Pelt Production Up 33 Percent Mink pelts produced during the 2005 crop year were valued at$160 million, up 33 percent from $120 million a year ago. The average price per pelt for the 2005 crop year was $60.90, up from$47.10 in 2004. .....snip.......end
TME
3.9.11 Mink Producers Mink offal is now rendered with other species and will decline in value under the first four regulatory options.
2.8 PROFILE OF MINK PRODUCERS Mink are raised for their pelts and oil. Most mink farmers kill and pelt their own animals once a year near the end of November or in early December. Once the pelts are removed, the fat is then scrapped from the hide. This fat is used to manufacture mink oil that is sought for cosmetic uses because of its hypoallergenic qualities and in leather treatments. The total value of mink production in 1995 was $143 million, an increase of 72 percent from 1994. In 1995, 446 mink farms produced a total of 2.69 million pelts (NASS, 1996b). Mink producers vary in size but most are small operations. Mink farming is concentrated in Utah (130 2-11 farms), Wisconsin (77 farms), and Minnesota (52 farms). There has been recent consolidation within the industry, with the number of farms decreasing by 8 percent from 1993 to 1994 and 3 percent from 1994 to 1995. The market price for mink pelts is subject to wide demand fluctuations based on fashion and weather. Once the pelt and fat are removed, the entire carcass is then rendered. Mink carcasses sent to rendering (minus the pelt and fat) weigh an average of 2.5 pounds, so the total estimated offal produced per year is 6.7 million pounds. Mink farmers are reported to have difficulty with getting renderers to pick-up their material because of its low volume and the infrequency of offal generation.
WHAT sort of TME surveillance program is in place now, if any??? DO they test for TSE in Mink and what are these figures if so ???
ONE FINAL COMMENT PLEASE, (i know this is long Dr. Freas but please bare with me)
THE USA is in a most unique situation, one of unknown circumstances with human and animal TSE. THE USA has the most documented TSE in different species to date, with substrains growing in those species (BSE/BASE in cattle and CWD in deer and elk, there is evidence here with different strains), and we know that sheep scrapie has over 20 strains of the typical scrapie with atypical scrapie documented and also BSE is very likely to have passed to sheep. all of which have been rendered and fed back to animals for human and animal consumption, a frightening scenario. WE do not know the outcome, and to play with human life around the globe with the very likely TSE tainted blood from the USA, in my opinion is like playing Russian roulette, of long duration, with potential long and enduring consequences, of which once done, cannot be undone. These are the facts as i have come to know through daily and extensive research of TSE over 9 years, since 12/14/97. I do not pretend to have all the answers, but i do know to continue to believe in the ukbsenvcjd only theory of transmission to humans of only this one strain from only this one TSE from only this one part of the globe, will only lead to further failures, and needless exposure to humans from all strains of TSE, and possibly many more needless deaths from TSE via a multitude of proven routes and sources via many studies with primates and rodents and other species. ...
Terry S. Singeltary Sr. P.O. Bacliff, Texas USA 77518
----- Original Message -----
From: Terry S. Singeltary Sr.
To: Terry S. Singeltary Sr. ; FREAS@CBER.FDA.GOV
Cc: william.freas@fda.hhs.gov ; rosanna.harvey@fda.hhs.gov
Sent: Thursday, November 30, 2006 1:47 PM
Subject: Re: TSE advisory committee for the meeting December 15, 2006 [TSS SUBMISSION PART II]
SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE
Draft minutes of the 94th meeting held on 21st September 2006
Approval of draft open minutes from SEAC 94
snip...
ITEM 5 – CJD UPDATE
16. Dr Richard Knight (NCJDSU) provided an update on the
epidemiology of cases of sporadic CJD (sCJD) and vCJD in the UK
and elsewhere. Between May 1990 and June 2006, 845 cases of
sCJD had been identified in the UK with a mean age at onset of 66
(range 15-94) years and mean age of death of 67 (range 20-95)
years. There is no significant gender difference in sCJD incidence.
There had been a trend towards an increasing number of cases
over time to almost 80 cases per year in 2003. This phenomenon
had also been observed in other countries and was considered to
be a result of better ascertainment. Fewer cases were identified in
the UK in 2004 compared to 2003 and 2005 but this finding may
not be significant. The genotype distribution of sCJD cases was
64% methionine (M) M, 18% M valine (V) and 18% VV at codon
129 of the prion protein gene.
17. The total number of definite and probable vCJD cases in the UK up
to September 2006 was 162, with six cases still alive. Two of
these are considered to have been infected by blood transfusion
rather than a dietary route. No statistically significant gender
difference had been observed in vCJD cases. The age distribution
of vCJD had not altered over the course of the UK epidemic, with
the median age of death of 28 (range 12-72) years. The median
duration of clinical vCJD was 14 (range 6-40) months. Statistical
analysis of the UK incidence of deaths from vCJD suggested the
epidemic had peaked in 2000 with 28 deaths. All 141 vCJD cases
tested to date are of the MM genotype. Elsewhere in the world up
to September 2006, 34 vCJD cases have been reported with 20 in
France, four in the Republic of Ireland (RoI), two in the USA, two in
the Netherlands and single cases in Italy, Canada, Japan, Saudi
Arabia, Spain and Portugal. The clinical, pathological and prion
protein gene PrP codon 129 genotype of all these cases is similar
to that of UK cases. Infection was likely to have occurred in the UK
in two RoI cases, both USA cases, one French case and the
Japanese and Canadian cases.
18. Dr Knight explained that evidence from experiments to compare
BSE transmission to bovinised and humanised mice suggested a
significant barrier to transmission of BSE between cattle and
humans. There appears to much less of a barrier between
humans, suggesting that secondary transfer from human to human
may be relatively efficient. This is borne out by the three recent
blood transfusion associated cases of vCJD. However, although
all clinical cases of vCJD that have been genotyped are of the MM
genotype, there is evidence that cases of non-MM genotypes
should be expected. Infected individuals of non-MM genotypes
may have longer incubation periods, subclinical infections and, or a
different clinico-pathological phenotype. Experiments on the
transmission of vCJD to humanised mice of the MM, MV or VV
genotype suggested that susceptibility to vCJD was highest in MM,
lower in MV and lowest in VV18. Mice of MM and MV genotypes
showed similar rates of brain involvement, however differences in
neuropathology were observed between the three genotypes. The
incubation period was shortest in MM mice and a higher rate of
subclinical disease was found in MV and VV mice.
19. Dr Knight explained that data from the UK appendix and tonsil
study19 provided further evidence for the existence of subclinical
vCJD infections. In this survey, three out of 12 674 samples had
tested positive for abnormal prion protein (PrPSc), indicating a
prevalence of 237 (95% confidence interval 49-692) cases per
million. An extrapolation of these data suggest 3 808 (95%
confidence interval 785-11 128) people could be infected out of
approximately 16 million in the 10 to 30 year old age group.
However, the actual number of clinical cases of vCJD observed in
the 10 to 30 age group was 102, and in decline. The discrepancy
in observed and predicted cases in the 10 to 30 year age group
could be due to subclinical infections. Whether these individuals
will eventually develop vCJD clinical disease, with a longer
incubation period, is unknown. Importantly, two out of the three
positive appendix samples were VV, a much higher proportion than
the 11% of VV individuals in the UK population. If it is assumed
that the third positive appendix is non-VV, statistical analysis
indicates a prevalence ratio of VV to non-VV of 18:1. If the third
positive appendix is MM, then the VV:MM prevalence ratio is 8:1.
This suggests that, although VV may have the longest incubation
period, it may be most susceptible genotype. However, this
18 Bishop et al. (2006) Predicting susceptibility and incubation time of human-to-human
transmission of vCJD. Lancet Neurol. 5, 374-375
19 Hilton et al. (2004) Prevalence of lymphoreticular prion protein accumulation in UK tissue
samples. J. Pathol. 203, 733-739.
seemed counterintuitive and not consistent with data from
humanised mice, thus there may be an important unidentified
factor involved. Although the downward trend in vCJD clinical
cases is reassuring, it is possible that subclinical infections may be
more widespread. Further peaks in vCJD cases could occur,
however the timescale in which these peaks could occur is
uncertain. It is therefore very important to ascertain the prevalence
of subclinical infection in the UK population.
20. Dr Knight explained that three blood transfusion associated vCJD
cases had been identified through the Transfusion Medicine and
Epidemiological review (TMER)20. The first case (MM), developed
vCJD 6.5 years after receiving non-leucodepleted red blood cells
(RBC) from a donor, who themselves developed vCJD 3.3 years
after donation21. The second case (MM), developed vCJD 7.8
years after receiving non-leucodepleted RBC from a donor, who
themselves developed vCJD 1.8 years after donation. The third
case22(MV) died of a non-neurological illness five years after
receiving non-leucodepleted RBC from a donor, who themselves
developed vCJD 1.5 years after donation. PrPSc was detected in
the spleen of this recipient, with no other clinical or
neuropathological evidence of vCJD infection. Statistical analysis
indicated that the chances of the three recipients having developed
vCJD through consuming BSE infected meat was one in a
thousand million, therefore it could be concluded that transmission
had occurred via blood transfusion.
21. The TMER also identified 66 individuals who received blood from
donors who later developed vCJD. Out of these individuals, 42
recipients have died and of those still alive, seven have survived
over 10 years after receiving the donation, without developing
vCJD. There were 25 blood donations from 11 individuals that
subsequently developed vCJD that were used for plasma
fractionation, however no cases of vCJD have occurred in
recipients of plasma.
22. In the reverse TMER study, seven vCJD cases were identified as
having received blood from 121 identified donors, two of which
were known vCJD cases. If these two cases are excluded,
together with a third case, because of the small amount of time
between the onset of disease and the timing of the transfusion,
20 Hewitt et al. (2006) Creutzfeld-Jakob disease and blood transfusion: results of the UK
Transfusion Medicine Epidemiological Review Study. Vox Sang. 91, 221-230.
21 Llewelyn et al. (2004) Possible transmission of variant Creutzfeld Jakob disease by blood
transfusion. Lancet 363, 417-421.
22 Peden et al. (2004) Preclinical vCJD after blood transfusion in a PRNP codon 129
heterozygous patient. Lancet 364, 527-529.
four cases remain. One of these recipients received two
transfusions in the same year and developed clinical vCJD four or
five years post transfusion. In a second recipient of two blood
transfusions, the onset of vCJD was 17 years after the first
transfusion and between six and seven years after the second
transfusion. The two other recipients each received one
transfusion with the onset of vCJD at around six and 14 years
following transfusion.
23. The Chair noted that although the incidence of clinical vCJD was
reducing, recent evidence suggested that there may be a
substantial number of subclinical carriers that could potentially give
rise to secondary transmissions. Therefore it was very important to
know the prevalence of subclinical vCJD.
24. A member asked how the incidence of vCJD and BSE compare in
other countries, relative to that of the UK. Dr Knight indicated that
the numbers of BSE and vCJD cases in some countries correlate
poorly. In addition, in some countries the historic incidence of BSE
is not well known or uncertain and numbers of vCJD cases are too
small to make meaningful comparisons.
25. A member noted that the genotype of the PrPSc positive samples
from the appendix and tonsil survey raised many questions. These
include whether individuals of the VV genotype were protected
from clinical disease, whether PrPSc resided in the appendix rather
than in the brain in these individuals and whether these individuals
were themselves infectious. Further studies were needed to
answer these questions. A member noted that the susceptibility to
vCJD could not be equated with incubation time and asked
whether transmission studies using the PrPSc positive appendix
material were underway. Dr Knight was not aware if transmission
studies had begun on this material.
26. A member asked if the genotype of the transfused patients
surviving for 10 years after receiving vCJD infected blood was
known. Dr Knight indicated this was not known and agreed these
are important data.
27. Regarding the possible barrier to transmission of BSE from cattle
to humans, a member noted that this could be due to inefficient
entry or inefficient replication of the BSE agent in humans and
these possibilities are under investigation.
28. Members agreed it was important to continue surveillance to be
able to detect the onset of secondary epidemics of vCJD. It was
noted that there may be periods of a number of years with few or
no cases of vCJD, before an increase in cases may be observed.
snip...
39. Dr Gleadle explained that FSA will continue to develop the
contingency policy, should BSE be found in sheep. The current
policy involves a graduated response, with increasing levels of
control proposed depending on the number of unrelated cases of
BSE in sheep that might be identified. FSA would be asking for
advice from SEAC on the criteria for determining whether cases of
BSE are related, should more than one case of BSE be identified
in the national sheep flock, and on the appropriate level of
surveillance should BSE be found in sheep. SEAC would also be
consulted on the emerging science and contingency plans under
development in relation to atypical scrapie. FSA would continue to
maintain a watching brief on chronic wasting disease in deer and
may wish SEAC to comment on its project examining the
transmissibility of BSE to deer.
snip...
NCJDSU
42. Dr Knight explained that NCJDSU is considering how it may
identify new cases of human illness should they arise from
exposure to atypical scrapie or TSE cases in cattle that appear
different from BSE and to examine whether, as has been
suggested by some, there are links between sCJD and atypical
scrapie. He noted that the possibility of vCJD infection in
individuals of non-MM genotypes and that these individuals may
present with a different clinical phenotype, were particular areas of
uncertainty in relation to the vCJD epidemic. As the incubation
period of human TSEs was long, continued surveillance was very
important to identify new types of TSE and to identify potential
routes of secondary transmission. Evaluation of the sensitivity and
specificity of ante mortem blood tests for subclinical vCJD and the
appropriate use of blood samples from vCJD cases was also of
importance. It is likely that very large numbers of false positive
results would arise from blood tests and it would be very important
to consider the implications and handling of the results, prior to the
introduction of blood testing.
Discussion
43. The Chair explained that Professor John Collinge (National Prion
Unit [NPU]) had been invited to contribute to the horizon scanning
session, however he was unable to attend. However, Professor
Collinge had personally informed the Chair that the NPU had
partially characterised a number of mouse and human genes that
appear to modify the incubation period and susceptibility to TSEs.
Thus, it was possible that the clinical cases of vCJD identified to
date were in individuals from a group that are genetically the most
susceptible to this disease and further, possibly larger, numbers of
cases might appear in the future in other genetic groups. A
member noted that the prion protein gene is the major gene
influencing susceptibility to TSEs. Although other genes may
modify susceptibility to infection, they may have relatively small,
but possibly, additive effects. Professor Collinge had suggested
that some of the genes identified had substantial effects on the
susceptibility to infection. Members considered it important to
review these data when published. Dr Knight noted that EU
funded projects were examining the existence of such modifier
genes, using large numbers of subjects.
snip...
ITEM 9 – EVALUATION CRITERIA FOR ANTE MORTEM
DIAGNOSTIC TESTS FOR SUBCLINICAL vCJD (SEAC 94/3)
56. The Chair explained that the UK blood services and DH requested
SEAC’s advice on the scientific criteria by which ante mortem
diagnostic tests for subclinical vCJD could be validated. A position
statement would be produced based on the committee’s
consideration.
57. Dr John Stephenson (DH) presented an overview of DH research
related to the development and evaluation of ante mortem tests for
vCJD, prototype tests developed by commercial companies and
the work of DH advisory committees that had considered issues
related to diagnostic tests for vCJD. The available information on
prototype tests was limited for reasons of commercial sensitivity,
however most, if not all, appear to be based on the detection of
PrPSc. DH had set up a CJD Tissue Management Group to
oversee the collection and allocation of human tissues with which
to evaluate tests. However a new group was being convened with
a wider remit that included the allocation of blood samples and
oversight of the vCJD tissue resource centre at the National
Institute of Biological Standards and Controls (NIBSC). A
Subgroup of the Committee of Microbiological Safety of Blood
Tissues and Organs had provided advice on the preparative work
required, should a screening test for subclinical vCJD become
available. The Subgroup concluded that, unless a test was
developed with very high specificity, large numbers of false positive
results would be obtained leading to an unnecessary shortage of
blood, therefore a reliable confirmatory test was required.
Establishment of a panel of blood samples from cohorts of UK and
USA blood donors to evaluate diagnostic tests was also
recommended. The HPA Expert Advisory Group on a Testing
Strategy for NATA was considering the criteria for screening tests
for tonsil samples. The UK blood services have also convened the
Prion Assay Working Group to provide guidance on the suitability
of diagnostic tests for use within the blood services. The ethical
implications of screening tests for subclinical vCJD had been
considered by the HPA, together with the Nuffield Council for
Bioethics and a report was due for release.
58. Dr Roger Eglin (National Blood Service) presented an overview of
the performance requirements for screening tests for subclinical
vCJD for use in the blood services. It was considered that a
screening test must be CE marked23 and meet an, as yet
undefined, Common Technical Specification (CTS) for an Annex
IIA assay, as specified in the In Vitro Diagnostic Medical Devices
(IVD) Directive 98/79/EC. Initially a test should have a sensitivity
of at least one infectious dose (ID)/mL and a specificity that gave
an initial reactive result rate of below 0.3% and for a repeat
reactive result rate of below 0.15%. A panel of blood samples is
being prepared from 5 000 UK and 5 000 USA blood donors
separated into plasma, red cells and white cells to assess the
specificity of blood tests. It was envisaged that one or two other
tests would be performed on reactive samples from a screening
test to confirm the presence of PrPSc, with repeat positive results
resulting in deferral of the blood donor. Reactive samples from the
screening test could be confirmed by the secondary or tertiary test,
as the tests would all use a different mechanism(s) to capture the
analyte.
59. Dr Philip Minor (NIBSC) presented an overview of the samples
available for use in evaluation of tests for subclinical vCJD. These
include dilution series of brain and spleen from vCJD cases and
classical scrapie infected sheep, blood spiked with brain or spleen
from vCJD cases or healthy individuals and blood samples from
classical scrapie infected and healthy sheep. It was proposed that
large numbers of blood samples from classical scrapie endemic
and classical scrapie free flocks, UK and non UK blood donors and
importantly blood from vCJD cases be collected to assess and
compare the performance of diagnostic tests. In addition, panels
of blood collected from mice and sheep through the TSE
incubation period, from individuals classified as ‘at risk of vCJD for
public health purposes’ and from haemophiliacs would also be
useful to assess the time in the incubation period when blood
become infectious and detectable by tests.
60. Dr Minor noted that, at present, the performance of tests was not
specified and they could be freely marketed. However, should
diagnostic tests for subclinical vCJD be included in Annex IIA of
the IVD Directive 98/79/EC, all such tests would have to comply
with a CTS.
23 CE (Conformité Européene) mark is a declaration by the manufacturer that a product meets
all the necessary requirements of the relevant EU legislation.
61. Dr John Parry (HPA) provided an overview of the issues arising
from the evaluation, validation and implementation of blood tests in
relation to the human immunodeficiency virus.
62. Members agreed that it was very important that diagnostic tests for
subclinical vCJD be included in Annex IIA of the IVD Directive
98/79/EC, to ensure proper evaluation against a CTS.
63. A member noted that all the diagnostic tests were based on the
major assumption that PrPSc is a good marker of the infectious
agent, however PrPSc does not always correlate with TSE
infectivity. As a better marker has not been identified, PrPSc is
currently the most appropriate marker, although this assumption
should be reviewed in light of any data that may become available.
It must be recognised that PrPSc levels are a non quantitative
measure of infectivity. As the relationship between PrPSc and the
infectious agent is unclear, tests that recognise different parts of
the PrPSc molecule may produce conflicting results, possibly
making it difficult to identify suitable confirmatory tests. Therefore,
it would be very important in the evaluation of screening and
confirmatory blood tests that blood from vCJD cases be tested, as
blood from animal models or blood spiked with vCJD brain or
spleen may not reflect the response from tests when applied to the
detection of the vCJD agent in blood. Preliminary evaluation of the
specificity and sensitivity of tests could be achieved by using
spiked blood or blood from animal models, however final
evaluation of tests must include blood from vCJD cases.
64. A member queried whether there was any evidence that PrPSc is in
a different form in blood than in spleen or brain. Dr Minor
responded that there were no such data, however some tests were
able to detect both PrPSc in the brain and spleen, providing some
assurance that the test may detect the form of PrPSc in blood. A
member suggested that PrPSc may be in a more soluble form in
blood compared with the form in spleen or brain, thus it was
important to collect blood from preclinical and clinical vCJD
patients for use in the assessment of the efficacy of blood tests
and to assess the point in the incubation period when blood
becomes infectious. Blood collected from individuals “at risk of
vCJD for public health purposes” would provide a valuable source
of blood from potentially preclinical vCJD cases. This issue was
being considered by CGAG.
65. Members agreed that independent evaluation of tests using the
same panels of blood was very important. Dr Eglin noted that the
blood services have a Kit Evaluation Group which independently
evaluates test kits, using staff trained by the companies in the use
of their products.
66. A member noted that two key considerations for the applicability of
a blood test were the volume of material required and the
reproducibility of a concentration step, should it be required. Dr
Minor responded that tests vary in the volume of sample required
and the requirement for sample concentration. However
manufacturers recognise the difficulty a concentration step poses
to the blood services.
67. It was noted that work with the vCJD agent requires a category 3
containment facility. Dr Eglin responded that, as for the blood born
viruses, the screening is conducted on a largely negative
population and can be derogated to category 2 laboratory
conditions. However, further testing on reactive samples would be
undertaken in a category 3 laboratory.
68. A member asked whether any of the prototype diagnostic tests had
been assessed using blood from classical scrapie infected and
healthy sheep. Dr Minor explained that some companies had
obtained these samples and had been able to correctly identify
blood from infected animals. It was important that the same panels
of blood samples be sent to manufacturers to ensure a consistent
approach. However, stocks of these samples may be insufficient
to evaluate the number of diagnostic tests that may become
available.
69. A member asked about the collection of blood from vCJD patients
and whether there were sufficient samples available to evaluate
tests. Dr Knight explained that relatively small amounts of blood
had been collected and this had been fractionated into plasma, red
cells and white cells. Dr Minor suggested there was insufficient
blood from vCJD patients to conduct proper evaluations with the
required number of replicate tests. A member suggested collection
of larger volumes of ante mortem blood from vCJD cases. It was
also suggested that blood collected at post mortem from vCJD
cases would be a source of large quantities of blood. Dr Knight
explained that not all vCJD cases underwent autopsy and many
were performed up to two days after death when significant
autolysis may have occurred. Furthermore, it is difficult to obtain
large volumes of blood post mortem. It was suggested that blood
from familial cases of CJD be collected. Members noted that the
form of PrPSc may be different between familial CJD and vCJD and
that, unlike vCJD, familial cases of CJD did not express PrPSc
systemically. Members suggested that a non-human primate
model of vCJD could provide large volumes of blood.
70. The Chair considered it important that the volume of blood required
to evaluate diagnostic tests be calculated and that a mechanism to
acquire sufficient blood from vCJD patients was developed.
Replicate tests to evaluate the efficacy of tests could be conducted
using spiked blood samples and, or, blood from animal models.
However it is very important that the final evaluation is conducted
using blood from vCJD cases. Dr Stephenson noted that the CJD
Tissue Management Group was established to ensure that tissue
samples from vCJD cases were used appropriately. The Chair
noted that a number of research organisations had collected blood
from vCJD patients and these samples should be made available.
A Group was required to calculate the quantities of blood required
to evaluate tests, oversee the collection of samples, develop clear
performance criteria that must be fulfilled by manufacturers before
they receive these very valuable samples and to make decisions
about the supply of these samples to manufacturers. Dr
Stephenson responded that such a group was being convened at
NIBSC. Members considered it important there is coordination of
collection and supply of animal as well as human tissues.
71. The Chair suggested that risk assessments be conducted to
examine the required sensitivity and specificity for blood tests and
to examine scenarios of the effect of such tests on the blood
supply and transmission of vCJD.
72. Members noted that use of screening tests was not restricted to
the blood services and tests could be used for other purposes with
less stringent performance criteria. Use of tests for other purposes
may create a market that encourages commercial companies to
develop improved tests.
73. A member asked when an evaluated test might be available. Dr
Minor responded that a preliminary evaluation of tests could be
started relatively soon, however it was difficult to predict when a
fully evaluated and validated test may be implemented. Members
recommended that the ethical issues must be resolved prior to the
introduction of a blood test.
74. The Chair summarised the discussion, noting that:
• Until diagnostic tests for subclinical vCJD are included in
Annex IIA of the IVD Directive 98/79/EC and validated against
a defined CTS, the CE mark cannot be relied upon to indicate
a test had been properly evaluated and validated. In the
meantime, tests should be independently validated using
blinded samples.
• Preliminary evaluation of the specificity and sensitivity of tests
could be achieved using blood spiked with brain or spleen
from vCJD cases or blood from animal models. However, it is
very important that the final evaluation include testing of blood
from vCJD cases.
• It is critical to collect sufficient quantities of appropriate
tissues, to prepare panels of samples with which to evaluate
and validate tests and to manage this material appropriately.
Mechanisms need to be put in place to ensure these are
readily available for testing potential products, but that guard
against inappropriate use of a valuable resource.
• Risk assessments are required to establish the performance
requirements of blood tests and to examine scenarios of the
effect of introduction of such tests on the blood supply and
transmission of vCJD.
• The ethical issues around ante mortem testing for subclinical
vCJD need to be resolved prior to implementation of such
tests.
ITEM 10 – ANY OTHER BUSINESS
75. There was no other business.
snip...
http://www.seac.gov.uk/papers/95-1.pdf
13 European Commission Scientific Committee on Emerging and Newly Identified Health Risks
(2006) Safety of Human-derived Products with regard to vCJD
14 http://www.food.gov.uk/aboutus/ourboard/boardmeetings/boardmeetings2006/boardmeeting130706/agenda13jul06
15 http://www.food.gov.uk/news/newsarchive/2006/aug/srmupdate0708
16 http://www.seac.gov.uk/statements/state260106.htm
see SEAC archives;
Report from the SEAC Sheep Subgroup
Are the numbers of cases of vCJD in line with model predictions if the
only source of infection was cattle or is there evidence of an ovine
origin? Have vCJD cases from food borne sources stabilised or
declined?
20. There have, up to September 2006, been 162 definite and probable
cases of vCJD in the UK16. The Sheep Subgroup accepted the
data and conclusions on the human vCJD epidemic, presented at
SEAC 9417, that the number of vCJD cases is entirely consistent
with infection originating from BSE-infected cattle. Specifically, the
peak of the current wave of human cases mirrors the peak of
infected cattle entering the human food chain with a delay of
approximately eight years. However it was not possible to exclude
the possibility that another source of dietary infection was the
cause of a small proportion of the clinical vCJD cases. It would
only become apparent that there were non-bovine sources of
primary infection in the circumstance that a significant number of
vCJD cases arise in individuals who could only have been infected
after the introduction of the feed and SRM controls for cattle.
21. It was not possible to answer the question of whether vCJD cases
from food borne sources had stabilised or declined. The current
profile of clinical cases shows a peak in 2000, and a subsequent
decline. However, all these individuals are of the MM genotype and
further peaks of vCJD cases may well occur, with longer incubation
periods, in non-MM individuals still attributable to the original BSE
epidemic in cattle. It was noted that there were a number of cases
of vCJD worldwide, with no history of UK residence, whose source
of infection was not yet elucidated.
If BSE is present in the national sheep flock, what is the amount of BSE
infectivity that might be entering the food chain and from how many
sheep? How does this compare with the amount of infectivity that is
estimated to have entered the food chain historically due to bovine
and/or ovine BSE?
SEAC 95/2 Annex 1
DRAFT
Page 8
©SEAC 2006
22. The Sheep Subgroup noted that modelling12 showed that one BSE
infected sheep, close to the end of its incubation period, may
contribute 10 to 1000 times more infectious material to the food
chain than an infected cow. This is because thirty per cent of the
risk from a BSE infected sheep is likely to come from infectivity in
lymphatic and peripheral tissue that cannot be completely removed
from a carcass by removal of SRM under normal abattoir
conditions. This modelling indicated that although a maximum of
four flocks might currently harbour an ongoing BSE epidemic, the
annual human exposure from four flocks could be as much as
0.5% of the total exposure from cattle over the whole BSE
epidemic. This is, of course, a worst case scenario. Given that, to
date 162 definite and probable vCJD cases have arisen in the UK
ascribed to the bovine epidemic, extrapolation suggests that, in the
worst case, if BSE were in the UK sheep flock it might add a further
1 to 2 deaths per annum, assuming that these 162 cases
represented the total number of people infected through exposure
to cattle BSE. The most likely number is, however, zero.
23. From the modelling study12, small reductions in the risk of food
chain exposure from sheep could be achieved by strategies based
on tissue testing, a 12 month age restriction or expanded
definitions of high risk tissues. However, the most effective risk
reduction strategies would remain genotype based.
24. It was also noted that recent unpublished studies suggested that
the BSE agent, once passaged through ovine transgenic mice,
might become more virulent, transmitting more quickly with faster
incubation times and infecting a greater number of species.18 If this
result can be confirmed, extrapolation suggests that ovine BSE
may be more infectious to humans than bovine BSE. However, the
Subgroup has not seen the primary, unpublished, data and
therefore cannot comment on their reliability.
What reduction in risk to public health is delivered by
(i) an aim to produce small year on year increases in the percentage of
resistant and semi-resistant animals being eaten?
(ii) reduce the incidence of classical scrapie and BSE if present?
What studies are needed to inform on whether there is a risk to public
health from atypical scrapie? What data would lead the subgroup to
consider that atypical scrapie is a greater potential risk to public health
than BSE in sheep? How long are such studies likely to take? Can the
risks to consumers, if any, from BSE or atypical scrapie in sheep be
compared and if so, how?
33. No studies examining the human health risks of atypical scrapie
have been completed. Therefore, such a risk cannot yet be
excluded. Current risk reduction measures such as SRM and MBM
feeding bans reduce any risk, should it exist. The Subgroup
referred to its position statement which contained
recommendations for further studies6. The Subgroup noted that
experiments were under way to assess the transmissibility of
atypical scrapie in mice expressing human PrP genotypes. They
were encouraged by a recent report25, although the unpublished
data was not presented to the Subgroup, that atypical scrapie was
present in sheep samples from 1989, making it less likely that it is
a new and rapidly spreading infection or a risk to human health.
The Subgroup agreed that studies to assess the risk of atypical
scrapie relative to BSE and classical scrapie in mice would take
many years, and it needs to be recognised that results from the
mouse model alone may not necessarily inform whether or not
atypical scrapie is a human health risk.
34. On the transmissibility of atypical scrapie, which may have
implications for human health, it was suggested that relevant
25 Unpublished information from the Institute for Animal Health
departments should consider in advance their responses to results
which may emerge.
If the RGS continues, what are the risks associated with potentially
creating a sheep population that is susceptible to atypical scrapie?
What are the implications for a) human health and b) animal health?
35. The Subgroup agreed that the current RGS would likely be less
effective in reducing susceptibility to atypical scrapie in the national
flock than it is in reducing susceptibility to classical scrapie. It was
not yet clear how the RGS would alter susceptibility to atypical
scrapie in the national flock, and the present data are so scarce
that it is not possible to be certain whether the RGS would increase
or decrease prevalence26. It was agreed that further work was
needed to establish the prevalence of atypical scrapie within the
different genotypes and breeds, and modelling of these data could
inform on the expected impact of the RGS over the next 5 to 10
years on atypical scrapie prevalence.
36. The Subgroup was informed of preliminary and limited
epidemiological data27 indicating, on the basis of trading
associations, that atypical scrapie is unlikely to be spreading
quickly. Given a slow spread of disease, the Subgroup considered
that, since atypical scrapie cases were present in many European
countries, this is consistent with the hypothesis that it is not a new
disease but has been present for some considerable time. If
atypical scrapie has been present for 200 years, as has classical
scrapie, it was considered that the risks to human health would be
small. Data collected long term were needed to inform on this
aspect. To date, the earliest case of atypical scrapie in GB dates
back to 198925.
37. The RGS operates on a 3 codon screening system for codons 136,
154 and 171. The Subgroup recommended consideration of the
inclusion of codon 141 in any genotyping programme for sheep, to
take account of the importance of this allele regarding susceptibility
to atypical scrapie28.
38. There have been six clinical cases of atypical scrapie to October
2006 in the GB flock, but others may have gone undetected. The
26 Baylis M., Bishop S., Hope J. and Kao R., (2006) Analysis for the SEAC sheep subgroup
27 Data provided by Rowland Kao
28 Saunders G.C., Cawthraw S., Mountjoy S.J., Hope J. and Windl O. (2006) PrP genotypes
of atypical scrapie cases in Great Britain. J.Gen. Virol. 87, 3141-9
SEAC 95/2 Annex 1
DRAFT
Page 13
©SEAC 2006
full clinical phenotype is still undefined. It was noted that clinical
signs tend to appear in older animals than for classical scrapie.
The Subgroup considered the data insufficient to assess the
potential impact of atypical scrapie on animal health. Additional
research is needed here.
snip...full text ;
http://www.seac.gov.uk/papers/95-2.pdf
SRM controls at abattoirs and cutting plants
http://www.seac.gov.uk/papers/95-3.pdf
Report from the SEAC Epidemiology Subgroup
snip...
SEAC 95/4 ANNEX 1
Revised position statement of the SEAC Epidemiology Subgroup
B L A N K PAGE
2
© SEAC 2006
B L A N K PAGE
3
© SEAC 2006
http://www.seac.gov.uk/papers/95-4.pdf
Terry S. Singeltary Sr.
Bacliff, Texas USA 77518
----- Original Message -----
From: Terry S. Singeltary Sr.
To: FREAS@CBER.FDA.GOV Cc: william.freas@fda.hhs.gov ; rosanna.harvey@fda.hhs.gov
Sent: Wednesday, November 29, 2006 1:24 PM
Subject: TSE advisory committee for the meeting December 15, 2006 [TSS SUBMISSION]
November 29, 2006
Greetings FDA, DHH, Dr. Freas, and Dr. Harvey et al,
snip.....end...........TSS
2023 TSE Prion Zoonosis Zoonotic Risk Factors Should Be Updated
THE exposure rate of Cervid CWD exposure via consumption, then going on to have surgical, medical, dental, tissue donations, blood donations, there from, then tracing back CJD TSE Prion victims there from, would be impossible to traceback with todays surveillance traceback efforts, especially when the USDA et al can't even traceback BSE cattle to date (i will spare you those details, but will be in a url link at the bottom.).
iatrogenic CJD TSE PrP
least we forget...
*** Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery ***
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.
Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.
Friendly fire, pass it forward, they call it iatrogenic cjd, or what i call 'tse prion poker', are you all in $$$
all iatrogenic cjd is, is sporadic cjd, before the iatrogenic event is discovered, traced back, proven, documented, put into the academic domain, and then finally the public domain, this very seldom happens, thus problem solved, it's all sporadic cjd...
Friday, March 11, 2022
Prevalence of Surgical Procedures at Symptomatic Onset of Prion Disease
Research Letter Surgery
March 9, 2022
3rd CWD Zoonosis Zoonotic Science To Date
TUESDAY, MAY 11, 2021
***> A Unique Presentation of Creutzfeldt-Jakob Disease in a Patient Consuming Deer Antler Velvet <***
Conclusion
We believe that our patient’s case of CJD is highly suspicious for cervid etiology given the circumstances of the case as well as the strong evidence of plausibility reported in published literature. This is the first known case of CJD in a patient who had consumed deer antler velvet. Despite the confirmed diagnosis of CJD, a causal relationship between the patient’s disease and his consumption of deer antler velvet cannot be definitively concluded.
Supplemental data including molecular tissue sample analysis and autopsy findings could yield further supporting evidence. Given this patient’s clinical resemblance to CBD and the known histological similarities of CBD with CJD, clinicians should consider both diseases in the differential diagnosis of patients with a similarly esoteric presentation. Regardless of the origin of this patient’s disease, it is clear that the potential for prion transmission from cervids to humans should be further investigated by the academic community with considerable urgency.
''We believe that our patient’s case of CJD is highly suspicious for cervid etiology given the circumstances of the case as well as the strong evidence of plausibility reported in published literature. This is the first known case of CJD in a patient who had consumed deer antler velvet. Despite the confirmed diagnosis of CJD, a causal relationship between the patient’s disease and his consumption of deer antler velvet cannot be definitively concluded.''
Singeltary submission to the BSE Inquiry on CJD and Nutritional Supplements 1998
ABOUT that deer antler spray and CWD TSE PRION...
I have been screaming this since my neighbors mom died from cjd, and she had been taking a supplement that contained bovine brain, bovine eyeball, and other SRMs specified risk materials, the most high risk for mad cow disease.
just saying...
I made a submission to the BSE Inquiry long ago during the BSE Inquiry days, and they seemed pretty interested.
Sender: "Patricia Cantos"
To: "Terry S Singeltary Sr. (E-mail)"
Subject: Your submission to the Inquiry
Date: Fri, 3 Jul 1998 10:10:05 +0100
3 July 1998
Mr Terry S Singeltary Sr.
E-Mail: Flounder at wt.net
Ref: E2979
Dear Mr Singeltary,
Thank you for your E-mail message of the 30th of June 1998 providing the Inquiry with your further comments.
Thank you for offering to provide the Inquiry with any test results on the nutritional supplements your mother was taking before she died.
As requested I am sending you our general Information Pack and a copy of the Chairman's letter. Please contact me if your system cannot read the attachments.
Regarding your question, the Inquiry is looking into many aspects of the scientific evidence on BSE and nvCJD. I would refer you to the transcripts of evidence we have already heard which are found on our internet site at ;
http://www.bse.org.uk.
Could you please provide the Inquiry with a copy of the press article you refer to in your e-mail? If not an approximate date for the article so that we can locate it?
In the meantime, thank you for you comments. Please do not hesitate to contact me on...
snip...end...tss
everyone I tell this too gets it screwed up...MY MOTHER WAS NOT TAKING THOSE SUPPLEMENTS IPLEX (that I ever knew of). this was my neighbors mother that died exactly one year _previously_ and to the day of sporadic CJD that was diagnosed as Alzheimer’s at first. my mother died exactly a year later from the Heidenhain Variant of Creutzfeldt Jakob Disease hvCJD, and exceedingly rare strains of the ever growing sporadic CJD’s. _both_ cases confirmed. ...kind regards, terry
TSEs i.e. mad cow disease's BSE/BASE and NUTRITIONAL SUPPLEMENTS
IPLEX, mad by standard process;
vacuum dried bovine BRAIN, bone meal, bovine EYE, veal Bone, bovine liver powder, bovine adrenal, vacuum dried bovine kidney, and vacuum dried porcine stomach.
also;
what about potential mad cow candy bars ?
see their potential mad cow candy bar list too...
THESE are just a few of MANY of just this ONE COMPANY...TSS
''So, in sum, dietary supplements sold in the United States often contain ruminant tissues from undisclosed sources. Personally, I am rather squeamish and I don't think I would be eating prostate or testicle or pituitary, but I am also a little bit wary of consuming products with those glands, not just out of personal repugnance but simply out of a health concern.''
DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION CENTER FOR BIOLOGICS EVALUATION AND RESEARCH
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES ADVISORY COMMITTEE
Friday, January 19, 2001
snip...
15 Open Public Hearing
16 DR. FREAS: We are opening the open public hearing
17 now. We have received one response to speak in this
18 afternoon's open public hearing. That is from Dr. Scott
19 Norton. If Dr. Norton is here, would you please come
20 forward. You can either use the podium or the microphone,
21 whichever is your choice.
22 DR. NORTON: I am Scott Norton and I am a
23 physician in the Washington D.C. area. I am here speaking
24 as a private citizen today.
25 I first became concerned about the presence of
231
1 tissues from ruminant animals in dietary supplements about
2 six months ago and expressed my concern in a letter that was
3 published in New England Journal of Medicine in July of Year
4 2000.
5 A couple of the products that I had looked at, and
6 examined their labels, that raised these concerns I brought
7 in right here. I will just read some of the organs that are
8 found in one that is called Male Power. Deer antler,
9 pancreas, orchic--despite what we just heard that the FDA
10 prefers the term "testicular tissue" to be written on the
11 labels, I have never seen a dietary supplement say
12 "testicle." They always say "orchis" or "orchic" which may
13 sound rather flowery to the etymologically impaired--thymus,
14 adrenal, heart, lymph node, prostate, spleen and pituitary.
15 There are actually seventeen organs in that particular
16 product.
17 There is another product that is called Brain
18 Nutrition that tells us that it is vitamins and minerals
19 essential for important brain function. It does not mention
20 that there is any glandulars on at least the bold print.
21 But if you look at the small print on the back, we learn
22 that it has brain extract and pituitary extract, raw, in
23 there.
24 We know that many of the organs that can be found
25 in the dietary supplements do fall in that list of organs
232
1 that are suspect for contamination with TSEs, the labels, in
2 nearly all cases, identify neither the animal source nor the
3 geographic location from which the organs were derived. I
4 have seen one line that did specify from New Zealand cattle
5 but no other manufacturer will list either the species or
6 the geographic location.
7 The FDA's and the USDA's import alerts that we
8 just learned about prohibit the use of these organs in
9 foods, medicines and medical devices. But my reading of the
10 alert, 17-04, suggests that DSHEA does allow some loopholes
11 for these tissues to possible slip in.
12 I will just read from 17-04 that we heard. On the
13 first page, it says that, "This alert does not establish any
14 obligations on regulated entities." I love seeing
15 legislation that starts out with that caveat.
16 Then it says, further, "The USDA regulations do
17 not apply to bovine-derived materials intended for human
18 consumption as finished dietary supplements." We also learn
19 that the prohibition, or the import alert, is limited to
20 bulk lots of these tissues, completed tissues, from BSE-
21 derived countries. It does not mention if it is not a bulk
22 import or if it is raw materials rather than finished
23 materials.
24 Further, we know that it is strongly recommended
25 but not actually prohibited in the language here. So I have
233
1 not taken the assurances from that import alert that Dr.
2 Moore was trying to convey to us.
3 So, in sum, dietary supplements sold in the United
4 States often contain ruminant tissues from undisclosed
5 sources. Personally, I am rather squeamish and I don't
6 think I would be eating prostate or testicle or pituitary,
7 but I am also a little bit wary of consuming products with
8 those glands, not just out of personal repugnance but simply
9 out of a health concern.
10 So my question to the advisory committee is this;
11 is my caution reasonable and, if it is, should we take
12 further efforts to inform, or even protect, the American
13 public from such exposure.
14 I was curious about Dr. Moore's remarks. I sensed
15 two messages. One was the initial reassurance that FDA has
16 the regulatory authority but then I also learned that it is
17 the manufacturer's responsibility to provide those
18 assurances, that the FDA doesn't actually inspect.
19 I think that the FDA commissioners from Harvey
20 Wylie to David Kessler would say that that track record has
21 proven itself.
22 Thank you very much.
23 [Applause.]
24 DR. BROWN: Thanks, Dr. Norton.
25 Committee Discussion
snip...
17 But I think that we could exhibit some quite
18 reasonable concern about blood donors who are taking dietary
19 supplements that contain a certain amount of unspecified-
20 origin brain, brain-related, brain and pituitary material.
21 If they have done this for more than a sniff or something
22 like that, then, perhaps, they should be deferred as blood
23 donors.
24 That is probably worse than spending six months in
25 the U.K.
1/19/01
3681t2.rtf(845) page 501
see actual paper;
-------- Original Message --------
Subject: METABOLIFE AND TSEs GAO-03-494 ''URGENT DATA''
Date: Thu, 01 May 2003 11:23:01 -0500
From: "Terry S. Singeltary Sr."
To: NelliganJ at gao.gov
The General Accounting Office (GAO) today released the following reports and testimonies:
REPORTS
1. Dietary Supplements: Review of Health-Related Call Records for Users of Metabolife 356. GAO-03-494, March 31.
see updated url link;
GREETINGS GAO:
i was suprised that i did not see any listing of bovine tissue in metabolife on it's label. have they ceased using these desiccated tissues???
i see that the lable on this product METABOLIFE 356, does not state that it has any tissues of desiccated bovine organs? i no the product use to, so i am curious if they have ceased the use of the tissues of cattle they _use_ to use (see below)???
METABOLIFE 356 BOVINE COMPLEX/GLANDULAR SYSTEM OVARIES, PROSTATE, SCROTUM AND ADRENAL USDA SOURCE CATTLE
i tried warning them years ago of this potential threat of CJD/TSEs;
From: Randy Smith To: "'flounder at wt.net'" Subject: Metabolife Date: Mon, 7 Dec 1998 14:21:35 -0800
Dear Sir,
We are looking at reformulation. I agree that slow virus diseases present a problem in some areas of the world.
Our product uses healthy USDA inspected cattle for the glandular extract.
If you have any links to more information on this subject I would like to examine them.
Thank you for your interest and concern,
Dr. Smith ============
snip...
see full text ;
PRION CONFERENCE 2022 ABSTRACTS CWD TSE PrP ZOONOSIS
Transmission of prion infectivity from CWD-infected macaque tissues to rodent models demonstrates the zoonotic potential of chronic wasting disease.
Samia Hannaouia, Ginny Chenga, Wiebke Wemheuerb, Walter J. Schulz-Schaefferb, Sabine Gilcha, and Hermann M. Schätzla aDepartment of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine & Hotchkiss Brain Institute; University of Calgary, Calgary, Canada; bInstitute of Neuropathology, Medical Faculty, Saarland University, Homburg/Saar, Germany
Aims: Chronic wasting disease (CWD) is a prion disease of cervids. Its rapid geographic expansion, shedding of infectivity and persistence in the environment for many years are of concern for humans. Here, we provide the first evidence by transmission experiments to different transgenic mouse models and bank voles that Cynomolgus macaques inoculated via different routes with CWD-positive cervid tissues harbor infectious prions that elicit clinical disease in rodents.
Material and Methods: We used tissue materials from macaques inoculated with CWD to inoculate transgenic mice overexpressing cervid PrPCfollowed by transmission into bank voles. We used RT-QuIC, immunoblot and PET blot analysis to assess brains, spinal cords, and tissues of the gastrointestinal tract (GIT) for the presence of prions.
Results: Our results show that of the macaque materials that induced clinical disease in transgenic mice,73% were from the CNS (46% spinal cord and 27% brain), and 27% were from the spleen, although attack rates were low around 20%. Clinical mice did not display PK-resistant PrPSc(PrPres) in immunoblot, but showed low-levels of prion seeding activity. Transmission into bank voles from clinical transgenic mice led to a 100% attack rate with typical PrPressignature in immunoblot, which was different from that of voles inoculated directly with CWD or scrapie prions. High-level prion seeding activity in brain and spinal cord and PrPresdeposition in the brain were present. Remarkably, we also found prion seeding activity in GIT tissues of inoculated voles. Second passage in bank voles led to a 100% attack rate in voles inoculated with brain, spinal cord and small intestine material from first round animals, with PrPresin immunoblot, prion seeding activity, and PrPresdeposition in the brain. Shortened survival times indicate adaptation in the new host. This also shows that prions detected in GIT tissues are infectious and transmissible. Transmission of brain material from sick voles back to cervidized mice revealed transmission in these mice with a 100% attack rate, and interestingly, with different biochemical signature and distribution in the brain.
Conclusions: Our findings demonstrate that macaques, considered the best model for the zoonotic potential of prions, were infected upon CWD challenge, including oral one. The disease manifested as atypical in macaques and transgenic mice, but with infectivity present at all times, as unveiled in the bank vole model with an unusual tissue tropism.
Funded by: The National Institutes of Health, USA, and the Alberta Prion Research Institute/Alberta Innovates Canada. Grant number: 1R01NS121016-01; 201,600,023
Acknowledgement: We thank Umberto Agrimi, Istituto Superiore di Sanità, Rome, Italy, and Michael Beekes, Robert-Koch Institute Berlin, Germany, for providing the bank vole model. We thank the University of Calgary animal facility staff and Dr. Stephanie Anderson for animal care.
Transmission of Cervid Prions to Humanized Mice Demonstrates the Zoonotic Potential of CWD
Samia Hannaouia, Irina Zemlyankinaa, Sheng Chun Changa, Maria Immaculata Arifina, Vincent Béringueb, Debbie McKenziec, Hermann M. Schatzla, and Sabine Gilcha
aDepartment of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine; Hotchkiss Brain Institute; University of Calgary, Calgary, Canada; bUniversité Paris-Saclay, INRAE, UVSQ, VIM, Jouy-en-Josas, France; cDepartment of Biological Sciences, Center for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Canada
Aims: Chronic wasting disease (CWD), a prion disease of cervids, spreads efficiently among wild and farmed animals. Potential transmission to humans of CWD is a growing concern due to its increasing prevalence. Here, we aimed to determine the zoonotic potential of CWD using a mouse model for human prion diseases.
Material and Methods: Transgenic mice overexpressing human PrPChomozygous for methionine at codon 129 (tg650) were inoculated intracerebrally with brain homogenates of white-tailed deer infected with Wisc-1/CWD1 or 116AG CWD strains. Mice were monitored for clinical signs and were euthanized at terminal disease. Brains were tested by RT-QuIC, western blot upon PK digestion, and immunohistochemistry; fecal homogenates were analyzed by RT-QuIC. Brain/spinal cord and fecal homogenates of CWD-inoculated tg650 mice were inoculated into tg650 mice or bank voles. Brain homogenates of bank voles inoculated with fecal homogenates of CWD-infected tg650 mice were used for second passage in bank voles.
Results: Here, we provide the strongest evidence supporting the zoonotic potential of CWD prions, and their possible phenotype in humans. Inoculation of mice expressing human PrPCwith deer CWD isolates (strains Wisc-1 and 116AG) resulted in atypical clinical manifestations in > 75% of the mice, with myoclonus as leading clinical sign. Most of tg650brain homogenates were positive for seeding activity in RT-QuIC. Clinical disease and presentation was transmissible to tg650 mice and bank voles. Intriguingly, protease-resistant PrP in the brain of tg650 mice resembled that found in a familial human prion disease and was transmissible upon passage. Abnormal PrP aggregates upon infection with Wisc-1 were detectable in thalamus, hypothalamus, and midbrain/pons regions.
Unprecedented in human prion disease, feces of CWD-inoculated tg650 mice harbored prion seeding activity and infectious prions, as shown by inoculation of bank voles and tg650 with fecal homogenates.
Conclusions: This is the first evidence that CWD can infect humans and cause disease with a distinctive clinical presentation, signature, and tropism, which might be transmissible between humans while current diagnostic assays might fail to detect it. These findings have major implications for public health and CWD-management.
Funded by: We are grateful for financial support from the Natural Sciences and Engineering Research Council of Canada, the National Institutes of Health, Genome Canada, and the Alberta Prion Research Institute. SG is supported by the Canada Research Chairs program.
Acknowledgement: We thank Dr. Trent Bollinger, WCVM, University of Saskatchewan, Saskatoon, Canada, for providing brain tissue from the WTD-116AG isolate, Dr. Stéphane Haïk, ICM, Paris, France, for providing brain tissue from vCJD and sCJD cases, and Dr. Umberto Agrimi, Istituto Superiore di Sanità, Italy, for the bank vole model. We thank animal facility staff for animal care, Dr. Stephanie Anderson for veterinary oversight, and Yo-Ching Cheng for preparing recombinant PrP substrates. Thank you to Dr. Stephanie Booth and Jennifer Myskiw, Public Health Agency of Canada, Canada.
The chronic wasting disease agent from white-tailed deer is infectious to humanized mice after passage through raccoons
Eric Cassmanna, Xu Qib, Qingzhong Kongb, and Justin Greenleea
aNational Animal Disease Center, Agricultural Research Service, US Department of Agriculture, Ames, IA, USA bDepartments of Pathology, Neurology, National Center for Regenerative Medicine, and National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, Ohio, USA
Aims: Evaluate the zoonotic potential of the raccoon passaged chronic wasting disease (CWD) agent in humanized transgenic mice in comparison with the North American CWD agent from the original white-tailed deer host.
Material and Methods: Pooled brain material (GG96) from a CWD positive herd was used to oronasally inoculate two white-tailed deer with wild-type prion protein genotype and intracranially inoculate a raccoon. Brain homogenates (10% w/v) from the raccoon and the two white-tailed deer were used to intracranially inoculate separate groups of transgenic mice that express human prion protein with methionine (M) at codon 129 (Tg40h). Brains and spleens were collected from mice at experimental endpoints of clinical disease or approximately 700 days post-inoculation. Tissues were divided and homogenized or fixed in 10% buffered neutral formalin. Immunohistochemistry, enzyme immunoassay, and western blot were used to detect misfolded prion protein (PrPSc) in tissue.
Results: Humanized transgenic mice inoculated with the raccoon passaged CWD agent from white-tailed deer exhibited a 100% (12/12) attack rate with an average incubation period of 605 days. PrPScwas detected in brain tissue by enzyme immunoassay with an average optical density of 3.6/4.0 for positive brains. PrPScalso was detected in brain tissue by western blot and immunohistochemistry. No PrPScwas detected in the spleens of mice inoculated with the raccoon passaged CWD agent. Humanized mice inoculated with the CWD agent from white-tailed deer did not have detectable PrPScusing conventional immunoassay techniques.
Conclusions: The host range of the CWD agent from white-tailed deer was expanded in our experimental model after one passage through raccoons.
Funded by: This research was funded in its entirety by congressionally appropriated funds to the United States Department of Agriculture, Agricultural Research Service. The funders of the work did not influence study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Acknowledgement: We thank Quazetta Brown, Lexi Frese, Rylie Frese, Kevin Hassall, Leisa Mandell, and Trudy Tatum for providing excellent technical support to this project.
Stable and highly zoonotic cervid prion strain is possible
Manuel Camacho, Xu Qi, Liuting Qing, Sydney Smith, Jieji Hu, Wanyun Tao, Ignazio Cali, and Qingzhong Kong Department of Pathology, Case Western Reserve University, Cleveland, USA
Aims: Whether CWD prions can infect humans remains unclear despite the very substantial scale and long history of human exposure of CWD in some areas. Multiple in vitro conversion experiments and in vivo animal studies suggest that the CWD-to-human transmission barrier is not unbreakable. A major public health concern on CWD zoonosis is the emergence of highly zoonotic CWD strains. We aim to address the question of whether highly zoonotic CWD strains are possible.
Material and Methods: We inoculated a few sCJD brain samples into cervidized transgenic mice, which were intended as negative controls for bioassays of brain tissues from sCJD cases who had hunted or consumed vension from CWD-endemic states. Some of these mice became infected and their brain tissues were further examined by serial passages in humanized or cervidized mice.
Results: Passage of sCJDMM1 in transgenic mice expressing elk PrP (Tg12) resulted in a ‘cervidized’ CJD strain that we termed CJDElkPrP. We observed 100% transmission of CJDElkPrPin transgenic mice expressing human PrP (Tg40h). We passaged CJDElkPrPtwo more times in the Tg12 mice. We found that such second and third passage CJDElkPrPprions also led to 100% infection in the Tg40h mice. In contrast, we and others found zero or poor transmission of natural elk CWD isolates in humanized mice, despite that natural elk CWD isolates and CJDElkPrPshare the same elk PrP sequence.
Conclusions: Our data demonstrate that highly zoonotic cervid prion strains are not only possible but also can be stably maintained in cervids and that CWD zoonosis is prion strain-dependent.
Funded by: NIH
Grant number: R01NS052319, R01NS088604, R01NS109532
Acknowledgement: We want to thank the National Prion Disease Pathology Surveillance Center and Drs. Allen Jenny and Katherine O’Rourke for providing the sCJD samples and the CWD samples, respectively.
Adaptation of chronic wasting disease (CWD) prion strains in hosts with different PRNP genotypes
Camilo Duque Velasqueza,c, Elizabeth Triscotta,c, Chiye Kima,c, Diana Morenoa,c, Judd Aikenb,c, and Debbie McKenziea,c
aDepartment of Biological Science, University of Alberta, Edmonton, AB T6G 2G8, Canada; bDepartment of Agriculture, Food & Nutritional Science, University of Alberta, Edmonton, AB T6G 2G8, Canada; cCentre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB T6G 2M8, Canada
Aims: The contagious nature of CWD epizootics and the PrPCamino acid variation of cervids (and susceptible sympatric species) guarantee the expansion of prion conformational diversity and selective landscapes where new strains can arise. CWD strains can have novel transmission properties including altered host range that may increase zoonotic risk as circulating strains diversify and evolve. We are characterizing the host adaptability of characterized CWD strains as well as CWD isolates from different cervid species in various enzootic regions.
Material and Methods: Characterized CWD strains as well as a number of isolates from hunter-harvested deer were bioassayed in our rodent panel (transgenic mice expressing cervid alleles G96, S96 and H95-PrPC, elk PrPC, bovine PrPC, and both hamsters and non-transgenic laboratory mice). Strain characteristics were compared using computer based scoring of brain pathology (e.g. PrPCWDbrain distribution), western blot and protein misfolding cyclic amplification (PMCA).
Results: Transmission of various isolates resulted in the selection of strain mixtures in hosts expressing similar PrPC, particularly for polymorphic white-tailed deer and for Norwegian reindeer. As of the second passage, transmission of P153 moose prions from Norway has not resulted in emergence of strains with properties similar to any North American CWD strains in our taxonomic collection (Wisc-1, CWD2, H95+and 116AG).
Conclusions: Our data indicates polymorphic white-tailed deer can favor infection with more than one strain. Similar to transmission studies of Colorado CWD isolates from cervids expressing a single PrPCprimary structure, the isolate from Norway reindeer (V214) represents a strain mixture, suggesting intrinsic strain diversity in the Nordfjella epizootic. The diversity of CWD strains with distinct transmission characteristics represents a threat to wildlife, sympatric domestic animals and public health.
Funded by: Genome Canada and Genome Alberta (Alberta Prion Research Institute and Alberta Agriculture & Forestry); NSERC Grant number: #LSARP 10205; NSERC RGPIN-2017-05539
Acknowledgement: We would like to thank Margo Pybus (Alberta Environment and Parks) Trent Bollinger (University of Saskatchewan) for providing us with tissue samples from hunter-harvested deer and Sylvie Benestad for providing moose and reindeer samples.
Application of PMCA to understand CWD prion strains, species barrier and zoonotic potential
Sandra Pritzkowa, Damian Gorskia, Frank Ramireza, Fei Wanga, Glenn C. Tellingb, Justin J. Greenleec, Sylvie L. Benestadd, and Claudio Sotoa aDepartment of Neurology, University of Texas Medical School at Houston, Houston, Texas, USA; bDepartment of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA; cVirus and Prion Research Unit, United States Department of Agriculture, Ames, Iowa, USA; dNorwegian Veterinary Institute, OIE Reference Laboratory for CWD, Ås, Norway
Aims: Chronic wasting disease (CWD) is a prion disease affecting various species of cervids that continues to spread uncontrollably across North America and has recently been detected in Scandinavia (Norway, Sweden and Finland). The mechanisms responsible for the natural transmission of CWD are largely unknown. Furthermore, the risk of CWD transmission to other species, including humans, is also unknown and remains a dangerous enigma. In this study, we investigated the potential of CWD prions to infect several other animal species (sheep, cattle, pig, hamster, and mouse) including humans, by examining their capacity to convert the normal prion protein of distinct species in a PMCA reaction. Moreover, we also investigated whether the in vivo passage of CWD through intermediate species alters their capacity for zoonotic transmission, which may represent a major hazard to human health.
Material and Methods: For these studies, we used brain material from CWD-infected white-tailed deer (Odocoileus virginianus), elk (Cervus canadensis), and mule deer (Odocoileus hemionus) as species native to North America. We also used CWD-infected Moose (Alces alces), reindeer (Rangifer tarandus) and red deer (Cervus elaphus) as Norwegian cervids. We also used brains from cattle, sheep and pigs experimentally infected by CWD. To study interspecies-transmission and zoonotic potential, samples were tested via PMCA for the conversion of PrPCinto PrPScusing different combinations of inoculum and host species. Based on these analyses we estimated the spillover and zoonotic potential for different CWD isolates. We define and quantify spillover and zoonotic potential indices as the efficiency by which CWD prions sustain prion generation in vitro at the expense of normal prion proteins from various mammals and human, respectively.
Results: Our results show that prions from some cervid species, especially those found in Northern Europe, have a higher potential to transmit disease characteristics to other animals. Conversely, CWD-infected cervids originated in North America appear to have a greater potential to generate human PrPSc. We also found that in vivo transmission of CWD to cattle, but not to sheep or pigs substantially increases the ability of these prions to convert human PrPCby PMCA.
Conclusions: Our findings support the existence of different CWD prion strains with distinct spillover and zoonotic potentials. We also conclude that transmission of CWD to other animal species may increase the risk for CWD transmission to humans. Our studies may provide a tool to predict the array of animal species that a given CWD prion could affect and may contribute to understanding the risk of CWD for human health.
Funded by: National Institute of Health Grant number: P01 AI077774
Generation of human chronic wasting disease in transgenic mice
Zerui Wanga, Kefeng Qinb, Manuel V. Camachoa, Ignazio Cali a,c, Jue Yuana, Pingping Shena, Tricia Gillilanda, Syed Zahid Ali Shaha, Maria Gerasimenkoa, Michelle Tanga, Sarada Rajamanickama, Anika Yadatia, Lawrence B. Schonbergerd, Justin Greenleee, Qingzhong Konga,c, James A. Mastriannib, and Wen-Quan Zoua,c
aDepartment of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA; bDepartment of Neurology and Center for Comprehensive Care and Research on Memory Disorders, the University of Chicago Pritzker School of Medicine, Chicago, USA; cNational Prion Disease Pathology Surveillance Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA; dDivision of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA, USA; eVirus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, 1920 Dayton Avenue, Ames, IA, USA
Aims: Chronic wasting disease (CWD) results from the accumulation of an infectious misfolded conformer (PrPSc) of cellular prion protein (PrPC) in the brains of deer and elk. It has been spreading rapidly throughout many regions of North America, exported inadvertently to South Korea, and more recently identified in Europe. Mad cow disease has caused variant Creutzfeldt-Jakob disease (vCJD) in humans and is currently the only known zoonotic prion disease. Whether CWD is transmissible to humans remains uncertain. The aims of our study were not only to confirm whether CWD prion isolates can convert human brain PrPCinto PrPScin vitro by serial protein misfolding cyclic amplification (sPMCA) but also to determine whether the sPMCA-induced CWD-derived human PrPScis infectious.
Material and Methods: Eight CWD prion isolates from 7 elks and 1 deer were used as the seeds while normal human brain homogenates containing either PrP-129 MM (n = 2) or PrP-129 VV (n = 1) were used as the substrates for sPMCA assay. A normal elk brain tissue sample was used as a negative control seed. Two lines of humanized transgenic (Tg) mice expressing either human PrP-129VV or −129 MM polymorphism were included for transmission studies to determine the infectivity of PMCA-amplified PrPSc. Wester blotting and immunohistochemistry and hematoxylin & eosin staining were used for determining PrPScand neuropathological changes of inoculated animals.
Results: We report here the generation of the first CWD-derived infectious human PrPScusing elk CWD PrPScto initiate conversion of human PrPCfrom normal human brain homogenates with PMCA in vitro. Western blotting with a human PrP selective antibody confirmed that the PMCA-generated protease-resistant PrPScwas derived from the human brain PrPCsubstrate. Two lines of humanized transgenic mice expressing human PrPCwith either Val or Met at the polymorphic codon 129 developed clinical prion disease following intracerebral inoculation with the PMCA-generated CWD-derived human PrPSc. Diseased mice exhibited distinct PrPScpatterns and neuropathological changes in the brain.
Conclusions: Our study, using PMCA and animal bioassays, provides the first evidence that CWD PrPSchas the potential to overcome the species barrier and directly convert human PrPCinto infectious PrPScthat can produce bona fide prion disease when inoculated into humanized transgenic mice.
Funded by: CJD Foundation and NIH
Mortality surveillance of persons potentially exposed to chronic wasting disease
R.A. Maddoxa, R.F. Klosb, L.R. Willb, S.N. Gibbons-Burgenerb, A. Mvilongoa, J.Y. Abramsa, B.S. Applebyc, L.B. Schonbergera, and E.D. Belaya aNational Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, USA; bWisconsin Department of Health Services (WDHS), Division of Public Health, Madison, USA; cNational Prion Disease Pathology Surveillance Center (NPDPSC), Case Western Reserve University, Cleveland, USA
Aims: It is unknown whether chronic wasting disease (CWD), a prion disease of cervids, can infect people, but consumption of meat from infected animals would be the most likely route of transmission. Wisconsin Department of Health Services, Division of Public Health (WDHS) personnel maintain a database consisting of information collected from hunters who reported eating, or an intention to eat, venison from CWD-positive cervids. These data, collected since 2003, allow for the evaluation of causes of mortality in individuals potentially exposed to CWD.
Material and Methods: The WDHS database contains the name, date of birth, when available, year of CWD-positive deer harvest, and city and state of residence for each potentially exposed individual. The database also includes information on how the deer was processed (self-processed or by a commercial operator) and when applicable, names of others with whom the venison was shared. Duplicate entries (i.e., those who consumed venison from CWD-positive deer in multiple hunt years) are determined by first name, last name, and date of birth. All names in the database are cross-checked with reported cases of human prion disease in Wisconsin and cases in the National Prion Disease Pathology Surveillance Center (NPDPSC) diagnostic testing database. Persons with date of birth available are also cross-checked with prion disease decedents identified through restricted-use national multiple cause-of-death data via a data use agreement with the National Center for Health Statistics (NCHS).
Results: The database currently consists of 1561 records for hunt years 2003–2017 and 87 additional records for 2018–2019. Of these, 657 records have accompanying date of birth; 15 entries were removed as duplicates leaving 642 unique individuals. Of these individuals, 278 of 426 (66%) who ate venison from a CWD-positive deer and provided processing information reported self-processing. No matches were found among any persons in the database cross-checked with WDHS human prion disease surveillance data, NPDPSC data (February 2022 update), and NCHS data through 2020.
Conclusions: Because of the linkage of person and CWD-positive animal in the WDHS database, reviewing the cause of mortality in potentially exposed persons is possible. The number of individuals cross-checked so far is likely only a small percentage of those potentially exposed to CWD in Wisconsin, and many more years of vital status tracking are needed given an expected long incubation period should transmission to humans occur. Nevertheless, the findings of this ongoing review are thus far reassuring.
Prion disease incidence, United States, 2003–2020
R.A. Maddoxa, M.K. Persona, K. Kotobellib, A. Mvilongoa, B.S. Applebyb, L.B. Schonbergera, T.A. Hammetta, J.Y. Abramsa, and E.D. Belaya aNational Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, USA; bNational Prion Disease Pathology Surveillance Center (NPDPSC), Case Western Reserve University, Cleveland, USA
Aims: Mortality data, in conjunction with neuropathological and genetic testing results, are used to estimate prion disease incidence in the United States.
Material and Methods: Prion disease decedents for 2003–2020 were identified from restricted-use U.S. national multiple cause-of-death data, via a data use agreement with the National Center for Health Statistics, and from the National Prion Disease Pathology Surveillance Center (NPDPSC) database. NPDPSC decedents with neuropathological or genetic test results positive for prion disease for whom no likely match was found in the NCHS multiple cause-of-death data were added as cases for incidence calculations, while those with negative neuropathology results but with cause-of-death data indicating prion disease were removed. Unmatched cases in the NPDPSC database lacking neuropathological testing but with a positive real-time quaking-induced conversion (RT-QuIC) test result were additionally assessed. Age-specific and age-adjusted average annual incidence rates were calculated from the combined data; the year 2000 as the standard population and the direct method were used for age-adjustment.
Results: A total of 7,921 decedents were identified as having prion disease during 2003–2020 for an age-adjusted average annual incidence of 1.2 per million population. The age-adjusted incidence between males and females (1.3 and 1.1 per million, respectively) differed significantly (p < 0.0001). The age-specific average annual incidence among those <55 and ≥55 years of age was 0.2 and 4.8 per million, respectively; incidence among those ≥65 was 6.1 per million. Eighteen cases were <30 years of age for an age-specific incidence of 8.0 per billion; only 6 of these very young cases were sporadic (3 sporadic CJD, 3 sporadic fatal insomnia), with the rest being familial (9), variant (2), or iatrogenic (1). The age-adjusted annual incidence for the most recent year of data, 2020, was 1.3 per million. However, assessment of RT-QuIC positive cases lacking neuropathology in the NPDPSC database suggested that approximately 20% more cases may have occurred in that year; the addition of a subset of these cases that had date of death information available (n = 44) increased the 2020 rate to 1.4 per million.
Conclusions: Mortality data supplemented with the results of neuropathological, CSF RT-QuIC, and genetic testing can be used to estimate prion disease incidence. However, the identification in the NPDPSC database of RT-QuIC-positive cases lacking date of death information suggests that this strategy may exclude a number of probable prion disease cases. Prion disease cases <30 years of age, especially those lacking a pathogenic mutation, continue to be very rare.
Shedding of Chronic Wasting Disease Prions in Multiple Excreta Throughout Disease Course in White-tailed Deer
Nathaniel D. Denkersa, Erin E. McNultya, Caitlyn N. Krafta, Amy V. Nallsa, Joseph A. Westricha, Wilfred Goldmannb, Candace K. Mathiasona, and Edward A. Hoovera
aPrion Research Center, College of Veterinary Medicine and Biological Sciences, Department of Microbiology, Immunology, and Pathology; Colorado State University, Fort Collins, CO, USA; bDivision of Infection and Immunity, The Roslin Institute and the Royal Dick School of Veterinary Studies, University of Edinburgh, Midlothian, UK
Aims: Chronic wasting disease (CWD) now infects cervids in South Korea, North America, and Scandinavia. CWD is unique in its efficient transmission and shedding of prions in body fluids throughout long course infections. Questions remain as to the magnitude of shedding and the route of prion acquisition. As CWD continues to expand, the need to better understand these facets of disease becomes more pertinent. The purpose of the studies described was to define the longitudinal shedding profile of CWD prions in urine, saliva, and feces throughout the course of infection in white-tailed deer.
Material and Methods: Twelve (12) white-tailed deer were inoculated with either 1 mg or 300ng of CWD. Urine, saliva, and feces were collected every 3-month post-inoculation (MPI) throughout the study duration. Cohorts were established based on PNRP genotype: codon 96 GG (n = 6) and alternate codons 96 GS (n = 5) & 103NT (n = 1). Urine and saliva were analyzed using iron-oxide magnetic extraction (IOME) and real-time quaking induced conversion (RT-QuIC)(IQ). Feces were subjected to IOME, followed by 4 rounds protein misfolding cyclic amplification (PMCA) with products analyzed by RT-QuIC (IPQ). To determine whether IPQ may be superior to IQ, a subset of urine and saliva were also tested by IPQ. Results were compared with clinical disease status.
Results: Within the 96 GG cohort, positive seeding activity was detected in feces from all deer (100%), in saliva from 5 of 6 (83%), and in urine from 4 of 6 (66%). Shedding in all excreta occurred at, or just after, the first positive tonsil biopsy result. In the 96 GS/103NT cohort, positive seeding activity could be detected in feces from 3 of 6 (50%) deer, saliva in 2 of 6 (33%), and urine in 1 of 6 (16%). Shedding in excreta was detected >5 months after the first tonsil positive result. Four of six 96 GG deer developed clinical signs of CWD, whereas only 2 of the 96 GS/103NT did. Shedding was more frequently detected in deer with clinical disease. The IPQ protocol did not significantly improve detection in saliva or urine samples, however, it significantly augmented detection in feces by eliminating non-specific background commonly experienced with IQ. Negative control samples remained negative in samples tested.
Conclusions: These studies demonstrate: (a) CWD prion excretion occurs throughout infection; (2) PRNP genotype (GG≫GS/NT) influences the excreta shedding; and (3) detection sensitivity in excreta can vary with different RT-QuIC protocols. These results provide a more complete perspective of prion shedding in deer during the course of CWD infection.
Funded by: National Institutes of Health (NIH)
Grant number: RO1-NS061902-09 R to EAH, PO1-AI077774 to EAH, and R01-AI112956-06 to CKM
Acknowledgement: We abundantly thank Sallie Dahmes at WASCO and David Osborn and Gino D’Angelo at the University of Georgia Warnell School of Forestry and Natural Resources for their long-standing support of this work through provision of the hand-raised, CWD-free, white-tailed deer used in these studies
Large-scale PMCA screening of retropharyngeal lymph nodes and in white-tailed deer and comparisons with ELISA and IHC: the Texas CWD study
Rebeca Benaventea, Paulina Sotoa, Mitch Lockwoodb, and Rodrigo Moralesa
aDepartment of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Texas, USA; bTexas Park and Wildlife Department, Texas, USA
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy that affects various species of cervids, and both free-ranging and captive animals. Until now, CWD has been detected in 3 continents: North America, Europe, and Asia. CWD prevalence in some states may reach 30% of total animals. In Texas, the first case of CWD was reported in a free-range mule deer in Hudspeth and now it has been detected in additional 14 counties. Currently, the gold standard techniques used for CWD screening and detection are ELISA and immunohistochemistry (IHC) of obex and retropharyngeal lymph nodes (RPLN). Unfortunately, these methods are known for having a low diagnostic sensitivity. Hence, many CWD-infected animals at pre-symptomatic stages may be misdiagnosed. Two promising in vitro prion amplification techniques, including the real-time quaking-induced conversion (RT-QuIC) and the protein misfolding cyclic amplification (PMCA) have been used to diagnose CWD and other prion diseases in several tissues and bodily fluids. Considering the low cost and speed of RT-QuIC, two recent studies have communicated the potential of this technique to diagnose CWD prions in RPLN samples. Unfortunately, the data presented in these articles suggest that identification of CWD positive samples is comparable to the currently used ELISA and IHC protocols. Similar studies using the PMCA technique have not been reported.
Aims: Compare the CWD diagnostic potential of PMCA with ELISA and IHC in RPLN samples from captive and free-range white-tailed deer. Material and Methods: In this study we analyzed 1,003 RPLN from both free-ranging and captive white-tailed deer collected in Texas. Samples were interrogated with the PMCA technique for their content of CWD prions. PMCA data was compared with the results obtained through currently approved techniques.
Results: Our results show a 15-fold increase in CWD detection in free-range deer compared with ELISA. Our results unveil the presence of prion infected animals in Texas counties with no previous history of CWD. In the case of captive deer, we detected a 16% more CWD positive animals when compared with IHC. Interestingly, some of these positive samples displayed differences in their electroforetic mobilities, suggesting the presence of different prion strains within the State of Texas.
Conclusions: PMCA sensitivity is significantly higher than the current gold standards techniques IHC and ELISA and would be a good tool for rapid CWD screening.
Funded by: USDA
Grant number: AP20VSSPRS00C143
ATYPRION project: assessing the zoonotic potential of interspecies transmission of CWD isolates to livestock (preliminary results).
Enric Vidala,b, Juan Carlos Espinosac, Samanta Gilera,b, Montserrat Ordóñeza,b, Guillermo Canteroa,b, Vincent Béringued, Justin J. Greenleee, and Juan Maria Torresc
aUnitat mixta d’Investigació IRTA-UAB en Sanitat Animal. Centre de Recerca en Sanitat Animal (CReSA). Campus de la Universitat Autònoma de Barcelona (UAB), Bellaterra, Catalonia; bIRTA. Programa de Sanitat Animal. Centre de Recerca en Sanitat Animal (CReSA). Campus de la Universitat Autònoma de Barcelona (UAB), Bellaterra, Catalonia; cCentro de Investigación en Sanidad Animal, CISA-INIA-CSIC, Valdeolmos, Madrid, Spain; dMolecular Virology and Immunology, French National Research Institute for Agriculture, Food and Environment (INRAE), Université Paris-Saclay, Jouy-en-Josas, France; eVirus and Prion Research Unit, National Animal Disease Center, ARS, United States Department of Agriculture, Ames, IA, USA
Aims: Since variant Creutzfeldt-Jackob disease was linked to the consumption of bovine spongiform encephalopathy prions, the study of the pathobiological features of animal prions, particularly their zoonotic potential, is of great concern to the scientific community and public health authorities. Furthermore, interspecies transmission of prions has been demonstrated as a putative evolutionary mechanism for prions, that can lead to the emergence of new features including the ability to infect humans. For instance, small ruminants’ atypical scrapie prions, when propagated in a bovine or porcine host, can shift to a classical BSE phenotype thus posing a potential risk in case of human exposure. So far, no hard evidence of zoonotic transmission of cervids’ chronic wasting disease (CWD) to humans has been published, however experimental transmission to bovine, ovine and caprine hosts has been achieved. Our goal is to investigate if, once passaged through these domestic species, CWD prions might become infectious to humans.
Material and Methods: Different CWD isolates experimentally adapted to cattle, sheep and goat (Hamir et al, 2005, 2006, 2007, Greenlee et al 2012) have been intracerebrally inoculated to transgenic mouse models expressing the human cellular prion protein either homozygous for methionine or valine at codon 129 (Tg340-Met129 and Tg362-Val129). Additionally, inocula obtained from experimental transmission of elk CWD to ovinized (Tg501) and bovinized (BoTg110) transgenic mice, as well as white-tailed deer CWD to BoTg110 mice, are currently being bioassayed in both human PrPCtransgenic models.
Results and conclusions: No evidence of transmission has been found on first passage for bovine adapted elk and mule deer CWD to none of the humanized models. The remaining bioassays are ongoing without showing clinical signs yet, as well as second passages for the negative 1stpassages.
Funded by: La Marató de TV3 foundation. Grant number: ATYPRION (201,821–30-31-32)
Prion Conference 2018 Abstracts
P190 Human prion disease mortality rates by occurrence of chronic wasting disease in freeranging cervids, United States
Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1)
(1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA.
Background
Chronic wasting disease (CWD) is a prion disease of deer and elk that has been identified in freeranging cervids in 23 US states. While there is currently no epidemiological evidence for zoonotic transmission through the consumption of contaminated venison, studies suggest the CWD agent can cross the species barrier in experimental models designed to closely mimic humans. We compared rates of human prion disease in states with and without CWD to examine the possibility of undetermined zoonotic transmission.
Methods
Death records from the National Center for Health Statistics, case records from the National Prion Disease Pathology Surveillance Center, and additional state case reports were combined to create a database of human prion disease cases from 2003-2015. Identification of CWD in each state was determined through reports of positive CWD tests by state wildlife agencies. Age- and race-adjusted mortality rates for human prion disease, excluding cases with known etiology, were determined for four categories of states based on CWD occurrence: highly endemic (>16 counties with CWD identified in free-ranging cervids); moderately endemic (3-10 counties with CWD); low endemic (1-2 counties with CWD); and no CWD states. States were counted as having no CWD until the year CWD was first identified. Analyses stratified by age, sex, and time period were also conducted to focus on subgroups for which zoonotic transmission would be more likely to be detected: cases <55 years old, male sex, and the latter half of the study (2010-2015).
Results
Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states (rate ratio [RR]: 1.12, 95% confidence interval [CI] = 1.01 - 1.23), as did low endemic states (RR: 1.15, 95% CI = 1.04 - 1.27). Moderately endemic states did not have an elevated mortality rate (RR: 1.05, 95% CI = 0.93 - 1.17). In age-stratified analyses, prion disease mortality rates among the <55 year old population were elevated for moderately endemic states (RR: 1.57, 95% CI = 1.10 – 2.24) while mortality rates were elevated among those ≥55 for highly endemic states (RR: 1.13, 95% CI = 1.02 - 1.26) and low endemic states (RR: 1.16, 95% CI = 1.04 - 1.29). In other stratified analyses, prion disease mortality rates for males were only elevated for low endemic states (RR: 1.27, 95% CI = 1.10 - 1.48), and none of the categories of CWD-endemic states had elevated mortality rates for the latter time period (2010-2015).
Conclusions
While higher prion disease mortality rates in certain categories of states with CWD in free-ranging cervids were noted, additional stratified analyses did not reveal markedly elevated rates for potentially sensitive subgroups that would be suggestive of zoonotic transmission. Unknown confounding factors or other biases may explain state-by-state differences in prion disease mortality.
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P172 Peripheral Neuropathy in Patients with Prion Disease
Wang H(1), Cohen M(1), Appleby BS(1,2)
(1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio.
Prion disease is a fatal progressive neurodegenerative disease due to deposition of an abnormal protease-resistant isoform of prion protein. Typical symptoms include rapidly progressive dementia, myoclonus, visual disturbance and hallucinations. Interestingly, in patients with prion disease, the abnormal protein canould also be found in the peripheral nervous system. Case reports of prion deposition in peripheral nerves have been reported. Peripheral nerve involvement is thought to be uncommon; however, little is known about the exact prevalence and features of peripheral neuropathy in patients with prion disease.
We reviewed autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017. We collected information regarding prion protein diagnosis, demographics, comorbidities, clinical symptoms, physical exam, neuropathology, molecular subtype, genetics lab, brain MRI, image and EMG reports. Our study included 104 patients. Thirteen (12.5%) patients had either subjective symptoms or objective signs of peripheral neuropathy. Among these 13 patients, 3 had other known potential etiologies of peripheral neuropathy such as vitamin B12 deficiency or prior chemotherapy. Among 10 patients that had no other clear etiology, 3 (30%) had familial CJD. The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%). The Majority of cases wasere male (60%). Half of them had exposure to wild game. The most common subjective symptoms were tingling and/or numbness of distal extremities. The most common objective finding was diminished vibratory sensation in the feet. Half of them had an EMG with the findings ranging from fasciculations to axonal polyneuropathy or demyelinating polyneuropathy.
Our study provides an overview of the pattern of peripheral neuropathy in patients with prion disease. Among patients with peripheral neuropathy symptoms or signs, majority has polyneuropathy. It is important to document the baseline frequency of peripheral neuropathy in prion diseases as these symptoms may become important when conducting surveillance for potential novel zoonotic prion diseases.
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P177 PrP plaques in methionine homozygous Creutzfeldt-Jakob disease patients as a potential marker of iatrogenic transmission
Abrams JY (1), Schonberger LB (1), Cali I (2), Cohen Y (2), Blevins JE (2), Maddox RA (1), Belay ED (1), Appleby BS (2), Cohen ML (2)
(1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA.
Background
Sporadic Creutzfeldt-Jakob disease (CJD) is widely believed to originate from de novo spontaneous conversion of normal prion protein (PrP) to its pathogenic form, but concern remains that some reported sporadic CJD cases may actually be caused by disease transmission via iatrogenic processes. For cases with methionine homozygosity (CJD-MM) at codon 129 of the PRNP gene, recent research has pointed to plaque-like PrP deposition as a potential marker of iatrogenic transmission for a subset of cases. This phenotype is theorized to originate from specific iatrogenic source CJD types that comprise roughly a quarter of known CJD cases.
Methods
We reviewed scientific literature for studies which described PrP plaques among CJD patients with known epidemiological links to iatrogenic transmission (receipt of cadaveric human grown hormone or dura mater), as well as in cases of reported sporadic CJD. The presence and description of plaques, along with CJD classification type and other contextual factors, were used to summarize the current evidence regarding plaques as a potential marker of iatrogenic transmission. In addition, 523 cases of reported sporadic CJD cases in the US from January 2013 through September 2017 were assessed for presence of PrP plaques.
Results
We identified four studies describing 52 total cases of CJD-MM among either dura mater recipients or growth hormone recipients, of which 30 were identified as having PrP plaques. While sporadic cases were not generally described as having plaques, we did identify case reports which described plaques among sporadic MM2 cases as well as case reports of plaques exclusively in white matter among sporadic MM1 cases. Among the 523 reported sporadic CJD cases, 0 of 366 MM1 cases had plaques, 2 of 48 MM2 cases had kuru plaques, and 4 of 109 MM1+2 cases had either kuru plaques or both kuru and florid plaques. Medical chart review of the six reported sporadic CJD cases with plaques did not reveal clinical histories suggestive of potential iatrogenic transmission.
Conclusions
PrP plaques occur much more frequently for iatrogenic CJD-MM cases compared to sporadic CJDMM cases. Plaques may indicate iatrogenic transmission for CJD-MM cases without a type 2 Western blot fragment. The study results suggest the absence of significant misclassifications of iatrogenic CJD as sporadic. To our knowledge, this study is the first to describe grey matter kuru plaques in apparently sporadic CJD-MM patients with a type 2 Western blot fragment.
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P180 Clinico-pathological analysis of human prion diseases in a brain bank series
Ximelis T (1), Aldecoa I (1,2), Molina-Porcel L (1,3), Grau-Rivera O (4), Ferrer I (5), Nos C (6), Gelpi E (1,7), Sánchez-Valle R (1,4)
(1) Neurological Tissue Bank of the Biobanc-Hospital ClÃnic-IDIBAPS, Barcelona, Spain (2) Pathological Service of Hospital ClÃnic de Barcelona, Barcelona, Spain (3) EAIA Trastorns Cognitius, Centre Emili Mira, Parc de Salut Mar, Barcelona, Spain (4) Department of Neurology of Hospital ClÃnic de Barcelona, Barcelona, Spain (5) Institute of Neuropathology, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona (6) General subdirectorate of Surveillance and Response to Emergencies in Public Health, Department of Public Health in Catalonia, Barcelona, Spain (7) Institute of Neurology, Medical University of Vienna, Vienna, Austria.
Background and objective:
The Neurological Tissue Bank (NTB) of the Hospital Clínic-Institut d‘Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain is the reference center in Catalonia for the neuropathological study of prion diseases in the region since 2001. The aim of this study is to analyse the characteristics of the confirmed prion diseases registered at the NTB during the last 15 years.
Methods:
We reviewed retrospectively all neuropathologically confirmed cases registered during the period January 2001 to December 2016.
Results:
176 cases (54,3% female, mean age: 67,5 years and age range: 25-86 years) of neuropathological confirmed prion diseases have been studied at the NTB. 152 cases corresponded to sporadic Creutzfeldt-Jakob disease (sCJD), 10 to genetic CJD, 10 to Fatal Familial Insomnia, 2 to GerstmannSträussler-Scheinker disease, and 2 cases to variably protease-sensitive prionopathy (VPSPr). Within sCJD subtypes the MM1 subtype was the most frequent, followed by the VV2 histotype.
Clinical and neuropathological diagnoses agreed in 166 cases (94%). The clinical diagnosis was not accurate in 10 patients with definite prion disease: 1 had a clinical diagnosis of Fronto-temporal dementia (FTD), 1 Niemann-Pick‘s disease, 1 Lewy Body‘s Disease, 2 Alzheimer‘s disease, 1 Cortico-basal syndrome and 2 undetermined dementia. Among patients with VPSPr, 1 had a clinical diagnosis of Amyotrophic lateral sclerosis (ALS) and the other one with FTD.
Concomitant pathologies are frequent in older age groups, mainly AD neuropathological changes were observed in these subjects.
Discussion:
A wide spectrum of human prion diseases have been identified in the NTB being the relative frequencies and main characteristics like other published series. There is a high rate of agreement between clinical and neuropathological diagnoses with prion diseases. These findings show the importance that public health has given to prion diseases during the past 15 years. Continuous surveillance of human prion disease allows identification of new emerging phenotypes. Brain tissue samples from these donors are available to the scientific community. For more information please visit:
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P192 Prion amplification techniques for the rapid evaluation of surface decontamination procedures
Bruyere-Ostells L (1), Mayran C (1), Belondrade M (1), Boublik Y (2), Haïk S (3), Fournier-Wirth C (1), Nicot S (1), Bougard D (1)
(1) Pathogenesis and control of chronic infections, Etablissement Français du Sang, Inserm, Université de Montpellier, Montpellier, France. (2) Centre de Recherche en Biologie cellulaire de Montpellier, CNRS, Université de Montpellier, Montpellier, France. (3) Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Université Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
Aims:
Transmissible Spongiform Encephalopathies (TSE) or prion diseases are a group of incurable and always fatal neurodegenerative disorders including Creutzfeldt-Jakob diseases (CJD) in humans. These pathologies include sporadic (sCJD), genetic and acquired (variant CJD) forms. By the past, sCJD and vCJD were transmitted by different prion contaminated biological materials to patients resulting in more than 400 iatrogenic cases (iCJD). The atypical nature and the biochemical properties of the infectious agent, formed by abnormal prion protein or PrPTSE, make it particularly resistant to conventional decontamination procedures. In addition, PrPTSE is widely distributed throughout the organism before clinical onset in vCJD and can also be detected in some peripheral tissues in sporadic CJD. Risk of iatrogenic transmission of CJD by contaminated medical device remains thus a concern for healthcare facilities. Bioassay is the gold standard method to evaluate the efficacy of prion decontamination procedures but is time-consuming and expensive. Here, we propose to compare in vitro prion amplification techniques: Protein Misfolding Cyclic Amplification (PMCA) and Real-Time Quaking Induced Conversion (RT-QuIC) for the detection of residual prions on surface after decontamination.
Methods:
Stainless steel wires, by mimicking the surface of surgical instruments, were proposed as a carrier model of prions for inactivation studies. To determine the sensitivity of the two amplification techniques on wires (Surf-PMCA and Surf-QuIC), steel wires were therefore contaminated with serial dilutions of brain homogenates (BH) from a 263k infected hamster and from a patient with sCJD (MM1 subtype). We then compared the different standard decontamination procedures including partially and fully efficient treatments by detecting the residual seeding activity on 263K and sCJD contaminated wires. We completed our study by the evaluation of marketed reagents endorsed for prion decontamination.
Results:
The two amplification techniques can detect minute quantities of PrPTSE adsorbed onto a single wire. 8/8 wires contaminated with a 10-6 dilution of 263k BH and 1/6 with the 10-8 dilution are positive with Surf-PMCA. Similar performances were obtained with Surf-QuIC on 263K: 10/16 wires contaminated with 10-6 dilution and 1/8 wires contaminated with 10-8 dilution are positive. Regarding the human sCJD-MM1 prion, Surf-QuIC allows us to detect 16/16 wires contaminated with 10-6 dilutions and 14/16 with 10-7 . Results obtained after decontamination treatments are very similar between 263K and sCJD prions. Efficiency of marketed treatments to remove prions is lower than expected.
Conclusions:
Surf-PMCA and Surf-QuIC are very sensitive methods for the detection of prions on wires and could be applied to prion decontamination studies for rapid evaluation of new treatments. Sodium hypochlorite is the only product to efficiently remove seeding activity of both 263K and sCJD prions.
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WA2 Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice
Schatzl HM (1, 2), Hannaoui S (1, 2), Cheng Y-C (1, 2), Gilch S (1, 2), Beekes M (3), SchulzSchaeffer W (4), Stahl-Hennig C (5) and Czub S (2, 6)
(1) University of Calgary, Calgary Prion Research Unit, Calgary, Canada (2) University of Calgary, Faculty of Veterinary Medicine, Calgary, Canada, (3) Robert Koch Institute, Berlin, Germany, (4) University of Homburg/Saar, Homburg, Germany, (5) German Primate Center, Goettingen, Germany, (6) Canadian Food Inspection Agency (CFIA), Lethbridge, Canada.
To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years. After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were found in spinal cord and brain of euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and preclinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles. Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate. The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology. Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP. The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.
See also poster P103
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.
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WA16 Monitoring Potential CWD Transmission to Humans
Belay ED
Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA.
The spread of chronic wasting disease (CWD) in animals has raised concerns about increasing human exposure to the CWD agent via hunting and venison consumption, potentially facilitating CWD transmission to humans. Several studies have explored this possibility, including limited epidemiologic studies, in vitro experiments, and laboratory studies using various types of animal models. Most human exposures to the CWD agent in the United States would be expected to occur in association with deer and elk hunting in CWD-endemic areas. The Centers for Disease Control and Prevention (CDC) collaborated with state health departments in Colorado, Wisconsin, and Wyoming to identify persons at risk of CWD exposure and to monitor their vital status over time. Databases were established of persons who hunted in Colorado and Wyoming and those who reported consumption of venison from deer that later tested positive in Wisconsin. Information from the databases is periodically cross-checked with mortality data to determine the vital status and causes of death for deceased persons. Long-term follow-up of these hunters is needed to assess their risk of development of a prion disease linked to CWD exposure.
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P166 Characterization of CJD strain profiles in venison consumers and non-consumers from Alberta and Saskatchewan
Stephanie Booth (1,2), Lise Lamoureux (1), Debra Sorensen (1), Jennifer L. Myskiw (1,2), Megan Klassen (1,2), Michael Coulthart (3), Valerie Sim (4)
(1) Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg (2) Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg (3) Canadian CJD Surveillance System, Public Health Agency of Canada, Ottawa (4) Division of Neurology, Department of Medicine Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton.
Chronic wasting disease (CWD) is spreading rapidly through wild cervid populations in the Canadian provinces of Alberta and Saskatchewan. While this has implications for tourism and hunting, there is also concern over possible zoonotic transmission to humans who eat venison from infected deer. Whilst there is no evidence of any human cases of CWD to date, the Canadian CJD Surveillance System (CJDSS) in Canada is staying vigilant. When variant CJD occurred following exposure to BSE, the unique biochemical fingerprint of the pathologic PrP enabled a causal link to be confirmed. However, we cannot be sure what phenotype human CWD prions would present with, or indeed, whether this would be distinct from that see in sporadic CJD. Therefore we are undertaking a systematic analysis of the molecular diversity of CJD cases of individuals who resided in Alberta and Saskatchewan at their time of death comparing venison consumers and non-consumers, using a variety of clinical, imaging, pathological and biochemical markers. Our initial objective is to develop novel biochemical methodologies that will extend the baseline glycoform and genetic polymorphism typing that is already completed by the CJDSS. Firstly, we are reviewing MRI, EEG and pathology information from over 40 cases of CJD to select clinically affected areas for further investigation. Biochemical analysis will include assessment of the levels of protease sensitive and resistant prion protein, glycoform typing using 2D gel electrophoresis, testing seeding capabilities and kinetics of aggregation by quaking-induced conversion, and determining prion oligomer size distributions with asymmetric flow field fractionation with in-line light scattering. Progress and preliminary data will be presented. Ultimately, we intend to further define the relationship between PrP structure and disease phenotype and establish a baseline for the identification of future atypical CJD cases that may arise as a result of exposure to CWD.
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Source Prion Conference 2018 Abstracts
Volume 24, Number 8—August 2018 Research Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions
Marcelo A. BarriaComments to Author , Adriana Libori, Gordon Mitchell, and Mark W. Head Author affiliations: National CJD Research and Surveillance Unit, University of Edinburgh, Edinburgh, Scotland, UK (M.A. Barria, A. Libori, M.W. Head); National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada (G. Mitchell)
Abstract Chronic wasting disease (CWD) is a contagious and fatal neurodegenerative disease and a serious animal health issue for deer and elk in North America. The identification of the first cases of CWD among free-ranging reindeer and moose in Europe brings back into focus the unresolved issue of whether CWD can be zoonotic like bovine spongiform encephalopathy. We used a cell-free seeded protein misfolding assay to determine whether CWD prions from elk, white-tailed deer, and reindeer in North America can convert the human prion protein to the disease-associated form. We found that prions can convert, but the efficiency of conversion is affected by polymorphic variation in the cervid and human prion protein genes. In view of the similarity of reindeer, elk, and white-tailed deer in North America to reindeer, red deer, and roe deer, respectively, in Europe, a more comprehensive and thorough assessment of the zoonotic potential of CWD might be warranted.
snip...
Discussion Characterization of the transmission properties of CWD and evaluation of their zoonotic potential are important for public health purposes. Given that CWD affects several members of the family Cervidae, it seems reasonable to consider whether the zoonotic potential of CWD prions could be affected by factors such as CWD strain, cervid species, geographic location, and Prnp–PRNP polymorphic variation. We have previously used an in vitro conversion assay (PMCA) to investigate the susceptibility of the human PrP to conversion to its disease-associated form by several animal prion diseases, including CWD (15,16,22). The sensitivity of our molecular model for the detection of zoonotic conversion depends on the combination of 1) the action of proteinase K to degrade the abundant human PrPC that constitutes the substrate while only N terminally truncating any human PrPres produced and 2) the presence of the 3F4 epitope on human but not cervid PrP. In effect, this degree of sensitivity means that any human PrPres formed during the PMCA reaction can be detected down to the limit of Western blot sensitivity. In contrast, if other antibodies that detect both cervid and human PrP are used, such as 6H4, then newly formed human PrPres must be detected as a measurable increase in PrPres over the amount remaining in the reaction product from the cervid seed. Although best known for the efficient amplification of prions in research and diagnostic contexts, the variation of the PMCA method employed in our study is optimized for the definitive detection of zoonotic reaction products of inherently inefficient conversion reactions conducted across species barriers. By using this system, we previously made and reported the novel observation that elk CWD prions could convert human PrPC from human brain and could also convert recombinant human PrPC expressed in transgenic mice and eukaryotic cell cultures (15).
A previous publication suggested that mule deer PrPSc was unable to convert humanized transgenic substrate in PMCA assays (23) and required a further step of in vitro conditioning in deer substrate PMCA before it was able to cross the deer–human molecular barrier (24). However, prions from other species, such as elk (15) and reindeer affected by CWD, appear to be compatible with the human protein in a single round of amplification (as shown in our study). These observations suggest that different deer species affected by CWD could present differing degrees of the olecular compatibility with the normal form of human PrP.
The contribution of the polymorphism at codon 129 of the human PrP gene has been extensively studied and is recognized as a risk factor for Creutzfeldt-Jakob disease (4). In cervids, the equivalent codon corresponds to the position 132 encoding methionine or leucine. This polymorphism in the elk gene has been shown to play an important role in CWD susceptibility (25,26). We have investigated the effect of this cervid Prnp polymorphism on the conversion of the humanized transgenic substrate according to the variation in the equivalent PRNP codon 129 polymorphism. Interestingly, only the homologs methionine homozygous seed–substrate reactions could readily convert the human PrP, whereas the heterozygous elk PrPSc was unable to do so, even though comparable amounts of PrPres were used to seed the reaction. In addition, we observed only low levels of human PrPres formation in the reactions seeded with the homozygous methionine (132 MM) and the heterozygous (132 ML) seeds incubated with the other 2 human polymorphic substrates (129 MV and 129 VV). The presence of the amino acid leucine at position 132 of the elk Prnp gene has been attributed to a lower degree of prion conversion compared with methionine on the basis of experiments in mice made transgenic for these polymorphic variants (26). Considering the differences observed for the amplification of the homozygous human methionine substrate by the 2 polymorphic elk seeds (MM and ML), reappraisal of the susceptibility of human PrPC by the full range of cervid polymorphic variants affected by CWD would be warranted.
In light of the recent identification of the first cases of CWD in Europe in a free-ranging reindeer (R. tarandus) in Norway (2), we also decided to evaluate the in vitro conversion potential of CWD in 2 experimentally infected reindeer (18). Formation of human PrPres was readily detectable after a single round of PMCA, and in all 3 humanized polymorphic substrates (MM, MV, and VV). This finding suggests that CWD prions from reindeer could be more compatible with human PrPC generally and might therefore present a greater risk for zoonosis than, for example, CWD prions from white-tailed deer. A more comprehensive comparison of CWD in the affected species, coupled with the polymorphic variations in the human and deer PRNP–Prnp genes, in vivo and in vitro, will be required before firm conclusions can be drawn. Analysis of the Prnp sequence of the CWD reindeer in Norway was reported to be identical to the specimens used in our study (2). This finding raises the possibility of a direct comparison of zoonotic potential between CWD acquired in the wild and that produced in a controlled laboratory setting. (Table).
The prion hypothesis proposes that direct molecular interaction between PrPSc and PrPC is necessary for conversion and prion replication. Accordingly, polymorphic variants of the PrP of host and agent might play a role in determining compatibility and potential zoonotic risk. In this study, we have examined the capacity of the human PrPC to support in vitro conversion by elk, white-tailed deer, and reindeer CWD PrPSc. Our data confirm that elk CWD prions can convert the human PrPC, at least in vitro, and show that the homologous PRNP polymorphisms at codon 129 and 132 in humans and cervids affect conversion efficiency. Other species affected by CWD, particularly caribou or reindeer, also seem able to convert the human PrP. It will be important to determine whether other polymorphic variants found in other CWD-affected Cervidae or perhaps other factors (17) exert similar effects on the ability to convert human PrP and thus affect their zoonotic potential.
Dr. Barria is a research scientist working at the National CJD Research and Surveillance Unit, University of Edinburgh. His research has focused on understanding the molecular basis of a group of fatal neurologic disorders called prion diseases.
Acknowledgments We thank Aru Balachandran for originally providing cervid brain tissues, Abigail Diack and Jean Manson for providing mouse brain tissue, and James Ironside for his critical reading of the manuscript at an early stage.
This report is independent research commissioned and funded by the United Kingdom’s Department of Health Policy Research Programme and the Government of Scotland. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health or the Government of Scotland.
Author contributions: The study was conceived and designed by M.A.B. and M.W.H. The experiments were conducted by M.A.B. and A.L. Chronic wasting disease brain specimens were provided by G.M. The manuscript was written by M.A.B. and M.W.H. All authors contributed to the editing and revision of the manuscript.
Prion 2017 Conference Abstracts
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress
Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1 University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen
This is a progress report of a project which started in 2009.
21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes.
Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product.
Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain).
Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments.
We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves.
Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem.
Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor.
In four animals wasting was observed, two of those had confirmed diabetes.
All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals.
Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice.
At present, a total of 10 animals are sacrificed and read-outs are ongoing.
Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years.
Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation.
PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS ABSTRACTS REFERENCE
8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data. In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available.
SATURDAY, FEBRUARY 23, 2019
Chronic Wasting Disease CWD TSE Prion and THE FEAST 2003 CDC an updated review of the science 2019
TUESDAY, NOVEMBER 04, 2014
Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: risk behaviours and health outcomes 2005–2011
Authors, though, acknowledged the study was limited in geography and sample size and so it couldn't draw a conclusion about the risk to humans. They recommended more study. Dr. Ermias Belay was the report's principal author but he said New York and Oneida County officials are following the proper course by not launching a study. "There's really nothing to monitor presently. No one's sick," Belay said, noting the disease's incubation period in deer and elk is measured in years. "
Transmission Studies
Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases {the following was written but with a single line marked through it ''first passage (by this route)}....TSS
resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculum (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in ALL of these species with the shortest incubation period in the ferret.
snip....
Prion Infectivity in Fat of Deer with Chronic Wasting Disease▿
Brent Race#, Kimberly Meade-White#, Richard Race and Bruce Chesebro* + Author Affiliations
In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species.
Prions in Skeletal Muscles of Deer with Chronic Wasting Disease
Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure.
*** now, let’s see what the authors said about this casual link, personal communications years ago, and then the latest on the zoonotic potential from CWD to humans from the TOKYO PRION 2016 CONFERENCE.
see where it is stated NO STRONG evidence. so, does this mean there IS casual evidence ???? “Our conclusion stating that we found no strong evidence of CWD transmission to humans”
From: TSS
Subject: CWD aka MAD DEER/ELK TO HUMANS ???
Date: September 30, 2002 at 7:06 am PST
From: "Belay, Ermias"
To: Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"
Sent: Monday, September 30, 2002 9:22 AM
Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Dear Sir/Madam,
In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD.. That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091). Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.
Ermias Belay, M.D. Centers for Disease Control and Prevention
-----Original Message-----
From: Sent: Sunday, September 29, 2002 10:15 AM
To: rr26k@nih.gov; rrace@niaid.nih.gov; ebb8@CDC.GOV
Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS
Sunday, November 10, 2002 6:26 PM .......snip........end..............TSS
Thursday, April 03, 2008
A prion disease of cervids: Chronic wasting disease 2008 1: Vet Res. 2008 Apr 3;39(4):41 A prion disease of cervids: Chronic wasting disease Sigurdson CJ.
snip...
*** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,
snip... full text ;
> However, to date, no CWD infections have been reported in people.
sporadic, spontaneous CJD, 85%+ of all human TSE, did not just happen. never in scientific literature has this been proven.
if one looks up the word sporadic or spontaneous at pubmed, you will get a laundry list of disease that are classified in such a way;
sporadic = 54,983 hits https://www.ncbi.nlm.nih.gov/pubmed/?term=sporadic
spontaneous = 325,650 hits https://www.ncbi.nlm.nih.gov/pubmed/?term=spontaneous
key word here is 'reported'. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can't, and it's as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it's being misdiagnosed as sporadic CJD. ...terry
*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***
> However, to date, no CWD infections have been reported in people.
key word here is ‘reported’. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can’t, and it’s as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it’s being misdiagnosed as sporadic CJD. …terry
*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***
*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***
CWD TSE PRION AND ZOONOTIC, ZOONOSIS, POTENTIAL
Subject: Re: DEER SPONGIFORM ENCEPHALOPATHY SURVEY & HOUND STUDY
Date: Fri, 18 Oct 2002 23:12:22 +0100
From: Steve Dealler
Reply-To: Bovine Spongiform Encephalopathy Organization: Netscape Online member
To: BSE-L@ References:
Dear Terry,
An excellent piece of review as this literature is desperately difficult to get back from Government sites.
What happened with the deer was that an association between deer meat eating and sporadic CJD was found in about 1993. The evidence was not great but did not disappear after several years of asking CJD cases what they had eaten. I think that the work into deer disease largely stopped because it was not helpful to the UK industry...and no specific cases were reported. Well, if you dont look adequately like they are in USA currenly then you wont find any!
Steve Dealler
===============
''The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).''
CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE UNITED KINGDOM THIRD ANNUAL REPORT AUGUST 1994
Consumption of venison and veal was much less widespread among both cases and controls. For both of these meats there was evidence of a trend with increasing frequency of consumption being associated with increasing risk of CJD. (not nvCJD, but sporadic CJD...tss)
These associations were largely unchanged when attention was restricted to pairs with data obtained from relatives. ...
Table 9 presents the results of an analysis of these data.
There is STRONG evidence of an association between ‘’regular’’ veal eating and risk of CJD (p = .0.01).
Individuals reported to eat veal on average at least once a year appear to be at 13 TIMES THE RISK of individuals who have never eaten veal.
There is, however, a very wide confidence interval around this estimate. There is no strong evidence that eating veal less than once per year is associated with increased risk of CJD (p = 0.51).
The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).
There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY OF LAMB EATING (p = 0.02).
The evidence for such an association between beef eating and CJD is weaker (p = 0.14). When only controls for whom a relative was interviewed are included, this evidence becomes a little STRONGER (p = 0.08).
snip...
It was found that when veal was included in the model with another exposure, the association between veal and CJD remained statistically significant (p = < 0.05 for all exposures), while the other exposures ceased to be statistically significant (p = > 0.05).
snip...
In conclusion, an analysis of dietary histories revealed statistical associations between various meats/animal products and INCREASED RISK OF CJD. When some account was taken of possible confounding, the association between VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS STATISTICALLY. ...
snip...
In the study in the USA, a range of foodstuffs were associated with an increased risk of CJD, including liver consumption which was associated with an apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3 studies in relation to this particular dietary factor, the risk of liver consumption became non-significant with an odds ratio of 1.2 (PERSONAL COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS)
snip...see full report ;
http://web.archive.org/web/20090506050043/http://www.bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf
http://web.archive.org/web/20090506050007/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf
http://web.archive.org/web/20090506050244/http://www.bseinquiry.gov.uk/files/yb/1994/07/00001001.pdf
Stephen Dealler is a consultant medical microbiologist deal@airtime.co.uk
BSE Inquiry Steve Dealler
Management In Confidence
BSE: Private Submission of Bovine Brain Dealler
snip...see full text;
MONDAY, FEBRUARY 25, 2019
***> MAD DOGS AND ENGLISHMEN BSE, SCRAPIE, CWD, CJD, TSE PRION A REVIEW 2019
***> ''The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).''
***> In conclusion, sensory symptoms and loss of reflexes in Gerstmann-Sträussler-Scheinker syndrome can be explained by neuropathological changes in the spinal cord. We conclude that the sensory symptoms and loss of lower limb reflexes in Gerstmann-Sträussler-Scheinker syndrome is due to pathology in the caudal spinal cord. <***
***> The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.<***
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***
***> All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals.<***
***> In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids.'' Scientific opinion on chronic wasting disease (II) <***
***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***
Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.
O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France
Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases).
Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.
*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,
***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),
***is the third potentially zoonotic PD (with BSE and L-type BSE),
***thus questioning the origin of human sporadic cases.
We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.
===============
***thus questioning the origin of human sporadic cases***
===============
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
==============
PRION 2015 CONFERENCE
***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.
***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
PRION 2016 TOKYO
Saturday, April 23, 2016
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
Title: Transmission of scrapie prions to primate after an extended silent incubation period)
*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.
*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.
*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.
WEDNESDAY, MARCH 16, 2022
SHEEP BY-PRODUCTS AND WHAT ABOUT Scrapie TSE PrP and Potential Zoonosis?
SO, WHO'S UP FOR SOME MORE TSE PRION POKER, WHO'S ALL IN $$$
SO, ATYPICAL SCRAPIE ROUGHLY HAS 50 50 CHANCE ATYPICAL SCRAPIE IS CONTAGIOUS, AS NON-CONTAGIOUS, TAKE YOUR PICK, BUT I SAID IT LONG AGO WHEN USDA OIE ET AL MADE ATYPICAL SCRAPIE A LEGAL TRADING COMMODITY, I SAID YOUR PUTTING THE CART BEFORE THE HORSE, AND THAT'S EXACTLY WHAT THEY DID, and it's called in Texas, TEXAS TSE PRION HOLDEM POKER, WHO'S ALL IN $$$
***> AS is considered more likely (subjective probability range 50–66%) that AS is a non-contagious, rather than a contagious, disease.
FRIDAY, DECEMBER 23, 2022
House and Senate Send Important Chronic Wasting Disease Legislation to President’s Desk
***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***
Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.
snip...
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"
Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.
snip...
76/10.12/4.6
Nature. 1972 Mar 10;236(5341):73-4.
Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek DC.
Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0
Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)
C. J. GIBBS jun. & D. C. GAJDUSEK
National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland
SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).
Although the current U.S. feed ban is based on keeping tissues from TSE infected cattle from contaminating animal feed, swine rations in the U.S. could contain animal derived components including materials from scrapie infected sheep and goats. These results indicating the susceptibility of pigs to sheep scrapie, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health.
2. Determined that pigs naturally exposed to chronic wasting disease (CWD) may act as a reservoir of CWD infectivity. Chronic wasting disease is a naturally occurring, fatal, neurodegenerative disease of cervids.
The potential for swine to serve as a host for the agent of CWD disease is unknown. The purpose of this study was to investigate the susceptibility of swine to the CWD agent following experimental oral or intracranial inoculation.
Pigs were assigned to 1 of 3 groups: intracranially inoculated; orally inoculated; or non-inoculated. At market weight age, half of the pigs in each group were tested ('market weight' groups). The remaining pigs ('aged' groups) were allowed to incubate for up to 73 months post inoculation (MPI).
Tissues collected at necropsy were examined for disease-associated prion protein (PrPSc) by multiple diagnostic methods.
Brain samples from selected pigs were bioassayed in mice expressing porcine prion protein.
Some pigs from each inoculated group were positive by one or more tests. Bioassay was positive in 4 out of 5 pigs assayed.
Although only small amounts of PrPSc were detected using sensitive methods, this study demonstrates that pigs can serve as hosts for CWD.
Detection of infectivity in orally inoculated pigs using mouse bioassay raises the possibility that naturally exposed pigs could act as a reservoir of CWD infectivity.
Currently, swine rations in the U.S. could contain animal derived components including materials from deer or elk.
In addition, feral swine could be exposed to infected carcasses in areas where CWD is present in wildlife populations.
The current feed ban in the U.S. is based exclusively on keeping tissues from TSE infected cattle from entering animal feeds.
These results indicating the susceptibility of pigs to CWD, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health.
CONFIDENTIAL
EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY
LINE TO TAKE
3. If questions on pharmaceuticals are raised at the Press conference, the suggested line to take is as follows:-
"There are no medicinal products licensed for use on the market which make use of UK-derived porcine tissues with which any hypothetical “high risk" ‘might be associated. The results of the recent experimental work at the CSM will be carefully examined by the CSM‘s Working Group on spongiform encephalopathy at its next meeting.
DO Hagger RM 1533 MT Ext 3201
While this clearly is a cause for concern we should not jump to the conclusion that this means that pigs will necessarily be infected by bone and meat meal fed by the oral route as is the case with cattle. ...
we cannot rule out the possibility that unrecognised subclinical spongiform encephalopathy could be present in British pigs though there is no evidence for this: only with parenteral/implantable pharmaceuticals/devices is the theoretical risk to humans of sufficient concern to consider any action.
May I, at the outset, reiterate that we should avoid dissemination of papers relating to this experimental finding to prevent premature release of the information. ...
3. It is particularly important that this information is not passed outside the Department, until Ministers have decided how they wish it to be handled. ...
But it would be easier for us if pharmaceuticals/devices are not directly mentioned at all. ...
Our records show that while some use is made of porcine materials in medicinal products, the only products which would appear to be in a hypothetically ''higher risk'' area are the adrenocorticotrophic hormone for which the source material comes from outside the United Kingdom, namely America China Sweden France and Germany. The products are manufactured by Ferring and Armour. A further product, ''Zenoderm Corium implant'' manufactured by Ethicon, makes use of porcine skin - which is not considered to be a ''high risk'' tissue, but one of its uses is described in the data sheet as ''in dural replacement''. This product is sourced from the United Kingdom.....
***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***
Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.
WEDNESDAY, MARCH 29, 2023
The use of animal by-products in a circular bioeconomy: Time for a TSE road map 3?
WEDNESDAY, FEBRUARY 8, 2023
NATIONAL PRION DISEASE PATHOLOGY SURVEILLANCE CENTER SURVEILLANCE TABLES OF CASES EXAMINED January 11th, 2023
Terry S. Singeltary Sr.
