VARIANT CJD (vCJD) or nvCJD

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Location: BACLIFF, Texas, United States

My mother was murdered by what I call corporate and political homicide i.e. FOR PROFIT! she died from a rare phenotype of CJD i.e. the Heidenhain Variant of Creutzfeldt Jakob Disease i.e. sporadic, simply meaning from unknown route and source. I have simply been trying to validate her death DOD 12/14/97 with the truth. There is a route, and there is a source. There are many here in the USA. WE must make CJD and all human TSE, of all age groups 'reportable' Nationally and Internationally, with a written CJD questionnaire asking real questions pertaining to route and source of this agent. Friendly fire has the potential to play a huge role in the continued transmission of this agent via the medical, dental, and surgical arena. We must not flounder any longer. ...TSS

Thursday, September 29, 2016

A case cluster of variant Creutzfeldt-Jakob disease linked to the Kingdom of Saudi Arabia

★ Editor's Choice

 

★ A case cluster of variant Creutzfeldt-Jakob disease linked to the Kingdom of Saudi Arabia

 

 Michael B. Coulthart, Michael D. Geschwind, Shireen Qureshi, Nicolas Phielipp, Alex Demarsh, Joseph Y. Abrams, Ermias Belay, Pierluigi Gambetti, Gerard H. Jansen, Anthony E. Lang, Lawrence B. Schonberger

 


 

2609-2616 First published online: 26 September 2016 Michael B. Coulthart

 

1 Canadian Creutzfeldt-Jakob Disease Surveillance System, Centre for Foodborne, Environmental and Zoonotic Infectious Diseases, Public Health Agency of Canada, Ottawa, ON K1A 0K9, Canada Michael D. Geschwind

 

2 Memory and Aging Center, Box 1207, University of California, San Francisco (UCSF), San Francisco, CA 94143-1207, USA Shireen Qureshi

 

3 Consultant Neurologist, Dhahran Health Center, Dhahran, Saudi Arabia Nicolas Phielipp

 

4 Department of Neurology, Parkinson’s and Movement Disorders Program, University of California Irvine, Irvine, CA 92697, USA Alex Demarsh

 

5 Zoonoses Division, Centre for Foodborne, Environmental and Zoonotic Infectious Diseases, Public Health Agency of Canada, Ottawa, ON K1A 0K9, Canada Joseph Y. Abrams

 

6 Division of High Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA Ermias Belay

 

6 Division of High Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA Pierluigi Gambetti

 

7 Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA Gerard H. Jansen

 

8 Eastern Ontario Regional Laboratory Association, Ottawa Hospital, Ottawa, ON K1Y 4E9, Canada Anthony E. Lang

 

7 Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA Lawrence B. Schonberger

 

6 Division of High Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA

 

Summary As of mid-2016, 231 cases of variant Creutzfeldt-Jakob disease—the human form of a prion disease of cattle, bovine spongiform encephalopathy—have been reported from 12 countries. With few exceptions, the affected individuals had histories of extended residence in the UK or other Western European countries during the period (1980–96) of maximum global risk for human exposure to bovine spongiform encephalopathy. However, the possibility remains that other geographic foci of human infection exist, identification of which may help to foreshadow the future of the epidemic. We report results of a quantitative analysis of country-specific relative risks of infection for three individuals diagnosed with variant Creutzfeldt-Jakob disease in the USA and Canada. All were born and raised in Saudi Arabia, but had histories of residence and travel in other countries. To calculate country-specific relative probabilities of infection, we aligned each patient’s life history with published estimates of probability distributions of incubation period and age at infection parameters from a UK cohort of 171 variant Creutzfeldt-Jakob disease cases. The distributions were then partitioned into probability density fractions according to time intervals of the patient’s residence and travel history, and the density fractions were combined by country. This calculation was performed for incubation period alone, age at infection alone, and jointly for incubation and age at infection. Country-specific fractions were normalized either to the total density between the individual’s dates of birth and symptom onset (‘lifetime’), or to that between 1980 and 1996, for a total of six combinations of parameter and interval. The country-specific relative probability of infection for Saudi Arabia clearly ranked highest under each of the six combinations of parameter × interval for Patients 1 and 2, with values ranging from 0.572 to 0.998, respectively, for Patient 2 (age at infection × lifetime) and Patient 1 (joint incubation and age at infection × 1980–96). For Patient 3, relative probabilities for Saudi Arabia were not as distinct from those for other countries using the lifetime interval: 0.394, 0.360 and 0.378, respectively, for incubation period, age at infection and jointly for incubation and age at infection. However, for this patient Saudi Arabia clearly ranked highest within the 1980–96 period: 0.859, 0.871 and 0.865, respectively, for incubation period, age at infection and jointly for incubation and age at infection. These findings support the hypothesis that human infection with bovine spongiform encephalopathy occurred in Saudi Arabia.

 

prion diseases variant Creutzfeldt-Jakob disease bovine spongiform encephalopathy Saudi Arabia

 

snip...

 

Discussion

 

We have presented clinical and diagnostic findings for patients with vCJD, including results of EEG, MRI, CSF protein marker assay, molecular genetic analysis, PrP immunoblot, and histopathological examination of brain and/or lymphoid tissue using PrP immunohistochemistry. All patients met established criteria according to internationally accepted vCJD case definitions. The diagnoses were supported by multiple forms of evidence, in two cases with neuropathology (final diagnosis: definite vCJD) and one with tonsil pathology (final diagnosis: probable vCJD). We also documented lifetime residence and travel histories for each patient. These were used to estimate relative probabilities of infectious exposure in the various countries in which each patient had resided or travelled, using distributions of incubation period and age at infection derived from probabilistic modelling of the best-studied cohort from the UK vCJD epidemic (Garske and Ghani, 2010). Our conclusion in each case was that the single most probable country in which infectious exposure took place was Saudi Arabia.

 

There is compelling evidence that BSE is the zoonotic cause of vCJD (Will et al., 1996; Bruce et al., 1997; Hill et al., 1997; Scott et al., 1999; Diack et al., 2014). Exposure to BSE-contaminated UK beef products between 1980, when epidemic transmission of BSE is estimated to have begun in the UK, and 1996 when reinforced regulation of animal feed was implemented there, is considered the major global risk factor for vCJD (Smith and Bradley, 2003). During this period nearly 170 000 cases of BSE were confirmed in the UK, over 28 times the total number of such cases reported in the rest of the world through 2014 [World Organization for Animal Health (OIE), 2014]. It is estimated that 1–3 million UK cattle were infected with BSE, of which most were undetected and processed for human consumption (Anderson et al., 1996; Donnelly et al., 2002). This is reflected in the fact that 178 of the 231 vCJD cases reported worldwide to date have occurred in UK residents (NCJDRSU, UK). For countries reporting vCJD cases not linked to UK residence, a significant correlation has been demonstrated between the number of vCJD cases and the volume of UK beef imported between 1980 and 1996 (Sanchez-Juan et al., 2007). Even in France, with over 1000 BSE cases and 27 vCJD cases reported as of 2015, imported UK beef was a major source of exposure to BSE (Chadeau-Hyam and Alperovitch, 2005).

 

For the same reasons, it is not surprising that four of the nine patients with vCJD who resided in countries outside the UK and Western Europe at time of onset—including three of the seven who became ill and/or were diagnosed in Canada and the USA—had resided in the UK for extended periods between 1980 and 1996 (Jansen et al., 2003; Holman et al., 2010; Yang et al., 2010). A fifth case, the only one reported to date in a Japanese resident, was attributed to exposure during a 24-day visit to the UK in early 1990, close to the peak of the human BSE exposure risk there (Yamada and Variant CJD Working Group, Creutzfeldt-Jakob Disease Surveillance Committee, Japan, 2006). The absence of other vCJD cases in Japan supports this interpretation; however, this is the only case to date in which infectious exposure has been attributed to such a brief period outside the patient’s main country of residence (Yamada and Variant CJD Working Group, Creutzfeldt-Jakob Disease Surveillance Committee, Japan, 2006).

 

In contrast with this general pattern, the three patients reported here were all born and raised in Saudi Arabia, and resided there for at least 10 years during the period (1980–96) of maximal global exposure risk to BSE-contaminated UK beef. None of the three had ever resided in the UK; two had not visited there between 1980 and 1996; and the third had visited there for 2 weeks in late 1995. These features of the patients’ histories alone suggest that their infectious exposures more likely occurred in Saudi Arabia than in the UK or Europe. The results of our analysis of country-specific relative probabilities of infectious exposure strongly support this conclusion. In all cases—even for Patient 3, who spent the most time outside Saudi Arabia—the single greatest weight of probability for country of infection was allocated to Saudi Arabia.

 

Consistent with this interpretation are UK Customs and Excise data indicating that over 19 000 tons of bovine carcass meat were exported to Saudi Arabia in the period 1980–96 inclusively, with >2900 tons from 1988–90, and >2580 tons during the period 1993–96. Only relatively small amounts (<8 1989="" 1990="" 1991="" 2="" a="" all="" and="" any="" applied="" arabia="" as="" be="" beef="" been="" bse="" by="" carcass="" case.="" communication="" could="" customs="" data="" demonstrate="" div="" during="" e.g.="" embargo="" epidemiological="" er="" even="" exposure="" for="" furthermore="" given="" has="" have="" human="" ig.="" importation="" in="" individual="" infected.="" inference="" it="" justify="" life-history="" likely="" majesty="" meat="" note="" occurred="" of="" or="" patients="" personal="" point="" products="" recorded="" reflecting="" revenue="" s="" saudi="" shipped="" short-term="" sufficient="" that="" the="" this="" three="" to="" tons="" uk="" we="" were="" would="">
 

Questions could be raised regarding the realism of the country-specific probability weightings we have estimated. For example, despite our use of incubation period and age at infection estimates from the largest, most recent and best-studied cohort of UK vCJD cases, these estimates arguably may not be directly applicable to non-UK populations (Garske and Ghani, 2010). A related point has to do with the fact that earlier studies had yielded different values (e.g. incubation periods in excess of 16 years)—presumably consistent with the relatively late dates of onset of the three patients described here (2003, 2006 and 2010) (Valleron et al., 2001; Boelle et al., 2003).

 

To address these questions, we first point out that there is no specific evidence to support such epidemiological differences and that, as noted above, all three patients described here displayed clinical, paraclinical and pathological features typical of vCJD cases reported from the UK and other countries (Heath et al., 2010). As also noted above, the risk of exposure to BSE-contaminated beef is considered to have applied globally, and not only in the UK, suggesting that in a broad sense all cases of vCJD can be considered to be part of the same epidemic. Lastly, to address the possibility that a longer incubation period would have a significant effect on the results of our analysis, we repeated the above computations using a mean incubation period of 16.7 years (Valleron et al., 2001). ***Although we found small differences in some country-specific probabilities (for Patient 3 only), the key conclusions were unchanged (results not shown).

 

The limited number of clinical cases of vCJD confirmed worldwide to date, with only one vCJD case reported in 2013 (in the UK), one in 2014 (in the USA), and two in 2016 (one each in the UK and Italy) supports an optimistic view that few additional vCJD deaths are likely. Nevertheless, uncertainty remains regarding size and duration of the rightward ‘tail’ of the epidemic curve (Garske and Ghani, 2010). This uncertainty is accentuated by the results of a laboratory-based survey of archived tonsil and appendix specimens, which estimated a subclinical vCJD infection prevalence of 493 per million (95% confidence interval: 282, 801) in the general UK population, much higher than suggested by the number of clinical vCJD cases reported in that country to date (Gill et al., 2013).

 

This tissue-based survey also demonstrated that even though almost all vCJD patients examined to date, including the three reported here, have been homozygous for the ATG (methionine) allele at codon 129 of the PRNP gene, individuals with any of the three possible genotypes at this codon can be infected by the BSE/vCJD agent. The potential epidemiologic significance of this genetic risk factor has been further highlighted by a recent report from the UK of an autopsy-confirmed case of vCJD in an individual who was heterozygous for ATG (methionine) and GTG (valine) alleles at PRNP codon 129 (Will et al., 2016). This finding is consistent with the hypothesis that future cases of vCJD may occur in individuals with longer incubation periods who are heterozygous for methionine and valine alleles at PRNP codon 129, or possibly homozygous for the valine allele (Garske and Ghani, 2010).

 

We also note that Patient 3, who was heterozygous for GAG (glutamic acid) and AAG (lysine) alleles at PRNP codon 219, is the third vCJD patient with this genotype reported to date (Lukic et al., 2010). This genotype is relatively common in Eastern and Southern Asia and the Pacific, where it reaches population frequencies in the range of 1–10% and is deemed to be protective against sporadic CJD, but very rare elsewhere (Shibuya et al., 1998; Jeong et al., 2005; Soldevila et al., 2006). Heterozygosity at codon 219 has also been proposed to increase susceptibility to vCJD, suggesting that the likelihood of future vCJD cases occurring in residents of non-European countries may be influenced by this genetic factor (Lukic et al., 2010). With the small number of such cases reported to date, however, and noting that our Patient 3 was of South Asian background, further investigation of this important hypothesis is warranted.

 

Still other questions relate to atypical forms of BSE that appear to arise spontaneously in cattle, as sporadic CJD is believed to originate in humans. It is presently unknown whether atypical BSE can cause human disease, or whether the original BSE outbreak emerged in this way (Comoy et al., 2008; Tranulis et al., 2011). These uncertainties, as well as the prolonged incubation period of vCJD and strong evidence of its transmissibility by blood transfusion, support ongoing precaution. Current measures to monitor and control BSE and CJD internationally remain key elements of a prudent long-term public health strategy (Diack et al., 2014).

 


 

4th case of nvCJD in USA, 2nd nvCJD case in TEXAS, please remember;

 

***The specific overseas country where this patient’s infection occurred is less clear largely because the investigation did not definitely link him to a country where other known vCJD cases likely had been infected.

 

3rd case nvCJD ;

 

***Although we found small differences in some country-specific probabilities (for Patient 3 only), the key conclusions were unchanged (results not shown).

 

 

Sunday, November 23, 2014

 

Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas in June 2014 confirmed as USA case NOT European

 

Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas

 

Updated: October 7, 2014

 

CDC and the Texas Department of State Health Services (DSHS) have completed the investigation of the recently reported fourth vCJD case in the United States. It confirmed that the case was in a US citizen born outside the Americas and indicated that the patient's exposure to the BSE/vCJD agent most likely occurred before he moved to the United States; the patient had resided in Kuwait, Russia and Lebanon. The completed investigation did not support the patient's having had extended travel to European countries, including the United Kingdom, or travel to Saudi Arabia. The specific overseas country where this patient’s infection occurred is less clear largely because the investigation did not definitely link him to a country where other known vCJD cases likely had been infected.

 


 

 >>>the patient had resided in Kuwait, Russia and Lebanon.

 

 >>>The completed investigation did not support the patient's having had extended travel to European countries, including the United Kingdom, or travel to Saudi Arabia.

 

 NOW we all know why the state of Texas or the CDC did not want to report this case, because it was a home grown case of nvCJD right here in Texas?...tss

 

 Monday, June 02, 2014

 

 Confirmed Variant CJD Case in Texas

 


 


 


 

 Variant Creutzfeldt-Jakob Disease Death, United States: 1st Case Report

 

The only variant Creutzfeldt-Jakob disease (vCJD) patient identified in the United States died in 2004, and the diagnosis was confirmed by analysis of autopsy tissue. The patient likely acquired the disease while growing up in Great Britain before immigrating to the United States in 1992. Additional vCJD patients continue to be identified outside the United Kingdom, including 2 more patients in Ireland, and 1 patient each in Japan, Portugal, Saudi Arabia, Spain and the Netherlands. The reports of bloodborne transmission of vCJD in 2 patients, 1 of whom was heterozygous for methionine and valine at polymorphic codon 129, add to the uncertainty about the future of the vCJD outbreak.

 

snip...

 

see case history on 1st nvCJD case in USA here ;

 


 

A 22-year-old Florida resident became the first person in the USA to be diagnosed with probable variant Creutzfeldt-Jakob disease (vCJD), according to the US Centers for Disease Control and Prevention (CDC). Because the young woman was raised in the UK when the BSE outbreak was at its peak, officials believe that she contracted the disease there. The case report, which is published in Morbidity and Mortality Weekly Report (2002; 51: 927—29;

 


 

Probable Variant Creutzfeldt-Jakob Disease in a US Resident—Florida, 2002

 

JAMA. 2002;288:2965-2967.

 

MMWR. 2002;51:927-929

 

On April 18, 2002, the Florida Department of Health and CDC announced the occurrence of a likely case of variant Creutzfeldt-Jakob disease (vCJD) in a Florida resident aged 22 years. This report documents the investigation of this case and underscores the importance of physicians increasing their suspicion for vCJD in patients presenting with clinical features described in this report who have spent time in areas in which bovine spongiform encephalopathy (BSE) is endemic.

 

In early November 2001, the patient sought medical care for depression and memory loss that adversely affected the patient's work performance. The primary-care physician referred the patient to a psychologist. In early December 2001, the patient received a traffic ticket for failing to yield the right of way. In mid-December 2001, the patient had involuntary muscular movements, gait changes, difficulty dressing, and incontinence. In January 2002, the patient was evaluated in a local emergency department for these symptoms. A computerized tomography scan of the head revealed no abnormalities; a panic attack was diagnosed, and the patient was treated with an anti-anxiety medication.

 

In late January 2002, the patient's mother, a resident of the United Kingdom, took the patient to England, where medical evaluations were conducted during the next 3 months. During this period, the patient's memory loss and other neurologic symptoms worsened. The patient experienced falls with minor injuries, had difficulty taking a shower and dressing, and was unable to remember a home telephone number or to make accurate mathematical calculations. The patient subsequently became confused, hallucinated, and had speech abnormalities with lack of content, bradykinesia, and spasticity. The patient was referred to a neurologist, who suspected vCJD and subsequently referred the patient to the National Prion Clinic in the United Kingdom.

 

Medical evaluations at the National Prion Clinic included an electroencephalogram (EEG), which revealed a normal alpharhythm, and magnetic resonance imaging (MRI) studies, which revealed signal abnormalities in the pulvinar and metathalamus region that were suggestive of vCJD. The patient had a tonsil biopsy, and a Western blot analysis of the biopsy tissue demonstrated the presence of protease-resistant prion protein (PrP-res) with the characteristic pattern of vCJD; an immunohistochemical test for PrP-res also supported a diagnosis of vCJD. Analysis of the prion protein gene detected no mutation and showed methionine homozygosity at codon 129, consistent with all 105 vCJD patients tested in the United Kingdom (R. Will, Western General Hospital, Edinburgh, Scotland, personal communication, 2002).

 

The patient received experimental treatment with quinacrine for 3 months. As of late September 2002, the patient had become bedridden, experienced considerable weight loss requiring surgical insertion of a feeding tube, and was no longer communicating with family members. On the basis of a case definition developed in the United Kingdom, the patient's illness met criteria for a probable case of vCJD.1

 

The patient was born in the United Kingdom in 1979 and moved to Florida in 1992. The patient never had donated or received blood, plasma, or organs and never had received human growth hormone. There was no family history of CJD. In October 2001, before the onset of the illness, the patient's wisdom teeth were extracted, but there was no history of major surgery.

 

Reported by:

 

S Wiersma, MD, State Epidemiologist, Florida Dept of Health. S Cooper, MRCP, R Knight, FRCP, National Creutzfeldt-Jakob Disease Surveillance Unit, Western General Hospital, Edinburgh, Scotland; AM Kennedy, MD, National Prion Clinic, Dept of Neurology, St. Mary's Hospital, London; S Joiner, MSc, Medical Research Council Prion Unit, Dept of Neurodegenerative Disease, Institute of Neurology, London, United Kingdom. E Belay, MD, LB Schonberger, MD, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC.

 

CDC Editorial Note:

 

snip...full text ;

 


 


 


 


 

 Variant Creutzfeldt-Jakob Disease Death, United States: 2nd Case Report

 

vCJD (Variant Creutzfeldt-Jakob Disease)

 

Update: Variant Creutzfeldt-Jakob Disease in a U.K. Citizen Who Had Temporarily Resided in Texas, 2001-2005

 

In November 2005, the U.K. National Creutzfeldt-Jakob Disease (CJD) Surveillance Unit in Edinburgh, Scotland notified the Centers for Disease Control and Prevention (CDC) about a probable variant CJD diagnosis in a 30-year-old man who resided in Texas during 2001-2005. The patient had onset of symptoms in early 2005 while in Texas. He then returned to the United Kingdom, where his illness progressed, and a diagnosis of variant CJD was made. This diagnosis was confirmed neuropathologically after the patient's death.

 

The variant CJD diagnosis was initially based on typical clinical manifestations of the disease and demonstration of the characteristic “pulvinar sign” on magnetic resonance imaging of the brain. No biopsy tissues are available for pathologic confirmation of the diagnosis. While living in the United States, the patient had no history of hospitalization, of having invasive medical procedures, or of donation or receipt of blood and blood products.

 

The patient almost certainly acquired the disease in the United Kingdom. He was born in the United Kingdom and lived there throughout the defined period of risk (1980-1996) for human exposure to the agent of bovine spongiform encephalopathy (BSE, commonly known as “mad cow” disease). His stay in the United States was too brief relative to what is known about the incubation period for variant CJD. For additional information about the incubation period for variant CJD, see Belay ED, Sejvar JJ, Shieh WJ, et al. “Variant Creutzfeldt-Jakob Disease Death, United States,” Emerg Infect Dis 2005; available at

 


 

By convention, variant CJD cases are ascribed to the country of initial symptom onset, regardless of where the exposure occurred. Since variant CJD was first reported in 1996, a total of 195 patients with this disease from 11 countries have been identified. As of August 11, 2006, variant CJD cases have been reported from the following countries: 162 from the United Kingdom, 20 from France, 4 from Ireland, 2 from the United States (including the current case), and one each from Canada, Italy, Japan, Netherlands, Portugal, Saudi Arabia, and Spain. Similar to the two U.S. cases, two of the four cases from Ireland and the single cases from Canada and Japan were likely exposed to the BSE agent while residing in the United Kingdom.One of the 20 French cases may also have been infected in the United Kingdom. Strong scientific evidence indicates that variant CJD results from the transmission to humans of the agent that causes BSE in cattle. The BSE outbreak in cattle that was first detected in the 1980s in the United Kingdom has spread to many other European countries, and cases in cattle have been identified outside of Europe, in Canada, Israel, Japan, and the United States.

 

Date: August 14, 2006 Content source: National Center for Infectious Diseases

 


 

Variant Creutzfeldt-Jakob Disease Death, United States: 3rd Case Report

 

NO DETAILED case report I could find on this very unusual and assumed case of nvCJD in the USA, but here is cdc short report ;

 

vCJD (Variant Creutzfeldt-Jakob Disease)

 

Confirmed Case of Variant Creutzfeldt Jakob Disease (vCJD) in the United States in a Patient from the Middle East

 

The Virginia Department of Health and the Centers for Disease Control and Prevention announce the recent confirmation of a vCJD case in a U.S. resident. This is the third vCJD case identified in a U.S. resident. This latest U.S. case occurred in a young adult who was born and raised in Saudi Arabia and has lived in the United States since late 2005. The patient occasionally stayed in the United States for up to 3 months at a time since 2001 and there was a shorter visit in 1989. In late November 2006, the Clinical Prion Research Team at the University of California San Francisco Memory and Aging Center confirmed the vCJD clinical diagnosis by pathologic study of adenoid and brain biopsy tissues. The two previously reported vCJD case-patients in U.S. residents were each born and raised in the United Kingdom (U.K.), where they were believed to have been infected by the agent responsible for their disease. There is strong scientific evidence that the agent causing vCJD is the same agent that causes bovine spongiform encephalopathy (BSE, commonly known as mad cow disease).

 

Variant CJD is a rare, degenerative, fatal brain disorder that emerged in the United Kingdom in the mid-1990s. Although experience with this new disease is limited, evidence to date indicates that there has never been a case transmitted from person-to-person except through blood transfusion. Instead, the disease is thought to result primarily from consumption of cattle products contaminated with the BSE agent. Although no cases of BSE in cattle have been reported in Saudi Arabia, potentially contaminated cattle products from the United Kingdom may have been exported to Saudi Arabia for many years during the large U.K. BSE outbreak.

 

The current case-patient has no history of receipt of blood, a past neurosurgical procedure, or residing in or visiting countries of Europe. Based on the patient's history, the occurrence of a previously reported Saudi case of vCJD attributed to likely consumption of BSE-contaminated cattle products in Saudi Arabia, and the expected greater than 7 year incubation period for food-related vCJD, this U.S. case-patient was most likely infected from contaminated cattle products consumed as a child when living in Saudi Arabia (1). The current patient has no history of donating blood and the public health investigation has identified no risk of transmission to U.S. residents from this patient.

 

As of November 2006, 200 vCJD patients were reported world-wide, including 164 patients identified in the United Kingdom, 21 in France, 4 in the Republic of Ireland, 3 in the United States (including the present case-patient), 2 in the Netherlands and 1 each in Canada, Italy, Japan, Portugal, Saudi Arabia and Spain. Of the 200 reported vCJD patients, all except 10 of them (including the present case-patient) had resided either in the United Kingdom (170 cases) for over 6 months during the 1980-1996 period of the large UK BSE outbreak or alternatively in France (20 cases).

 

As reported in 2005 (1), the U.S. National Prion Disease Pathology Surveillance Center at Case Western Reserve University confirmed the diagnosis in the one previously identified case of vCJD in a Saudi resident. He was hospitalized in Saudi Arabia and his brain biopsy specimen was shipped to the United States for analysis. This earlier vCJD case-patient was believed to have contracted his fatal disease in Saudi Arabia (1).

 

1) Belay ED, Sejvar JJ, Shieh W-J, Wiersma ST, Zou W-Q, Gambetti P, Hunter S, Maddox RA, Crockett L, Zaki SR, Schonberger LB. Variant Creutzfeldt-Jakob disease death, United States. Emerg Infect Dis 2005, 11 (9):1351-1354.

 

Date: November 29, 2006

 


 

The third US resident with vCJD was born and raised in Saudi Arabia and beginning in 2001 he occasionally stayed in the United States for periods of up to 3 months duration [30], [31]. The patient relocated to the United States in 2005 where onset of vCJD symptoms was experienced in the spring of 2006. The diagnosis of vCJD was confirmed based on pathological study of adenoid and brain biopsy tissues in November 2006. The patient died later in 2006. The patient had no past history of neurosurgical procedures or visits to European countries. A previous case of vCJD attributed to consumption of BSE-contaminated cattle products had been reported in a Saudi Arabian resident [13].

 


 

The Virginia Department of Health and the Centers for Disease Control and Prevention announce the recent confirmation of a case of variant Creutzfeldt-Jakob disease (vCJD) in a Virginia resident. There is no evidence to suggest that this case of vCJD was caused by anything the patient was exposed to while residing in the U.S. or that this situation represents a public health threat to any U.S. resident.

 

For more information on vCJD, visit CDC’s Web site at http://www.cdc.gov/ncidod/dvrd/vcjd/other/vCJD_112906.htm.

 

Virginia CJD Epidemiology CJD is currently a reportable condition in Virginia only if the ill person is less than 55 years of age; therefore data on this condition are very limited.

 

snip...

 

One limitation to our understanding of CJD in Virginia and the US is that surveillance mainly uses death certificate data. However, it is very likely that some cases do not get recorded. CJD is an uncommon disease and physicians who are not familiar with the signs and symptoms may mistake it for other conditions. Evidence of the under-reporting of cases comes from some European countries, where enhanced surveillance has found higher than expected rates due to increased awareness and better diagnosis. 11 In addition, one small study reported that as many as 13% of patients diagnosed with Alzheimer’s disease were found upon autopsy to have actually had CJD.12 Therefore, it seems likely that the current data underestimate the true incidence of CJD in Virginia and in the US.

 


 

Creutzfeldt-Jakob Disease (CJD) In 2006, a case of Creutzfeldt- Jakob Disease (CJD) in an individual less than 55 years of age was reported. Sporadic CJD occurs in Virginia; the age criteria is intended to screen for potential cases of new variant CJD (nvCJD). On further investigation, this individual was found to have new variant CJD. Epidemiologic investigation suggested that it was extremely unlikely that this individual acquired the infection in the U.S. However, this counted as only the third case of nvCJD ever diagnosed in the U.S. A high index of suspicion and early testing is important for diagnosing CJD, since arranging for brain biopsy or autopsy to confirm the diagnosis may be important for families and healthcare professionals.

 


 

From: TSS Subject: Third case of vCJD reported in the United States Date: December 7, 2006 at 11:08 am PST

 

##################### Bovine Spongiform Encephalopathy #####################

 

Third case of vCJD reported in the United States Editorial Team (eurosurveillance.weekly@hpa.org.uk), Eurosurveillance editorial office

 

A clinical diagnosis of variant Creutzfeldt Jakob Disease (vCJD) was confirmed after brain biopsy investigations in a United States (US) resident and reported in November [1]. The patient is a young man who grew up in Saudi Arabia and lived in the US since late 2005. Before that he visited the US once in 1989 and several times after 2001. He has never visited any country in Europe or received a blood transfusion nor has he undergone any neurosurgical procedure. This vCJD case is the third in a US resident. The previous two patients both grew up in the United Kingdom (UK), and this is where they were believed to have been infected [2].

 

In Saudi Arabia, the first and only previous case of vCJD was reported in 2005. This was suspected to be related to consumption of meat contaminated with the prion agent which causes bovine spongiform encephalitis in cattle (BSE). The European Food Safety Authority (http://www.efsa.org) has not published a geographical BSE risk assessment for Saudi Arabia [3] and there have been no cases of BSE in cattle reported by Saudi Arabia to the World Organisation for Animal Health (http://www.oie.int). Although the UK is not the only potential beef exporter to have had a BSE epidemic, it remains plausible, subject to Saudi Arabia's import policy, that contaminated beef was inadvertently imported from the UK to Saudi Arabia in the period before 1996 (when the EU banned the export of UK beef and cattle).

 

Based on this patient's history, the occurrence of a previously reported case of vCJD in Saudi Arabia, and the expected length of the incubation period for food-related vCJD, the most likely source of infection is thought to be contaminated meat products the patient consumed as a child when living in Saudi Arabia. The patient has no known history of donating blood, and investigations have identified no risk of onwards transmission within the US.

 

Variant Creutzfeldt-Jakob disease was first identified in the United Kingdom in the mid-1990s. As of November 2006, worldwide there have been 200 vCJD cases: 164 patients in the United Kingdom, 21 in France, four in Ireland, three in the US (including the present case), two in the Netherlands and one each in Canada, Italy, Japan, Portugal, Saudi Arabia and Spain [4]. All patients, except 10 (including the present case) had lived either in the United Kingdom (170 cases) or in France (20 cases). Evidence so far indicates that the most probable source of infection in most cases was consumption of meat products contaminated with the prion agent causing BSE.

 

References: Centers for Disease Control and Prevention.

 

Confirmed Case of Variant Creutzfeldt Jakob Disease (vCJD) in the United States in a Patient from the Middle East.

 


 

Belay ED, Sejvar JJ, Shieh W-J, Wiersma ST, Zou W-Q, Gambetti P, Hunter S, Maddox RA, Crockett L, Zaki SR, Schonberger LB. Variant Creutzfeldt-Jakob disease death, United States. Emerg Infect Dis 2005, 11 (9):1351-1354. European Food Safety Authority . Geographical BSE Risk (GBR) assessments covering 2000-2006. List of countries and their GBR level of risk as assessed by the Scientific Steering Committee and the (EFSA). 1 August 2006.

 


 

The most recent assessments (and reassessments) were published in June 2005 (Table I; 18), and included the categorisation of Canada, the USA, and Mexico as GBR III. Although only Canada and the USA have reported cases, the historically open system of trade in North America suggests that it is likely that BSE is present also in Mexico.

 


 

Variant Creuzfeldt-Jakob disease. Current data – December 2006.

 


 


 

Wednesday, December 06, 2006

 

vCJD USA THIRD CASE DOCUMENTED

 

Wednesday, December 06, 2006

 

vCJD USA THIRD CASE DOCUMENTED

 

 

I propose that this third case of nvCJD documented in the USA has as much, or even more of a chance of being an indigenous home grown nvCJD case in the USA, as that of being exposed the short time this person was in Saudi Arabia, a country that has never had a case of mad cow disease documented. THE USA import of highly infectious materials from documented BSE countries, including the U.K. was phenomenal, let alone it's own TME exposed MBM from right here in the USA. Strange there is no case history of this supposedly Saudi Arabia source case and history of time in the USA compared to time in Saudi Arabia, food habits, and such? It would be nice to compare and try and figure up incubation time periods with this third case, age, symptoms, beginning clinical signs to death, etc, a good case study in other words, where is it ???

 

let's look at a few factors ;

 


 


 


 


 

>>>The patient is a young man who grew up in Saudi Arabia and lived in the US since late 2005. Before that he visited the US once in 1989 and several times after 2001. He has never visited any country in Europe or received a blood transfusion nor has he undergone any neurosurgical procedure.<<<

 

Heaven forbid anyone suggest that this unlucky Soul was contaminated in the USA from vCJD. This would just be preposterous, wouldn't it $$$ i am reminded of a few things deep throat told me years ago;

 

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

 

 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 a least a million bovine tested as soon as possible and agressively 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!"

 

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! I hope there is a confidential panel organized by the new government to really investigate this thing.

 

You need to watch your back........but keep picking at them.......like a buzzard to the bone...you just may get to the truth!!! (You probably have more support than you know. Too many people are afraid to show you or let anyone else know. I have heard a few things myself... you ask the questions that everyone else is too afraid to ask.)

 

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

 

 12/07/06

 

HOWEVER, if you ONLY consider an OUTSIDE source of mbm from the UK, you will see that indeed the UK did dump a great deal of mad cow poison on the middle east, compared to the amount they dumped on USA. comparing from my records from the U.K., the USA imported about 44 tons of UK mbm or greaves, Canada got 83 tons in 3 years, 1993, 1994, and 1995. compared to about 6,985 tons exported from the UK to Saudi Arabia over a period of about 20 years, with Saudi importing mbm from UK as late as 1995. ISRAEL ALSO IMPORTED A GREAT DEAL OF THIS POISON, 30,006 TONS of MBM FROM UK. A great deal was also imported to Asian Countries as well. HOWEVER, we cannot state that this is indeed a case of vCJD exported to the USA from Saudi with certainty. now we all know that the USDA will paint this pig with lipstick and take it to the dance, to the prom and anywhere else they can take it, but the fact still remains, they cannot state this with scientific proof. IF you look at the USA and it's TSE problem, the rendering industry, and the fact that the USA shipped the technology of continous rendering to the UK, only to start using 5 years later, then look at the 100s, if not thousands of tons of potentially and most likely TSE tainted feed used in the USA for the last 2 decades, the likelyhood of this being a USA source of vCJD, in my opinion, is possible as well. In 2006 alone, the amount of ruminant protein still being fed to USA cattle is not only phenominal, but also very very disturbing. ...TSS

 

 see full text ;

 


 


 


 

*** Grant Agreement number: 222887 ***

 

*** Project acronym: PRIORITY ***

 

*** Project title: Protecting the food chain from prions: shaping European priorities through basic and applied research Funding ***

 

Scheme: Large-scale integrating project Period covered: from Oct. 1, 2009 to Sept. 30, 2014

 

Name of the scientific representative of the project's co-ordinator1, Title and Organisation: Jesús R. Requena, Ph.D., Associate Professor, Department of medicine, University of Santiago de Compostela, Spàin. Tel: 34-881815464 Fax: 34-881815403 E-mail: jesus.requena@usc.es

 

Project website¡Error! Marcador no definido. address: www.prionpriority.eu

 

PRIORITY, PROJECT FINAL REPORT

 

*** 14) Concluding that atypical scrapie can transmit to Humans and that its strain properties change as it transmits between species ***

 

snip...

 

Block D: Prion epidemiology

 

Studies on atypical scrapie were identified as a key element of this block, given the potential risk associated to this agent. We studied the permeability of Human, bovine and porcine species barriers to atypical scrapie agent transmission. Experiments in transgenic mice expressing bovine, porcine or human PrPC suggest that this TSE agent has the intrinsic ability to propagate across these species barriers including the Human one. Upon species barrier passage the biological properties and phenotype of atypical scrapie seem to be altered. Further experiments are currently ongoing (in the framework of this project but also in other projects) in order to: (i) characterize the properties of the prion that emerged from the propagation of atypical scrapie in tg Hu; (ii) to confirm that the phenomena we observed are also true for atypical scrapie isolates other than the ones we have studied.

 

In parallel, studies in shep have concluded that: 

 

*** Atypical scrapie can be transmitted by both oral and intracerebral route in sheep with various PRP genotypes 

 

*** Low but consistent amount of infectivity accumulates in peripheral tissue (mammary gland, lymph nodes, placenta, skeletal muscles, nerves) of sheep incubating atypical scrapie.

 

*** The combination of data from all our studies leads us to conclude that: 

 

*** Atypical scrapie passage through species barriers can lead to the emergence of various prions including classical BSE (following propagation in porcine PRP transgenic mice). 

 

*** Atypical scrapie can propagate, with a low efficacy, in human PrP expressing mice. This suggests the existence of a zoonotic potential for this TSE agent.

 

snip...

 

We advance our main conclusions and recommendations, in particular as they might affect public policy, including a detailed elaboration of the evidence that led to them. Our main recommendations are:

 

a. The issue of re-introducing ruminant protein into the food-chain The opinion of the members of Priority is that sustaining an absolute feed ban for ruminant protein to ruminants is the essential requirement, especially since the impact of non-classical forms of scrapie in sheep and goats is not fully understood and cannot be fully estimated. Therefore, the consortium strongly recommends prohibiting re-introduction of processed ruminant protein into the food-chain. Arguments in support of this opinion are:

 

• the large (and still uncharacterized) diversity of prion agents that circulate in animal populations;

 

• the uncertainties related to prion epidemiology in animal populations;

 

• the unknown efficacy of industrial processes applied to reduce microbiological risk during processed animal protein (PAP) production on most prion agents; • the intrinsic capacity of prions to cross interspecies transmission barriers; • the lack of sensitive methodology for identifying cross contamination in food.

 

• the evolution of natural food chains in nature (i.e. who eats whom or what) has generated an efficient barrier preventing, to some extent, novel prion epidemies and that this naturally evolved ecology should be respected.

 

The consortium is also hesitant to introduce processed ruminant proteins into fish food considering the paucity of data on prion infections in fishes and sea animals including those of mammalian origin, and the risk of establishing an environmental contamination of the oceans that cannot be controlled.

 

b. Atypical prion agents and surveillance

 

Atypical prion agents (see below) will probably continue to represent the dominant form of prion diseases in the near future, particularly in Europe.

 

*** Atypical L-type BSE has clear zoonotic potential, as demonstrated in experimental models.

 

*** Similarly, there are now some data that seem to indicate that the atypical scrapie agent can cross various species barriers.

 

*** Moreover, the current EU policy for eradicating scrapie (genetic selection in affected flocks) is ineffective for preventing atypical scrapie.

 

*** The recent identification of cell-to-cell propagation and the protein-encoded strain properties of human neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, suggest that they bear the potential to be transmissible even if not with the same efficiency as CJD. More epidemiological data from large cohorts are necessary to reach any conclusion on the impact of their transmissibility on public health. Re-evaluations of safety precautions may become necessary depending on the outcome of these studies. In that context it would appear valuable

 

• to develop knowledge related to the pathogenesis and inter-individual transmission of atypical prion agents in ruminants (both intra- and inter-species)

 

• to improve the sensitivity of detection assays that are applied in the field towards this type of agent

 

• to maintain a robust surveillance of both animal and human populations

 

c. The need for extended research on prions

 

Intensified searching for a molecular determinants of the species barrier is recommended, since this barrier is a key for many important policy areas - risk assessment, proportional policies, the need for screening of human products and food. In this respect, prion strain structural language also remains an important issue for public health for the foreseeable future. Understanding the structural basis for strains and the basis for adaptation of a strain to a new host will require continued fundamental research. Prions maintain a complex two-way relationship with the host cell and fundamental research is needed on mechanisms for their transmission, replication and cause of nervous system dysfunction and death.

 

Early detection of prion infection, ideally at preclinical stage, also remains crucial for development of effective treatment strategies in humans affected by the disease.

 

Position of the Priority consortium

 

Nearly 30 years ago, the appearance in the UK of Bovine Spongiform Encephalopathy (BSE) quickly brought the previously obscure “prion diseases” to the spotlight. The ensuing health and food crises that spread throughout Europe had devastating consequences. In the UK alone, there were more than 36,000 farms directly affected by BSE and the transmission of BSE prions to humans via the food chain has caused over 200 people in Europe to die from variant Creutzfeldt-Jakob disease (vCJD) (http://www.cjd.ed.ac.uk

 

Origins of prion epidemies

 

Classical BSE now appears to be under control, with 18 EU Member States having achieved the World Organisation for Animal Health (Office International Epizooties) „negligible risk‟ status (May 2014; http://www.oie.int/en/animal-health-in-the-world/official-disease-status/bse/list-of-bse-risk-status/), and the remaining MS assessed as „controlled‟ risk. Of note, research, including EU-funded research, has played a key role in this success: while the origin of the infection was never defined, the principle driver of the epidemic was identified as prions in Meat and Bone Meal (MBM). Tests based on prion protein-specific antibodies were developed, allowing detection of infected animals, and a better understanding of disease pathogenesis and the distribution of infectivity in edible tissues; experimental investigation of transmission barriers between different species allowed a rational estimation of risks, etc. All of this led to the implementation of rational and effective policies, such as the MBM ban to protect the animal feed chain, and the Specified Risk Material (SRM) regulations to protect the human food chain.

 

In spite of this progress, prions are still a threat. Epidemiological re-assessment indicates that the ∼10 year incubation period separating the peaks of the BSE and the vCJD epidemics is probably too short. In addition, results from a large number of human tonsil and appendix analyses in the UK suggest that there may be a high number of asymptomatic individuals who are positive for the disease-associated conformer prion protein PrPSc. While vCJD is the only form of human prion disease that has been consistently demonstrated to have lymphoreticular involvement, there has been no systematic investigation of lymphoid tissue in cases with other prion diseases.

 

The human prion problem

 

The clinical cases of vCJD identified to date have all shared a common PrP genotype (M129M), although one pre-clinical case was confirmed as an M129V heterozygote, and it has been mooted that perhaps only the M129M proportion of the population is susceptible. However, in the UK appendix study, PrP accumulation was described in samples representing every codon 129 genotype, raising the possibility that genotype does not confer resistance but instead modulates incubation period. Apart from the two UK studies, the lymphoid tissues of non-CJD patients have not been examined for the presence of PrPSc, so, these cases may not solely represent pre-clinical vCJD, but also other forms of prion disease.

 

Recent experiments in highly susceptible mouse models indicate the presence of infectivity in blood or blood components at late disease stages in sporadic CJD. The significance of this experimental finding for humans has to be explored in more detail and, at the present time, there is no evidence for the transmission of prions via blood in sporadic CJD. However a likely scenario is that all those with signs of infection or abnormal PrP accumulation in peripheral tissue could have infective blood, posing the risk for transmission via blood products, which has been clearly demonstrated in experimental models, and confirmed in several cases of vCJD in man. Altogether, these data clearly demonstrate the potential risk of a second wave of vCJD, particularly when the number people identified with lymphoid accumulation of PrPSc (16/32,411) gives a prevalence estimate in the UK of 493 per million, much higher than the number of clinical cases seen to date.

 

The animal prion problem

 

An increasing number of reports on cases of “atypical” BSE in cattle throughout the EU and beyond may lead to a new epidemic, particularly since we still do not understand all factors determining the species barrier. Ovine scrapie is another concern, because it could mask ovine BSE, presumably transmissible to humans. Scrapie is endemic and not likely to be eradicated soon, although current control measures are effective at greatly reducing disease incidence. Atypical forms, which may be spontaneous, are not affected by these control measures and these forms of disease will persist in the global animal population. The low prevalence of these disease forms makes effective surveillance very challenging. However, there is a clear risk attendant on ignoring these cases without an understanding of their possible zoonotic potential, particularly when most forms of human disease have no established aetiology. In summary, atypical cases of BSE and scrapie presently clearly outnumber classical cases in cattle and sheep in all member states.

 

We will highlight the state-of-the-art knowledge and point out scientific challenges and the major questions for research. Strategic objectives and priorities in Europe in the future for research that aims to control, eliminate or eradicate the threat posed by prions to our food and health are also indicated.

 

The Priority project has focused on 4 themes, namely the structure, function, conversion and toxicity of prions; detection of prions; mechanisms of prion transmission and spreading and epidemiology of prion diseases. This paper summarizes the opinions/positions reached within these themes at the end of the project.

 


 

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

 

Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,

 

Natalia Fernandez-Borges a. and Alba Marin-Moreno a

 

"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France

 

Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion. Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.

 

To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.

 

These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.

 

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.

 


 


 


 


 

P.86: Estimating the risk of transmission of BSE and scrapie to ruminants and humans by protein misfolding cyclic amplification

 

Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama National Institute of Animal Health; Tsukuba, Japan

 

To assess the risk of the transmission of ruminant prions to ruminants and humans at the molecular level, we investigated the ability of abnormal prion protein (PrPSc) of typical and atypical BSEs (L-type and H-type) and typical scrapie to convert normal prion protein (PrPC) from bovine, ovine, and human to proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding cyclic amplification (PMCA).

 

Six rounds of serial PMCA was performed using 10% brain homogenates from transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc seed from typical and atypical BSE- or typical scrapie-infected brain homogenates from native host species. In the conventional PMCA, the conversion of PrPC to PrPres was observed only when the species of PrPC source and PrPSc seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA and heparin), both bovine and ovine PrPC were converted by PrPSc from all tested prion strains. On the other hand, human PrPC was converted by PrPSc from typical and H-type BSE in this PMCA condition.

 

*** Although these results were not compatible with the previous reports describing the lack of transmissibility of H-type BSE to ovine and human transgenic mice, 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. ***

 

O.08: H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism: Clinical and pathologic features in wild-type and E211K cattle following intracranial inoculation

 

S Jo Moore, M Heather West Greenlee, Jodi Smith, Eric Nicholson, Cathy Vrentas, and Justin Greenlee United States Department of Agriculture; Ames, IA USA

 

In 2006 an H-type bovine spongiform encephalopathy (BSE) case was reported in an animal with an unusual polymorphism (E211K) in the prion protein gene. Although the prevalence of this polymorphism is low, cattle carrying the K211 allele are predisposed to rapid onset of H-type BSE when exposed. The purpose of this study was to investigate the phenotype of this BSE strain in wild-type (E211E) and E211K heterozygous cattle. One calf carrying the wild-type allele and one E211K calf were inoculated intracranially with H-type BSE brain homogenate from the US 2006 case that also carried one K211 allelle. In addition, one wild-type calf and one E211K calf were inoculated intracranially with brain homogenate from a US 2003 classical BSE case. All animals succumbed to clinical disease. Survival times for E211K H-type BSE inoculated catttle (10 and 18 months) were shorter than the classical BSE inoculated cattle (both 26 months). Significant changes in retinal function were observed in H-type BSE challenged cattle only. Animals challenged with the same inoculum showed similar severity and neuroanatomical distribution of vacuolation and disease-associated prion protein deposition in the brain, though differences in neuropathology were observed between E211K H-type BSE and classical BSE inoculated animals. Western blot results for brain tissue from challenged animals were consistent with the inoculum strains.

 

This study demonstrates that the phenotype of E211K H-type BSE remains stable when transmitted to cattle without the E211K polymorphism, and exhibits a number of features that differ from classical BSE in both wild-type and E211K cattle.

 

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.

 

P.73: Oral challenge of goats with atypical scrapie

 

Silvia Colussi1, Maria Mazza1, Francesca Martucci1, Simone Peletto1, Cristiano Corona1, Marina Gallo1, Cristina Bona1, Romolo Nonno2, Michele Di Bari2, Claudia D’Agostino2, Nicola Martinelli3, Guerino Lombardi3, and Pier Luigi Acutis1 1Istituto Zooprofilattico Sperimentale del Piemonte; Liguria e Valle d’Aosta; Turin, Italy; 2Istituto Superiore di Sanit a; Rome, Italy; 3Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna; Brescia, Italy

 

Atypical scrapie transmission has been demonstrated in sheep by intracerebral and oral route (Simmons et al., Andreoletti et al., 2011) but data about goats are not available yet. In 2006 we orally challenged four goats, five months old, with genotype R/H and R/R at codon 154. Animals died starting from 24 to 77 months p.i. without clinical signs. They all resulted negative for scrapie in CNS and peripheral tissues using Western blot and immunohistochemistry. Nevertheless these goats could still represent carriers. This hypothesis was investigated through bioassay in tg338 mice, a sensitive animal model for atypical scrapie infectivity. By end-point dilution titration, the starting inoculum contained 106.8 ID50/g. In contrast, all tissues from challenged goats were negative by bioassay. These negative results could be explained with the low infectivity of the starting inoculum, which could have been unable to induce Prion 2015 Poster Abstracts S49 disease or infectivity within our period of observation. However the challenge conditions could have been a bias too: as the matter of the fact, while the oral challenge of classical scrapie is still effective in sheep 6–10 months old (Andreoletti et al., 2011), Simmons et al. (2011) demonstrated a very short efficacy period for atypical scrapie (24 hours after birth), hypothesizing that natural transmission could occur mainly via milk. Our work suggests that this could be true also for goats and it should be taken into account in oral challenges. However a low susceptibility of goats to atypical scrapie transmission via oral route cannot be excluded.

 


 

>>> These results suggest that (i) at the level of protein-protein interactions, CWD adapts to a new species more readily than does BSE and (ii) the barrier preventing transmission of CWD to humans may be less robust than estimated.

 

Accepted manuscript posted online 8 July 2015.

 

Insights into Chronic Wasting Disease and Bovine Spongiform Encephalopathy Species Barriers by Use of Real-Time Conversion

 

Kristen A. Davenport, Davin M. Henderson, Jifeng Bian, Glenn C. Telling, Candace K. Mathiason and Edward A. Hoover Prion Research Center, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA K. L. Beemon, Editor + Author Affiliations

 

Next Section ABSTRACT The propensity for transspecies prion transmission is related to the structural characteristics of the enciphering and new host PrP, although the exact mechanism remains incompletely understood. The effects of variability in prion protein on cross-species prion transmission have been studied with animal bioassays, but the influence of prion protein structure versus that of host cofactors (e.g., cellular constituents, trafficking, and innate immune interactions) remains difficult to dissect. To isolate the effects of protein-protein interactions on transspecies conversion, we used recombinant PrPC and real-time quaking-induced conversion (RT-QuIC) and compared chronic wasting disease (CWD) and classical bovine spongiform encephalopathy (cBSE) prions. To assess the impact of transmission to a new species, we studied feline CWD (fCWD) and feline BSE (i.e., feline spongiform encephalopathy [FSE]). We cross-seeded fCWD and FSE into each species' full-length, recombinant PrPC and measured the time required for conversion to the amyloid (PrPRes) form, which we describe here as the rate of amyloid conversion. These studies revealed the following: (i) CWD and BSE seeded their homologous species' PrP best; (ii) fCWD was a more efficient seed for feline rPrP than for white-tailed deer rPrP; (iii) conversely, FSE more efficiently converted bovine than feline rPrP; (iv) and CWD, fCWD, BSE, and FSE all converted human rPrP, although not as efficiently as homologous sCJD prions. These results suggest that (i) at the level of protein-protein interactions, CWD adapts to a new species more readily than does BSE and (ii) the barrier preventing transmission of CWD to humans may be less robust than estimated.

 

IMPORTANCE We demonstrate that bovine spongiform encephalopathy prions maintain their transspecies conversion characteristics upon passage to cats but that chronic wasting disease prions adapt to the cat and are distinguishable from the original prion. Additionally, we showed that chronic wasting disease prions are effective at seeding the conversion of normal human prion protein to an amyloid conformation, perhaps the first step in crossing the species barrier.

 

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Enciphering characteristics of cBSE and cBSE-derived prions are conserved after transspecies transmission.cBSE and CWD are prion diseases that have been naturally passaged in their respective species (cattle and deer), whereas feline spongiform encephalopathy (FSE) and feline chronic wasting disease (fCWD) are first-passage infections in a new host species (cat). To investigate the biochemical properties of cBSE and CWD after transspecies transmission to felines, we compared the amyloidogenicity of fCWD and FSE in the original host and in feline substrate. We found fCWD to be a more efficient seed for its new (feline) host, suggesting that adaptation to the new host had occurred (Fig. 4A). In contrast, FSE remained a more efficient seed for its enciphering (bovine) host, despite its derivation from feline brain PrPC (Fig. 4B). Thereby, these cross-species seeding experiments in RT-QuIC indicated that the characteristics of cBSE were maintained upon passage to a new species whereas CWD had adapted to its new host. These findings in felids suggest that cBSE may retain its ability to cross species barriers even after transmission to a new host species and that CWD may change substantially upon transspecies transmission.

 

Human rPrPC can be converted by bovine, feline, and cervid prions.The threat of zoonotic transmission of prion disease is evident and well documented, yet such transmission is uncommonly observed and incompletely understood. We thereby explored the propensity of heterologous prions to convert human rPrP. In these human rPrPC experiments, we used sporadic CJD brain as a positive control and normal bovine, white-tailed deer, and feline brain as negative controls. sCJD, as expected, seeded human rPrPC most efficiently, so all other seeds were normalized to the rate of conversion of sCJD. We found human rPrPC to be a competent substrate in RT-QuIC for CWD, fCWD, cBSE, and FSE (Fig. 5A). Interestingly, CWD and fCWD converted human rPrPC more efficiently than did cBSE and FSE. These data suggest that at the level of PrPC-PrP seed interaction, CWD has the ability to template the conversion of human rPrPC to ThT-positive amyloid. In order to assess whether CWD was faster than cBSE due to an increased concentration of prion seed, we performed Western blotting on the seed inocula. Western blots indicated that the cBSE sample had a higher concentration of PrPRes than the CWD sample, indicating that CWD was not a better seed than cBSE due to PrPRes content (Fig. 5B). Finally, we assessed the behavior of 8 CWD field isolates, brain samples from white-tailed deer infected naturally and verified to be positive using full-length white-tailed deer RT-QuIC (Fig. 5C). All 8 of these isolates converted human rPrPC, confirming that our observations were not due to the use of experimentally CWD (Fig. 5D). In all, these experiments suggest that the CWD prions naturally circulating in the western United States have the capacity to convert human rPrPC in this assay of protein-protein interactions.

 

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In summary, real-time conversion demonstrates that CWD and BSE prions differ in their enciphering rigidity and plasticity across species barriers. One illustration is the conservation versus adaptation of enciphering prion characteristics upon passage to cats. These experiments also demonstrate that human rPrP can be converted to amyloid by both cBSE and CWD prions. These data point to the importance of deciphering the mechanisms by which prions infect and adapt to a new species and of prompt continued vigilance regarding indirect pathways that may facilitate transspecies prion transmission.

 


 

Monday, September 19, 2016

 

Evidence of scrapie transmission to sheep via goat milk

 


 

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research

 

2015 Annual Report

 

1a. Objectives (from AD-416): 1. Investigate the pathobiology of atypical transmissible spongiform encephalopathies (TSEs) in natural hosts. A. Investigate the pathobiology of atypical scrapie. B. Investigate the pathobiology of atypical bovine spongiform encephalopathy (BSE). 2. Investigate the horizontal transmission of TSEs. A. Assess the horizontal transmission of sheep scrapie in the absence of lambing. B. Determine routes of transmission in chronic wasting disease (CWD) infected premises. C. Assess oral transmission of CWD in reindeer. 3. Investigate determinants of CWD persistence. A. Determine CWD host range using natural routes of transmission. B. Investigate the pathobiology of CWD.

 

1b. Approach (from AD-416): The studies will focus on three animal transmissible spongiform encephalopathy (TSE) agents found in the United States: bovine spongiform encephalopathy (BSE); scrapie of sheep and goats; and chronic wasting disease (CWD) of deer, elk, and moose. The research will address sites of accumulation, routes of infection, environmental persistence, and ante mortem diagnostics with an emphasis on controlled conditions and natural routes of infection. Techniques used will include clinical exams, histopathology, immunohistochemistry and biochemical analysis of proteins. The enhanced knowledge gained from this work will help mitigate the potential for unrecognized epidemic expansions of these diseases in populations of animals that could either directly or indirectly affect food animals.

 

3. Progress Report: Research efforts directed toward meeting objective 1 of our project plan include work in previous years starting with the inoculation of animals for studies designed to address the pathobiology of atypical scrapie, atypical bovine spongiform encephalopathy (BSE), as well as a genetic version of BSE. Post-mortem examination of the animals inoculated with atypical scrapie has been initiated and laboratory analysis of the tissues is ongoing. Atypical BSE animals have developed disease and evaluation of the samples is currently underway. Animals inoculated with a genetic version of BSE have developed disease with a manuscript reporting these results was published (2012), and additional laboratory comparisons of genetic BSE to atypical and classical BSE are ongoing. In addition, we have investigated the possibility that atypical scrapie was present earlier than previously detected in the national flock by analyzing archived field isolates using methods that were unavailable at the time of original diagnosis. Sample quality was sufficiently degraded that modern methods, beyond those applied to the tissues at the time the tissues were archived, were not suitable for evaluation. In research pertaining to objective 2, "Investigate the horizontal transmission of TSEs", we have initiated a study to determine if cohousing non-lambing scrapie inoculated sheep is sufficient to transmit scrapie to neonatal lambs. At this time, scrapie free ewes have lambed in the presence of scrapie inoculated animals and the lambs are cohoused with these inoculated animals.

 

4. Accomplishments 1. Changes in retinal function in cattle can be used to identify different types of bovine spongiform encephalopathy (BSE). BSE belongs to a group of fatal, transmissible protein misfolding diseases known as transmissible spongiform encephalopathies (TSEs). Like other protein misfolding diseases including Parkinson's disease and Alzheimer's disease, TSEs are generally not diagnosed until the onset of disease after the appearance of unequivocal clinical signs. As such, identification of the earliest clinical signs of disease may facilitate diagnosis. The retina is the most accessible part of the central nervous system. ARS scientist in Ames IA described antemortem changes in retinal function and thickness that are detectable in BSE inoculated animals up to 11 months prior to the appearance of any other signs of clinical disease. Differences in the severity of these clinical signs reflect the amount of PrPSc accumulation in the retina and the resulting inflammatory response of the tissue. These results are the earliest reported clinical signs associated with TSE infection and provide a basis for understanding the pathology and evaluating therapeutic interventions. Further, this work shows that High-type BSE and classical BSE can be differentiated by eye examination alone, the first time BSE strains have been differentiable in a live animal.

 

2. Sheep genetics influences the susceptibility of sheep to scrapie. Sheep scrapie is a transmissible spongiform encephalopathy that can be transmitted between affected animals resulting in significant economic losses in affected flocks. The prion protein gene (PRNP) profoundly influences the susceptibility of sheep to the scrapie agent and the tissue levels and distribution of PrPSc in affected sheep. In this study, sheep of 3 different prion genetic types (denoted VRQ/VRQ, VRQ/ARR and ARQ/ARR) were inoculated and subsequently euthanized upon onset of disease. Disease aspects were uniform across genotypes and consistent with manifestations of classical scrapie. Mean survival time differences were associated with the genetic type such that VRQ/VRQ sheep survived 18 months, whereas VRQ/ARR and ARQ/ARR sheep survived 60 and 56 months, respectively. Microscopic evaluation revealed similar accumulations in central nervous system tissues regardless of host genetic type. PrPSc in lymphoid tissue was consistently abundant in VRQ/VRQ, present but confined to tonsil or retropharyngeal lymph node in 4/5 VRQ/ARR, and totally absent in ARQ/ARR sheep. The results of this study demonstrate the susceptibility of sheep with the ARQ/ARR genotype to scrapie by the intracranial inoculation route with PrPSc accumulation in CNS tissues, but prolonged incubation times and lack of PrPSc in lymphoid tissue. These results are important for science based policy with regard to testing of sheep for scrapie where some live animal testing is conducted using lymphoid tissues which would not detect scrapie in some specific genetic types which could limit the national scrapie eradication program.

 

Review Publications Greenlee J.J. 2014. The prion diseases of animals. In: McManus, L.M., Mitchell, R.N., editors. Pathobiology of Human Disease. San Diego: Elsevier. p. 1124-1133. Greenlee, J.J., Kunkle, R.A., Richt, J.A., Nicholson, E.M., Hamir, A.N. 2014. Lack of prion accumulation in lymphoid tissues of PRNP ARQ/ARR sheep intracranially inoculated with the agent of scrapie. PLoS One. 9(9):e108029. Greenlee, J.J., West Greenlee, M.,H. 2015. The transmissible spongiform encephalopathies of livestock. ILAR Journal. 56(1):7-25. Munoz-Gutierrez, J.F., Schneider, D.A., Baszler, T.V., Dinkel, K.D., Greenlee, J.J., Nicholson, E.M., Stanton, J.J. 2015. hTERT-immortalized ovine microglia propagate natural scrapie isolates. Virus Research. 198:35-43. Nicholson, E.M. 2015. Detection of the disease-associated form of the prion protein in biological samples. Bioanalysis. 7(2):253-261. West Greenlee, M.H., Smith, J.D., Platt, E.M., Juarez, J.R., Timms, L.L, Greenlee, J.J. 2015. Changes in retinal function and morphology are early clinical signs of disease in cattle with bovine spongiform encephalopathy. PLoS ONE. 10(3):e0119431. 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.

 


 

***Our study demonstrates susceptibility of adult cattle to oral transmission of classical BSE. ***

 

***our findings suggest that possible transmission risk of H-type BSE to sheep and human. ***

 

P.86: Estimating the risk of transmission of BSE and scrapie to ruminants and humans by protein misfolding cyclic amplification

 

Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama National Institute of Animal Health; Tsukuba, Japan

 

To assess the risk of the transmission of ruminant prions to ruminants and humans at the molecular level, we investigated the ability of abnormal prion protein (PrPSc) of typical and atypical BSEs (L-type and H-type) and typical scrapie to convert normal prion protein (PrPC) from bovine, ovine, and human to proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding cyclic amplification (PMCA).

 

Six rounds of serial PMCA was performed using 10% brain homogenates from transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc seed from typical and atypical BSE- or typical scrapie-infected brain homogenates from native host species. In the conventional PMCA, the conversion of PrPC to PrPres was observed only when the species of PrPC source and PrPSc seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA and heparin), both bovine and ovine PrPC were converted by PrPSc from all tested prion strains. On the other hand, human PrPC was converted by PrPSc from typical and H-type BSE in this PMCA condition.

 

Although these results were not compatible with the previous reports describing the lack of transmissibility of H-type BSE to ovine and human transgenic mice, ***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.

 

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***Our study demonstrates susceptibility of adult cattle to oral transmission of classical BSE. ***

 

P.86: Estimating the risk of transmission of BSE and scrapie to ruminants and humans by protein misfolding cyclic amplification

 

Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama National Institute of Animal Health; Tsukuba, Japan

 

To assess the risk of the transmission of ruminant prions to ruminants and humans at the molecular level, we investigated the ability of abnormal prion protein (PrPSc) of typical and atypical BSEs (L-type and H-type) and typical scrapie to convert normal prion protein (PrPC) from bovine, ovine, and human to proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding cyclic amplification (PMCA).

 

Six rounds of serial PMCA was performed using 10% brain homogenates from transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc seed from typical and atypical BSE- or typical scrapie-infected brain homogenates from native host species. In the conventional PMCA, the conversion of PrPC to PrPres was observed only when the species of PrPC source and PrPSc seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA and heparin), both bovine and ovine PrPC were converted by PrPSc from all tested prion strains. On the other hand, human PrPC was converted by PrPSc from typical and H-type BSE in this PMCA condition.

 

Although these results were not compatible with the previous reports describing the lack of transmissibility of H-type BSE to ovine and human transgenic mice, ***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.

 

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Saturday, May 30, 2015

 

PRION 2015 ORAL AND POSTER CONGRESSIONAL ABSTRACTS

 


 


 

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.

 

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***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.***

 

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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.

 

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

 

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***P.170: Potential detection of oral transmission of H type atypical BSE in cattle using in vitro conversion

 

Sandor Dudas, John G Gray, Renee Clark, and Stefanie Czub Canadian Food Inspection Agency; Lethbridge, AB Canada

 

Keywords: Atypical BSE, oral transmission, RT-QuIC

 

The detection of bovine spongiform encephalopathy (BSE) has had a significant negative impact on the cattle industry worldwide. In response, governments took actions to prevent transmission and additional threats to animal health and food safety. While these measures seem to be effective for controlling classical BSE, the more recently discovered atypical BSE has presented a new challenge. To generate data for risk assessment and control measures, we have challenged cattle orally with atypical BSE to determine transmissibility and mis-folded prion (PrPSc) tissue distribution. Upon presentation of clinical symptoms, animals were euthanized and tested for characteristic histopathological changes as well as PrPSc deposition.

 

The H-type challenged animal displayed vacuolation exclusively in rostral brain areas but the L-type challenged animal showed no evidence thereof. To our surprise, neither of the animals euthanized, which were displaying clinical signs indicative of BSE, showed conclusive mis-folded prion accumulation in the brain or gut using standard molecular or immunohistochemical assays. To confirm presence or absence of prion infectivity, we employed an optimized real-time quaking induced conversion (RT-QuIC) assay developed at the Rocky Mountain Laboratory, Hamilton, USA.

 

Detection of PrPSc was unsuccessful for brain samples tests from the orally inoculated L type animal using the RT-QuIC. It is possible that these negative results were related to the tissue sampling locations or that type specific optimization is needed to detect PrPSc in this animal. We were however able to consistently detect the presence of mis-folded prions in the brain of the H-type inoculated animal. Considering the negative and inconclusive results with other PrPSc detection methods, positive results using the optimized RT-QuIC suggests the method is extremely sensitive for H-type BSE detection. This may be evidence of the first successful oral transmission of H type atypical BSE in cattle and additional investigation of samples from these animals are ongoing.

 

P.169: PrPSc distribution in brain areas of a natural German H-type BSE case

 

Anne Balkema-Buschmann, Grit Priemer, Markus Keller, and Martin H Groschup Friedrich Loeffler Institut, Institute for Novel and Emerging Infectious Diseases; Greifswald, Insel Riems, Germany

 

Keywords: BSE H-type, brain, muscle

 

Ten years after the initial description of atypical BSE cases of the H-type and L-type, the distribution of PrPSc in different brain areas and peripheral tissues of natural cases of these BSE forms is still not fully understood. Intracerebral challenge experiments have been performed with both atypical BSE forms in cattle, and the distribution of the abnormal prion protein and infectivity has been analysed in a variety of tissues, confirming the general restriction to the central nervous system as it was already generally acknowledged for classical BSE, but showing a slightly earlier and stronger involvement of the peripheral nervous system and the skeletal muscle. www.landesbioscience.com Prion 105

 

However, data from cattle orally challenged with atypical BSE, which might mimic the natural situation, are not yet available. Unfortunately, for most natural cases of atypical BSE, only the obex region is available for further analysis. The PrPSc distribution in the brains of natural L-type BSE cases in Italy has been described in some detail, but comparably few such data are yet available for natural H-type cases. Here we describe the analysis of different brain areas and muscle samples of a natural H-type BSE case diagnosed in Germany in 2014, and compare these data with those obtained from the respective samples collected from cattle challenged intracerebrally with H-type BSE.

 

*** P.159: Transgenic mice overexpressing rabbit prion protein are susceptible to BSE, BASE and scrapie prion strains but resistant to CWD and atypical scrapie

 

Natalia Fernández-Borges,1 Enric Vidal,2 Belén Pintado,4 Hasier Eraña,1 Montserrat Ordóñez,3 Mercedes Márquez,5 Francesca Chianini,6 Dolors Fondevila,5 Manuel A Sánchez-Martín,7 Olivier Andréoletti,8 Mark P Dagleish,6 Martí Pumarola,5 and Joaquín Castilla1,3 1CIC bioGUNE; Parque tecnológico de Bizkaia; Derio; Bizkaia, Spain; 2Centre de Recerca en Sanitat Animal (CReSA); UAB-IR TA, Campus de la Universitat Autònoma de Barcelona; Bellaterra; Barcelona, Catalonia, Spain; 3IKERBASQUE; Basque Foundation for Science; Bilbao, Bizkaia, Spain; 4Centro Nacional de Biotecnología (CNB), Campus de Cantoblanco; Cantoblanco; Madrid, Spain; 5Department of Animal Medicine and Surgery; Veterinary faculty; Universitat Autònoma de Barcelona (UAB); Bellaterra (Cerdanyola del Vallès); Barcelona, Catalonia, Spain; 6Moredun Research Institute; Bush Loan, Penicuik, Scotland, UK; 7Unidad de Generación de OMGs. S.E.A. Department of Medicine; University of Salamanca; Salamanca, Spain; 8Ecole Nationale du Veterinaire; Service de Pathologie du Bétail; Toulouse, France

 

Interspecies transmission of prions is a well established phenomenon, both experimentally and in field conditions. Upon passage through new hosts prion strains have proven their capacity to change their properties. It is, in fact, a source of strain diversity which needs to be considered when assessing the potential risks associated with consumption of prion contaminated protein sources.

 

Rabbits were considered for decades a prion resistant species until proven recently otherwise. To determine the extent of rabbit susceptibility to prions and to assess their effects on the passage of different prion strains through this species, a transgenic mouse model overexpressing rabbit PrPC was developed (TgRab). Intracerebral challenges with prion strains originating from a variety of species including field isolates (SSBP1 scrapie, Nor98-like scrapie, BSE, BASE and CWD), experimental murine strains (ME7 and RML), experimentally obtained strains (sheepBSE) and strains obtained by in vitro crossing of the species barrier using saPMCA (BSE-RabPrPres, SSBP1-RabPrPres and CWD-RabPrPres) have been performed.

 

Interestingly, on first passage, TgRab were susceptible to the majority of prions tested with the exception of SSBP1 scrapie, CWD and Nor98 scrapie. Furthermore TgRab were capable of propagating strain-specific features such as differences in incubation periods, brain lesion and PrPd deposition profiles and PK resistant western blotting band patterns. Our results confirm previous studies shattering the myth that rabbits are resistant to prion infection and this should be taken into account when choosing protein sources to feed rabbits.

 

P.168: Evolution of the biological properties of L-BSE after passage in sheep with susceptible and resistant PrP genotypes

 

Michele A Di Bari, Umberto Agrimi, Claudia D’Agostino, Geraldina Riccardi, Stefano Marcon, Elena Esposito, Paolo Frassanito, Flavio Torriani, Shimon Simson, and Romolo Nonno Istituto Superiore di Sanità (ISS) Department of Veterinary Public Health and Food Safety; Rome, Italy

 

Background. Cattle L-BSE was efficiently transmitted to sheep with susceptible (QQ171) and resistant (QR171) PrP genotypes. 1 Notably, the PrPSc signature of L-BSE was preserved in QQ171 sheep but not in QR171 sheep.2 Notwithstanding, bioassay in transgenic mice expressing bovine or ovine (ARQ) PrPC showed that L-BSE strain was preserved in both, QQ171 and QR171 sheep-passaged L-BSE.3

 

Here we studied the biological properties of sheep-passaged L-BSE by bioassay in bank voles and transgenic mice expressing the ovine VRQ PrP (tg338), both characterized by a comparatively low susceptibility to cattle L-BSE.

 

Material and Methods. Voles and tg338 mice were intracerebrally inoculated with cattle L-BSE and sheep-passaged (QQ171 and QR171) L-BSE isolates. Survival time, lesion profiles, Pet-blot and WB analysis were used for strain typing. Results. Cattle L-BSE transmitted quite inefficiently to tg338 mice, with survival time >400 days post-infection (d.p.i.), while sheep-passaged inocula were much more efficient and all gave terminal disease by ~140 d.p.i. However, after sub-passage all inocula converged to a survival time of ~145 d.p.i.. and showed overlapping pathological phenotypes.

 

In voles, cattle L-BSE transmitted with very long survival times (~800 d.p.i.) and was accompanied by an upward shift of the PrPSc type. Again, all sheep-passaged L-BSE isolates transmitted much more efficiently, with similar survival times of ~360 d.p.i.. Upon second passage, three different strains were isolated in vole, characterized by distinct pathological phenotypes. This divergence is epitomized by the different survival times of vole-adapted L-BSE strains, which were ~400 d.p.i. for cattle L-BSE, ~130 d.p.i. for QQ171-passaged L-BSE and ~225 d.p.i. for QR171-passaged L-BSE.

 

Conclusions. These findings, along with previously published data,3 show that the original L-BSE strain was recovered after passage in sheep when bioassay was performed in animal models expressing bovine or ovine PrPC. In contrast, strain changes were observed in both, QQ171- and QR171-passaged L-BSE by bioassay in vole, a species with divergent PrP sequence compared to ruminants. Importantly, QQ171- and QR171-passaged L-BSE were characterised by different PrPSc types and, accordingly, showed different biological properties when transmitted to voles, but not when transmitted to other animal models.

 

Overall, our work support the hypothesis that prion isolates are likely composed of multiple prion components, emphasizes the role of host PrP polymorphisms on strain selection and mutation, and highlights the risk for new potentially zoonotic strains that could emerge from prion evolution in animal reservoirs.

 

P.172: BSE exposure risk from bovine intestine and mesentery

 

Fulvio Barizzone,1 Herbert Budka,2 Christine Fast,3 John N Griffin,4 Giuseppe Ru,5 Pietro Stella1 and Olivier Andréoletti6 1European Food Safety Authority; Parma, Italy; 2Institute of Neuropathology; University Hospital Zurich; Zurich, Switzerland; 3Friedrich-Loeffler-Institut; Institute of Novel and Emerging Infectious Diseases; Isle of Riems, Germany; 4Department of Agriculture, Food and the Marine; Backweston, Celbridge, Co. Kildare, Ireland; 5Istituto Zooprofilattico Sperimentale del Piemonte; Liguria e Valle d’Aosta; Biostatistics Epidemiology and Analysis of Risk (BEAR) unit; Turin, Italy; 6UMR Interactions Hôtes Agents Pathogènes; Ecole Nationale Vétérinaire INR A; ENVT; Toulouse, France

 

Keywords: Bovine Spongiform Encephalopathy (BSE), cattle, intestine, mesentery, specified risk material (SRM), quantitative risk assessment (QRA)

 

Bovine intestines and mesenteries in the European Union (EU) are considered among the tissues potentially containing the highest level of BSE infectivity and have to be removed from the food and feed chain. A quantitative assessment of the BSE infectious load potentially entering the food and feed chain yearly in the European Union (EU) was developed. The evolution of the BSE infectious titre and of the weight of the structures accumulating infectivity was considered. The number of BSE infected cattle entering undetected in the food and feed chain yearly was estimated. A model (TSEi) was developed to estimates the evolution of the BSE infectious load in animals and the total yearly infectious load that could enter the food and feed chain. In a BSE infected bovine, the distribution of infectivity in intestines and mesentery varies with the age. Up to 36 months of age the infectivity is mainly associated (on average more than 90%) with the last 4 metres of small intestine and the caecum, over 36 and under 60 months of age, there is an inter-individual variability, from 60 months of age the infectivity is mainly associated (on average more than 90%) with the mesenteric nerves and the celiac and mesenteric ganglion complex. The total amount of infectivity peaks, about 15 BoID50, in animals younger than 18 months, it declines to 8-9 BoID50 (24–48 months of age) and it drops to 0.7 BoID50 in animals older than 60 months. The ileocaecal plate is the most infectious part of the intestine and it can be used to estimate the potential maximum level of exposure for an individual consumer.

 

In the EU, between 2007 and 2012, the yearly amount of BSE infectivity associated with intestine and mesentery from animals entering the food and feed chain was reduced by a factor of 10 (from about 23,000 to about 2,000 BoID50).

 

However, the maximum level of exposure to the BSE agent from intestine remained stable (on average about 1.5-1.6 BoID50 per meter).

 

In case of re-emergence of BSE in the EU there would be an increase of the potential maximum level of exposure to BSE from intestine. According to the TSEi model the removal of the last four metres of the small intestine and of the caecum from the food and feed chain would result in a major reduction of the BSE exposure risk associated with intestine and mesentery in cattle.

 

P.131: Transmission of sheep-bovine spongiform encephalopathy in pigs

 

Carlos Hedman,1 Belén Marín,1 Fabian Corbière,3 Hicham Filali,1 Francisco Vázquez, José Luis Pitarch,1 William Jirón,1 Rodrigo S Hernandez,1 Bernardino Moreno,1 Martí Pumarola,2 Olivier Andréoletti,3 Juan José Badiola,1 and Rosa Bolea1 1University of Zaragoza; Zaragoza, Spain; 2University of Barcelona; Barcelona, Spain; 3Institut National de la Recherche (INR A); Toulouse, France

 

Introduction. The transmissible spongiform encephalopathies (TSE) don´t occur in swine in natural conditions. However, the bovine spongiform encephalopathy (BSE) agent, inoculated by 3 simultaneous routes in pigs, is able to reproduce a neurological disease in these animals. On the other hand, the BSE agent after passage in sheep under experimental conditions (sheep- BSE) exhibits altered pathobiologic properties. This new agent is able to cross the cattle-pig transmission barrier more efficiently than BSE. The potential propagation of TSE in animals from the human food chain, including pigs, needs to be assessed regarding the risk for human infection by animals other than TSE-infected ruminants. The aim of this work was to determine the susceptibility of pigs to the Sheep-BSE agent and describe the pathological findings and PrPSc deposition in different tissues.

 

Material and Methods. Seven minipigs were challenged intracerebrally with sheep-BSE agent. Clinical observation and postmortem histopathology, immunohistochemistry (antibody 2G11) and Western blotting were performed on central nervous system (CNS), peripheral nervous system (PNS) and other tissues.

 

Results. One pig was culled in an early incubation stage, and remaining six were culled at the presence of clinical sings. Pigs developed a clinical disease with locomotor disorders in an average time of 23 months post inoculation, showing clinical findings in most of them earlier than those described in the BSE in pigs experimental infection. TSE wasn´t confirmed in the preclinical pig. In clinical pigs, the entire cerebral cortex showed severe neuropil vacuolation, extensive and severe vacuolar changes affecting the thalamus, hippocampus and cerebellum. PrPSc was found in CNS of all clinical pigs (6/6). Intracellular (intraneuronal and intraglial) and neuropil-associated PrPSc deposition was consistently observed in the brainstem, thalamus, and deeper layers of the cerebral cortex. Also, PrPSc was observed in PNS, mainly in the myenteric plexus and also in nerves belonging to the skeleton muscle. Moreover, the glycosylation profile showed a 3 band pattern with a predominant monoglycosylated band in positive pig samples.

 

This features concern on the potential risk of utilization of meat and bound meal of small ruminants in feeding pigs.

 

P.177: Elements modulating the prion species barrier and its passage consequences

 

Juan-Carlos Espinosa,1 Patricia Aguilar-Calvo,1 Ana Villa-Diaz,1 Olivier Andréoletti,2 and Juan María Torres1 1Centro de Investigación en Sanidad Animal (CISA-INI A); Valdeolmos, Madrid, Spain; 2UMR INR A-ENVT 1225; Interactions Hôte Agent Pathogène; École Nationale Vétérinaire de Toulouse; Toulouse, France

 

The phenotypic features of Transmissible Spongiform Encephalopathy (TSE) strains may be modified during passage across a species barrier. In this study we investigated the biochemical and biological characteristics of Bovine Spongiform Encephalopathy (BSE) infectious agent after transmission in both natural host species (cattle, sheep, pigs, and mice) and in transgenic mice overexpressing the corresponding cellular prion protein (PrPC) in comparison with other non-BSE related prions from the same species. After these passages, most characteristics of the BSE agent remained unchanged. BSE-derived agents only showed slight modifications in the biochemical properties of the accumulated PrPSc, which were demonstrated to be reversible upon re-inoculation into transgenic mice expressing bovine-PrPC. Transmission experiments in transgenic mice expressing bovine, porcine or human-PrP revealed that all BSE-derived agents were transmitted with no or a weak transmission barrier. In contrast, a high species barrier was observed for the non-BSE related prions that harboured an identical PrP amino acid sequence such as sheep-scrapie, mouse RML or human sCJD isolates, supporting the theory that the prion transmission barrier is modulated by strain properties (presumably conformation-dependent) rather than by PrP amino acid sequence differences between host and donor.

 

As identical results were observed with prions propagated either in natural hosts or in transgenic mouse models, we postulate that the species barrier and its passage consequences are uniquely governed by the host PrPC sequence and not influenced by the PrPC expression level or genetic factors other than the PrPC amino acid sequence. All these findings unequivocally demonstrate that the species barrier and its passage consequences are uniquely driven by the PrPC sequence, and not by other host genetic factors, demonstrating the validity of transgenic PrP animals as models for studies of the species barrier.

 

The results presented herein reinforce the idea that the BSE agent is highly promiscuous, infecting other species, maintaining its properties in the new species, and even increasing its capabilities to jump to other species including humans. These data are essential for the development of an accurate risk assessment for BSE.

 

SNIP...SEE FULL TEXT ;

 

Monday, June 23, 2014

 

*** PRION 2014 TYPICAL AND ATYPICAL BSE AND CJD REPORT UPDATES

 


 

Sunday, June 29, 2014

 

*** Transmissible Spongiform Encephalopathy TSE Prion Disease North America 2014

 


 

snip...see full report here ;

 


 

*** Calling Canadian beef unsafe is like calling your twin sister ugly," Dopp said.

 

Thursday, August 25, 2016

 

*** FSIS Green Bay Dressed Beef Recalls Beef Products Due To Possible Specified Risk Materials Contamination the most high risk materials for BSE TSE PRION AKA MAD COW TYPE DISEASE ***

 


 

Tuesday, August 9, 2016

 

*** Concurrence with OIE Risk Designations for Bovine Spongiform Encephalopathy [Docket No. APHIS-2015-0055]

 


 

Saturday, July 23, 2016

 

*** BOVINE SPONGIFORM ENCEPHALOPATHY BSE TSE PRION SURVEILLANCE, TESTING, AND SRM REMOVAL UNITED STATE OF AMERICA UPDATE JULY 2016

 


 

Tuesday, July 26, 2016

 

*** Atypical Bovine Spongiform Encephalopathy BSE TSE Prion UPDATE JULY 2016

 


 

SPECIFIED RISK MATERIALS SRMs

 


 

USDA BSE TSE PRION SURVEILLANCE, FEED, TESTING, SRM FIREWALLS...LMAO!

 

THE USDA FDA TRIPLE MAD COW DISEASE FIREWALL, WERE NOTHING MORE THAN INK ON PAPER !

 

infamous august 4, 1997 BSE TSE prion mad cow feed ban, part of usda fda et al TRIPLE MAD COW FIREWALL, 10 YEARS AFTER ;

 

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

 

Date: March 21, 2007 at 2:27 pm PST RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II PRODUCT Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007 CODE Cattle feed delivered between 01/12/2007 and 01/26/2007 RECALLING FIRM/MANUFACTURER Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.

 

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

 

VOLUME OF PRODUCT IN COMMERCE 42,090 lbs. DISTRIBUTION WI

 

___________________________________

 

PRODUCT Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007 CODE The firm does not utilize a code - only shipping documentation with commodity and weights identified. RECALLING FIRM/MANUFACTURER Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007.

 

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

 

VOLUME OF PRODUCT IN COMMERCE 9,997,976 lbs. DISTRIBUTION ID and NV

 

END OF ENFORCEMENT REPORT FOR MARCH 21, 2007

 


 

16 years post mad cow feed ban August 1997

 

2013

 

Sunday, December 15, 2013

 

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OIA UPDATE DECEMBER 2013 UPDATE

 


 

17 years post mad cow feed ban August 1997

 

Tuesday, December 23, 2014

 

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE DECEMBER 2014 BSE TSE PRION

 


 

*** Monday, October 26, 2015 ***

 

*** FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OIA UPDATE October 2015 ***

 


 

Thursday, July 24, 2014

 

*** Protocol for further laboratory investigations into the distribution of infectivity of Atypical BSE SCIENTIFIC REPORT OF EFSA New protocol for Atypical BSE investigations

 


 

*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply ;

 


 

SPECIFIED RISK MATERIAL SRM

 


 

DID YOUR CHILD CONSUME SOME OF THESE DEAD STOCK DOWNER COWS, THE MOST HIGH RISK FOR MAD COW DISEASE ??? this recall was not for the welfare of the animals. ...tss

 


 

you can check and see here ; (link now dead, does not work...tss)

 


 

see listings of schools from state to state, county to county, was your child exposed ;

 

try this link ;

 


 


 

*** Calling Canadian beef unsafe is like calling your twin sister ugly," Dopp said.

 

Thursday, August 25, 2016

 

*** FSIS Green Bay Dressed Beef Recalls Beef Products Due To Possible Specified Risk Materials Contamination the most high risk materials for BSE TSE PRION AKA MAD COW TYPE DISEASE ***

 


 

Saturday, July 16, 2016

 

*** Importation of Sheep, Goats, and Certain Other Ruminants [Docket No. APHIS-2009-0095]RIN 0579-AD10

 

WITH great disgust and concern, I report to you that the OIE, USDA, APHIS, are working to further legalize the trading of Transmissible Spongiform Encephalopathy TSE Pion disease around the globe.

 

THIS is absolutely insane. it’s USDA INC.

 


 

Thursday, October 22, 2015

 

*** Former Ag Secretary Ann Veneman talks women in agriculture and we talk mad cow disease USDA and what really happened those mad cows in Texas ***

 


 

Monday, June 20, 2016

 

*** Specified Risk Materials SRMs BSE TSE Prion Program ***

 


 

Tuesday, September 06, 2016

 

A comparison of classical and H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism in wild type and EK211 cattle following intracranial inoculation

 


 

***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.***

 


 

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

 

***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.

 

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

 

Monday, May 09, 2016

 

A comparison of classical and H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism in wild type and EK211 cattle following intracranial inoculation

 


 

I ask Professor Kong ;

 

Thursday, December 04, 2008 3:37 PM Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk Assessment

 

''IS the h-BSE more virulent than typical BSE as well, or the same as cBSE, or less virulent than cBSE? just curious.....''

 

Professor Kong reply ;

 

.....snip

 

''As to the H-BSE, we do not have sufficient data to say one way or another, but we have found that H-BSE can infect humans. I hope we could publish these data once the study is complete. Thanks for your interest.''

 

Best regards, Qingzhong Kong, PhD Associate Professor Department of Pathology Case Western Reserve University Cleveland, OH 44106 USA

 

END...TSS

 

Thursday, December 04, 2008 2:37 PM

 

"we have found that H-BSE can infect humans."

 

personal communication with Professor Kong. ...TSS

 

BSE-H is also transmissible in our humanized Tg mice.

 

The possibility of more than two atypical BSE strains will be discussed.

 

Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.

 


 


 

Monday, March 19, 2012

 

Infectivity in Skeletal Muscle of Cattle with Atypical Bovine Spongiform Encephalopathy PLoS One. 2012; 7(2): e31449.

 


 

Tuesday, August 9, 2016

 

*** Concurrence with OIE Risk Designations for Bovine Spongiform Encephalopathy [Docket No. APHIS-2015-0055]

 


 

2016 PIGS TSE PRION UPDATE

 

WS-02

 

Scrapie in swine: A diagnostic challenge

 

Justin J Greenlee1, Robert A Kunkle1, Jodi D Smith1, Heather W. Greenlee2

 

1National Animal Disease Center, US Dept. of Agriculture, Agricultural Research Service, United States; 2Iowa State University College of Veterinary Medicine

 

A naturally occurring prion disease has not been recognized in swine, but the agent of bovine spongiform encephalopathy does transmit to swine by experimental routes. Swine are thought to have a robust species barrier when exposed to the naturally occurring prion diseases of other species, but the susceptibility of swine to the agent of sheep scrapie has not been thoroughly tested.

 

Since swine can be fed rations containing ruminant derived components in the United States and many other countries, we conducted this experiment to test the susceptibility of swine to U.S. scrapie isolates by intracranial and oral inoculation. Scrapie inoculum was a pooled 10% (w/v) homogenate derived from the brains of clinically ill sheep from the 4th passage of a serial passage study of the U.S scrapie agent (No. 13-7) through susceptible sheep that were homozygous ARQ at prion protein residues 136, 154, and 171, respectively. Pigs were inoculated intracranially (n=19) with a single 0.75 ml dose or orally (n=24) with 15 ml repeated on 4 consecutive days. Necropsies were done on a subset of animals at approximately six months post inoculation (PI), at the time the pigs were expected to reach market weight. Remaining pigs were maintained and monitored for clinical signs of TSE until study termination at 80 months PI or when removed due to intercurrent disease (primarily lameness). Brain samples were examined by immunohistochemistry (IHC), western blot (WB), and enzyme-linked immunosorbent assay (ELISA). Brain tissue from a subset of pigs in each inoculation group was used for bioassay in mice expressing porcine PRNP.

 

At six-months PI, no evidence of scrapie infection was noted by any diagnostic method. However, at 51 months of incubation or greater, 5 animals were positive by one or more methods: IHC (n=4), WB (n=3), or ELISA (n=5). Interestingly, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study).

 

Swine inoculated with the agent of scrapie by the intracranial and oral routes do not accumulate abnormal prion protein (PrPSc) to a level detectable by IHC or WB by the time they reach typical market age and weight. However, strong support for the fact that swine are potential hosts for the agent of scrapie comes from positive bioassay from both intracranially and orally inoculated pigs and multiple diagnostic methods demonstrating abnormal prion protein in intracranially inoculated pigs with long incubation times.

 

Curriculum Vitae

 

Dr. Greenlee is Research Veterinary Medical Officer in the Virus and Prion Research Unit at the National Animal Disease Center, US Department of Agriculture, Agricultural Research Service. He applies his specialty in veterinary anatomic pathology to focused research on the intra- and interspecies transmission of prion diseases in livestock and the development of antemortem diagnostic assays for prion diseases. In addition, knockout and transgenic mouse models are used to complement ongoing experiments in livestock species. Dr. Greenlee has publications in a number of topic areas including prion agent decontamination, effects of PRNP genotype on susceptibility to the agent of sheep scrapie, characterization of US scrapie strains, transmission of chronic wasting disease to cervids and cattle, features of H-BSE associated with the E211 K polymorphism, and the development of retinal assessment for antemortem screening for prion diseases in sheep and cattle. Dr. Greenlee obtained his DVM degree and completed the PhD/residency program in Veterinary Pathology at Iowa State University. He is a Diplomate of the American College of Veterinary Pathologists.

 


 

Prion

 

Volume 9, Issue 4, 2015

 

Porcine prion protein amyloid

 

DOI:10.1080/19336896.2015.1065373Per Hammarströma & Sofie Nyströma*

 

pages 266-277

 

Received: 1 Jun 2015 Accepted: 17 Jun 2015 Accepted author version posted online: 28 Jul 2015

 

© 2015 The Author(s). Published with license by Taylor & Francis Group, LLC Additional license information

 

ABSTRACT

 

Mammalian prions are composed of misfolded aggregated prion protein (PrP) with amyloid-like features. Prions are zoonotic disease agents that infect a wide variety of mammalian species including humans. Mammals and by-products thereof which are frequently encountered in daily life are most important for human health. It is established that bovine prions (BSE) can infect humans while there is no such evidence for any other prion susceptible species in the human food chain (sheep, goat, elk, deer) and largely prion resistant species (pig) or susceptible and resistant pets (cat and dogs, respectively). PrPs from these species have been characterized using biochemistry, biophysics and neurobiology. Recently we studied PrPs from several mammals in vitro and found evidence for generic amyloidogenicity as well as cross-seeding fibril formation activity of all PrPs on the human PrP sequence regardless if the original species was resistant or susceptible to prion disease. Porcine PrP amyloidogenicity was among the studied. Experimentally inoculated pigs as well as transgenic mouse lines overexpressing porcine PrP have, in the past, been used to investigate the possibility of prion transmission in pigs. The pig is a species with extraordinarily wide use within human daily life with over a billion pigs harvested for human consumption each year. Here we discuss the possibility that the largely prion disease resistant pig can be a clinically silent carrier of replicating prions.

 

SNIP...

 

CONCLUDING REMARKS Should the topic of porcine PrP amyloid be more of a worry than of mere academic interest? Well perhaps. Prions are particularly insidious pathogens. A recent outbreak of peripheral neuropathy in human, suggests that exposure to aerosolized porcine brain is deleterious for human health.43,44 Aerosolization is a known vector for prions at least under experimental conditions.45-47 where a mere single exposure was enough for transmission in transgenic mice. HuPrP is seedable with BoPrP seeds and even more so with PoPrP seed (Fig. 1), indicating that humans could be infected by porcine APrP prions while neurotoxicity associated with spongiform encephalopathy if such a disease existed is even less clear. Importantly transgenic mice over-expressing PoPrP are susceptible to BSE and BSE passaged through domestic pigs implicating that efficient downstream neurotoxicity pathways in the mouse, a susceptible host for prion disease neurotoxicity is augmenting the TSE phenotype.25,26 Prions in silent carrier hosts can be infectious to a third species. Data from Collinge and coworkers.21 propose that species considered to be prion free may be carriers of replicating prions. Especially this may be of concern for promiscuous prion strains such as BSE.19,48 It is rather established that prions can exist in both replicating and neurotoxic conformations.49,50 and this can alter the way in which new host organisms can react upon cross-species transmission.51 The na€ıve host can either be totally resistant to prion infection as well as remain non-infectious, become a silent non-symptomatic but infectious carrier of disease or be afflicted by disease with short or long incubation time. The host can harbor and/or propagate the donor strain or convert the strain conformation to adapt it to the na€ıve host species. The latter would facilitate infection and shorten the incubation time in a consecutive event of intra-species transmission. It may be advisable to avoid procedures and exposure without proper biosafety precautions as the knowledge of silence carrier species is poor. One case of iatrogenic CJD in recipient of porcine dura mater graft has been reported in the literature.52 The significance of this finding is still unknown. The low public awareness in this matter is exemplified by the practice of using proteolytic peptide mixtures prepared from porcine brains (Cerebrolysin) as a nootropic drug. While Cerebrolysin may be beneficial for treatment of severe diseases such as vascular dementia,53 a long term follow-up of such a product for recreational use is recommended.

 


 

Friday, August 21, 2015

 

Porcine prion protein amyloid or mad pig disease PSE Porcine Spongiform Encephalopathy ?

 


 


 


 

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

 


 

*** 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.

 


 

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

 

Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,

 

Natalia Fernandez-Borges a. and Alba Marin-Moreno a

 

"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France

 

Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion. Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.

 

To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.

 

These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.

 

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.

 

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

 


 

1978 SCRAPIE IN CONFIDENCE SCJD

 


 


 


 


 


 


 


 


 


 

1979

 

SILENCE ON CJD AND SCRAPIE

 

1980

 

SILENCE ON CJD AND SCRAPIE

 

*** 1981 NOVEMBER

 


 


 

Thursday, August 04, 2016

 

*** MEETING ON THE FEASIBILITY OF CARRYING OUT EPIDEMIOLOGICAL STUDIES ON CREUTZFELDT JAKOB DISEASE 1978 THE SCRAPIE FILES IN CONFIDENCE CONFIDENTIAL SCJD

 


 

Tuesday, September 06, 2016

 

A comparison of classical and H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism in wild type and EK211 cattle following intracranial inoculation

 


 

Monday, September 05, 2016

 

*** Pathological features of chronic wasting disease in reindeer and demonstration of horizontal transmission Major Findings for Norway ***

 


 

see more here ;

 

Monday, September 05, 2016

 

*** Pathological features of chronic wasting disease in reindeer and demonstration of horizontal transmission Major Findings for Norway ***

 


 

Wednesday, September 7, 2016

 

*** An assessment of the long-term persistence of prion infectivity in aquatic environments

 


 

Friday, September 02, 2016

 

*** Chronic Wasting Disease Drives Population Decline of White-Tailed Deer

 


 

Monday, August 29, 2016

 

*** NWHC USGS CHRONIC WASTING DISEASE CWD TSE PRION UPDATE

 


 

Thursday, August 18, 2016

 

*** PROCEEDINGS ONE HUNDRED AND Nineteenth ANNUAL MEETING of the USAHA BSE, CWD, SCRAPIE, PORCINE TSE PRION October 22 28, 2015 ***

 


 

Wednesday, September 28, 2016

 

Norway sides with OIE, decides to expose millions of consumers to the ATYPICAL BSE SRM TSE Prion aka mad cow type disease

 


 

*** Journal Journal of Toxicology and Environmental Health, Part A Volume 79, 2016 - Issue 16-17 Prion Research in Perspective IV CANADA BSE CWD SCRAPIE CJD TSE Prion Disease

 


 

*** Calling Canadian beef unsafe is like calling your twin sister ugly," Dopp said. ***

 

Thursday, August 25, 2016

 

*** FSIS Green Bay Dressed Beef Recalls Beef Products Due To Possible Specified Risk Materials Contamination the most high risk materials for BSE TSE PRION AKA MAD COW TYPE DISEASE ***

 


 

Saturday, July 16, 2016

 

Importation of Sheep, Goats, and Certain Other Ruminants [Docket No. APHIS-2009-0095]RIN 0579-AD10

 

WITH great disgust and concern, I report to you that the OIE, USDA, APHIS, are working to further legalize the trading of Transmissible Spongiform Encephalopathy TSE Pion disease around the globe.

 

THIS is absolutely insane. it’s USDA INC.

 


 

Monday, September 19, 2016

 

Evidence of scrapie transmission to sheep via goat milk

 


 

Saturday, April 16, 2016

 

*** APHIS [Docket No. APHIS-2016-0029] Secretary's Advisory Committee on Animal Health; Meeting May 2, 2016, and June 16, 2016 Singeltary Submission ***

 


 

Wednesday, January 20, 2016

 

Exportation of Live Animals, Hatching Eggs, and Animal Germplasm From the United States [Docket No. APHIS-2012-0049] RIN 0579-AE00 2016-00962

 


 

Thursday, January 14, 2016

 

EMERGING ANIMAL DISEASES Actions Needed to Better Position USDA to Address Future Risks Report to the Chairman, Committee on Energy and Commerce, House of Representatives December 2015 GAO-16-132

 

GAO

 


 

Saturday, September 24, 2016

 

Assessment of the PrPc amino-terminal domain in prion species barriers

 


 

Tuesday, July 12, 2016

 

*** Chronic Wasting Disease CWD, Scrapie, Bovine Spongiform Encephalopathy BSE, TSE, Prion Zoonosis Science History see history of NIH may destroy human brain collection

 


 

Saturday, December 12, 2015

 

CREUTZFELDT JAKOB DISEASE CJD TSE PRION REPORT DECEMBER 14, 2015

 


 

Monday, August 22, 2016

 

CREUTZFELDT JAKOB DISEASE USA 2015 SPORADIC CJD TOTAL FIGURES REACHES HIGHEST ANNUAL COUNT TO DATE AT 239 CONFIRMED CASES

 


 

>>> We can prevent, effectively treat, and make an Alzheimer’s cure possible by 2025.

 

PREVENT

 

this must be on the forefront of research i.e. ‘iatrogenic’ transmission.

 

Alzheimer’s disease, iatrogenic, and Transmissible Spongiform Encephalopathy TSE Prion disease, that is the question ???

 

>>> 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 ?

 


 


 

SWISS MEDICAL WEEKLY

 

Alzheimer-type brain pathology may be transmitted by grafts of dura mater 26/01/2016 Singeltary comment ;

 


 

re-Evidence for human transmission of amyloid-β 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)

 

snip...see full Singeltary Nature comment here;

 


 

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

 

*** 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

 


 

Sunday, November 22, 2015

 

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

 

Purchase options Price * Issue Purchase USD 511.00 Article Purchase USD 54.00

 


 


 

*** 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.

 


 

CONFIDENTIAL

 

Transmissible Spongiform Encephalopathy TSE Prion and how Politics and Greed by the Industry spread madcow type diseases from species to species and around the globe

 

TSE PRIONS AKA MAD COW TYPE DISEASE, LIONS AND TIGERS AND BEARS, OH MY!

 


 


 

Monday, August 22, 2016

 

CREUTZFELDT JAKOB DISEASE USA 2015 SPORADIC CJD TOTAL FIGURES REACHES HIGHEST ANNUAL COUNT TO DATE AT 239 CONFIRMED CASES

 


 

*** Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle ***

 

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

 

snip...

 

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

 


 


 


 

In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells

 

3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. ...

 


 

”The occurrence of CWD must be viewed against the contest of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite it’s subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA veiwed it as a wildlife problem and consequently not their province!” ...page 26.

 


 

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.

 


 

IBNC Tauopathy or TSE Prion disease, it appears, no one is sure

 

Posted by flounder on 03 Jul 2015 at 16:53 GMT

 


 

Human Prion Diseases in the United States Robert C. Holman ,

 

Ermias D. Belay, Krista Y. Christensen, Ryan A. Maddox, Arialdi M. Minino, Arianne M. Folkema, Dana L. Haberling, Teresa A. Hammett, Kenneth D. Kochanek, James J. Sejvar, Lawrence B. Schonberger

 

PLOS

 

Published: January 1, 2010 • http://dx.doi.org/10.1371/journal.pone.0008521 re-Human Prion Diseases in the United States Posted by flounder on 01 Jan 2010 at 18:11 GMT I kindly disagree with your synopsis for the following reasons ;

 

The Pathological Protein:

 

Mad Cow, Chronic Wasting, and Other Deadly Prion Diseases

 

Philip Yam

 

*** ''Answering critics like Terry Singeltary, who feels that the US undercounts CJD, Schonberger _conceded_ that the current surveillance system has errors but stated that most of the errors will be confined to the older population'' ***

 


 


 

The Lancet Infectious Diseases, Volume 3, Issue 8, Page 463, August 2003 doi:10.1016/S1473-3099(03)00715-1Cite or Link Using DOI

 

Tracking spongiform encephalopathies in North America

 

Original

 

Xavier Bosch

 

“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem.” 49-year—old Singeltary is one of a number of people who have remained largely unsatisfied after being told that a close relative died from a rapidly progressive dementia compatible with spontaneous Creutzfeldt—Jakob ...

 


 

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?

 


 

Sent: Monday, January 08,2001 3:03 PM

 

TO: freas@CBS5055530.CBER.FDA.GOV

 

FDA CJD BSE TSE Prion Scientific Advisors and Consultants Staff January 2001 Meeting Singeltary Submission

 

2001 FDA CJD TSE Prion Singeltary Submission

 


 

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.

 


 

2001 FDA CJD TSE Prion Singeltary Submission TSEAC

 


 

Terry S. Singeltary Sr. Bacliff, Texas USA 77518 flounder9@verizon.net