Monday, December 26, 2011

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

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

Pekka Kujala1, Claudine R. Raymond2¤, Martijn Romeijn1, Susan F. Godsave1, Sander I. van Kasteren1, Holger Wille3, Stanley B. Prusiner3, Neil A. Mabbott2*, Peter J. Peters1,4*

1 Section of Cell Biology II, Netherlands Cancer Institute, Amsterdam, The Netherlands, 2 The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Easter Bush, Midlothian, United Kingdom, 3 Institute for Neurodegenerative Diseases and Department of Neurology, University of California, San Francisco, California, United States of America, 4 Kavli Institute of Nanoscience, Delft University of Technology, Delft, The Netherlands


After oral exposure, prions are thought to enter Peyer's patches via M cells and accumulate first upon follicular dendritic cells (FDCs) before spreading to the nervous system. How prions are actually initially acquired from the gut lumen is not known. Using high-resolution immunofluorescence and cryo-immunogold electron microscopy, we report the trafficking of the prion protein (PrP) toward Peyer's patches of wild-type and PrP-deficient mice. PrP was transiently detectable at 1 day post feeding (dpf) within large multivesicular LAMP1-positive endosomes of enterocytes in the follicle-associated epithelium (FAE) and at much lower levels within M cells. Subsequently, PrP was detected on vesicles in the late endosomal compartments of macrophages in the subepithelial dome. At 7–21 dpf, increased PrP labelling was observed on the plasma membranes of FDCs in germinal centres of Peyer's patches from wild-type mice only, identifying FDCs as the first sites of PrP conversion and replication. Detection of PrP on extracellular vesicles displaying FAE enterocyte-derived A33 protein implied transport towards FDCs in association with FAE-derived vesicles. By 21 dpf, PrP was observed on the plasma membranes of neurons within neighbouring myenteric plexi. Together, these data identify a novel potential M cell-independent mechanism for prion transport, mediated by FAE enterocytes, which acts to initiate conversion and replication upon FDCs and subsequent infection of enteric nerves.

Author Summary Top

Prion diseases are orally transmissible, but how the abnormally folded isoform of the prion protein (PrPSc) transits from the gastrointestinal tract to infect neural tissues is not known. Here we demonstrate that in contrast to the current literature, PrPSc enters Peyer's patches primarily through specialised enterocytes with much lower levels trafficking through M cells. Proteins from homogenized PrPSc infected brain tissue are transcytosed across the follicle-associated epithelium and delivered to macrophages and follicular dendritic cells, which appear to serve as the primary site of PrP conversion and replication following oral exposure to PrPSc before infecting the enteric nerves.




Together, these data suggest that uptake via large late endosomal compartments of FAE enterocytes represents a novel potential M cell-independent mechanism through which prions are acquired from the gut lumen. While these data do not exclude a role for M cells or villous enterocytes in the initial uptake of prions from the gut lumen, much lower levels of PrP were detected within them when compared to FAE enterocytes. Our data show that the transcytosis of prions to the germinal centres of Peyer's patches is PrPC-independent as it occurs also in PrPC-deficient animals. In contrast, PrPC expression is required for the observed high labelling densities on plasma membranes of FDCs and enteric neurons. Indeed, our data suggest that FDCs within Peyer's patches are the first site of prion conversion and replication after oral exposure. These findings provide insight into the subcellular localisation and trafficking of prions, which might provide suitable targets to arrest oral prion infection. Furthermore, these data identify a novel, previously unrecognised, enterocyte-dependent route of prion uptake and transfer from the gut lumen that may have an important influence on susceptibility to oral prion infection.

Citation: Kujala P, Raymond CR, Romeijn M, Godsave SF, van Kasteren SI, et al. (2011) Prion Uptake in the Gut: Identification of the First Uptake and Replication Sites. PLoS Pathog 7(12): e1002449. doi:10.1371/journal.ppat.1002449

Editor: Umberto Agrimi, Istituto Superiore di Sanità, Italy

Received: June 6, 2011; Accepted: November 4, 2011; Published: December 22, 2011

Copyright: © 2011 Kujala et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work was supported by European Union grants StrainBarrier FOOD-CT-2006-023183, ImmunoPrion FOOD-CT-2006-023144 and Priority FP7 222887, and Institute Strategic Grant funding from the Biotechnology and Biological Research Council (NAM). The funders have no role in study design, data collection and analysis, no decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

* E-mail: (PJP); (NAM)

¤ Current address: Canadian Food Inspection Agency, Ottawa, Ontario, Canada

see full text ;

Date submitted: 3 Jun 2002

>> eLetter ID: gutjnl_el;21

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

>> >>Name: Terry S. Singeltary Sr.


>>Title/position: disabled {neck injury}

>>Place of work: CJD WATCH

>>IP address:


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

>>Gecko/20011019 Netscape6/6.2

>> >>Parent ID: 50/6/888


>> Creutzfeldt-Jakob disease: implications for gastroenterology

>> M G Bramble and J W Ironside

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


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

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

>>regarding your article;


>> Creutzfeldt-Jakob disease: implications for gastroenterology >>

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

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

>>endoscopy equipment and how many victims of CJDs have

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

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

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

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

>>suggests a substantial TSE infectivity in the gut wall

>>of species infected with TSEs. If such transmissions

>>occur, the ramifications of spreading TSEs from

>>endoscopy equipment to the general public would be

>>horrible, and could potential amplify the transmission

>>of TSEs through other surgical procedures in that

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

>>infection. Science to date, has well established

>>transmission of sporadic CJDs with medical/surgical


Terry S. Singeltary Sr. >>CJD WATCH

Again, many thanks, Kindest regards,

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

[scroll down past article for my comments]



Greetings List Members,

This is _very_ disturbing to me:


The distribution of PrPSc in the body is different in sporadic and variant CJD, reflecting the different pathogenesis of the two forms. In the case ot sporadic CJD, prion infectivity is largely limited to the CNS (including the retina) and only operations involving the brain and eye have resulted in iatrogenic transmission of the disease. Gastro-intestinal endoscopy is unlikely to be a vector for the transmission of sporadic CJD as infected tissue is not encountered during the procedure. No special precautions are necessary during or after the procedure and the endoscope should be cleaned and disinfected in the normal thorough way.4


i personally believe it is irresponsible for anyone to state in this day and time, that sporadic CJDs (now at 6 variants) will not transmit the disease by this route. considering infective dose cannot be quantified, only speculated, such a statement is thus, irresponsible. to hypothosize that sporadic CJD just happens spontaneously (with no scientific proof), that the PrPSc distribution in tissues of all sporadic CJDs is entirely different than that of vCJD, without being able to quantify the titre of infection, or even confirm all the different variants yet, again is _not_ based on all scientific data, then it's only a hypothosis. who is to say that some of these variants of sporadic CJD were not obtained _orally_?

also stated:


Although thorough cleaning of flexible endoscopes ensures patient safety for ''normal'' pathogens, the same process may not be adequate for the PrPSc.


The sporadic form of CJD affects approximately one person per mil-lion per annum in the population on a worldwide basis.

who is to say how much infectivity are in some of these variants of sporadic CJDs, without confirming this? if we look at the 6 different variants of sporadic CJDs, has the infective dose for all 6 _documented_ variants been quantified, and documented as being 'measurable'?

will there be more variants of sporadic CJDs, and what of the ramifications from them?

what of other strains/variants of TSE in cattle, BSE in sheep, CWD in cattle, or any of the 20+ strains of Scrapies in deer/elk? i get dizzy thinking of the different scenerio's. what would the human TSEs from these species look like and how can anyone quantify any tissue infectivity from these potential TSE transmissions to humans, and the risk scenerio described here from this potential route? could not some of these sporadic CJDs have derived directly or indirectly from one of these species, and if so, pose a risk by the route described here?

something else to consider, in the recent finding of the incubation period of 38 years from a _small_ dose of human growth hormone;


We describe the second patient with hGH related CJD in the Netherlands. The patient developed the disease 38 years after hGH injections. To our knowledge, this is the longest incubation period described for any form of iatrogentic CJD. Furthermore, our patient was _not_ treated with hGH, but only received a _low_ dose as part of a diagnostic procedure. (see full text below).


so my quesion is, how low is 'low' in quantifing the infectious dose in vCJD, comparing to _all_ sporadic CJDs, from the different potential routes, sources, and infectivity dose?

will the titre of infectivity in every tissue and organ of all sporadic CJDs stay exact or constant, no matter what the infective dose, route and species may be? this is considering you don't buy the fact that sporadic CJDs 85%+ of _all_ CJDs, are a happen stance of bad luck, happen spontaneously without cause, and are one-in-a-million world wide, with no substantial surveillance to confirm this.

Diagnosis and Reporting of Creutzfeldt-Jakob Disease T. S. Singeltary, Sr; D. E. Kraemer; R. V. Gibbons, R. C. Holman, E. D. Belay, L. B. Schonberger

and what of Dr. Prusiner et al recent work about tissue infectivity;

Prions in skeletal muscle


Our data demonstrate that factors in addition to the amount of PrP expressed determine the tropism of prions for certain tissues. That some muscles are intrinsically capable of accumulating substantial titers of prions is of particular concern. Because significant dietary exposure to prions might occur through the consumption of meat, even if it is largely free of neural and lymphatic tissue, a comprehensive effort to map the distribution of prions in the muscle of infected livestock is needed. Furthermore, muscle may provide a readily biopsied tissue from which to diagnose prion disease in asymptomatic animals and even humans.


can the science/diagnostic measures used to date, measure this, and at the same time guarantee that no titre of infectivity exists from sporadic CJDs (all of the variants), from this potential mode and route of transmission?

i don't think so, this is just my opinion. this is why i get paid nothing, and these scientists get the big bucks. i just hope i am wrong and the big bucks are correct in their _hypothisis_ of this potential mode/route of transmission with endoscopy equipment, from _all_ human TSEs.

i understand we have to weigh the risks of what we know to what we don't know, to the disease we _may_ catch to what we are having the procedure for, but to categorically state at this present time of scientific knowledge;


"Gastro-intestinal endoscopy is unlikely to be a vector for the transmission of sporadic CJD as infected tissue is not encountered during the procedure. No special precautions are necessary during or after the procedure and the endoscope should be cleaned and disinfected in the normal thorough way.4"


but, to categorically state this, in my opinion, is not only wrong, but potentially very dangerous to the future of human health...TSS


Creutzfeldt-Jakob disease 38 years after diagnostic use of human growth hormone

E A Croes, G Roks, G H Jansen, P C G Nijssen, C M van Duijn ...............................................................

J Neurol Neurosurg Psychiatry 2002;72:792-793

A 47 year old man is described who developed pathology proven Creutzfeldt-Jakob disease (CJD) 38 years after receiving a low dose of human derived growth hormone (hGH) as part of a diagnostic procedure. The patient presented with a cerebellar syndrome, which is compatible with iatrogenic CJD. This is the longest incubation period described so far for iatrogenic CJD. Furthermore, this is the first report of CJD after diagnostic use of hGH. Since the patient was one of the first in the world to receive hGH, other cases of iatrogenic CJD can be expected in the coming years.

Prion diseases are potentially transmissible. Human to human transmission was first reported in 1974, when a 55 year old woman was described who developed symptoms of Creutzfeldt-Jakob disease (CJD) 18 months after a corneal transplant.1 Since then, transmission has been reported after stereotactic electroencephalographic (EEG) depth recording, human growth hormone (hGH) and gonadotrophin treatment, and dura mater transplantation.2-5 More than 267 patients with iatrogenic CJD are known today and their number is growing.6 The most important iatrogenic cause of CJD is still contaminated cadaveric hGH. Exposure to contaminated hGH occurred before 1985, when recombinant growth hormone became available. In a recent study, incubation periods in 139 patients with hGH associated CJD were found to range from 5-30 years, with a median of 12 years.6 One of the factors influencing incubation time is genotype on polymorphic codon 129 of the prion protein gene.7 The incubation time is significantly shorter in people who are homozygous for either methionine or valine on this polymorphism.7

We describe the second patient with hGH related CJD in the Netherlands. The patient developed the disease 38 years after hGH injections. To our knowledge, this is the longest incubation period described for any form of iatrogenic CJD. Further-more, our patient was not treated with hGH but only received a low dose as part of a diagnostic procedure.


This patient presented at the age of 47 years with paraesthesia in both arms for six months, difficulty with walking for four weeks, and involuntary movements of mainly the upper extremities of two weeks' duration. He did not notice any change in cognitive function, although his twin sister had noticed minor memory disturbances. There was no family history of neurological disease. During childhood the patient had experienced a growth delay compared with his twin sister and with the average in the Netherlands. When he was 9 years old, a nitrogen retention test with 6 IU hGH over five days was performed to exclude growth hormone deficiency. Since the result was not decisive, a quantitative amino acid test was performed, which measures 30 amino acids during fasting and one, two, and three hours after growth hormone injection. No abnormal amino acid concentrations were found making the diagnosis of primordial dwarfism most likely. Therefore, no treatment with hGH was given.

On neurological examination we found a slight dysarthria without aphasia. Cranial nerve function was normal. Walking was unstable and wide based. During movements of the upper extremities myoclonic jerks were present. Sensation, muscle tone, and strength were normal. Co-ordination was impaired in all four limbs with a disturbed balance. Tendon reflexes were brisk at the arms and increased at the legs with a clonus in the ankle reflex. Plantar responses were both normal. On the mini mental state examination, the patient scored 30/30. Routine laboratory investigation, thyroid function, vitamin concentrations (B-1, B-6, B-12, and E), and copper metabolism were normal. Admission EEG examination showed generalised arrhythmic slow activity with diffuse spikes and spike waves. EEG examination two months later showed a further slowing of the rhythm with bilateral diphasic sharp waves but was not typical for CJD. Cerebral magnetic resonance imaging was normal. Cerebrospinal fluid examination showed 1 cell/3 µl, normal glucose and protein concentrations, and a strongly positive 14-3-3 protein test. The patient was homozygous for methionine on the PRNP codon 129 polymorphism. On clinical grounds, CJD was diagnosed. Within one month the patient's condition deteriorated rapidly and because of severe disturbances in coordination and progressive myoclonus he became bedridden. An eye movement disorder developed with slow saccadic and dysmetric eye movements. Temperature became unstable with peaks of 39°C without an infectious focus, for which a disorder of autoregulation was presumed. Until a very advanced stage, cognitive function was intact. The patient died five months after admission. The diagnosis of CJD was confirmed at necropsy. The brain weighed 990 g and showed clear cortical and cerebellar atrophy. Spongiosis, neuronal loss, and gliosis were found predominantly in the putamen, caudate nucleus, and basotemporal and cerebellar cortex; the cerebellum was the most severely affected of these. Vacuoles ranged from 2-12 µm. No amyloid or Kuru plaques were found. Immunohistochemical staining (3F4 antibody 1:1000, Senetek, USA) was clearly positive for prion protein accumulation in a "synaptic" distribution. Most deposition was found in the stratum moleculare of the cerebellum.


We describe a 47 year old patient who developed pathology proven CJD 38 years after hGH injections. The patient was never treated with hGH but received a small dose as part of a diagnostic procedure. The onset of CJD was signalled by prodromal symptoms of paraesthesia followed by a rapidly progressive ataxia. The disease presentation and course with predominantly cerebellar and eye movement disorders are compatible with iatrogenic CJD caused by hGH treatment.6 8

Growth hormone treatment was first described in 1958 but hGH was not produced on a larger scale from human pituitary glands until the beginning of the 1960s. In the Netherlands growth hormone extraction started in 1963 and was soon centrally coordinated. Until 1979 growth hormone was extracted non-commercially from pituitaries by a pharmaceutical company. In 1971 commercial products also became available. Our patient was one of the first to receive hGH in the Netherlands but the origin of this product was not recorded. A causal relation can therefore not be established with full certainty, but coincidentally receiving growth hormone and developing this very rare disease is unlikely. Since the clinical course in this relatively young patient is in accordance with an iatrogenic cause, we think the probability is high that the hGH injections explain the development of CJD in this patient.

The first Dutch patient with hGH related CJD died in 1990. 9 During several periods from 1963 to 1969 she received intramuscular injections of hGH. During an unknown period the hGH was derived from South America. At age 39, 27 years after starting the treatment, she developed an ataxic gait, slurred speech, sensory disorders, and myoclonus, but her cognitive function remained normal. Postmortem examination of the brain confirmed the diagnosis of CJD.9 Following the identification of this patient, a retrospective study was started to trace all 564 registered hGH recipients who were treated before May 1985. Until January 1995, none of these was suspected of having CJD.10 Since 1993 prospective surveillance for all forms of human prion disease has been carried out in the Netherlands and, apart from the patient described above, a further two patients with iatrogenic CJD have been identified, who developed the disease after dura mater transplantation.11

An incubation period as long as 38 years had never been reported for iatrogenic CJD. Huillard d'Aignaux et al7 studied the incubation period in 55 patients with hGH related CJD in a cohort of 1361 French hGH recipients. The median incubation period was between 9 and 10 years. Under the most pessimistic model, the upper limit of the 95% confidence interval varied between 17 and 20 years. Although the infecting dose cannot be quantified, it can be speculated that the long incubation period in our patient is partly explained by the administration of a limited amount of hGH. This hypothesis is supported by experimental models, in which higher infecting doses usually produce shorter incubation periods.6 Since our patient was one of the first in the world to receive hGH, this case indicates that still more patients with iatrogenic CJD can be expected in the coming years. Another implication of our study is that CJD can develop even after a low dose of hGH. This case once more testifies that worldwide close monitoring of any form of iatrogenic CJD is mandatory.


We are grateful to M Jansen PhD MD for his search for the origin of the growth hormone and P P Taminiau MD. CJD surveillance in the Netherlands is carried out as part of the EU Concerted Action on the Epidemiology of CJD and the the EU Concerted Action on Neuropathology of CJD, both funded through the BIOMED II programme, and is supported by the Dutch Ministry of Health. This surveillance would not have been possible without the cooperation of all Dutch neurologists and geriatricians. ........................................

Authors' affiliations

E A Croes, G Roks*, C M van Duijn, Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, Erasmus University Medical Centre Rotterdam, PO Box 1738, 3000 DR Rotterdam, Netherlands

P C G Nijssen, Department of Neurology, St Elisabeth Hospital, PO Box 90151, 5000 LC Tilburg, Netherlands

G H Jansen, Department of Pathology, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, Netherlands

*Also the Department of Neurology, St Elisabeth Hospital

Correspondence to: Professor C M van Duijn, Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, Erasmus University Medical Centre Rotterdam, PO Box 1738, 3000 DR Rotterdam, Netherlands;

Received 27 December 2001 In revised form 1 March 2002 Accepted 12 March 2002

Competing interests: none declared


1 Duffy P, Wolf J, Collins G, et al. Possible person-to-person transmission of Creutzfeldt-Jakob disease. N Engl J Med 1974;290:692-3.

2 Bernoulli C, Siegfried J, Baumgartner G, et al. Danger of accidental person-to-person transmission of Creutzfeldt-Jakob disease by surgery. Lancet 1977;i:478-9.

3 Koch TK, Berg BO, De Armond SJ, et al. Creutzfeldt-Jakob disease in a young adult with idiopathic hypopituitarism: possible relation to the administration of cadaveric human growth hormone. N Engl J Med 1985;313:731-3.

4 Cochius JI, Burns RJ, Blumbergs PC, et al. Creutzfeldt-Jakob disease in a recipient of human pituitary-derived gonadotrophin. Aust NZ J Med 1990;20:592-3.

5 Thadani V, Penar PL, Partington J, et al. Creutzfeldt-Jakob disease probably acquired from a cadaveric dura mater graft: case report. J Neurosurg 1988;69:766-9.

6 Brown P, Preece M, Brandel JP, et al. Iatrogenic Creutzfeldt-Jakob disease at the millennium. Neurology 2000;55:1075-81.

7 Huillard d'Aignaux J, Costagliola D, Maccario J, et al. Incubation period of Creutzfeldt-Jakob disease in human growth hormone recipients in France. Neurology 1999;53:1197-201.

8 Billette de Villemeur T, Deslys JP, Pradel A, et al. Creutzfeldt-Jakob disease from contaminated growth hormone extracts in France. Neurology 1996;47:690-5.

9 Roos RA, Wintzen AR, Will RG, et al. Een patiënt met de ziekte van Creutzfeldt-Jakob na behandeling met humaan groeihormoon. Ned Tijdschr Geneeskd 1996;140:1190-3.

10 Wientjens DP, Rikken B, Wit JM, et al. A nationwide cohort study on Creutzfeldt-Jakob disease among human growth hormone recipients. Neuroepidemiology 2000;19:201-5.

11 Croes EA, Jansen GH, Lemstra AF, et al. The first two patients with dura mater associated Creutzfeldt-Jakob disease in the Netherlands. J Neurol 2001;248:877-81.

re-CJD after diagnostic use of human growth hormone

from a donor sourcing aspect, seems the record keeping here has a lot to be desired for, let us hope it has improved for recipients sake.

also, they speak of 'low dose fitting long incubation'. what about KURU still existing after some 40 years exposure had ceased. i don't believe in most instances the dose with kuru is low. just something else to ponder?


1: Ann Neurol 1999 Aug;46(2):224-33

Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects.

Division of Neuropathology, Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.


The present data demonstrate the existence of six phenotypic variants of sCJD. The physicochemical properties of PrP(Sc) in conjunction with the PRNP codon 129 genotype largely determine this phenotypic variability, and allow a molecular classification of the disease variants.


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

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

Professor Michael Farthing wrote:

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

snip...see full text ;

Saturday, January 16, 2010

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

Evidence For CJD/TSE Transmission Via Endoscopes

From Terry S. Singletary, Sr 1-24-3


December 20, 2005 Division of Dockets Management (HFA-305) Food and Drug Administration 5630 Fishers Lane Room 1061 Rockville, MD 20852

Re: Docket No: 2002N-0273 (formerly Docket No. 02N-0273) Substances Prohibited From Use in Animal Food and Feed

Dear Sir or Madame:

As scientists and recognized experts who have worked in the field of TSEs for decades, we are deeply concerned by the recent discoveries of indigenous BSE infected cattle in North America and appreciate the opportunity to submit comments to this very important proposed rule We strongly supported the measures that USDA and FDA implemented to protect public health after the discovery of the case of bovine spongiform encephalopathy (BSE) found in Washington State in 2003. We know of no event or discovery since then that could justify relaxing the existing specified risk material (SRM) and non-ambulatory bans and surveillance that were implemented at that time. Further, we strongly supported the codification of those changes, as well as additional measures to strengthen the entire feed and food system. The discovery of additional cases of indigenous BSE in North America since that time has validated our position and strengthened our convictions.

We caution against using the 18 month enhanced surveillance as a justification to relax or impede further actions. While this surveillance has not uncovered an epidemic, it does not clear the US cattle herd from infection. While it is highly likely that US and Canadian cattle were exposed to BSE prior to the 1997 feed ban, we do not know how many cattle were infected or how widely the infection was dispersed. BSE cases are most likely clustered in time and location, so while enhanced surveillance provides an 18 month snapshot, it does not negate the fact that US and Canadian cattle were exposed to BSE. We also do not know in any quantitative or controlled way how effective the feed ban has been, especially at the farm level. At this point we cannot even make a thorough assessment of the USDA surveillance as details such as age, risk category and regional distribution have not been released.


03-025IFA 03-025IFA-2 Terry S. Singeltary

From: Terry S. Singeltary Sr. []

Sent: Thursday, September 08, 2005 6:17 PM


Subject: [Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirements for the Disposition of Non-Ambulatory Disabled Cattle

Owens, Julie

From: Terry S. Singeltary Sr. []

Sent: Monday, July 24, 2006 1:09 PM

To: FSIS RegulationsComments

Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE) Page 1 of 98 8/3/2006

Greetings FSIS, I would kindly like to comment on the following ;

[Federal Register: July 12, 2006 (Volume 71, Number 133)] [Notices] [Page 39282-39283] From the Federal Register Online via GPO Access [] [DOCID:fr12jy06-35]


DEPARTMENT OF AGRICULTURE Food Safety and Inspection Service [Docket No. FSIS-2006-0011] Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE) Update; Notice of Availability and Technical Meeting

Owens, Julie

From: Terry S. Singeltary Sr. []

Sent: Monday, July 24, 2006 1:09 PM To: FSIS RegulationsComments

Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE) Page 1 of 98 8/3/2006

Greetings FSIS, I would kindly like to comment on the following ;

Response to Public Comments on the Harvard Risk Assessment of Bovine Spongiform Encephalopathy Update, October 31, 2005


The United States Department of Agriculture’s Food Safety and Inspection Service (FSIS) held a public meeting on July 25, 2006 in Washington, D.C. to present findings from the Harvard Risk Assessment of Bovine Spongiform Encephalopathy Update, October 31, 2005 (report and model located on the FSIS website: Comments on technical aspects of the risk assessment were then submitted to FSIS. Comments were received from Food and Water Watch, Food Animal Concerns Trust (FACT), Farm Sanctuary, R-CALF USA, Linda A Detwiler, and Terry S. Singeltary. This document provides itemized replies to the public comments received on the 2005 updated Harvard BSE risk assessment. Please bear the following points in mind:

Suppressed peer review of Harvard study October 31, 2002.

October 31, 2002 Review of the Evaluation of the Potential for Bovine Spongiform Encephalopathy in the United States Conducted by the Harvard Center for Risk Analysis, Harvard School of Public Health and Center for Computational Epidemiology, College of Veterinary Medicine, Tuskegee University Final Report Prepared for U.S. Department of Agriculture Food Safety and Inspection Service Office of Public Health and Science Prepared by RTI Health, Social, and Economics Research Research Triangle Park, NC 27709 RTI Project Number 07182.024

03-025IF 03-025IF-631 Linda A. Detwiler [PDF] Page 1. 03-025IF 03-025IF-631 Linda A. Detwiler Page 2. Page 3. Page 4. Page 5. Page 6. Page 7. Page 8. Page 9. Page 10. Page 11. Page 12.


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


see full text ;

03-025IF 03-025IF-634 Linda A. Detwiler [PDF] Page 1. 03-025IF 03-025IF-634 Linda A. Detwiler Page 2. Page 3. Page 4. Page 5. Page 6. Page 7. Page 8.

Linda A. Detwiler, DVM

225 Hwy 35

Red Bank, New Jersey 07701

Phone: 732-741-2290

Cell: 732-580-9391

Fax: 732-741-7751

June 22, 2005

FSIS Docket Clerk

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

RE: DEPARTMENT OF AGRICULTURE Food Safety and Inspection Service

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

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

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

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

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

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

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

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

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

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

Thank you for the opportunity to clarify my comments.

Linda A. Detwiler, DVM


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

----- Original Message -----

From: Terry S. Singeltary Sr.


Sent: Wednesday, September 07, 2005 9:44 PM

Subject: Use of Materials Derived From Cattle in Human Food and Cosmetics [Docket No. 2004N-0081] RIN 0910-AF47

-------- Original Message -------- Subject: Docket No, 04-047-l Regulatory Identification No. (RIN) 091O-AF46 NEW BSE SAFEGUARDS (comment submission) Date: Sun, 11 Jul 2004 21:34:22 -0500 From: "Terry S. Singeltary Sr." To: CC:,

Docket No. 04-047-l No. 04-021ANPR No. 2004N-0264 NEW BSE SAFEGUARDS Federal Measures to Mitigate BSE Risks: Considerations for Further Action

Greetings FDA,

USDA and APHIS et al, I would kindly like to comment on the continued delay of the regulations that have been proposed for years to reduce the risk of BSE/TSE in the USA. Each day that is wasted debating this issue allows this agent to spread, and many many more humans and animals become needlessly exposed to this agent via a multitude of potential routes and sources right here in the USA. TO continue to ignore the new findings from several scientists about the fact that BSE is not the only strain of TSE in cattle, the fact that new atypical strains of TSE are showing up in not only cattle, but sheep and the fact that the new strain of TSE in cattle seems to be more similar to sporadic CJD as opposed to the nv/v CJD, to continue to ignore these findings will only further spread this agent. CWD and Scrapie have been running rampant in the USA for decades. BOTH of which have been rendered and fed back to animals for human/animal consumption for decades. All of which transmits to primates by the natural and non-forced oral consumption of TSE scrapie, CJD, Kuru agent (and CWD by inoculation). Strong Scientific evidence discovered back in the 80s support the fact that a TSE has been prevalent in the USA bovine for decades, either undetected or ignored. IF you consider the recent stumbling and staggering TEXAS cow that was showing all signs of a CNS/TSE disorder that was ordered to be rendered without BSE/TSE test, brains, spinal cord, head and all (as to no possible evidence left of TSE), I would think the 'ignored' or 'covered up' to be the better terminology. Then you have the Downer in Washington state that was actually a good walker and then all the banned Canadian products that some how found it's way across the border into the USA, considering all this, it is very difficult for me to believe that the FDA/USDA/APHIS et al are doing everything possible to protect the 'consumer'. Hardly the case;

Congressman Henry Waxmans Letter to the Honorable Ann Veneman


From: TSS () Subject: Re: Docket No. 2004N-0081 Use of Materials Derived From Cattle in Human Food and Cosmetics [TSS SUBMISSION] Date: September 7, 2005 at 7:35 pm PST

In Reply to: Docket No. 2004N-0081 Use of Materials Derived From Cattle in Human Food and Cosmetics posted by TSS on September 7, 2005 at 7:07 am:

----- Original Message ----- From: Terry S. Singeltary Sr. To: Sent: Wednesday, September 07, 2005 9:44 PM Subject: Use of Materials Derived From Cattle in Human Food and Cosmetics [Docket No. 2004N-0081] RIN 0910-AF47

Greetings FDA,

I would kindly like to comment on ;

Use of Materials Derived From Cattle in Human Food and Cosmetics [Docket No. 2004N-0081] RIN 0910-AF47

SUMMARY: The Food and Drug Administration (FDA) is amending the interim final rule on use of materials derived from cattle in human food and cosmetics published in the Federal Register of July 14, 2004. In the July 14, 2004, interim final rule, FDA designated certain materials from cattle, including the entire small intestine, as ``prohibited cattle materials'' and banned the use of such materials in human food, including dietary supplements, and in cosmetics. FDA is taking this action in response to comments received on the interim final rule. Information was provided in comments that persuaded the agency that the distal ileum, one of three portions of the small intestine, could be consistently and effectively removed from the small intestine, such that the remainder of the small intestine, formerly a prohibited cattle material, could be used for human food or cosmetics. We (FDA) are also clarifying that milk and milk products, hide and hide-derived products, and tallow derivatives are not prohibited cattle materials. Comments also led the agency to reconsider the method cited in the interim final rule for determining insoluble impurities in tallow and to cite instead a method that is less costly to use and requires less specialized equipment. FDA issued the interim final rule to minimize human exposure to materials that scientific studies have demonstrated are highly likely to contain the bovine spongiform encephalopathy (BSE) agent in cattle infected with the disease. FDA believes that the amended provisions of the interim final rule provide the same level of protection from human exposure to the agent that causes BSE as the original provisions. ...

I would kindly like to submit the following ;

I find it very very disturbing that FDA now takes the position;

>>>Information was provided in comments that persuaded the agency that the distal ileum, one of three portions of the small intestine, could be consistently and effectively removed from the small intestine, such that the remainder of the small intestine, formerly a prohibited cattle material, could be used for human food or cosmetics. <<<

TSE science is emerging and the old testing techniques for TSEs are becoming much more sensitive than when some of these old BSE tissue bio-assays were done in the distant past. I urge once again for the FDA and the USDA to put forth sound science instead of the political and corporate science they have floundered with for the last 3 decades. THERE is much new data out that dispute the position the FDA/USDA have taken on SRMs.



1. The views of the Committee were sought on unpublished results from an

ongoing long-term study of the pathogenesis of BSE in cattle. This study is

being carried out by the Veterinary Laboratory Agency and is funded by the

Food Standards Agency (FSA).

2. In this study, cattle were orally dosed with 100g of BSE-infected bovine

brain material. At various times after oral dosing, cattle were killed and

different tissues tested for infectivity. In the first instance, the presence of

infectivity was assessed by injection of various tissues into inbred mice

("mouse bioassay "). In this research infectivity was detected in:

• distal ileum (the earliest infectivity was detected at 6 months after


• brain and spinal cord and closely associated nervous tissue

(infectivity was detected in the months just prior to the clinical onset

of BSE in cattle)

• at a single time point (around the time of clinical onset) bone marrow

was also found to contain infectivity. ...snip







following the submission of (1) a risk assessment by the German Federal Ministry of

Consumer Protection, food and Agriculture and (2) new scientific evidence

regarding BSE infectivity distribution in tonsils

3. New work, work still in progress and future work

The infectivity of neural and non-neural tissues by intracerebral inoculation of cattle is being

assayed in projects M03006 and M03007. These studies are important since it is possible

that some tissues may not yet have been found to be infective, due to the fact that

infectivity in these tissues is below the detection limits of the tests applied so far. To date,

this study has shown infectivity in CNS tissues, the distal ileum, tonsil tissue and the

nictitating membrane (the nictitating membrane is also known as the third eyelid). Other

challenged and control cattle continue to be closely monitored for clinical signs of BSE.

Research is ongoing to determine the susceptibility of other food animal species to TSEs.

These include a project to determine the susceptibility of pigs to scrapie through oral

exposure (M03005) and a project to further study the transmission of BSE to pigs (M03010).

Project M03024 aims to determine whether UK red deer are susceptible to BSE by oral

exposure. These studies are important since it is highly probable that pigs and deer were

historically exposed to ruminant derived meat and bone meal (MBM). ...

TSEs And The Environment

The LANCET Volume 351, Number 9110 18 April 1998

BSE: the final resting place


The first matter to consider is the distribution of infectivity in the bodies of infected animals. The brain (and more generally, the central nervous system) is the primary target in all transmissible spongiform encephalopathies (TSE), and it contains by far the highest concentration of the infectious agent. In naturally occuring disease, infectivity may reach levels of up to about one million lethal doses per gram of brain tissue, whether the disease be kuru, CJD, scrapie, or BSE. The infectious agent in BSE-infected cattle has so far been found only in brain, spinal cord, cervical and thoracic dorsal root ganglia, trigeminal ganglia, distal ileum, and bone marrow.4 However, the much more widespread distribution of low levels of infectivity in human beings with kuru or CJD, and in sheep and goats with scrapie, suggests that caution is advisable in prematurely dismissing as harmless other tissues of BSE-infected cattle.



BY reducing or weakening the SRM list due to the Economic Impact of BSE on the U.S. Beef Industry and while doing so, ignoring all 'sound science', again the FDA/USDA et al are willing to put every human and animal out there at risk to further exposure to this TSE agent, all for a buck. this is not 'sound science' this is what i call 'corporate science', and it is and will continue to expose people. some of these people will die from this agent either directly or indirectly via a multitude of scientific proven routes and sources. WE must remove all political and corporate science from TSE research.

I find it disturbing that products that carry SRMs are still on the market for humans such as nutritional supplements ;

ODD, I just picked up a catalog from STANDARD PROCESS INC. 2003 - 2004 Product Catalog (a chiropractor had just left this catalog in my wife's foot doctors office 4/5/05) and it's full of THOSE SRMS FOR HUMANS. I wonder how much is still left on the market, and how much is still in production, how much crosses the borders? 5 pages of products full of SRMs for humans. THIS is a really fine catalog, i am just now going over. LOADED with SRMs for humans. NO wonder my neighbors mom died from CJD while taking these damn mad cow pills. THEY even have a candy bars loaded with SRMs. HERE is one ;

NATURAL COCOA STANDARDBAR (mad cow candy bar) (i will just list animal organs)

bovine adrenal, bovine liver, bovine spleen, ovine spleen, bovine kidney...


bovine adrenal, bovine liver, bovine spleen, ovine spleen, bovine kidney...


bovine orhic glandular extract


bovine uterus PMG


bovine heart PMG extract, veal bone PMG extract, bovine liever, porcine duodenum, bovine adrenal Cytosol extract, bovine spleen, ovine spleen (some yummy stuff)

IPLEX (neighbors mom died from CJD while taking these pills for years)

bovine eye PMG extract, veal bone PMG, bovine liver, porcine stomach, bovine adrenal, bovine kidney, bovine adrenal Cytosol extract, BOVINE BRAIN, bovine bone, veal bone meal


bovine heart PMG, bovine liver, porcine stomach, bovine orchic extract, bovine spleen, ovine spleen, bovine adrenal Cytosol extract, BOVINE BRAIN






bovine liver, porcine stomach, bovine spleen ovine spleen, BOVINE BRAIN



bovine liver, bovine orchic Cytosol extract, porcine stomch, bovine spleen, ovine spleen, BOVINE BRAIN


veal bone PMG extract, veal bone PMG extract, bovine liver, porcine stomach, bovine adrenal, bovine spleen, ovine spleen, BOVINE BRAIN


bovine pancreas PMG extract, porcine duodenum, bovine adrenal PMG, BOVINE PITUITARY PMG EXTRACT, bovine thyroid PMG extract



BOVINE BRAIN, veal bone PMG extract, bovine adrenal, bovine prostate Cytosol extract, veal bone meal, bovine liver PMG extract, bovine spleen, ovine spleen, bovine liver


bovine liver PMG extract, bovine adrenal, BOVNE BRAIN, veal bone meal, bovine kidney, bovine orchic extract, bovine spleen, ovine spleen ..........

THESE are just a few of MANY of just this ONE COMPANY.

Docket Management Docket: 96N-0417 - Current Good Manufacturing Practice in Manufacturing, Packing, or Holding Dietary Ingredients a Comment Number: EC -2 Accepted - Volume 7

253 1 DR. BOLTON:

I have an additional question about 2 that. What is the assurance that additional locally sourced 3 tracheas are not added into that manufacturing process, thus 4 boosting the yield, if you will, but being returned to the 5 U.S. as being produced from U.S.-sourced raw material? 6 DR. McCURDY: Are there data to indicate how many 7 grams, or whatever, of infected brain are likely to infect 8 an organism, either animal or man, when taken orally? 9 DR. BROWN: If I am not mistaken, and I can be 10 corrected, I think a half a gram is enough in a cow, orally; 11 in other words, one good dietary-supplement pill. 12 DR. McCURDY: What I am driving at is the question 13 we are asked is really not do we wish to regulate these 14 things coming in. I think the statements about difficulties 15 in regulating things in the future or near future for new 16 regulations were probably accurate. 17 But I think that we could exhibit some quite 18 reasonable concern about blood donors who are taking dietary 19 supplements that contain a certain amount of unspecified- 20 origin brain, brain-related, brain and pituitary material. 21 If they have done this for more than a sniff or something 22 like that, then, perhaps, they should be deferred as blood 23 donors. 24 That is probably worse than spending six months in 25 the U.K. 254 1 DR. BROWN: That is exactly right. I think that 2 is why the discussion has apparently been on things that are 3 not directly related to these questions because, in order to 4 think about deferrals for blood donors who are taking 5 dietary supplements with things like bovine brain in them, 6 it is very important that we know that those products are 7 safe. 8 I think we have heard enough to suggest that they 9 may not be. 10 DR. McCURDY: There is one other item that needs 11 to be considered and that is what proportion of blood donors 12 are doing this; that is, how many blood donors would you 13 lose, and I don't know what the demographics--there is 14 fairly good information on the demography of blood donors. 15 I have no idea what the demography of people who take these 16 supplements is. Maybe they are old men like me and aren't 17 going to be blood donors anymore. 18 DR. BROWN: The wording of the question is not as 19 demanding as the wording of other deferral questions; that 20 is, the question here is consider recommending. We are 21 not even recommending at this point. We are saying to the 22 FDA, please think about this. It is worth thinking about. 23 DR. DETWILER: One point about brain from Europe, 24 and Jean Philippe is still here, those are considered 25 specified risk material and it is not correct to be 255 1 incinerated; correct? Or destroyed? Brain and spinal cord 2 and other high-risk tissues in Europe? 3 DR. NORTON: In tomorrow morning's British Medical 4 Journal, which has appeared on-line today, there is an 5 article called U.S. Takes Precautions against BSE. One 6 paragraph says, Even though the U.S. and U.K. governments 7 ban the practice of feeding cattle products to cows, in the 8 early 1990s, some U.K. renderers continued to manufacture 9 and ship contaminated meat and bonemeal around the world. 10 British export statistics show that thirty-seven tons of 11 meal made from offal was sent to the United States in 1997, 12 well after the U.S. government banned imports of such risky 13 meat. The ultimate use of these imports has not been 14 identified. 15 That will appear tomorrow morning. 16 DR. DETWILER: That actually was in The New York 17 Times. That is a direct quote out of The New York Times 18 article. We called the reporter on that. That statement, 19 the thirty-seven tons, was taken out of the U.S. 20 Geographical BSE Risk Assessment. What they didn't put in 21 there, in the statement, was the remainder of the GBR is at 22 that time, the big labeling for that category in the U.K., 23 because it was illegal for them to ship it to us from their 24 own regs. It is illegal for us to get that. 25 We did go and try and trace that so that wasn't [FULL TEXT ABOUT 600 PAGES] 3681t2.rtf

IN fact, we are now finding that as little as 1 mg (or 0.001 gm) caused 7% (1 of 14) of the cows to come down with BSE ;

Published online

January 27, 2005

Risk of oral infection with bovine spongiform

encephalopathy agent in primates

Corinne Ida Lasmézas, Emmanuel Comoy, Stephen Hawkins, Christian Herzog, Franck Mouthon, Timm Konold, Frédéric Auvré, Evelyne Correia,

Nathalie Lescoutra-Etchegaray, Nicole Salès, Gerald Wells, Paul Brown, Jean-Philippe Deslys

The uncertain extent of human exposure to bovine spongiform encephalopathy (BSE)—which can lead to variant

Creutzfeldt-Jakob disease (vCJD)—is compounded by incomplete knowledge about the ef.ciency of oral infection

and the magnitude of any bovine-to-human biological barrier to transmission. We therefore investigated oral

transmission of BSE to non-human primates. We gave two macaques a 5 g oral dose of brain homogenate from a

BSE-infected cow. One macaque developed vCJD-like neurological disease 60 months after exposure, whereas the

other remained free of disease at 76 months. On the basis of these .ndings and data from other studies, we made a

preliminary estimate of the food exposure risk for man, which provides additional assurance that existing public

health measures can prevent transmission of BSE to man.


BSE bovine brain inoculum

100 g 10 g 5 g 1 g 100 mg 10 mg 1 mg 0·1 mg 0·01 mg

Primate (oral route)* 1/2 (50%)

Cattle (oral route)* 10/10 (100%) 7/9 (78%) 7/10 (70%) 3/15 (20%) 1/15 (7%) 1/15 (7%)

RIII mice (ic ip route)* 17/18 (94%) 15/17 (88%) 1/14 (7%)

PrPres biochemical detection

The comparison is made on the basis of calibration of the bovine inoculum used in our study with primates against a bovine brain inoculum with a similar PrPres concentration that was

inoculated into mice and cattle.8 *Data are number of animals positive/number of animals surviving at the time of clinical onset of disease in the .rst positive animal (%). The accuracy of

bioassays is generally judged to be about plus or minus 1 log. ic ip=intracerebral and intraperitoneal.

Table 1: Comparison of transmission rates in primates and cattle infected orally with similar BSE brain inocula

snip...end Published online January 27, 2005

THEN you must consider cross contamination at feed mills and such. this has been well proven in both the UK and the USA to date via r-to-r feed ban violations. IT was proven in the UK that they indeed put profits before human health;

[PDF] The BSE Inquiry / Statement No. 14 Issued 20 March 1998 THE ...

The BSE Inquiry / Statement No. 14. Issued 20 March 1998 ... number of feed compounders and it became clear that cross contamination of feeds could occur. ...

[PDF] The BSE Inquiry / Statement No 76F (Supplementary) Mr Alan ...

But the mainbut the main problem was probably cross-contamination. ...



To minimise the risk of farmers' claims for compensation from feed compounders.

To minimise the potential damage to compound feed markets through adverse publicity.

To maximise freedom of action for feed compounders, notably by maintaining the availability of meat and bone meal as a raw material in animal feeds, and ensuring time is available to make any changes which may be required.




MAFF remains under pressure in Brussels and is not skilled at handling potentially explosive issues.

5. Tests _may_ show that ruminant feeds have been sold which contain illegal traces of ruminant protein. More likely, a few positive test results will turn up but proof that a particular feed mill knowingly supplied it to a particular farm will be difficult if not impossible.

6. The threat remains real and it will be some years before feed compounders are free of it. The longer we can avoid any direct linkage between feed milling _practices_ and actual BSE cases, the more likely it is that serious damage can be avoided. ...

SEE full text ;


From: TSS

Subject: Inspector to file charges against USDA for them charging him with misconduct on telling the truth about SRM mad cow violations

Date: September 7, 2005 at 1:37 pm PST

Consumer Health

Inspector to file charges against USDA By Steve Mitchell Sep 6, 2005, 22:46 GMT

WASHINGTON, DC, United States (UPI) -- The federal meat inspector who was charged with misconduct by the U.S. Department of Agriculture after he claimed mad cow disease safeguards were being violated at slaughterhouses told United Press International he plans to file charges against the agency.

Stan Painter, a USDA inspector and chair of the National Joint Council of Food Inspection Locals, the inspectors union, notified the agency`s management in a letter last December he was aware of instances where the riskiest parts of older cows were not being marked or removed from processing.

Painter worried these risky parts -- known as specified risk materials, or SRMs -- could enter the food supply and infect people, causing a fatal brain illness called variant Creutzfeldt Jakob disease.

Two cases of mad cow have been detected in U.S. herds, and some suspect there are more. The USDA put the SRM safeguards in place in 2004 to protect the public from mad cow disease -- also known as bovine spongiform encephalopathy or BSE -- if more cases are detected.

The USDA did not respond to Painter`s concerns until he made his letter known to news outlets.

On Dec. 28, 2004, the agency charged Painter with personal misconduct for not revealing the names of the inspectors who told him of the SRM violations. Officials also told him he was under a formal investigation, which was dropped last month after the release of internal documents revealing more than 1,000 violations of the USDA`s SRM regulations.

Painter said he thinks the USDA was attempting 'to harass and intimidate him (and) to have a chilling effect' on other inspectors.

'I plan to file charges against the agency,' he told UPI, adding he has not yet decided if he will go through the legal system, through internal USDA procedures or another avenue.

Asked about Painter`s intent to bring charges, agency spokesman Steven Cohen told UPI the documents -- called noncompliance reports, or NRs -- demonstrate 'that BSE safeguard regulations are being enforced and prohibited materials did not reach the public.'

Mad cow disease remains a sensitive topic for the USDA because it can have significant economic ramifications. The U.S. beef industry lost billions of dollars because more than 60 nations closed their borders in 2003 to American beef after the report of the first detected case in U.S. herds. Japan, formerly the largest importer of American beef, still has not reopened its borders.

For months, USDA officials denied Painter`s allegations in media reports, saying they had investigated and found no evidence to substantiate his claims. The NRs released last month under the Freedom of Information Act, however, showed 1,036 violations of SRM regulations in at least 35 states, Puerto Rico and the Virgin Islands, with some plants being cited repeatedly for infractions. The USDA delayed releasing the documents for eight months despite a federal law mandating a response within 30 days.

Patty Lovera, of the watchdog group Public Citizen, which requested the USDA documents, said some of the violations cited in the NRs are egregious. In one, an employee at a plant in Michigan was not properly marking older cows to have their SRMs removed because he did not have a pencil. In another, an employee in a Missouri plant was loading cow heads onto his pickup truck to take home to feed to his dog.

Lovera charged the USDA with attempting to silence Painter and failing to address problems with the SRM ban.

'Their behavior through this whole thing is appalling,' she told UPI. 'Stan brought them concerns about a policy and instead of investigating the policy, they investigated him.'

Last December, after Painter made his letter known publicly, the USDA sent an officer to Painter`s house while he was on leave to question him about the allegations in his letter. Later, USDA officials interrogated Painter twice, asking him for the names of the inspectors who told him about the violations.

Painter said he intentionally was kept ignorant of the inspectors` names because he feared the agency would retaliate against them. Painter also said USDA officials did not need the inspectors` names because they could determine where the infractions were occurring by looking at their database of NRs.

Sometime around June the U.S. Embassy in Japan posted a notice on its Web site stating USDA officials had found no evidence to substantiate Painter`s claims and had requested a criminal investigation into his actions. The notice was removed in July after UPI reported its existence.

Although Cohen acknowledged more than 1,000 NRs were written by USDA inspectors, he minimized their significance, saying they 'amount to less than one-half of one percent of the total written for all reasons by (USDA) inspection program personnel.'

Lovera said any infraction of mad cow safeguards should be of concern, because this disease always is fatal in humans and cooking does not destroy the pathogen.

'You have very little margin of error for something you don`t want to get because you can`t cook it away and you can`t disinfect it,' she said.

Painter said his concern now is what the agency will do to fix what he sees as shortcomings in the SRM policy.

'It`s a failed policy,' he said. 'It doesn`t protect the consumer.'

Cohen did not respond to whether the USDA planned to change the SRM regulations.

The USDA`s Office of Inspector General has launched an investigation to determine whether the regulations are being implemented effectively, and results are due out soon.


Copyright 2005 by United Press International

makes no difference, GW will change the SRM rules like he has the BSE GBR risk assessment to the terribly flawed BSE MRR policy, the legal trading of all strains of TSE, the 'gold card'. ...TSS

IN a time when FDA/USDA et al should be strengthening the TSE regulations, it seems corporate interest has won out again over sound science and consumer protection from an agent that is 100% fatal for the ones that go clinical. With the many different atypical TSEs showing up in different parts of the world, and with GWs BSE MRR policy (the legal policy of trading all strains of TSEs), the battle that has waged for the last 25 years to eradicate this agent from this planet will be set back decades, if not lost for good. ...TSS


APHIS-2006-0041-0006 TSE advisory committee for the meeting December 15, 2006

Thursday, April 17, 2008

Use of Materials Derived From Cattle in Human Food and Cosmetics [Docket No. 2004N-0081] RIN 0910-AF47

[Federal Register: April 17, 2008 (Volume 73, Number 75)] [Rules and Regulations] [Page 20785-20794] From the Federal Register Online via GPO Access [] [DOCID:fr17ap08-7]

Scientific Opinion on BSE Risk in Bovine Intestines Question number: EFSA-Q-2009-00226

Adopted: 10 September 2009 Summary (0.1Mb)

Opinion (0.1Mb)


Following a request from the European Commission (EC), the Panel on Biological Hazards (BIOHAZ) was asked to deliver a scientific opinion on the BSE related risk of bovine intestines used for casings. Regulation (EC) No 999/2001 of the European Parliament and of the Council stipulates that certain tissues from bovine, ovine and caprine animals must be considered as Specified Risk Material (SRM) and must be removed from the food and feed chain to protect the health of consumers against the risk of bovine transmissible spongiform encephalopathies (BSE). The intestines, from the duodenum to the rectum, of bovine animals of all ages are currently included in the list of SRM. The "TSE roadmap" prepared by the EC details the short, middle and long term actions on TSE measures such as SRM removal and sets the objectives to ensure and maintain the existing high level of consumer protection. It allows for amendments of the current SRM list based on new evolving scientific knowledge while ensuring and maintaining a high level of consumer protection.

Specifically, the mandate asked the BIOHAZ panel to evaluate the scientific validity of a report prepared by Det Norske Veritas Ltd" (DNV) for the Swiss Cervelas task force. This report provides an assessment of the current potential human exposure to BSE infectivity that could result from eating sausages made with EU bovine casings. The BIOHAZ panel was further requested to evaluate the conclusions of the DNV report and, if it was considered necessary based on the report and any other new relevant scientific information, to provide a re-assessment of the BSE related risk of bovine intestines after processing into natural sausage casings.

The BIOHAZ panel evaluated the risk assessment as described in the DNV report, and took into account the relevant previous EFSA opinions as well as new scientific data on the same subject.

New but limited experimental scientific data demonstrate that in addition to ileum, also jejunum may harbour infectivity when a large BSE inoculum dose was used to experimentally infect cattle. With regard to the DNV Report, the BIOHAZ Panel considers its approach (concept and methodology) scientifically sound, whereas the interpretation of the results as obtained is not shared by the Panel. Its assumptions were based on limited scientific data obtained from a single morphometric study (which was already found to be inadequate in the previous EFSA Opinion on bovine casings) and on limited and earlier data on the presence of PrPsc/infectivity in bovine gut after experimental oral BSE inoculation. There is uncertainty about the relative BSE risk of neural and lymphoid tissues in casings compared to CNS that might have significant impact on the calculated results of the DNV Report. The Panel notes that the DNV Report considers the individual human BSE exposure risk from bovine casings, excluding ileum, to be "very low". However, when the upper confidence limits are taken into account, along with the uncertainties in key parameter assumptions, the calculated total human exposure per year in the EU from bovine casings, even when ileum is excluded (based on the calculated BSE prevalence in 2007) is 11.000 cattle oral ID50 units per year (when all casings would have been sourced in the UK) and about 1.000 cattle oral ID50 units per year (when all casings would have been sourced in the Netherlands) and therefore cannot be considered negligible. Thus the conclusion in the DNV report that sausage casings sourced from intestines of cattle in EU Member States would lead to a negligible risk for human consumption cannot be considered valid. Moreover, when considering other new relevant scientific information it is concluded that the previous EFSA assessment of the BSE related risk of bovine intestines after processing into natural sausage casings remains valid. The Panel recommends that future considerations on the risk in bovine casings should take into account the BSE prevalence in cattle at that time.

Published: 22 September 2009




6. Overview of current scientific knowledge on BSE risk in Bovine Intestines. The previous EFSA Opinion on BSE risk from bovine intestine summarised the scientific knowledge that was available until early 2007. Since then, additional publications have become available on a natural BSE case in Japan (Kimura and Haritani, 2008) and two experimental studies that examined

presence of PrPsc and/or infectivity in the intestines of cattle challenged orally with 100g (Espinosa et al., 2007; Hoffmann et al., 2007). Moreover, a new study performed by the VLA in the UK on PrPsc in BSE-infected cattle (Stack, 2009) and preliminary results from the German BSE pathogenesis study have recently be made available to EFSA and were also taken into account.

6.1. New experimental studies on intestines of BSE infected cattle

Espinosa et al. (2007) examined pooled tissues from 13 cattle inoculated at ages between 4 and 6 months and culled at ages between 24 and 39 months. Infectivity in Tgbov mice but not PrPsc by ELISA/WB was found in Peyer's patches dissected from distal ileum at all ages. Hoffmann et al (2007) demonstrated PrPsc by IHC in Peyer's patches of distal ileum in one of two preclinical animals sacrificed at 24 and 28 months post inoculation (mpi). Most recently, Arnold et al. (2009) estimated the titre of infectivity in the distal ileum from the incubation time found by bioassay in wild type mice. Over time, the infectivity in the distal ileum showed an initial increase up to 14-18 months post exposure, followed by a decrease, which was likely to be highly variable between animals. However, these estimates were based on mouse titration of brain material, while the incubation period to dose relationship may differ between brain and intestines (Robinson et al., 1990).

6.2. Infectivity of intestines in cattle with natural BSE infection

Data on presence of PrPsc or infectivity in intestines of natural BSE cases are sparse. The immunohistochemistry (IHC) and Western blot examinations of three BSE infected cattle detected in Japan in the course of active surveillance (but showing locomotor deficits) found PrPsc in distal ileum of two (by IHC confined to the myenteric plexus) (Iwata et al., 2006). No PrPsc was detected in Peyer's patches of distal ileum, or in samples of other regions of small and large intestine, or in a range of other lymphoid tissues. Labelling of myenteric plexus was also detected in 9/29 confirmed field cases of BSE examined in the UK (Terry et al., 2003). Infectivity by wild-type mouse assay or the presence of PrPsc has not been found in the distal ileum, or other levels of intestine in a total of some six natural BSE cases studied (Fraser and Foster, 1994; Buschmann and Groschup 2005; Iwata et al., 2006). In one of these cases in Germany, however, infectivity was detected in the distal ileum by bioassay in TgBov XV mice (Buschmann and Groschup, 2005). More recently, another BSE case (94 months of age) in Japan showed definite or equivocal immunoreactivity in nerve cells of the myenteric plexus in ileum, caecum and colon, and in Schwann cells of the myenteric plexus in duodenum, jejunum, ileum, caecum and colon (Kimura and Haritani, 2008).

6.3. Study commissioned by ENSCA

This ENSCA commissioned study investigated the presence of BSE PrPsc in small intestines of cattle that had been orally challenged at 4-6 months of age with 100g or 1 g doses of BSE affected brain tissue. These animals were culled and examined 18-30 months post inoculation (p.i.). Three methods to identify PrPsc were applied: a commercial ELISA test, Western immunoblotting, and IHC. Results confirmed previous observations that PrPsc was mainly confined to lymphoid tissue of the ileum, whereas the duodenum was negative and no part of the enteric nervous system tested positive. The lymphoid tissue of the jejunum of one high-dosed animal tested positive. As expected, the low-dosed animals had a much lower frequency of positive ileum samples (1/18 vs. 15/18 in the high-dose group) and some longer incubation times (24 months in the one animal with positive ileum), whereas the high-dose group included animals positive at all ages examined.

As the ENSCA commissioned study was performed retrospectively on archival tissue, sampling was limited by availability, and the study authors themselves concede that "it is possible tissue sampling was not optimal" for duodenum and jejunum of low-dosed animals. The 1g-dosed group included 6 animals sampled at 18 months p.i., 6 at 24 months, and 6 at 30 months. The 100g-dosed group included 6 animals sampled for ileum at 18 months p.i., 6 at 24 months, and 6 at 30 months;

duodenum and jejunum, however, were sampled only in 2 animals each at 18, 24 and 30 months p.i., respectively. From each level of the intestine, three sections were examined by IHC per case. While at least two of the three sections of the ileum per case contained lymphoid follicles, in 36% of the duodenum cases, and in 39% of the jejunum cases lymphoid follicles were absent in any of the examined sections. The frequency of positive follicles per section ranged between 1% and 14% in ileum of the high-dose group, and 0,7% in the one positive ileum of the low-dose group, and was 6,7% and 11,1% in the two positive jejunum sections of one high-dosed animal.

Conclusions on the ENSCA commissioned study:

. This study confirms that detectable PrPsc is mainly confined to lymphoid tissue of the ileum in cattle orally challenged with 100g of BSE brain and culled at 18, 24 and 30 months postinoculation (p.i.)

. One out of 18 animals challenged orally with 1g of BSE brain was positive in ileum.

. One out of 18 animals challenged orally with 100g of BSE brain was positive in jejunum.

. The duodenum was always negative.

. However, the sampling in particular of duodenum and jejunum was limited and contained lymphoid tissue only in a part of sections examined.

. In contrast to previous reports on natural BSE cases in older animals, the enteric nervous system was always negative.

. In consideration of the previous EFSA opinion on bovine intestine that gives detailed advice for future studies, in particular concerning the lower frequency of lymphoid follicles in parts of the intestine other than the distal ileum, the present ENSCA commissioned study meets some but not all recommendations; in particular the mostly negative results obtained for jejunum and duodenum should not be over-interpreted when tissue sampling was limited.

6.4. New preliminary data on bovine intestine from the German BSE Pathogenesis study

In the German BSE pathogenesis study performed at the Friedrich-Loeffler-Institute (FLI), 56 Simmental cross-breed calves aged about four months were challenged orally with 100g brainstemhomogenate pooled out of clinically BSE diseased cattle. The infectivity load in the homogenate was about 106.1 ID50 (grams of tissue)-1 as determined by end-point titration in Tgbov XV mice (Buschmann & Groschup, 2005, Hoffmann et al., 2007). Furthermore, as controls, 18 calves were inoculated orally with a BSE-negative brainstem homogenate. Four to five animals were selected randomly and euthanised every four months. More than 150 tissue and body fluid samples were sampled at subsequent necropsies from each animal under TSE-sterile conditions.

After oral exposure with the TSE agent, previous studies had demonstrated consistently early prion accumulation in the gut associated lymphatic tissue, about six months post infection (mpi) in cattle (Terry et al., 2003), and at two mpi in scrapie infected sheep (van Keulen et al., 2002) and in 21 days old lambs (Andreoletti et al., 2002). In contrast to scrapie, the accumulation of PrPd in the distal ileum of BSE-infected cattle was confined to an only minor proportion of follicles respectively neurons/glial cells of the enteric nervous system (Terry et al., 2003).

Normally when performing IHC, a three micrometer section per paraffin block is used, reflecting a very small proportion of the tissue sample. Therefore a serial section procedure was newly established at the FLI to increase the total amounts of tissue structures examined per sample and consequently increasing the probability of detecting PrPsc accumulation. Thereby, five sections per paraffin block with a plane distance of about 25-30 µm were examined. Hence, a tissue depth of about 150-200 µm per block was screened for positive immunosignals. Additionally two different PrP-specific monoclonal antibodies, highly sensitive for the detection of bovine PrPsc were used.

According to this method, representative samples of the small intestine, in particular Peyer's patches of the distal ileum but also the ileo-caecal junction from most of the infected animals of the German BSE Pathogenesis study were examined by IHC. From 4 mpi until 44 mpi in most animals (38/43), PrPsc was detectable, initially in the follicles of the Peyer's patches and at later stages of the incubation period in the enteric nervous system too.

Conclusions on the German pathogenesis study

. With improved sampling, nearly all animals dosed with 100 g of BSE brain tissue showed PrPsc in distal ileum between 4 and 44 mpi, first in lymphoid tissue and later in enteric nervous system.

7. Review of the DNV report

7.1. Summary of the report

DNV makes an attempt to quantify the amount of BSE infectious load in bovine sausage casings. This is then extrapolated to the risk carried in an individual sausage, a normal persons risk per year and the overall exposure within the EU in a year. The key points of the DNV Report are as follows:

. The DNV Report assumes that the ileum is not used for the production of casings and is removed and discarded.

. The DNV Report is based on the assumption that potential infectivity in bovine intestine used for sausage casing production would be 2 logs less than in the ileum. Based on experimental data, the infectivity in the distal ileum was considered to be at a titre equivalent to that in the CNS at the late stage of infection. Thus infectivity in non-ileal parts of the intestines used for casings production was assumed to be 100 fold less than in the CNS.

. The DNV Report uses a value of 0.43g/m (obtained from Wijnker et al.) of casing to quantify the amount of lymphoid and neural tissue that might harbour infectivity in a sausage casing,

. The results of the DNV Report calculate that an exposure per person per year from bovine casings produced in the Netherlands "would be very low" even when a high consumption pattern like in Germany is assumed (upper range 7 x 10-6 cattle oral (CO) ID50 units). For casings sourced in the UK, the exposure would be about one log higher.

. When the calculated total amount of cumulative human exposure per year in the EU is considered, the following scenario emerges: 11.000 CO ID50 units per year when all casings would have been sourced in the UK, and about 1.000 CO ID50 units when all casings would have been sourced in the Netherlands, a country with an about average prevalence of BSE in the EU4.

4 How can the output of the DNV calculations be interpreted in terms of potential human infections? If we follow, as in the previously adopted EFSA Opinions on Tallow and MBM (EFSA 2005 a and b) the cautionary advice of the original QRA WG and assume the species barrier is 1 as a worst case scenario, then there would be up to 5500 infected person in the EU per year in the first scenario, and up to about 500 in the second. This would have to assume a linear dose-response curve of infectivity at very low doses. If the species barrier was given a more realistic value obtained from the analysis carried out on the exposure of the British population to the BSE agent (EFSA, 2006) of around 1000 - 4000, this would mean that there might be up to around 1 to 5 infected person in the EU per year in the first scenario, and less than 1 in the second.

snip... see full text ;

Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (Singeltary submission)

Tuesday, September 14, 2010

Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010 (COMMENT SUBMISSION)

Monday, February 7, 2011 FDA’s Currently-Recommended Policies to Reduce the Possible Risk of Transmission of CJD and vCJD by Blood and Blood Products 2011 ???

Monday, May 30, 2011

CEPs for gelatin and impact of the revised EU Note for Guidance on the TSE risk EMEA/410/01 Rev.3) will come into force in July 2011

Note concerning CEPs for gelatin and impact of the revised EU Note for Guidance on the TSE risk

Thursday, December 22, 2011

Risk of Prion Disease Transmission through Bovine-Derived Bone Substitutes: A Systematic Review Clin Implant Dent Relat Res. 2011 Dec 15. doi: 10.1111/j.1708-8208.2011.00407.x. [Epub ahead of print]

Volume 18, Number 1—January 2012 Dispatch

Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate Model

Nadine Mestre-Francés , Simon Nicot, Sylvie Rouland, Anne-Gaëlle Biacabe, Isabelle Quadrio, Armand Perret-Liaudet, Thierry Baron, and Jean-Michel Verdier Author affiliations: Institut National de la Santé et de la Recherche Médicale (INSERM) U710, Montpellier, France (N. Mestre-Francés, S. Rouland, J.-M. Verdier); Université Montpellier 2, Montpellier (N. Mestre-Francés, S. Rouland, J.-M. Verdier); École Pratique des Hautes Etudes, Paris, France (N. Mestre-Francés, S. Rouland, J.-M. Verdier); Agence Nationale de Sécurité Sanitaire, Lyon, France (S. Nicot, A.-G. Biacabe, T. Baron); Hopitaux Civils de Lyon, Lyon, France (I. Quadrio, A. Perret-Liaudet); Université Lyon 1, Lyon (I. Quadrio, A. Perret-Liaudet); INSERM U1028, Lyon (I. Quadrio, A. Perret-Liaudet); Centre National de la Recherche Scientifique, Lyon (I. Quadrio, A. Perret-Liaudet)


We report transmission of atypical L-type bovine spongiform encephalopathy to mouse lemurs after oral or intracerebral inoculation with infected bovine brain tissue. After neurologic symptoms appeared, transmissibility of the disease by both inoculation routes was confirmed by detection of disease-associated prion protein in samples of brain tissue.


The Study A total of 12 mouse lemurs of both sexes (Center for Breeding and Experimental Conditioning of Animal Models, University Montpellier 2, Montpellier, France) were maintained in animal Biosafety Level 3 facilities, according to requirements of the French ethics committee (authorization CE-LR-0810). Young and adult lemurs were fed (8 animals) or IC inoculated (4 animals) with 5 or 50 mg of L-BSE–infected brain tissue (10% homogenate in 5% glucose) (Table). The isolate for the L-BSE agent (02–2528) was derived from cattle in France (11). When progression of prion disease was evident, the lemurs were euthanized and their brains were isolated. Brains were processed for Western blot analysis with SHa31 monoclonal antibody against PrP for PrPres detection, as described in mice (11); for histologic examination by using hematoxylin and eosin staining; and for disease-associated prion protein (PrPd) immunochemical detection by using the paraffin-embedded tissue blot method or immunohistochemical analysis with monoclonal antibody 3F4 against PrP.

Beginning ≈3 months before the terminal stage of the disease (19–22 months after inoculation), neurologic symptoms developed in the 4 mouse lemurs that received IC inoculations (Table). In all 4 animals, initial clinical signs and symptoms were blindness, thigmotaxic behavior, and poor appearance of the fur. Appetite and general fitness were maintained; anxiety and aggressiveness were not observed. Next, locomotion became slower, followed by incoordination and loss of balance in the last month of life. Ipsilateral circling behavior was reported, indicating unilateral degeneration of the striatum. This behavior stopped 15 days after onset, suggesting damage to the contralateral striatum. Disequilibrium, with frequent falls, became more noticeable. At the terminal stage of the disease, the animals were prostrate.

One orally inoculated lemur, which was fed 5 mg of infected brain and euthanized 27 months later, had signs and symptoms of disease similar to those in IC-inoculated animals, except for the ipsilateral circling behavior. In 2 lemurs fed 50 mg and 2 others fed 5 mg of L-BSE–infected brain, clinical signs and symptoms of prion disease developed just a few weeks before the animals were euthanized (18 and 32 months and 33 and 34 months after inoculation, respectively). Disease was characterized by progressive prostration, loss of appetite, and poor appearance of the fur, without incoordination or disequilibrium. The 3 remaining lemurs were orally inoculated at 2 years of age and were still alive and healthy 28 months after inoculation (Table).



We demonstrated that the agent of L-BSE can be transmitted by the oral route from cattle to mouse lemurs. As expected, orally inoculated animals survived longer than IC-inoculated animals. Orally inoculated lemurs had less severe clinical signs and symptoms, with no evidence of motor dysfunction. It was previously suggested that the agent of L-BSE might be involved in the foodborne transmission of a prion disease in mink (11,12), a species in which several outbreaks of transmissible mink encephalopathy had been identified, notably in the United States (13).

Our study clearly confirms, experimentally, the potential risk for interspecies oral transmission of the agent of L-BSE. In our model, this risk appears higher than that for the agent of classical BSE, which could only be transmitted to mouse lemurs after a first passage in macaques (14). We report oral transmission of the L-BSE agent in young and adult primates. Transmission by the IC route has also been reported in young macaques (6,7). A previous study of L-BSE in transgenic mice expressing human PrP suggested an absence of any transmission barrier between cattle and humans for this particular strain of the agent of BSE, in contrast to findings for the agent of classical BSE (9). Thus, it is imperative to maintain measures that prevent the entry of tissues from cattle possibly infected with the agent of L-BSE into the food chain.

Dr Mestre-Francés is an assistant professor at the École Pratique des Hautes Études. Her research focuses on neurodegenerative diseases (Alzheimer disease, prion diseases) in the nonhuman primate model Microcebus murinus.

October 2009 O.11.3 Infectivity in skeletal muscle of BASE-infected cattle

Silvia Suardi1, Chiara Vimercati1, Fabio Moda1, Ruggerone Margherita1, Ilaria Campagnani1, Guerino Lombardi2, Daniela Gelmetti2, Martin H. Groschup3, Anne Buschmann3, Cristina Casalone4, Maria Caramelli4, Salvatore Monaco5, Gianluigi Zanusso5, Fabrizio Tagliavini1 1Carlo Besta" Neurological Institute,Italy; 2IZS Brescia, Italy; 33FLI Insel Riems, D, Germany; 4CEA-IZS Torino, Italy; 5University of Verona, Italy

Background: BASE is an atypical form of bovine spongiform encephalopathy caused by a prion strain distinct from that of BSE. Upon experimental transmission to cattle, BASE induces a previously unrecognized disease phenotype marked by mental dullness and progressive atrophy of hind limb musculature. Whether affected muscles contain infectivity is unknown. This is a critical issue since the BASE strain is readily transmissible to a variety of hosts including primates, suggesting that humans may be susceptible.

Objectives: To investigate the distribution of infectivity in peripheral tissues of cattle experimentally infected with BASE. Methods: Groups of Tg mice expressing bovine PrP (Tgbov XV, n= 7-15/group) were inoculated both i.c. and i.p. with 10% homogenates of a variety of tissues including brain, spleen, cervical lymph node, kidney and skeletal muscle (m. longissimus dorsi) from cattle intracerebrally infected with BASE. No PrPres was detectable in the peripheral tissues used for inoculation either by immunohistochemistry or Western blot.

Results: Mice inoculated with BASE-brain homogenates showed clinical signs of disease with incubation and survival times of 175±15 and 207±12 days. Five out of seven mice challenged with skeletal muscle developed a similar neurological disorder, with incubation and survival times of 380±11 and 410±12 days. At present (700 days after inoculation) mice challenged with the other peripheral tissues are still healthy. The neuropathological phenotype and PrPres type of the affected mice inoculated either with brain or muscle were indistinguishable and matched those of Tgbov XV mice infected with natural BASE.

Discussion: Our data indicate that the skeletal muscle of cattle experimentally infected with BASE contains significant amount of infectivity, at variance with BSE-affected cattle, raising the issue of intraspecies transmission and the potential risk for humans. Experiments are in progress to assess the presence of infectivity in skeletal muscles of natural BASE.

see much more here ;

Friday, December 23, 2011

Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate Model

Volume 18, Number 1—January 2012 Dispatch

Saturday, June 25, 2011

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque

"BSE-L in North America may have existed for decades"

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


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


When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures. This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

Wednesday, March 31, 2010

Atypical BSE in Cattle

To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

Thursday, August 12, 2010

Seven main threats for the future linked to prions

First threat

The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.

***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.

Second threat


P.9.21 Molecular characterization of BSE in Canada

Jianmin Yang1, Sandor Dudas2, Catherine Graham2, Markus Czub3, Tim McAllister1, Stefanie Czub1 1Agriculture and Agri-Food Canada Research Centre, Canada; 2National and OIE BSE Reference Laboratory, Canada; 3University of Calgary, Canada

Background: Three BSE types (classical and two atypical) have been identified on the basis of molecular characteristics of the misfolded protein associated with the disease. To date, each of these three types have been detected in Canadian cattle.

Objectives: This study was conducted to further characterize the 16 Canadian BSE cases based on the biochemical properties of there associated PrPres.

Methods: Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases was determined using modified Western blot analysis. Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and changes in glycosylation similar to other atypical BSE cases. PK digestion under mild and stringent conditions revealed a reduced protease resistance of the atypical cases compared to the C-type cases. N terminal- specific antibodies bound to PrPres from H type but not from C or L type. The C-terminal-specific antibodies resulted in a shift in the glycoform profile and detected a fourth band in the Canadian H-type BSE.

Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada. *** It also suggests a similar cause or source for atypical BSE in these countries.

Saturday, July 23, 2011


Saturday, November 6, 2010

TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU


Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject PRO/AH/EDR>

Prion disease update 2010 (11) PRION DISEASE UPDATE 2010 (11)


Transmission of atypical BSE in humanized mouse models

Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1 1Case Western Reserve University, USA; 2Instituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University (Previously at USDA National Animal Disease Center), USA

Background: Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Atypical BSE cases have been discovered in three continents since 2004; they include the L-type (also named BASE), the H-type, and the first reported case of naturally occurring BSE with mutated bovine PRNP (termed BSE-M). The public health risks posed by atypical BSE were largely undefined.

Objectives: To investigate these atypical BSE types in terms of their transmissibility and phenotypes in humanized mice. Methods: Transgenic mice expressing human PrP were inoculated with several classical (C-type) and atypical (L-, H-, or Mtype) BSE isolates, and the transmission rate, incubation time, characteristics and distribution of PrPSc, symptoms, and histopathology were or will be examined and compared.

Results: Sixty percent of BASE-inoculated humanized mice became infected with minimal spongiosis and an average incubation time of 20-22 months, whereas only one of the C-type BSE-inoculated mice developed prion disease after more than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse brains was biochemically different from bovine BASE or sCJD. PrPSc was also detected in the spleen of 22% of BASE-infected humanized mice, but not in those infected with sCJD. Secondary transmission of BASE in the humanized mice led to a small reduction in incubation time.*** The atypical BSE-H strain is also transmissible with distinct phenotypes in the humanized mice, but no BSE-M transmission has been observed so far.

Discussion: Our results demonstrate that BASE is more virulent than classical BSE, has a lymphotropic phenotype, and displays a modest transmission barrier in our humanized mice. 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.


Liuting Qing1, Fusong Chen1, Michael Payne1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5*, and Qingzhong Kong1 1Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA; 2CEA, Istituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University, Diagnostic Medicine/Pathobiology Department, Manhattan, KS 66506, USA. *Previous address: USDA National Animal Disease Center, Ames, IA 50010, USA

Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Two atypical BSE strains, BSE-L (also named BASE) and BSE-H, have been discovered in three continents since 2004. The first case of naturally occurring BSE with mutated bovine PrP gene (termed BSE-M) was also found in 2006 in the USA. The transmissibility and phenotypes of these atypical BSE strains/isolates in humans were unknown. We have inoculated humanized transgenic mice with classical and atypical BSE strains (BSE-C, BSE-L, BSE-H) and the BSE-M isolate. We have found that the atypical BSE-L strain is much more virulent than the classical BSE-C.*** The atypical BSE-H strain is also transmissible in the humanized transgenic mice with distinct phenotype, but no transmission has been observed for the BSE-M isolate so far.


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 ;


''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


Tuesday, November 02, 2010

BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992

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.

Thursday, June 23, 2011

Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits

Thursday, December 22, 2011

Risk of Prion Disease Transmission through Bovine-Derived Bone Substitutes: A Systematic Review

Clin Implant Dent Relat Res. 2011 Dec 15. doi: 10.1111/j.1708-8208.2011.00407.x. [Epub ahead of print]

Friday, December 16, 2011

Creutzfeldt-Jacob Disease Question Asked by Lord Walton of Detchant P-Capt filter

Saturday, December 3, 2011

Candidate Cell Substrates, Vaccine Production, and Transmissible Spongiform Encephalopathies

Volume 17, Number 12—December 2011

Wednesday, August 24, 2011

All Clinically-Relevant Blood Components Transmit Prion Disease following a Single Blood Transfusion: A Sheep Model of vCJD

14th ICID International Scientific Exchange Brochure -

Final Abstract Number: ISE.114

Session: International Scientific Exchange

Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America update October 2009

T. Singeltary

Bacliff, TX, USA


An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.


12 years independent research of available data


I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.


I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.

Wednesday, August 24, 2011

There Is No Safe Dose of Prions

2011 Monday, September 26, 2011 L-BSE BASE prion and atypical sporadic CJD

Tuesday, November 08, 2011

Can Mortality Data Provide Reliable Indicators for Creutzfeldt-Jakob Disease Surveillance? A Study in France from 2000 to 2008 Vol. 37, No. 3-4, 2011

Original Paper

Conclusions:These findings raise doubt about the possibility of a reliable CJD surveillance only based on mortality data.

Editorial: The European Response to BSE: A Success Story

EFSA Journal 2011; 9(9):e991 [3 pp.]. doi:10.2903/j.efsa.2011.e991 Author Herbert Budka, Member and Vice-Chair of EFSA's Panel on Biological Hazards (BIOHAZ)Contact

Type: Editorial Published: 02 September 2011 Affiliation: European Food Safety Authority (EFSA), Parma, Italy Article

Editorial Bovine spongiform encephalopathy (BSE, "mad cow disease") was officially first reported in November 1986 in the UK. It became quickly interpreted as likely counterpart in bovines of scrapie, the paramount transmissible spongiform encephalopathy (TSE, prion disease) in sheep and goats. A landmark epidemiological study by John Wilesmith and co-workers (Wilesmith et al., 1988) identified in 1988 cattle feedstuffs containing ruminant-derived protein (meat-bone meal, MBM) as source for the evolving epidemic that numbered almost 185.000 diagnosed cases in total in the UK and a further 5.500 elsewhere in the EU, with some 2 million infected bovines estimated to have entered the human food chain in the UK. The first UK response was a ban on feeding MBM to ruminants, as a measure that significantly curbed but did not eliminate the epidemic.

A likely link between BSE and the human disease variant Creutzfeldt-Jakob disease (vCJD) was published in early April 1996 (Will et al., 1996), followed by a media outbreak of apocalyptic scenarios sketching a man-made disaster of then unpredictable proportions. Health authorities were frantically acting to limit damage from BSE not only to human health, but also to agriculture, economies, political credibility and public confidence. In the UK, the Phillips Inquiry (Lord Phillips et al., 2000) took two and a half years to accrue insight into why and how the BSE saga developed. The key conclusions depicted BSE as a consequence of intense farming practices, with significant shortcomings in the way things were done, with sensible measures taken that were not always timely and adequately implemented and enforced, and implicitly guided by the belief that BSE was not a real threat to human health. Moreover, there was too much secrecy and unjustified reassurance by governmental bodies in order to protect the agricultural industry.

Almost simultaneously with publication of the Phillips Report, the second public BSE crisis started in 2000 when first results of active BSE surveillance on the European continent confirmed scientists' opinion that political claims of "freedom from BSE" in several countries were wishful thinking rather than reality. As a result, the EU TSE Regulation of 2001[1] laid down a comprehensive set of harmonised rules for the prevention, control and eradication of TSEs, including an EU-wide total ban on the feeding of animal proteins to farmed animals. More or less independent national food safety authorities were now established in most EU countries, and the need to separate risk assessment from risk management could no longer be ignored.

Since the first BSE crisis of 1996, the European Commission (EC) has embarked on a science-guided response, establishing a TSE/BSE ad hoc Group of their Scientific Steering Committee (SSC) that provided up to 2003 a plethora of opinions on all aspects of BSE and other TSEs (SSC, 1997-2003). The SSC was a risk assessment and risk advisory body, separated from risk management which remained with the EC Directorate General for Health & Consumers (DG SANCO). From December 1997, the SSC adopted their first important documents on the scientific basis to protect human health from BSE, such as the definition of tissues containing most of infectious TSE agents (prions), termed Specific Risk Materials (SRM). Regrettably, politicians in several EU Member States (MS) were then unwilling to translate this into legislation, still sticking to their "freedom from BSE" illusion. It was only after a delay of almost 3 years that the EU-wide SRM ban, the most important measure to protect public health from BSE, became implemented.

Since 2003, EFSA has taken over the role of science-based advice to the EC on BSE/TSE-related matters, with the BIOHAZ Panel producing an equally impressive amount of opinions and reports (EFSA, 2003-2011) as the former SSC. As a whole, these scientific risk assessments - first by the SCC, then by EFSA - and their translation into adequate measures by national and EC risk managers were the basis of the European response to BSE, which has been a spectacular success story. This is evident from quantitative data on both the animal and human disease. First, the prevalence of BSE as detected by current surveillance has come down steadily in the EU to a trickle, from several thousands of cases in the early 2000s, to 44 in 2010 in the EU (11 in the UK) (OIE, 2011). Second, surveillance of vCJD in the UK indicates that the epidemic, having reached a peak in the year 2000 when there were 28 deaths, has declined to a current incidence of about one diagnosis/death per year (Andrews, 2011). Clearly, it is now time to be re-assured but still too early for complacency (Budka et al., 2008).

Given the quantitative indicators of what seems, in the EU, to be the near-extinction of the animal epidemic and control of cattle-to-human transmission, is there anything left for concern? Unfortunately, there is. With BSE, the global disease burden is far from clear in countries with less well-developed surveillance. In humans, the potential continuing person to person spread by blood and blood products remains a problem as seen with the four cases of transfusion-associated vCJD infection to date (Andrews, 2011). With BSE and other TSEs in animals, the recognition of the wide diversity of prion strains in the field, including three new forms of animal TSEs (L-type Atypical BSE, H-type Atypical BSE and Atypical scrapie), has complicated disease diagnosis and surveillance, as well as scientific assessment of their potential risks to humans. EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential. In particular the L-type Atypical BSE agent might be similarly or even more virulent to humans than the Classical BSE agent. While mankind has been in contact with the major TSE of small ruminants for centuries, there is no epidemiological evidence to suggest that classical scrapie is zoonotic; however, experimental transmission data on humanised mice and non-human primates have been very scarce so far.

What does this mean for the future? The decline of the BSE epidemic seen by 2005 led to consideration of some relaxation of costly BSE control measures as depicted in the EU TSE Roadmap (EC, 2005), and will inevitably be followed by further relaxation as already outlined in another EU TSE Roadmap 2 of 2010 (EC, 2010). It remains critical that current levels of consumer protection are maintained and all future changes from well established and highly effective current risk management measures are based upon sound scientific advice that EFSA will continue to provide.

Which old issues will remain, and which new issues will become relevant? For Atypical BSE, the most widely accepted hypothesis is that of a spontaneously arising ("sporadic") disease in relatively old bovines. If this holds true, it will be impossible to eradicate such a disease which originates de novo; probably we then have to live forever with a ban on SRMs, in particular the central nervous system (CNS), of older cattle. Given our insufficient knowledge about the true prevalence of atypical animal prion strains in the field, it will be important to continue and improve the systematic surveillance of animal TSEs, and to refine our diagnostic and laboratory methods and experiments. As some scientific data suggest that there is probably no absolute molecular barrier to transmission of TSE agents between mammalian species (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011), the issue of a zoonotic potential of prions is likely to remain with us a time. For human TSEs including sporadic CJD, it will be important to continue systematic surveillance that should be able, as clearly shown with vCJD in the past, eventually to identify emerging new phenotypes or new prion strains. In sum, at a time when many scientists and most decision makers are no longer interested in prions and their risk, it will be prudent to stay vigilant, although this must be in a way that is balanced with other risks to human and animal health. In the risk assessment area, this will continue to be a challenge for EFSA in the years to come.


[1] Regulation (EC) No 999/2001 of the European Parliament and of the Council of 22 May 2001 laying down rules for the prevention, control and eradication of certain transmissible spongiform encephalopathies. OJ L 147, 31.05.2001, p. 1-40.

see full text and more here ;

Tuesday, October 4, 2011

De novo induction of amyloid-ß deposition in vivo

Molecular Psychiatry advance online publication 4 October 2011; doi: 10.1038/mp.2011.120

Molecular Psychiatry advance online publication 4 October 2011; doi: 10.1038/mp.2011.120

De novo induction of amyloid-ß deposition in vivo

R Morales1,2, C Duran-Aniotz1,3, J Castilla2,4, L D Estrada2,5 and C Soto1,2

1Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, TX, USA 2University of Texas Medical Branch at Galveston, Galveston, TX, USA 3Universidad de Los Andes, Facultad de Medicina. Av. San Carlos de Apoquindo 2200, Las Condes, Santiago, Chile 4CIC bioGUNE, Parque Tecnologico de Biskaia, Ed 800, 48160 Derio and IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain

Correspondence: Dr C Soto, Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, 6431 Fannin St, Houston, TX 77030, USA. E-mail:

5Current address: Laboratorio de Señalización Celular, Centro de Envejecimiento y Regeneración. P. Universidad Catolica de Chile, Santiago, Chile.

Received 8 March 2011; Revised 15 August 2011; Accepted 25 August 2011; Published online 4 October 2011.


Alzheimer's disease (AD), the most common type of senile dementia, is associated to the build-up of misfolded amyloid-ß (Aß) in the brain. Although compelling evidences indicate that the misfolding and oligomerization of Aß is the triggering event in AD, the mechanisms responsible for the initiation of Aß accumulation are unknown. In this study, we show that Aß deposition can be induced by injection of AD brain extracts into animals, which, without exposure to this material, will never develop these alterations. The accumulation of Aß deposits increased progressively with the time after inoculation, and the Aß lesions were observed in brain areas far from the injection site. Our results suggest that some of the typical brain abnormalities associated with AD can be induced by a prion-like mechanism of disease transmission through propagation of protein misfolding. These findings may have broad implications for understanding the molecular mechanisms responsible for the initiation of AD, and may contribute to the development of new strategies for disease prevention and intervention.


amyloid; prion; protein misfolding; disease transmission

see more here ;

Wednesday, September 21, 2011

PrioNet Canada researchers in Vancouver confirm prion-like properties in Amyotrophic Lateral Sclerosis (ALS)

Monday, September 26, 2011

Variably Protease-Sensitive Prionopathy, Prionpathy, Prionopathy, FFI, GSS, gCJD, hvCJD, sCJD, TSE, PRION, update 2011

Mad Cow Scaremongers

Mad Cow Scaremongers by Terry S. Singeltary Sr. a review of the TSE prion agent 2003-2011


"he also blindly insists upon a mad-cow with Alzheimer's, Parkinson's, and Lou Gehrig's disease."




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

Monday, December 26, 2011

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

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