Thursday, January 14, 2016

Preventable Tragedies: Superbugs and How Ineffective Monitoring of Medical Device Safety Fails Patients REPORT

how can it be, HOW CAN IT BE $$$ not a word about CJD GSS FFI VPSPR TSE Prions that I saw...absolutely crazy, WE ARE MISSING THE BIGGER PICTURE!

 
Preventable Tragedies: Superbugs and How Ineffective Monitoring of Medical Device Safety Fails Patients REPORT
 

United States Senate

 

HEALTH, EDUCATION, LABOR, AND PENSIONS COMMITTEE

 

Patty Murray, Ranking Member

 

Minority Staff Report January 13, 2016

 


 

06.09.15 Murray Presses Scope Manufacturer Linked to Superbug Outbreak at Virginia Mason For Answers, Accountability

 

Murray indicates “growing concern” in letters to manufacturers of medical scopes linked to antibiotic resistant infections across the country

 

(Washington, D.C.) – Today, Senate Health, Education, Labor, and Pensions (HELP) Committee Ranking Member Patty Murray (D-WA) wrote a letter to Karl Watanabe, President of Olympus Corporation of the Americas, raising questions about the company’s actions to protect patients treated with Olympus duodenoscopes, which are medical devices linked to an outbreak of antibiotic-resistant infections at Virginia Mason Medical Center in Seattle, Washington. Duodenoscopes manufactured by Olympus, Pentax Medical, and Fujifilm have also been linked to antibiotic-resistant infections at other hospitals nationwide.

 

 Murray expressed serious concern about reports that Olympus knew its cleaning and reprocessing standards were ineffective, but failed to appropriately warn patients and providers in the United States of the potential for antibiotic-resistant infections. Murray requested that Olympus provide information on the timeline of events and the company’s response to reports of infections related to their duodenoscopes by June 19, 2015.

 

 “As questions continue to arise regarding your company’s actions to adequately protect patients treated with your duodenoscopes, I write to seek more information and express my serious and growing concern,” Murray wrote in the letter. “I am committed to ensuring that the families impacted by these tragic outbreaks in Washington state and across the country get answers and accountability.”

 

 Murray also sent letters to Pentax Medical and Fujifilm requesting similar information. Earlier this year, Murray called for a full FDA review of practices surrounding duodenoscopes, and also urged the agency to provide health care professionals with updated safety guidance and best practices, which the agency has now done.‎

 

 Full text of Senator Murray’s letter to Olympus:

 

 Dear Mr. Watanabe:

 

 As questions continue to arise regarding your company’s actions to adequately protect patients treated with your duodenoscopes, I write to seek more information and express my serious and growing concern. As you are aware, between late 2012 and January 2014, Virginia Mason hospital in Seattle, Washington experienced an outbreak of deadly carbapenem-resistant Enterobacteriaceae (CRE) infections which were subsequently traced to duodenoscopes manufactured by Olympus. In all, 32 individuals were infected with CRE, an additional 7 people developed a separate E coli infection, and 18 of those who developed infections later died.

 

 In addition, multiple cases of CRE infections traced back to Olympus duodenoscopes have now been confirmed at two other hospitals in 2014, as well as a series of CRE infections involving an Olympus duodenoscope in Florida in 2009. In all, the Food and Drug Administration (FDA) confirmed at the recently convened Advisory Committee Meeting of the Gastroenterology-Urology Devices Panel that there have been at least nine hospital outbreaks of multidrug-resistant infections traced to duodenoscopes in the United States, and that six of those outbreaks are traceable to scopes manufactured by Olympus. Olympus is reported to have told health care professionals in February that the company was aware of 95 complaints of infection in patients who had undergone procedures with TJF-Q180V, the “closed elevator” duodenoscope sold since 2010, without Olympus seeking FDA approval or clearance before marketing.

 

 Overall, FDA has informed me it received 139 separate reports of contamination or infection related medical device reports, or adverse event reports involving duodenoscopes between 2011 and 2014, including 69 reports affecting 135 patients in 2014 alone. Ninety-four percent of these reports were received directly from the manufacturers, which include Olympus (85 percent market share of duodenoscopes), Fujifilm, and Pentax Medical.

 

 I have become increasingly concerned by the failure of Olympus to proactively warn patients and providers in the United States of the potential for infections. It is my understanding that in November of 2013, at the invitation of officials at Virginia Mason concerned about the CRE infections at the hospital, an endoscopy support specialist from Olympus spent two days at the hospital and validated that the hospital was properly cleaning Olympus duodenoscopes between uses. That review by Olympus staff demonstrated that “endoscope reprocessing procedures at [the hospital] were above the industry standard, and all technicians performed manual endoscope cleaning in a manner consistent with manufacturer guidelines.” Olympus officials subsequently removed a number of the scopes in use at Virginia Mason for repair.

 

 Thus, as early as November 2013, it appears that Olympus knew or should have known that even in cases where hospital staff were carefully executing Olympus’ instructions for cleaning, duodenoscopes continued to be contaminated with CRE and other bacteria. Further, it strongly suggests that Olympus knew its current cleaning and reprocessing standards were insufficient, and that use of the company’s duodenoscopes, particularly the TJF-Q180V model sold since 2010 and featuring a “closed elevator,” were placing patients undergoing procedures at risk of multi-bacteria resistant infections. Moreover, although medical device manufacturers are required to file reports of possible safety risks within 30 days, press reports suggest that Olympus did not even file the required Medical Device Report with the FDA in connection with the Virginia Mason infections until August 2014. And as recently as February of this year, more than a year after the Virginia Mason CRE outbreak, I understand that the Olympus manager of infection control told a meeting of health care professionals that “endoscopes reprocessed properly pose virtually no risk of patient-borne or environmental organisms.”

 

 This stands in marked contrast to the actions taken by Olympus in Europe. According to press reports, as early as January 2013, Olympus is reported to have issued “important safety advice” to European hospitals instructing staff to use a specific brush supplied by Olympus to clean duodenoscopes. This action is reported to have been taken following a series of infections at Erasmus University in Rotterdam in early 2012. Dr. Margreet Vos provided testimony at the recent FDA Advisory Committee meeting that in 2012 independent reviewers found bacteria present in reprocessed Olympus scopes.

 

 Again in August 2014, Olympus is reported to have sent a second safety alert to European hospitals that asked hospital staff to sign and return an acknowledgement that the warning had been shared with staff. No such alert was sent in this country until February of this year, and the cleaning brushes apparently sent to European hospitals in early 2013 were not provided to U.S. hospitals until last month.

 

 These facts build upon my existing concerns regarding Olympus’ 2010 failure to seek clearance or approval from the FDA prior to marketing TJF-Q180V, the “closed elevator” duodenoscope at issue in a number of the infections. I find it very troubling that when Olympus became aware of increased reports of infections linked to the TJF-Q180V, the company appears not to have taken additional steps to alert health professionals and regulators in the United States to the risks this particular device posed. Moreover, when asked by the FDA in the spring of 2014 to provide the data that validated that Olympus duodenoscopes could be cleaned of bacteria within acceptable safety margins using recommended procedures, Olympus (as well as Fujifilm and Pentax Medical) was unable to do so through two rounds of testing. New cleaning guidance was finally approved by FDA in March 2015.

 

 I find it similarly troubling that Olympus (as well as Fujifilm and Pentax Medical) declined to participate in the subsequently convened FDA Advisory Committee Meeting on “Effective Reprocessing of Endoscopes used in Endoscopic Retrograde Cholangiopancreatography (ERCP) Procedures,” despite manufacturing 85 percent of the scopes used in these procedures. But at the same time, the company was apparently able to have representatives present at two large professional conferences in Washington, D.C. that same week. Just days before the FDA Advisory Panel meeting, Olympus announced that the company was reducing its expected earnings forecast for this year as a result of an ongoing investigation by the Department of Justice into potential violations of the Anti-Kickback Statute, and last week Olympus announced that it is under investigation by the United States Attorney for the District of New Jersey relating to the duodenoscope infections.

 

 Even with enhanced cleaning procedures adopted earlier this year, these necessary and important devices must be handled with extreme care to help prevent infections. At the FDA panel meeting, two-thirds of hospitals reported that scope cultures were positive for organisms after reprocessing. While representatives of Virginia Mason explained that the hospital has established a protocol requiring that, after a duodenoscope has been thoroughly cleaned and reprocessed, it is cultured for bacteria, this process requires a 48-hour waiting period between uses of a scope, and has required the hospital to purchase additional scopes. Yet the hospital believes it has little alternative to purchasing additional scopes given that they continue to experience a 3 percent contamination rate.

 

 I am committed to ensuring that the families impacted by these tragic outbreaks in Washington State and across the country get answers and accountability. In order to better understand the timeline of events and your company’s response to reports of infections related to duodenoscopes manufactured by Olympus, including the TJF-160, TJF-Q180V-1 and TJF-Q180V-2, please provide the following information by June 19, 2015.

 

 1.Copies of all alerts, cleaning guidance, safety advice or warnings provided to any hospital or regulatory agency, foreign or domestic, mentioning any scope manufactured by Olympus used in Endoscopic Retrograde Cholangiopancreatography Procedures from 2005-2015.

 

 1.Unredacted copies of all medical device reports or adverse event reports sent by Olympus to FDA regarding the TJF-Q180V-1 and TJF-Q180V-2 or any other scope used in Endoscopic Retrograde Cholangiopancreatography Procedures between 2005 and present.

 

 1.Copies of all documents between 2010 and present that reference or refer to CRE or other infections and any endoscope, including any duodenoscope, manufactured by Olympus.

 


 

 FDA Executive Summary Prepared for the May 14-15, 2015 meeting of the Gastroenterology-Urology Devices Panel of the Medical Devices Advisory Committee Effective Reprocessing of Endoscopes used in Endoscopic Retrograde Cholangiopancreatography (ERCP) Procedures

 


 

 March 26, 2015

 

URGENT SAFETY NOTIFICATION IMPORTANT UPDATED LABELING INFORMATION: NEW REPROCESSING INSTRUCTIONS FOR THE OLYMPUS TJF-Q180V DUODENOSCOPE

 

ATTENTION: Endoscopy Department, Risk Management and Reprocessing Units

 

Dear Health Care Professional:

 


 

Senate report faults hospitals, device makers, FDA for deadly ‘superbug’ outbreaks

 

January 14, 2016 By Brad Perriello —Leave a Comment

 

superbug-scope-3x2A report by Democrats on the U.S. Senate’s health committee issued this week blames hospitals, medical device companies and the FDA for the deadly outbreaks of so-called “superbug” infections linked to duodenoscopes.

 

The devices are used for a procedure called endoscopic retrograde cholangiopancreatography, in which a reusable tube-like camera is inserted into the throat of a patient. More than 500,000 ERCPs using the devices are performed in the U.S. annually. Hospitals in Connecticut, Virginia, California and Washington state all reported superbug outbreaks in February and March 2014, some of which led to patients’ deaths.

 

Staffers under Sen. Patty Murray (D-Wash.), the ranking member of the Senate Health, Education, Pensions & Labor Committee, found that it took 17 months for ‘scope makers Olympus (TYO:7733), Fujifilm Holdings‘ (TSE:4901) and Hoya (TYO:7741) subsidiary Pentax to raise the alarm about the infections.

 

“At least 68 patients in 7 different hospitals in the U.S. were infected with antibiotic-resistant bacteria linked to duodenoscopes during this period,” according to the HELP panel’s report. “Between 2012 and spring 2015, closed-channel duodenoscopes were linked to at least 25 different incidents of antibiotic-resistant infections that sickened at least 250 patients worldwide.”

 

The report also found that Olympus, which owns some 85% of the U.S. market for duodenoscopes, knew as early as 2013 that a new “closed-channel” design allowed the devices to harbor and spread bacteria even after sterilization procedures.

 

“Olympus never brought this information to FDA, and did not alert hospitals, physicians or patients in the U.S. to the risk of infection until February 2015,” according to the report.

 

Mark Miller, corporate & medical communications VP at Olympus, said in prepared remarks that the company spent several months cooperating with the Senate panel’s enquiry.

 

“We appreciate that the staff report noted Olympus’ cooperation and that the report demonstrates the shared responsibilities of duodenoscope manufacturers, hospitals, manufacturers of automated endoscope reprocessors, and the FDA, each of which can contribute to increasing patient safety. Although we do not agree with all of the report’s conclusions, we are closely reviewing the recommendations in the report as part of Olympus’ ongoing efforts to increase patient safety associated with use of Olympus duodenoscopes,” Miller said.

 

The Senate report also found that Olympus, Fujifilm, Pentax and automated sterilization provider Custom Ultrasonics “failed to meet the obligations placed upon them by the current regulatory system.”

 

“Two of the manufacturers failed to seek FDA clearance before selling the ‘closed-channel’ duodenoscopes, all failed to adequately test whether the scopes could be cleaned reliably in real-world settings, and fully comply with adverse events reporting requirements,” according to the report.

 

But the companies were not solely to blame for the superbug outbreaks, according to the report.

 

“Additionally, although at least 16 separate U.S. hospitals traced antibiotic-resistant infections directly to duodenoscopes, the hospitals generally did not raise alarms about these infections with federal regulators. It appears that not a single hospital that experienced infection outbreaks tied to the duodenoscopes sent the required adverse event form to the device manufacturers,” Murray’s aides wrote. “When hospitals did take required action to report adverse events to device manufacturers it was often late, notification was made informally by phone or email, and reports were not inclusive of all the information necessary for the manufacturers to themselves submit accurate and complete information to FDA.”

 

And the FDA played its part in the deadly fiasco, they wrote, citing the safety watchdog’s often-maligned Manufacturer & User Facility Device Experience database, which is designed to track adverse events linked to medical devices.

 

“Problems with FDA’s outmoded adverse event device database, as well as slow and incomplete reporting by manufacturers and hospitals, appear to have left FDA staff unable to develop an accurate sense of the frequency and severity of the infection outbreaks. FDA was also unaware that by early 2013, 2 independent labs in Europe had documented the Olympus closed-channel duodenoscope remaining contaminated after repeated cleaning, or that a Dutch Health Ministry report in 2013 had already concluded that Olympus did not have the data to show their cleaning instructions worked consistently and effectively,” according to the report.

 

In March 2014, hospitals in Los Angeles and Connecticut reported superbug outbreaks linked to the scopes. Cedars-Sinai Medical Center reported 4 infections and 67 more at-risk patients. coinciding with a hospital in Hartford, Conn., reporting a similar outbreak involving at least 5 infections and more than 280 potential exposures.

 

The Cedars-Sinai cases, like the larger number of infections and potential exposures reported in February at the UCLA Ronald Reagan Medical Center in Los Angeles, involved a family of germs called carbapenem-resistant Enterobacteriaceae. The bacteria identified in the Hartford Hospital outbreak was a drug-resistant strain of E.coli. Seven patients were infected with CRE during endoscopies at the UCLA teaching hospital between Oct. 3 and Jan. 28, and 2 died. Officials warned at the time that as many as 179 people may have been exposed to the so-called superbug.

 

Between 2012 and 2014, at least 32 patients at Virginia Mason Medical Center were infected with strains of multidrug-resistant E. coli bacteria spread through contaminated scopes that had been sterilized to the manufacturer’s guidelines, according to state health officials. At least 11 people eventually died, though the role of the superbug in their demise was unclear because all the patients were critically ill at the time of their infection, Washington state public health officials said.

 

The outbreaks prompted the FDA to inspect 11 plants where the 3 companies make the endoscopes, leading to the August 12 warning letters to Olympus, Fujifilm and Pentax. The FDA said it found numerous violations at the plants, ranging from inadequate quality controls to failures to report serious adverse events, including deaths. The violations turned up at plants in Japan, New Jersey, Pennsylvania and California, according to the FDA.

 

Filed Under: Endoscopic / Arthroscopic

 

Tagged With: Capitol Hill, Fujifilm Holdings, Hoya Corp., Olympus, Pentax

 


 

More infections from dirty scopes, Sen. Murray investigation finds

 

Originally published January 12, 2016 at 9:00 pm | Updated January 13, 2016 at 10:24 am

 

At least 250 people, mostly in the U.S., have contracted potentially deadly infections spread by contaminated medical scopes in the past three years, according to a new report commissioned by Sen. Patty Murray.

 


 

 

how can it be, HOW CAN IT BE $$$ not a word about CJD GSS FFI VPSPR TSE Prions that I saw...absolutely crazy!

 

 

*** 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.

 


 

98 | Veterinary Record | January 24, 2015

 

EDITORIAL

 

Scrapie: a particularly persistent pathogen

 

Cristina Acín

 

Resistant prions in the environment have been the sword of Damocles for scrapie control and eradication. Attempts to establish which physical and chemical agents could be applied to inactivate or moderate scrapie infectivity were initiated in the 1960s and 1970s,with the first study of this type focusing on the effect of heat treatment in reducing prion infectivity (Hunter and Millson 1964). Nowadays, most of the chemical procedures that aim to inactivate the prion protein are based on the method developed by Kimberlin and collaborators (1983). This procedure consists of treatment with 20,000 parts per million free chlorine solution, for a minimum of one hour, of all surfaces that need to be sterilised (in laboratories, lambing pens, slaughterhouses, and so on). Despite this, veterinarians and farmers may still ask a range of questions, such as ‘Is there an official procedure published somewhere?’ and ‘Is there an international organisation which recommends and defines the exact method of scrapie decontamination that must be applied?’

 

From a European perspective, it is difficult to find a treatment that could be applied, especially in relation to the disinfection of surfaces in lambing pens of affected flocks. A 999/2001 EU regulation on controlling spongiform encephalopathies (European Parliament and Council 2001) did not specify a particular decontamination measure to be used when an outbreak of scrapie is diagnosed. There is only a brief recommendation in Annex VII concerning the control and eradication of transmissible spongiform encephalopathies (TSE s).

 

Chapter B of the regulation explains the measures that must be applied if new caprine animals are to be introduced to a holding where a scrapie outbreak has previously been diagnosed. In that case, the statement indicates that caprine animals can be introduced ‘provided that a cleaning and disinfection of all animal housing on the premises has been carried out following destocking’.

 

Issues around cleaning and disinfection are common in prion prevention recommendations, but relevant authorities, veterinarians and farmers may have difficulties in finding the specific protocol which applies. The European Food and Safety Authority (EFSA ) published a detailed report about the efficacy of certain biocides, such as sodium hydroxide, sodium hypochlorite, guanidine and even a formulation of copper or iron metal ions in combination with hydrogen peroxide, against prions (EFSA 2009). The report was based on scientific evidence (Fichet and others 2004, Lemmer and others 2004, Gao and others 2006, Solassol and others 2006) but unfortunately the decontamination measures were not assessed under outbreak conditions.

 

The EFSA Panel on Biological Hazards recently published its conclusions on the scrapie situation in the EU after 10 years of monitoring and control of the disease in sheep and goats (EFSA 2014), and one of the most interesting findings was the Icelandic experience regarding the effect of disinfection in scrapie control. The Icelandic plan consisted of: culling scrapie-affected sheep or the whole flock in newly diagnosed outbreaks; deep cleaning and disinfection of stables, sheds, barns and equipment with high pressure washing followed by cleaning with 500 parts per million of hypochlorite; drying and treatment with 300 ppm of iodophor; and restocking was not permitted for at least two years. Even when all of these measures were implemented, scrapie recurred on several farms, indicating that the infectious agent survived for years in the environment, even as many as 16 years after restocking (Georgsson and others 2006).

 

In the rest of the countries considered in the EFSA (2014) report, recommendations for disinfection measures were not specifically defined at the government level. In the report, the only recommendation that is made for sheep is repopulation with sheep with scrapie-resistant genotypes. This reduces the risk of scrapie recurrence but it is difficult to know its effect on the infection.

 

Until the EFSA was established (in May 2003), scientific opinions about TSE s were provided by the Scientific Steering Committee (SSC) of the EC, whose advice regarding inactivation procedures focused on treating animal waste at high temperatures (150°C for three hours) and high pressure alkaline hydrolysis (SSC 2003). At the same time, the TSE Risk Management Subgroup of the Advisory Committee on Dangerous Pathogens (ACDP) in the UK published guidance on safe working and the prevention of TSE infection. Annex C of the ACDP report established that sodium hypochlorite was considered to be effective, but only if 20,000 ppm of available chlorine was present for at least one hour, which has practical limitations such as the release of chlorine gas, corrosion, incompatibility with formaldehyde, alcohols and acids, rapid inactivation of its active chemicals and the stability of dilutions (ACDP 2009).

 

In an international context, the World Organisation for Animal Health (OIE) does not recommend a specific disinfection protocol for prion agents in its Terrestrial Code or Manual. Chapter 4.13 of the Terrestrial Code, General recommendations on disinfection and disinsection (OIE 2014), focuses on foot-and-mouth disease virus, mycobacteria and Bacillus anthracis, but not on prion disinfection. Nevertheless, the last update published by the OIE on bovine spongiform encephalopathy (OIE 2012) indicates that few effective decontamination techniques are available to inactivate the agent on surfaces, and recommends the removal of all organic material and the use of sodium hydroxide, or a sodium hypochlorite solution containing 2 per cent available chlorine, for more than one hour at 20ºC.

 

The World Health Organization outlines guidelines for the control of TSE s, and also emphasises the importance of mechanically cleaning surfaces before disinfection with sodium hydroxide or sodium hypochlorite for one hour (WHO 1999).

 

Finally, the relevant agencies in both Canada and the USA suggest that the best treatments for surfaces potentially contaminated with prions are sodium hydroxide or sodium hypochlorite at 20,000 ppm. This is a 2 per cent solution, while most commercial household bleaches contain 5.25 per cent sodium hypochlorite. It is therefore recommended to dilute one part 5.25 per cent bleach with 1.5 parts water (CDC 2009, Canadian Food Inspection Agency 2013).

 

So what should we do about disinfection against prions? First, it is suggested that a single protocol be created by international authorities to homogenise inactivation procedures and enable their application in all scrapie-affected countries. Sodium hypochlorite with 20,000 ppm of available chlorine seems to be the procedure used in most countries, as noted in a paper summarised on p 99 of this issue of Veterinary Record (Hawkins and others 2015). But are we totally sure of its effectiveness as a preventive measure in a scrapie outbreak? Would an in-depth study of the recurrence of scrapie disease be needed?

 

What we can conclude is that, if we want to fight prion diseases, and specifically classical scrapie, we must focus on the accuracy of diagnosis, monitoring and surveillance; appropriate animal identification and control of movements; and, in the end, have homogeneous and suitable protocols to decontaminate and disinfect lambing barns, sheds and equipment available to veterinarians and farmers. Finally, further investigations into the resistance of prion proteins in the diversity of environmental surfaces are required.

 

References

 

snip...

 

98 | Veterinary Record | January 24, 2015

 


 

Original Article

 

Effect of heating on the stability of amyloid A (AA) fibrils and the intra- and cross-species transmission of AA amyloidosis

 

DOI:10.3109/13506129.2015.1095735Saki Ogawaa, Tomoaki Murakamib, Yasuo Inoshimaa & Naotaka Ishiguroa*

 

Publishing models and article dates explained

 

Received: 5 May 2015 Accepted: 14 Sep 2015 Published online: 20 Nov 2015 .

 

Abstract

 

Amyloid A (AA) amyloidosis is a protein misfolding disease characterized by extracellular deposition of AA fibrils. AA fibrils are found in several tissues from food animals with AA amyloidosis. For hygienic purposes, heating is widely used to inactivate microbes in food, but it is uncertain whether heating is sufficient to inactivate AA fibrils and prevent intra- or cross-species transmission. We examined the effect of heating (at 60 °C or 100 °C) and autoclaving (at 121 °C or 135 °C) on murine and bovine AA fibrils using Western blot analysis, transmission electron microscopy (TEM), and mouse model transmission experiments. TEM revealed that a mixture of AA fibrils and amorphous aggregates appeared after heating at 100 °C, whereas autoclaving at 135 °C produced large amorphous aggregates. AA fibrils retained antigen specificity in Western blot analysis when heated at 100 °C or autoclaved at 121 °C, but not when autoclaved at 135 °C. Transmissible pathogenicity of murine and bovine AA fibrils subjected to heating (at 60 °C or 100 °C) was significantly stimulated and resulted in amyloid deposition in mice. Autoclaving of murine AA fibrils at 121 °C or 135 °C significantly decreased amyloid deposition. Moreover, amyloid deposition in mice injected with murine AA fibrils was more severe than that in mice injected with bovine AA fibrils. Bovine AA fibrils autoclaved at 121 °C or 135 °C did not induce amyloid deposition in mice. These results suggest that AA fibrils are relatively heat stable and that similar to prions, autoclaving at 135 °C is required to destroy the pathogenicity of AA fibrils. These findings may contribute to the prevention of AA fibril transmission through food materials to different animals and especially to humans.

 

AA amyloidosis, AA fibrils, Image J software, immunohistochemistry, prion, silver nitrate, transmission electron microscopy, Western blot analysis

 


 

*** These results suggest that AA fibrils are relatively heat stable and that similar to prions, autoclaving at 135 °C is required to destroy the pathogenicity of AA fibrils.

 

*** These findings may contribute to the prevention of AA fibril transmission through food materials to different animals and especially to humans.

 

New studies on the heat resistance of hamster-adapted scrapie agent: Threshold survival after ashing at 600°C suggests an inorganic template of replication

 

The infectious agents responsible for transmissible spongiform encephalopathy (TSE) are notoriously resistant to most physical and chemical methods used for inactivating pathogens, including heat. It has long been recognized, for example, that boiling is ineffective and that higher temperatures are most efficient when combined with steam under pressure (i.e., autoclaving). As a means of decontamination, dry heat is used only at the extremely high temperatures achieved during incineration, usually in excess of 600°C. It has been assumed, without proof, that incineration totally inactivates the agents of TSE, whether of human or animal origin.

 


 

Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production

 

Histochemical analysis of hamster brains inoculated with the solid residue showed typical spongiform degeneration and vacuolation. Re-inoculation of these brains into a new cohort of hamsters led to onset of clinical scrapie symptoms within 75 days, suggesting that the specific infectivity of the prion protein was not changed during the biodiesel process. The biodiesel reaction cannot be considered a viable prion decontamination method for MBM, although we observed increased survival time of hamsters and reduced infectivity greater than 6 log orders in the solid MBM residue. Furthermore, results from our study compare for the first time prion detection by Western Blot versus an infectivity bioassay for analysis of biodiesel reaction products. We could show that biochemical analysis alone is insufficient for detection of prion infectivity after a biodiesel process.

 


 

Detection of protease-resistant cervid prion protein in water from a CWD-endemic area

 

The data presented here demonstrate that sPMCA can detect low levels of PrPCWD in the environment, corroborate previous biological and experimental data suggesting long term persistence of prions in the environment2,3 and imply that PrPCWD accumulation over time may contribute to transmission of CWD in areas where it has been endemic for decades. This work demonstrates the utility of sPMCA to evaluate other environmental water sources for PrPCWD, including smaller bodies of water such as vernal pools and wallows, where large numbers of cervids congregate and into which prions from infected animals may be shed and concentrated to infectious levels.

 


 

A Quantitative Assessment of the Amount of Prion Diverted to Category 1 Materials and Wastewater During Processing

 

Keywords:Abattoir;bovine spongiform encephalopathy;QRA;scrapie;TSE

 

In this article the development and parameterization of a quantitative assessment is described that estimates the amount of TSE infectivity that is present in a whole animal carcass (bovine spongiform encephalopathy [BSE] for cattle and classical/atypical scrapie for sheep and lambs) and the amounts that subsequently fall to the floor during processing at facilities that handle specified risk material (SRM). BSE in cattle was found to contain the most oral doses, with a mean of 9864 BO ID50s (310, 38840) in a whole carcass compared to a mean of 1851 OO ID50s (600, 4070) and 614 OO ID50s (155, 1509) for a sheep infected with classical and atypical scrapie, respectively. Lambs contained the least infectivity with a mean of 251 OO ID50s (83, 548) for classical scrapie and 1 OO ID50s (0.2, 2) for atypical scrapie. The highest amounts of infectivity falling to the floor and entering the drains from slaughtering a whole carcass at SRM facilities were found to be from cattle infected with BSE at rendering and large incineration facilities with 7.4 BO ID50s (0.1, 29), intermediate plants and small incinerators with a mean of 4.5 BO ID50s (0.1, 18), and collection centers, 3.6 BO ID50s (0.1, 14). The lowest amounts entering drains are from lambs infected with classical and atypical scrapie at intermediate plants and atypical scrapie at collection centers with a mean of 3 × 10−7 OO ID50s (2 × 10−8, 1 × 10−6) per carcass. The results of this model provide key inputs for the model in the companion paper published here.

 


 

*** Infectious agent of sheep scrapie may persist in the environment for at least 16 years ***

 

Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3

 


 

PL1

 

Using in vitro prion replication for high sensitive detection of prions and prionlike proteins and for understanding mechanisms of transmission.

 

Claudio Soto

 

Mitchell Center for Alzheimer's diseases and related Brain disorders, Department of Neurology, University of Texas Medical School at Houston.

 

Prion and prion-like proteins are misfolded protein aggregates with the ability to selfpropagate to spread disease between cells, organs and in some cases across individuals. I n T r a n s m i s s i b l e s p o n g i f o r m encephalopathies (TSEs), prions are mostly composed by a misfolded form of the prion protein (PrPSc), which propagates by transmitting its misfolding to the normal prion protein (PrPC). The availability of a procedure to replicate prions in the laboratory may be important to study the mechanism of prion and prion-like spreading and to develop high sensitive detection of small quantities of misfolded proteins in biological fluids, tissues and environmental samples. Protein Misfolding Cyclic Amplification (PMCA) is a simple, fast and efficient methodology to mimic prion replication in the test tube. PMCA is a platform technology that may enable amplification of any prion-like misfolded protein aggregating through a seeding/nucleation process. In TSEs, PMCA is able to detect the equivalent of one single molecule of infectious PrPSc and propagate prions that maintain high infectivity, strain properties and species specificity. Using PMCA we have been able to detect PrPSc in blood and urine of experimentally infected animals and humans affected by vCJD with high sensitivity and specificity. Recently, we have expanded the principles of PMCA to amplify amyloid-beta (Aβ) and alphasynuclein (α-syn) aggregates implicated in Alzheimer's and Parkinson's diseases, respectively. Experiments are ongoing to study the utility of this technology to detect Aβ and α-syn aggregates in samples of CSF and blood from patients affected by these diseases.

 

=========================

 

***Recently, we have been using PMCA to study the role of environmental prion contamination on the horizontal spreading of TSEs. These experiments have focused on the study of the interaction of prions with plants and environmentally relevant surfaces. Our results show that plants (both leaves and roots) bind tightly to prions present in brain extracts and excreta (urine and feces) and retain even small quantities of PrPSc for long periods of time. Strikingly, ingestion of prioncontaminated leaves and roots produced disease with a 100% attack rate and an incubation period not substantially longer than feeding animals directly with scrapie brain homogenate. Furthermore, plants can uptake prions from contaminated soil and transport them to different parts of the plant tissue (stem and leaves). Similarly, prions bind tightly to a variety of environmentally relevant surfaces, including stones, wood, metals, plastic, glass, cement, etc. Prion contaminated surfaces efficiently transmit prion disease when these materials were directly injected into the brain of animals and strikingly when the contaminated surfaces were just placed in the animal cage. These findings demonstrate that environmental materials can efficiently bind infectious prions and act as carriers of infectivity, suggesting that they may play an important role in the horizontal transmission of the disease.

 

========================

 

Since its invention 13 years ago, PMCA has helped to answer fundamental questions of prion propagation and has broad applications in research areas including the food industry, blood bank safety and human and veterinary disease diagnosis.

 


 

Wednesday, December 16, 2015

 

Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission

 

Objects in contact with classical scrapie sheep act as a reservoir for scrapie transmission

 

Timm Konold1*, Stephen A. C. Hawkins2, Lisa C. Thurston3, Ben C. Maddison4, Kevin C. Gough5, Anthony Duarte1 and Hugh A. Simmons1

 

1 Animal Sciences Unit, Animal and Plant Health Agency Weybridge, Addlestone, UK, 2 Pathology Department, Animal and Plant Health Agency Weybridge, Addlestone, UK, 3 Surveillance and Laboratory Services, Animal and Plant Health Agency Penrith, Penrith, UK, 4 ADAS UK, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK, 5 School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK

 

Classical scrapie is an environmentally transmissible prion disease of sheep and goats. Prions can persist and remain potentially infectious in the environment for many years and thus pose a risk of infecting animals after re-stocking. In vitro studies using serial protein misfolding cyclic amplification (sPMCA) have suggested that objects on a scrapie affected sheep farm could contribute to disease transmission. This in vivo study aimed to determine the role of field furniture (water troughs, feeding troughs, fencing, and other objects that sheep may rub against) used by a scrapie-infected sheep flock as a vector for disease transmission to scrapie-free lambs with the prion protein genotype VRQ/VRQ, which is associated with high susceptibility to classical scrapie. When the field furniture was placed in clean accommodation, sheep became infected when exposed to either a water trough (four out of five) or to objects used for rubbing (four out of seven). This field furniture had been used by the scrapie-infected flock 8 weeks earlier and had previously been shown to harbor scrapie prions by sPMCA. Sheep also became infected (20 out of 23) through exposure to contaminated field furniture placed within pasture not used by scrapie-infected sheep for 40 months, even though swabs from this furniture tested negative by PMCA. This infection rate decreased (1 out of 12) on the same paddock after replacement with clean field furniture. Twelve grazing sheep exposed to field furniture not in contact with scrapie-infected sheep for 18 months remained scrapie free. The findings of this study highlight the role of field furniture used by scrapie-infected sheep to act as a reservoir for disease re-introduction although infectivity declines considerably if the field furniture has not been in contact with scrapie-infected sheep for several months. PMCA may not be as sensitive as VRQ/VRQ sheep to test for environmental contamination.

 

snip...

 

Discussion

 

Classical scrapie is an environmentally transmissible disease because it has been reported in naïve, supposedly previously unexposed sheep placed in pastures formerly occupied by scrapie-infected sheep (4, 19, 20). Although the vector for disease transmission is not known, soil is likely to be an important reservoir for prions (2) where – based on studies in rodents – prions can adhere to minerals as a biologically active form (21) and remain infectious for more than 2 years (22). Similarly, chronic wasting disease (CWD) has re-occurred in mule deer housed in paddocks used by infected deer 2 years earlier, which was assumed to be through foraging and soil consumption (23).

 

Our study suggested that the risk of acquiring scrapie infection was greater through exposure to contaminated wooden, plastic, and metal surfaces via water or food troughs, fencing, and hurdles than through grazing. Drinking from a water trough used by the scrapie flock was sufficient to cause infection in sheep in a clean building. Exposure to fences and other objects used for rubbing also led to infection, which supported the hypothesis that skin may be a vector for disease transmission (9). The risk of these objects to cause infection was further demonstrated when 87% of 23 sheep presented with PrPSc in lymphoid tissue after grazing on one of the paddocks, which contained metal hurdles, a metal lamb creep and a water trough in contact with the scrapie flock up to 8 weeks earlier, whereas no infection had been demonstrated previously in sheep grazing on this paddock, when equipped with new fencing and field furniture. When the contaminated furniture and fencing were removed, the infection rate dropped significantly to 8% of 12 sheep, with soil of the paddock as the most likely source of infection caused by shedding of prions from the scrapie-infected sheep in this paddock up to a week earlier.

 

This study also indicated that the level of contamination of field furniture sufficient to cause infection was dependent on two factors: stage of incubation period and time of last use by scrapie-infected sheep. Drinking from a water trough that had been used by scrapie sheep in the predominantly pre-clinical phase did not appear to cause infection, whereas infection was shown in sheep drinking from the water trough used by scrapie sheep in the later stage of the disease. It is possible that contamination occurred through shedding of prions in saliva, which may have contaminated the surface of the water trough and subsequently the water when it was refilled. Contamination appeared to be sufficient to cause infection only if the trough was in contact with sheep that included clinical cases. Indeed, there is an increased risk of bodily fluid infectivity with disease progression in scrapie (24) and CWD (25) based on PrPSc detection by sPMCA. Although ultraviolet light and heat under natural conditions do not inactivate prions (26), furniture in contact with the scrapie flock, which was assumed to be sufficiently contaminated to cause infection, did not act as vector for disease if not used for 18 months, which suggest that the weathering process alone was sufficient to inactivate prions.

 

PrPSc detection by sPMCA is increasingly used as a surrogate for infectivity measurements by bioassay in sheep or mice. In this reported study, however, the levels of PrPSc present in the environment were below the limit of detection of the sPMCA method, yet were still sufficient to cause infection of in-contact animals. In the present study, the outdoor objects were removed from the infected flock 8 weeks prior to sampling and were positive by sPMCA at very low levels (2 out of 37 reactions). As this sPMCA assay also yielded 2 positive reactions out of 139 in samples from the scrapie-free farm, the sPMCA assay could not detect PrPSc on any of the objects above the background of the assay. False positive reactions with sPMCA at a low frequency associated with de novo formation of infectious prions have been reported (27, 28). This is in contrast to our previous study where we demonstrated that outdoor objects that had been in contact with the scrapie-infected flock up to 20 days prior to sampling harbored PrPSc that was detectable by sPMCA analysis [4 out of 15 reactions (12)] and was significantly more positive by the assay compared to analogous samples from the scrapie-free farm. This discrepancy could be due to the use of a different sPMCA substrate between the studies that may alter the efficiency of amplification of the environmental PrPSc. In addition, the present study had a longer timeframe between the objects being in contact with the infected flock and sampling, which may affect the levels of extractable PrPSc. Alternatively, there may be potentially patchy contamination of this furniture with PrPSc, which may have been missed by swabbing. The failure of sPMCA to detect CWD-associated PrP in saliva from clinically affected deer despite confirmation of infectivity in saliva-inoculated transgenic mice was associated with as yet unidentified inhibitors in saliva (29), and it is possible that the sensitivity of sPMCA is affected by other substances in the tested material. In addition, sampling of amplifiable PrPSc and subsequent detection by sPMCA may be more difficult from furniture exposed to weather, which is supported by the observation that PrPSc was detected by sPMCA more frequently in indoor than outdoor furniture (12). A recent experimental study has demonstrated that repeated cycles of drying and wetting of prion-contaminated soil, equivalent to what is expected under natural weathering conditions, could reduce PMCA amplification efficiency and extend the incubation period in hamsters inoculated with soil samples (30). This seems to apply also to this study even though the reduction in infectivity was more dramatic in the sPMCA assays than in the sheep model. Sheep were not kept until clinical end-point, which would have enabled us to compare incubation periods, but the lack of infection in sheep exposed to furniture that had not been in contact with scrapie sheep for a longer time period supports the hypothesis that prion degradation and subsequent loss of infectivity occurs even under natural conditions.

 

In conclusion, the results in the current study indicate that removal of furniture that had been in contact with scrapie-infected animals should be recommended, particularly since cleaning and decontamination may not effectively remove scrapie infectivity (31), even though infectivity declines considerably if the pasture and the field furniture have not been in contact with scrapie-infected sheep for several months. As sPMCA failed to detect PrPSc in furniture that was subjected to weathering, even though exposure led to infection in sheep, this method may not always be reliable in predicting the risk of scrapie infection through environmental contamination. These results suggest that the VRQ/VRQ sheep model may be more sensitive than sPMCA for the detection of environmentally associated scrapie, and suggest that extremely low levels of scrapie contamination are able to cause infection in susceptible sheep genotypes.

 

Keywords: classical scrapie, prion, transmissible spongiform encephalopathy, sheep, field furniture, reservoir, serial protein misfolding cyclic amplification

 


 

 03-025IF 03-025IF-631 Linda A. Detwiler [PDF] Page 1. 03-025IF 03-025IF-631 Linda A. Detwiler

 

Intestine

 

The scenario describe above is essentially true for the intestine. Infectivity was readily detectable in the distal ileum of cattle infected with BSE. While certain additional sections of the intestine were tested with no infectivity identified, not every section of the intestine was included in the bioassays. Positive immunostaining for Prpres was identified along the length of the intestine providing evidence for the entire intestine to be considered as SRM per EU regulations. (personal communication Danny Matthews, UK, VLA). The International Advisory Committee appointed by Secretary Veneman also recommended that the SRM ban in the US be amended to the entire intestine from duodenum to rectum. I recommend that the USDA adjust the definition of SRM to include the entire intestine from the duodenum to the rectum .

 

snip...

 

see full text ;

 


 

Linda A. Detwiler, DVM

 

225 Hwy 35

 

Red Bank, New Jersey 07701

 

Phone: 732-741-2290

 

Cell: 732-580-9391

 

Fax: 732-741-7751

 

June 22, 2005

 

FSIS Docket Clerk

 

U.S. Department of Agriculture Food Safety and Inspection Service 300 12th Street, SW. Room 102 Cotton Annex Washington, DC 20250

 

RE: DEPARTMENT OF AGRICULTURE Food Safety and Inspection Service

 

9 CFR Parts 301, 309, 310, 311, 313, 318, 319 and 320

 

Prohibition of the Use of Specified Risk Materials for Human Food and Requirements for the Disposition of Non-Ambulatory Disabled Cattle; Meat Produced by Advanced Meat/Bone Separation Machinery and Meat Recovery (AMR) Systems;

 

Prohibition of the Use of Certain Stunning Devices Used To Immobilize Cattle During Slaughter; Bovine Spongiform Encephalopathy (BSE) Surveillance Program

 

Docket Number 03-025IF: Prohibition of the Use of Specified Risk Materials for Human Food and Requirements for the Disposition of Nonambulatory Disabled Cattle

 

I am writing to clarify a comment I submitted to the above mentioned docket on May 7, 2004. I had previously written that the entire length of the intestine should be excluded as SRM. I still hold this opinion and submit the same recommendation, however one of the reasons behind this opinion needs to be further clarified. I had misunderstood comments made by Dr. Danny Matthews in that immunostaining (of PrPbse) was not found throughout the entire length of the intestine. There was however immunostaining in the myenteric plexus of the distal ileum in both naturally infected and experimentally challenged cattle with BSE. (Terry et al.,2003) Given that the myenteric plexus exists throughout the intestine one cannot eliminate the possibility of infectivity being in other sections. In fact this was some of the thought behind the designation of the entire intestine as SRM in the EU:

 

In its opinion of 7-8 December 2000 (EC 2000), the SSC concluded that the entire bovine intestine is a risk issue and Commission Regulation (EC) No.

 

270/2002 (14th February 2002) ANNEX II designates “the entire intestines from the duodenum to the rectum and the mesentery of bovine animals of all ages;” as SRM. Also, in the SSC opinion of 28-29 JUNE 2001, Adipose tissue associated with the digestive tract of cattle, sheep and goats: an appreciation of possibleTSE risks (EC 2001) the view was expressed that for cattle, “due to the infectivity titre that could be theoretically reached in nervous tissues and in some parts of intestine, and due to the risk of contamination with intestine tissue….

 

The International Advisory Committee appointed by Secretary Veneman also recommended that the SRM ban in the US be amended to the entire intestine from duodenum to rectum.

 

Although certain additional sections of the intestine were tested with no infectivity identified, not every section of the intestine was included in the bioassays. In addition, the study involving immunostaining was also extremely limited in regard to the testing of tissues other than the distal ileum. Specifically, other sections of intestinal tissues (excluding the distal ileum work) were limited to those collected from 3 calves inoculated with BSE at a timeframe of 6 months post inoculation. Instead of assuming that the untested sections are devoid of infectivity, it is my belief that we should err on the side of caution when it comes to protecting public health. Hence I maintain my opinion that the entire intestine should be considered SRM.

 

This clarification is also intended for my comments submitted to the FDA’s ANPR.

 

Thank you for the opportunity to clarify my comments.

 

Linda A. Detwiler, DVM

 

REFERENCES

 

Terry, L. A.., Marsh, S., Ryder, S. J., Hawkins, S. A. C., Wells, G. H., and Spencer, Y. I. (2003) Detection of disease-specific PrP in the distal ileum of cattle exposed orally to the agent of bovine spongiform encephalopathy. Vet Rec., 152, 387-392 Wells G.A.H., Dawson M., Hawkins, S.A.C., Green R. B., Dexter I., Francis M. E., Simmons M. M., Austin A. R., & Horigan M. W. (1994) Infectivity in the ileum of cattle challenged orally with bovine spongiform encephalopathy. Vet. Rec., 135, 40-41. Wells G.A.H., Hawkins, S.A.C., Green R. B., Austin A. R., Dexter I., Spencer, Y. I., Chaplin, M. J., Stack, M. J., & Dawson, M. (1998) Preliminary observations on the pathogenesis of experimental bovine spongiform encephalopathy (BSE): an update. Vet. Rec., 142, 103-106.

 


 

see full text ;

 


 

 

*** Interpretation ***

 

Our findings suggest that the possible risk of vCJD linked to endoscopic procedures might be currently underestimated. Human iatrogenic vCJD cases infected intravenously raise the same public-health concerns as primary cases and need the same precautionary measures with respect to blood and tissue donations and surgical procedures.

 

We noted that PrPres was present in lymphoreticular tissues such as spleen and tonsils and in the entire gut from the duodenum to the rectum.

 


 


 

FDA Says Endoscope Makers Failed to Report Superbug Problems OLYMPUS... Prions, iatrogenic, what if?

 

Monday, August 17, 2015

 

FDA Says Endoscope Makers Failed to Report Superbug Problems OLYMPUS

 


 

 I told Olympus 15 years ago about these risk factors from endoscopy equipment, disinfection, even spoke with the Doctor at Olympus, this was back in 1999. I tried to tell them that they were exposing patients to dangerous pathogens such as the CJD TSE prion, because they could not properly clean them. even presented my concern to a peer review journal GUT, that was going to publish, but then it was pulled by Professor Michael Farthing et al... see ;

 

 some old history on Endoscopy equipment and CJD TSE Prion concerns ;

 

 1999

 

 Subject: CJD * Olympus Endoscope

 

 Date: Sun, 10 Oct 1999 16:41:49 –0500

 

 From: "Terry S. Singeltary Sr."

 

 To: GOLDSS@...

 

 Dear Dr. Goldstine,

 

 Hello Sir, I understand that Olympus has issued a letter to the medical institutions and the CDC, about the dangers of _not_ being able to decontaminate the instruments (endoscope's) via modern autoclaving techniques (boil 3 minutes in 3% SDS or another ionic detergent and autoclave for 1 hour at 134 degrees C). I understand that; "Olympus" has issued a warning, _not_ to attempt to decontaminate the instrument, that they are instructed to destroy them.

 

 (very very wise move);

 

 Please Sir, it is imminent that I receive a copy of this letter, it is very important. This could lead to other company's following through, and lead to awareness of the potential health threats from human T.S.E.'s and the risks through surgery, and not just from endoscopes. It would be most appreciated, if you could send a copy of this document to;

 

 Fax: xxxxx

 

 I look forward, to hearing back from you....

 

 Many Thanks,

 

 Terry S. Singeltary Sr./ Mom DOD 12-14-97 hvCJD

 

 Subject: Re: CJD * Olympus Endoscope

 

 Date: Tue, 12 Oct 1999 15:57:03 –0500

 

 From: "Terry S. Singeltary Sr."

 

 To: GOLDSS@...

 

 References: 1

 

 Dear Mr. Goldstine, Hello again, I hope the CDC has not changed your mind, since our phone call, about sending me the information, in which we spoke of. I am still waiting for the information, re-fax. Someone had told me, you would not send me the information, but I told them you would, due to the importance of it pertaining to public safety, and the fact, you are a Doctor. I hope you don't disappoint me, and the rest of the public, and hide the facts, as the CDC and NIH have for years. Olympus can be part of the Truth, or you can be part of the cover-up. We are going to find out, sooner or later.

 

 I already know, as do many more.

 


 

 Still waiting,

 

 Kind Regards,

 

 Terry S. Singeltary Sr.

 

 "Terry S. Singeltary Sr." wrote:

 

 Dear Dr. Goldstine,

 

 Hello Sir, I understand that Olympus has issued a letter to the medical institutions and the CDC, about the dangers of _not_ being able to decontaminate the instruments (endoscope's) via modern autoclaving techniques (boil 3 minutes in 3% SDS or another ionic detergent and autoclave for 1 hour at 134 degrees C). I understand that; "Olympus" has issued a warning, _not_ to attempt to decontaminate the instrument, that they are instructed to destroy them.

 

 (very very wise move);

 

 Please Sir, it is imminent that I receive a copy of this letter, it is very important. This could lead to other company's following through, and lead to awareness of the potential health threats from human T.S.E.'s and the risks through surgery, and not just from endoscopes. It would be most appreciated, if you could send a copy of this document to;

 

 Fax: xxxxxxx

 

 I look forward, to hearing back from you....

 

 Many Thanks,

 

 Terry S. Singeltary Sr./ Mom DOD 12-14-97 hvCJD

 

 =================================================================

 

 Something I submitted to GUT previously;

 

 Subject: Re: gutjnl_el;21 Terry S. Singeltary Sr. (3 Jun 2002) "CJDs (all human TSEs) and Endoscopy Equipment"

 

 Date: Thu, 20 Jun 2002 16:19:51 –0700

 

 From: "Terry S. Singeltary Sr."

 

 To: Professor Michael Farthing

 

 CC: lcamp@BMJgroup.com

 

 References: 001501c21099$5c8bc620$7c58d182@mfacdean1.cent.gla.ac.uk

 

 Greetings again Professor Farthing and BMJ,

 

 I was curious why my small rebuttal of the article described below was not listed in this month's journal of GUT? I had thought it was going to be published, but I do not have full text access. Will it be published in the future? Regardless, I thought would pass on a more lengthy rebuttal of mine on this topic, vCJD vs sCJDs and endoscopy equipment. I don't expect it to be published, but thought you might find it interesting, i hope you don't mind and hope to hear back from someone on the questions I posed...

 

 Here is my short submission I speak of, lengthy one to follow below that:

 

 Date submitted: 3 Jun 2002

 

 >> eLetter ID: gutjnl_el;21

 

 >> >> Gut eLetter for Bramble and Ironside 50 (6): 888

 

 >> >>Name: Terry S. Singeltary Sr.

 

 >>Email: flounder@wt.net

 

 >>Title/position: disabled {neck injury}

 

 >>Place of work: CJD WATCH

 

 >>IP address: 216.119.162.85

 

 >>Hostname: 216-119-162-85.ipset44.wt.net

 

 >>Browser: Mozilla/5.0 (Windows; U; Win98; en-US; rv:0.9.4)

 

 >>Gecko/20011019 Netscape6/6.2

 

 >> >>Parent ID: 50/6/888

 

 >>Citation:

 

 >> Creutzfeldt-Jakob disease: implications for gastroenterology

 

 >> M G Bramble and J W Ironside

 

 >> Gut 2002; 50: 888-890 (Occasional viewpoint)

 


 


 

 >>-----------------------------------------------------------------

 

 >>"CJDs (all human TSEs) and Endoscopy Equipment"

 

 >>-----------------------------------------------------------------

 

 regarding your article;

 

 Creutzfeldt-Jakob disease: implications for gastroenterology

 

 >>I belong to several support groups for victims and relatives

 

 >>of CJDs. Several years ago, I did a survey regarding

 

 >>endoscopy equipment and how many victims of CJDs have

 

 >>had any type of this procedure done. To my surprise, many

 

 >>victims had some kind of endoscopy work done on them.

 

 >>As this may not be a smoking gun, I think it should

 

 >>warrant a 'red flag' of sorts, especially since data now

 

 >>suggests a substantial TSE infectivity in the gut wall

 

 >>of species infected with TSEs. If such transmissions

 

 >>occur, the ramifications of spreading TSEs from

 

 >>endoscopy equipment to the general public would be

 

 >>horrible, and could potential amplify the transmission

 

 >>of TSEs through other surgical procedures in that

 

 >>persons life, due to long incubation and sub-clinical

 

 >>infection. Science to date, has well established

 

 >>transmission of sporadic CJDs with medical/surgical

 

 >>procedures.

 

 Terry S. Singeltary Sr. >>CJD WATCH

 

 Again, many thanks, Kindest regards,

 

 Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518 flounder@wt.net CJD WATCH

 

 [scroll down past article for my comments]

 

 snip...

 

 were not all CJDs, even nvCJD, just sporadic, until proven otherwise?

 

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

 


 

 Professor Michael Farthing wrote: Louise Send this to Bramble (author) for a comment before we post. Michael

 

 =======================================================

 

 snip... see full text ;

 

 2003

 

 Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to Bramble et al

 

 Evidence For CJD/TSE Transmission Via Endoscopes

 

 From Terry S. Singletary, Sr flounder@wt.net 1-24-3

 


 

 Monday, December 26, 2011

 

 Prion Uptake in the Gut: Identification of the First Uptake and Replication Sites

 


 

 Friday, August 10, 2012

 

 Incidents of Potential iatrogenic Creutzfeldt-Jakob disease (CJD) biannual update (July 2012)

 


 

 SNIP...

 

 see more history here ;

 

 OLYMPUS ENDOSCOPY CJD

 


 


 

 Tuesday, May 26, 2015

 

 Minimise transmission risk of CJD and vCJD in healthcare settings

 

 Last updated 15 May 2015

 


 

 Saturday, February 21, 2015

 

 Design of Endoscopic Retrograde Cholangiopancreatography (ERCP) Duodenoscopes May Impede Effective Cleaning: FDA Safety Communication

 


 


 

Thursday, September 10, 2015

 

*** 25th Meeting of the Transmissible Spongiform Encephalopathies Advisory Committee Food and Drug Administration Silver Spring, Maryland June 1, 2015

 


 

Congress is all set to give NIH it's largest increase in 12 years.

 

Included in the bill: $350 million increase for Alzheimer’s research and an $85 million increase for the BRAIN Initiative, the project to map the human brain.

 

Full story at: http://ow.ly/VYKBv

 

great news, with not a minute to spare...

 

Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy

 


 

07 02:27 AM

 

Terry S. Singeltary Sr. said:

 

re-Evidence for human transmission of amyloid-? pathology and cerebral amyloid angiopathy

 

Nature 525, 247?250 (10 September 2015) doi:10.1038/nature15369 Received 26 April 2015 Accepted 14 August 2015 Published online 09 September 2015 Updated online 11 September 2015 Erratum (October, 2015)

 


 

I would kindly like to comment on the Nature Paper, the Lancet reply, and the newspaper articles.

 

snip...

 

see Singeltary full text ;

 


 

Subject: 1992 IN CONFIDENCE TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES POSSIBILITY ON A TRANSMISSIBLE PRION REMAINS OPEN

 

BSE101/1 0136

 

IN CONFIDENCE

 

CMO

 

From: . Dr J S Metiers DCMO

 

4 November 1992

 

TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES

 

1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have recognised the public sensitivity of these findings and intend to report them in their proper context. 'This hopefully will avoid misunderstanding and possible distortion by the media to portray the results as having more greater significance than the findings so far justify.

 

2. Using a highly unusual route of transmission (intra-cerebral injection) the researchers have demonstrated the transmission of a pathological process from two cases one of severe Alzheimer's disease the other of Gerstmann-Straussler disease to marmosets. However they have not demonstrated the transmission of either clinical condition as the "animals were behaving normally when killed". As the report emphasises the unanswered question is whether the disease condition would have revealed itself if the marmosets had lived longer. They are planning further research to see if the conditions, as opposed to the partial pathological process, is transmissible.

 

what are the implications for public health?

 

3. The route 'of transmission is very specific and in the natural state of things highly unusual. However it could be argued that the results reveal a potential risk, in that brain tissue from these two patients has been shown to transmit a pathological process. Should therefore brain tissue from such cases be regarded as potentially infective? Pathologists, morticians, neuro surgeons and those assisting at neuro surgical procedures and others coming into contact with "raw" human brain tissue could in theory be at risk. However, on a priori grounds given the highly specific route of transmission in these experiments that risk must be negligible if the usual precautions for handling brain tissue are observed.

 

1

 

92/11.4/1.1

 

BSE101/1 0137

 

4. The other dimension to consider is the public reaction. To some extent the GSS case demonstrates little more than the transmission of BSE to a pig by intra-cerebral injection. If other prion diseases can be transmitted in this way it is little surprise that some pathological findings observed in GSS were also transmissible to a marmoset. But the transmission of features of Alzheimer's pathology is a different matter, given the much greater frequency of this disease and raises the unanswered question whether some cases are the result of a transmissible prion. The only tenable public line will be that "more research is required’’ before that hypothesis could be evaluated. The possibility on a transmissible prion remains open. In the meantime MRC needs carefully to consider the range and sequence of studies needed to follow through from the preliminary observations in these two cases. Not a particularly comfortable message, but until we know more about the causation of Alzheimer's disease the total reassurance is not practical.

 

J S METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH 832 llllYc!eS 2 92/11.4/1.2

 


 

>>> The only tenable public line will be that "more research is required’’ <<<

 

>>> possibility on a transmissible prion remains open<<<

 

O.K., so it’s about 23 years later, so somebody please tell me, when is "more research is required’’ enough time for evaluation ?

 

Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease

 

Received July 24, 2014; Accepted September 16, 2014; Published November 3, 2014

 


 

*** Singeltary comment PLoS ***

 

Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?

 

Posted by flounder on 05 Nov 2014 at 21:27 GMT

 


 

again, sporadic and familial is a red herring, in my opinion.

 

also, in my opinion, when you start have disease such as sporadic Fatal Familial Insomnia, (and or sporadic GSS, or the VPSPr type prion disease), and there is NO familial genetic linkage to the family of the diseased, I have serious questions there as to a familial type disease, and thus, being defined as such.

 

*UPDATE* NOVEMBER 16, 2014

 

vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???

 

Friday, January 10, 2014

 

Greetings again Friends, Neighbors, and Colleagues,

 

snip...see ;

 


 

Friday, October 09, 2015

 

*** An alarming presentation level II trauma center of Creutzfeldt-Jakob disease following a self-inflicted gunshot wound to the head

 


 

Saturday, December 12, 2015

 

CREUTZFELDT JAKOB DISEASE CJD TSE PRION REPORT DECEMBER 14, 2015

 


 

Thursday, December 24, 2015

 

Revisiting the Heidenhain Variant of Creutzfeldt-Jakob Disease: Evidence for Prion Type Variability Influencing Clinical Course and Laboratory Findings

 

Article type: Research Article

 


 

Wednesday, January 06, 2016

 

CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE U.K. 23rd ANNUAL REPORT 2014 (published 18th November 2015)

 


 

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

 

Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA

 

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

 

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

 

Terry S. Singeltary, Sr Bacliff, Tex

 

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

 


 

26 March 2003

 

Terry S. Singeltary, retired (medically) CJD WATCH

 

I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?

 


 

 2 January 2000

 

 British Medical Journal

 

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

 


 

 15 November 1999

 

 British Medical Journal

 

 vCJD in the USA * BSE in U.S.

 


 

Saturday, December 12, 2015

 

CHRONIC WASTING DISEASE CWD TSE PRION REPORT DECEMBER 14, 2015

 


 

==========================================

 

***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 FT. COLLINS CWD RISK FACTORS TO HUMANS

 

*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***

 

O18

 

Zoonotic Potential of CWD Prions

 

Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1, Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western Reserve University, Cleveland, Ohio, USA, 2Second University of Naples, Naples, Italy, 3Encore Health Resources, Houston, Texas, USA

 

*** These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.

 

==================

 

***These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.***

 

==================

 

P.105: RT-QuIC models trans-species prion transmission

 

Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward Hoover Prion Research Center; Colorado State University; Fort Collins, CO USA

 

Conversely, FSE maintained sufficient BSE characteristics to more efficiently convert bovine rPrP than feline rPrP. Additionally, human rPrP was competent for conversion by CWD and fCWD.

 

***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.

 

================

 

***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.***

 

================

 


 

THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE

 

R. G. WILL

 

1984

 

*** 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). (SEE LINK IN REPORT HERE...TSS) PLUS, THE CDC DID NOT PUT THIS WARNING OUT FOR THE WELL BEING OF THE DEER AND ELK ;

 

snip...

 


 

*** 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).***

 


 

*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies.

 


 

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, Val erie 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 longe 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...TSS

 

===============

 


 

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

 

Title: Transmission of scrapie prions to primate after an extended silent incubation period

 

Authors

 

item Comoy, Emmanuel - item Mikol, Jacqueline - item Luccantoni-Freire, Sophie - item Correia, Evelyne - item Lescoutra-Etchegaray, Nathalie - item Durand, Valérie - item Dehen, Capucine - item Andreoletti, Olivier - item Casalone, Cristina - item Richt, Juergen item Greenlee, Justin item Baron, Thierry - item Benestad, Sylvie - item Hills, Bob - item Brown, Paul - item Deslys, Jean-Philippe -

 

Submitted to: Scientific Reports Publication Type: Peer Reviewed Journal Publication Acceptance Date: May 28, 2015 Publication Date: June 30, 2015 Citation: Comoy, E.E., Mikol, J., Luccantoni-Freire, S., Correia, E., Lescoutra-Etchegaray, N., Durand, V., Dehen, C., Andreoletti, O., Casalone, C., Richt, J.A., Greenlee, J.J., Baron, T., Benestad, S., Brown, P., Deslys, J. 2015. Transmission of scrapie prions to primate after an extended silent incubation period. Scientific Reports. 5:11573.

 

Interpretive Summary:

 

The transmissible spongiform encephalopathies (also called prion diseases) are fatal neurodegenerative diseases that affect animals and humans. The agent of prion diseases is a misfolded form of the prion protein that is resistant to breakdown by the host cells. Since all mammals express prion protein on the surface of various cells such as neurons, all mammals are, in theory, capable of replicating prion diseases. One example of a prion disease, bovine spongiform encephalopathy (BSE; also called mad cow disease), has been shown to infect cattle, sheep, exotic undulates, cats, non-human primates, and humans when the new host is exposed to feeds or foods contaminated with the disease agent. The purpose of this study was to test whether non-human primates (cynomologous macaque) are susceptible to the agent of sheep scrapie. After an incubation period of approximately 10 years a macaque developed progressive clinical signs suggestive of neurologic disease. Upon postmortem examination and microscopic examination of tissues, there was a widespread distribution of lesions consistent with a transmissible spongiform encephalopathy. This information will have a scientific impact since it is the first study that demonstrates the transmission of scrapie to a non-human primate with a close genetic relationship to humans. This information is especially useful to regulatory officials and those involved with risk assessment of the potential transmission of animal prion diseases to humans.

 

Technical Abstract:

 

Classical bovine spongiform encephalopathy (c-BSE) is an animal prion disease that also causes variant Creutzfeldt-Jakob disease in humans. Over the past decades, c-BSE's zoonotic potential has been the driving force in establishing extensive protective measures for animal and human health. 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.

 


 

O35

 

J. Mikol1, S. Luccantoni-Freire1, E. Correia1, N. Lescoutra-Etchegaray1, V. Durand1, C. Dehen1, J.P. Deslys1, E. Comoy1

 

1Institute of Emerging Diseases and Innovative Therapies, Service of Prion Diseases, Atomic Energy Commission, 18 Route du Panorama 92265 Fontenayaux- Roses, France

 

E-mail: jacqueline.mikol@wanadoo.fr

 

Uncommon prion disease induced in macaque ten years after scrapie inoculation

 

Introduction: Bovine Spongiform Encephalopathy (BSE) is the single animal prion disease reputed to be zoonotic, inducing variant of Creutzfeldt-Jakob Disease (vCJD) in man, and therefore strongly conditioned the protective measures. Among different sources of animal prion diseases, we show here that after more than ten years of incubation, intracerebral injection of a sheep scrapie isolate can induce a prion disease in cynomolgus macaque, a relevant model of human situation towards several prion strains. Neuropathological studies showed classical and uncommon data.

 

Material and method: The cynomolgus macaque was intracerebrally exposed to a classical scrapie isolate issued from a naturally infected sheep flock. Upon onset of clinical signs, euthanasia was performed for ethical reasons. Classical methods of biochemistry and neuropathology were used.

 

Results: The three elements of the triad were present:

 

spongiosis was predominant in the cortex, the striatum, the cerebellum. Neuronal loss and gliosis were moderate.

 

The notable data were the following

 

(i) the brain was small, the atrophy involved mostly the temporal lobe in which axonal loss was histologically demonstrated

 

(ii) the spongiosis of the Purkinje cells was so intense that most of them were destroyed

 

(iii) there was a neuronal loss and a massive gliosis of the dorsomedialis nucleus of the thalamus

 

(iv) iron deposits were present in the lenticular nucleus. PrPres heavily distributed in the cortex, the basal ganglia and the cerebellum consisted in synaptic deposits and aggregates. Western Blot exhibited a type 1 PrPres in all parts of the brain.

 

Conclusion: We described here the successful transmission of a scrapie prion disease to a non-human primate after an extended incubation period, leading to a fatal, non-relapsing neurological disease with all the features of a prion disease. The cerebral lesional profile we observed was original in comparison to other animal prion diseases (c-BSE, L-type BSE, TME) we previously experimentally transmitted in this model.

 


 

Tuesday, December 16, 2014

 

Evidence for zoonotic potential of ovine scrapie prions

 

Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier Andréoletti1, Affiliations Contributions Corresponding author Journal name: Nature Communications Volume: 5, Article number: 5821 DOI: doi:10.1038/ncomms6821 Received 07 August 2014 Accepted 10 November 2014 Published 16 December 2014 Article tools Citation Reprints Rights & permissions Article metrics

 

Abstract

 

Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie prions remains unknown. Mice genetically engineered to overexpress the human ​prion protein (tgHu) have emerged as highly relevant models for gauging the capacity of prions to transmit to humans. These models can propagate human prions without any apparent transmission barrier and have been used used to confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie prions transmit to several tgHu mice models with an efficiency comparable to that of cattle BSE. The serial transmission of different scrapie isolates in these mice led to the propagation of prions that are phenotypically identical to those causing sporadic CJD (sCJD) in humans. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

 

Subject terms: Biological sciences• Medical research At a glance

 


 

why do we not want to do TSE transmission studies on chimpanzees $

 

5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.

 

snip...

 

R. BRADLEY

 


 

***there goes the damn bacon too...tss

 

Saturday, January 9, 2016

 

Transmission of sheep-bovine spongiform encephalopathy to pigs

 

Research article

 


 

Sunday, October 18, 2015

 

World Organisation for Animal Health (OIE) and the Institut Pasteur Cooperating on animal disease and zoonosis research

 


 

Thursday, December 17, 2015

 

Annual report of the Scientific Network on BSE-TSE 2015 EFSA-Q-2015-00738 10 December 2015

 


 

Saturday, December 12, 2015

 

*** BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION REPORT DECEMBER 14, 2015

 


 

Friday, January 1, 2016

 

South Korea Lifts Ban on Beef, Veal Imports From Canada

 


 

US CONGRESS, another failed entity...tss

 

Tuesday, December 29, 2015

 

*** Congress repeals country-of-origin labeling rule for beef and pork

 


 

December 28, 2015 at 2:21am

 

*** Australian government assessing risk of importing beef from US, Japan and the Netherlands

 


 

Thursday, December 24, 2015

 

Infectious disease spread is fueled by international trade

 


 

*** you can find some history of the BSE cases in Canada and Klein’s BSE SSS policy comment here ;

 


 

Monday, January 4, 2016

 

Long live the OIE, or time to close the doors on a failed entity?

 


 

sporadic cjd, 85%+ of all human TSE prion disease, sporadic simply meaning _unknown_ route, source, ... iatrogenic, what if ?

 

iatrogenic medical surgical tissue friendly fire mode of transmission i.e. second hand transmission. it’s real folks, just not documented much, due to lack of trace back efforts. all iatrogenic cjd is, is sporadic cjd, until the iatrogenic event is tracked down and documented, and put into the academic and public domain, which very seldom happens. ...

 

Terry S. Singeltary Sr., on the bottom, Galveston Bay flounder9@verizon.net

 

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