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From: TSS ()
Subject: TSE ADVISORY meeting October 31, 2005 [FR Doc. 05-20558] TSS SUBMISSION
Date: October 14, 2005 at 9:56 am PST

Greetings FDA TSE Advisory Committee Dr. Freas and Dr. Langford et al,

I wish to submit to the following [FR Doc. 05-20558],

[Federal Register: October 14, 2005 (Volume 70, Number 198)]
[Page 60095]
From the Federal Register Online via GPO Access []



Food and Drug Administration

Transmissible Spongiform Encephalopathies Advisory Committee;
Notice of Meeting

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.


This notice announces a forthcoming meeting of a public advisory
committee of the Food and Drug Administration (FDA). The meeting will
be open to the public.
Name of Committee: Transmissible Spongiform Encephalopathies
Advisory Committee.
General Function of the Committee: To provide advice and
recommendations to the agency on FDA's regulatory issues.
Date and Time: The meeting will be held on October 31, 2005, from 8
a.m. to 5:30 p.m.
Location: Holiday Inn Select, 8120 Wisconsin Ave., Bethesda, MD.
Contact Person: William Freas or Sheila D. Langford, Center for
Biologics Evaluation and Research (HFM-71), Food and Drug
Administration, 1401 Rockville Pike, Rockville, MD 20852, 301-827-0314,
or FDA Advisory Committee Information Line, 1-800-741-8138 (301-443-
0572 in the Washington, DC area), code 3014512392. Please call the
Information Line for up-to-date information on this meeting.
Agenda: On October 31, 2005, the committee will hear updates on the
following topics: Current status of bovine spongiform encephalopathy
(BSE) in the United States, incidence and prevalence worldwide of
variant Creutzfeldt-Jakob Disease (vCJD), and a summary of FDA's device
panel discussion on September 27, 2005, on criteria for considering
label claims of effective decontamination for surgical instruments
exposed to transmissible spongiform encephalopathy (TSE) agents. The
committee will then discuss progress in development of a risk
assessment model for vCJD in U.S.-licensed human plasma-derived
Antihemophilic Factor (Factor VIII). The latter discussion will focus
on selection of input parameters for the model. In the afternoon, the
committee will discuss labeling claims for TSE clearance studies for
blood component filters.
Procedure: Interested persons may present data, information, or
views, orally or in writing, on issues pending before the committee.
Written submissions may be made to the contact person by October 21,
2005. Oral presentations from the public will be scheduled between
approximately 12:30 p.m. and 1 p.m., and 4:15 p.m. and 4:45 p.m. on
October 31, 2005. Time allotted for each presentation may be limited.
Those desiring to make formal oral presentations should notify the
contact person before October 25, 2005, and submit a brief statement of
the general nature of the evidence or arguments they wish to present,
the names and addresses of proposed participants, and an indication of
the approximate time requested to make their presentation.
Persons attending FDA's advisory committee meetings are advised
that the agency is not responsible for providing access to electrical
FDA welcomes the attendance of the public at its advisory committee
meetings and will make every effort to accommodate persons with
physical disabilities or special needs. If you require special
accommodations due to a disability, please contact William Freas or
Sheila Langford at least 7 days in advance of the meeting.
Notice of this meeting is given under the Federal Advisory
Committee Act (5 U.S.C. app. 2).

Dated: October 6, 2005.
Jason Brodsky,
Acting Associate Commissioner for External Relations.
[FR Doc. 05-20558 Filed 10-13-05; 8:45 am]


Greetings again FDA et al,

NOTHING like ignoring the obvious, i.e. sporadic CJDs. sporadic CJDs are not one strain, but potentially multiple
strains with some being atypical. WITH the documentation of transmission of vCJD to humans by blood.
the recent study by Aguzzi et al Coincident Scrapie Infection and Nephritis Lead to Urinary Prion Excretion.
the recent study by Yoshifumi Iwamaru et al that Muscle tissue has recently been detected with PrPSc in the peripheral nerves
(sciatic nerve, tibial nerve, vagus nerve) of the 11th BSE cow in Japan.
and all the old studies from decades of research where sporadic CJD has transmitted via a multitude of routes and sources via the medical and surgical arena.
to continue to blatantly ignore the real ramifications of low level infectivity and accumulation with sporadic CJD and continue to only base risk assessment on
vCJD will only aid in the continued spreading and exposure of the sporadic CJDs in the medical and surgical arena. sCJD being just as deadly (100% fatal for those
that go clinical), just as hideous as the death of a nv/v CJD victim. I wish to reference the following studies in my previous submissions to Federal Dockets;


SEAC Statement7th August 2004--------------------------------------------------------------------------------Summary of SEAC’s discussion on the second presumed case of blood transfusion-associated infection with vCJD TSS ()Subject: Coincident Scrapie Infection and Nephritis Lead to Urinary Prion Excretion {FULL TEXT}Date: October 14, 2005 at 7:20 am PSTScience, Vol 310, Issue 5746, 324-326 , 14 October 2005 ReportsCoincident Scrapie Infection and Nephritis Lead to Urinary Prion Excretion Harald Seeger,1* Mathias Heikenwalder,1* Nicolas Zeller,1 Jan Kranich,1 Petra Schwarz,1 Ariana Gaspert,2 Burkhardt Seifert,3 Gino Miele,1 Adriano Aguzzi1 Prion infectivity is typically restricted to the central nervous and lymphatic systems of infected hosts, but chronic inflammation can expand the distribution of prions. We tested whether chronic inflammatory kidney disorders would trigger excretion of prion infectivity into urine. Urinary proteins from scrapie-infected mice with lymphocytic nephritis induced scrapie upon inoculation into noninfected indicator mice. Prionuria was found in presymptomatic scrapie-infected and in sick mice, whereas neither prionuria nor urinary PrPSc was detectable in prion-infected wild-type or PrPC-overexpressing mice, or in nephritic mice inoculated with noninfectious brain. Thus, urine may provide a vector for horizontal prion transmission, and inflammation of excretory organs may influence prion spread. 1 Institute of Neuropathology, University Hospital of Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.2 Institute of Clinical Pathology, University Hospital of Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.3 Institute of Biostatistics, University of Zürich, Sumatrastrasse 30, CH-8006 Zürich, Switzerland. * These authors contributed equally to this work. To whom correspondence should be addressed. E-mail: snip...

Materials and Methods

Figs. S1 to S5

Table S1


15 August 2005; accepted 18 September 2005
Include this information when citing this paper.


Importation of Whole Cuts of Boneless Beef from Japan [Docket No. 05-004-1] RIN 0579-AB93 TSS SUBMISSION

[Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirementsfor the Disposition of Non-Ambulatory Disabled Cattle Original Message --------
Subject: Blood Products Advisory Committee [FR Doc. 04-21283 Filed 9-21-04; 8:45 am] TSS SUBMISSIONDate: Wed, 22 Sep 2004 15:31:55 -0500From: "Terry S. Singeltary Sr." To: fdadockets@oc.fda.govCC:,, langfords@cber.FDA.govTSS SUBMISSION TO;Blood Products Advisory Committee[FR Doc. 04-21283 Filed 9-21-04; 8:45 am]Greetings Dr. Smallwood and all FDA,I kindly wish to submit the following information andcomments to the Blood Products Advisory Committee.I kindly wish to submit the following information andcomments to the TSE Advisory Committee on blood products.IF you remember correctly, in my submission of;Freas, William TSS SUBMISSIONFile Format: PDF/Adobe Acrobat -Page 1. J Freas, William From: Sent: To: Subject: Terry S. SingeltarySr. [] Monday, January 08, 200l 3:03 PM freas ...snip...I am beginning to think that the endless attempt to trackdown and ban, potential victims from known BSE Countriesfrom giving blood will be futile. You would have to baneveryone on the Globe eventually? AS well, I think weMUST ACT SWIFTLY to find blood test for TSE's,whether it be blood test, urine test, eyelid test,anything at whatever cost, we need a test FAST. ,DO NOT let the incubation time period of theseTSEs fool you.snip..., some 3+ years later, seems we are faced with just thisnightmare scenario. Seems we have floundered too long, but myfear is that we are still missing the bigger picture, sporadic CJD.I have made several submissions to the FDA about my concernwith the transmission of the TSE agent from sporadic CJD viathe medical surgical arena and tissue transplantation;Docket ManagementDocket: 02N-0370 - Neurological Devices; Classification of Human Dura MaterComment Number: EC -1Accepted - Volume 1 WISH to make the following submission and comments about alltopics of this meeting about human/animal TSEs. My comments andsubmissions as follows please;>USDA-licensed tests for the diagnosis of bovine>spongiform encephalopathy (BSE) and other transmissible spongiform>encephalopathies (TSE), >IN the past all we have heard is the fact that the present BSEs test do notguarantee public health safety. I request that the USA implement a BSE/TSE test that DOES guarantee public health safety, one approvedfor consumer protection, a test for live cattle, one that would detect allTSEs in the bovine, one that would detect sub clinical TSEs;EFSA Scientific Report on the Design of a Field Trial Protocol for theEvaluation of BSE Tests for Live CattlePublication date: 17 September 2004Adopted on 1 July 2004 (Question N° EFSA-Q-2003-084)* 146 kB Report* 90 kB Summary Summary of the ReportThe European Food Safety Authority and its Scientific Expert WorkingGroup on Transmissible Spongiform Encephalopathy (TSE) Testing wereasked by the European Commission (EC) to take over the mandate of theformer Scientific Steering Committee (SSC) for the scientific evaluationof rapid TSE/BSE (Bovine Spongiform Encephalopathy) tests. At present 5rapid BSE test kits are approved by the EC for the routine post mortemtesting of slaughtered cattle over 30 months of age in accordance withthe TSE Regulation (EC) No 999/2001. Following a call for expression ofinterest in the Official Journal of the European Union (No C15) on 22January 2003, several parties indicated their interest in participatingin an EC evaluation exercise of their newly developed rapid BSE postmortem and live animal tests.It has been recognized that the availability of a rapid test for livecattle would be a major advance in dealing with the problem of BSE andTSE in general, but particularly with regard to epidemiologicalscreening. In the long term an accurate live animal test might offer thepossibility to reduce the number of culled animals after the detectionof one positive animal.A rapid BSE test for live cattle could be approved for the purpose ofconsumer protection, for epidemiological screening or for both. For thepurpose of consumer protection any new rapid BSE test including testsfor live animals should not be statistically inferior to that of thecurrently approved post mortem tests.This report provides a protocol for the design of a field trial protocolfor the evaluation of BSE tests for live cattle for the purpose ofconsumer protection only. TEXT; >review of the worldwide BSE situation, >THE most disturbing factor of this topic are the new atypical TSEsshowing up in not only cattle, but also sheep, and no one know's yetabout how many different strains of cwdTSE in deer/elk. WITH evidence ofsporadic CJD being very similar to these atypical TSEs in cattle and sheep,and the findings from Asante, Collinge et al that BSE prions propagateas either nvCJD or sporadic CJD, the ramifications of these findings are very very worrysome and should not go ignored any further. WITHthe fact that there are over 20 documented strains of scrapie, and themost logical hypothisis is scrapie to BSE, why would one believe inonly one phenotype of TSE in the bovine;BSE prions propagate as either variant CJD-like or sporadic CJD-likeprion strains in transgenic mice expressing human prion proteinEmmanuel A. Asante, Jacqueline M. Linehan, Melanie Desbruslais, Susan Joiner, Ian Gowland, Andrew L. Wood, Julie Welch, Andrew F. Hill, Sarah E. Lloyd, Jonathan D.F. Wadsworth and John Collinge1MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK 1 Corresponding author e-mail: Received August 1, 2002; revised September 24, 2002; accepted October 17, 2002AbstractVariant CreutzfeldtJakob disease (vCJD) has been recognized to date only in individuals homozygous for methionine at PRNP codon 129. Here we show that transgenic mice expressing human PrP methionine 129, inoculated with either bovine spongiform encephalopathy (BSE) or variant CJD prions, may develop the neuropathological and molecular phenotype of vCJD, consistent with these diseases being caused by the same prion strain. Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrPSc type 2. These data suggest that more than one BSE-derived prion strain might infect humans; it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure... new findings of BASE in cattle in Italy of Identification of asecond bovine amyloidotic spongiform encephalopathy: Molecularsimilarities with sporadic Creutzfeldt-Jakob disease of two distinct prion strainsderived from bovine spongiform encephalopathytransmissions to inbred miceSarah E. Lloyd, Jacqueline M. Linehan, Melanie Desbruslais,Susan Joiner, Jennifer Buckell, Sebastian Brandner,Jonathan D. F. Wadsworth and John CollingeCorrespondenceJohn Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology,University College, London WC1N 3BG, UKReceived 9 December 2003Accepted 27 April 2004Distinct prion strains can be distinguished by differences in incubation period, neuropathologyand biochemical properties of disease-associated prion protein (PrPSc) in inoculated mice.Reliable comparisons of mouse prion strain properties can only be achieved after passage ingenetically identical mice, as host prion protein sequence and genetic background are knownto modulate prion disease phenotypes. While multiple prion strains have been identified insheep scrapie and CreutzfeldtJakob disease, bovine spongiform encephalopathy (BSE) isthought to be caused by a single prion strain. Primary passage of BSE prions to different linesof inbred mice resulted in the propagation of two distinct PrPSc types, suggesting that twoprion strains may have been isolated. To investigate this further, these isolates weresubpassaged in a single line of inbred mice (SJL) and it was confirmed that two distinct prionstrains had been identified. MRC1 was characterized by a short incubation time (110±3 days),a mono-glycosylated-dominant PrPSc type and a generalized diffuse pattern of PrP-immunoreactivedeposits, while MRC2 displayed a much longer incubation time (155±1 days),a di-glycosylated-dominant PrPSc type and a distinct pattern of PrP-immunoreactive depositsand neuronal loss. These data indicate a crucial involvement of the host genome in modulatingprion strain selection and propagation in mice. It is possible that multiple disease phenotypesmay also be possible in BSE prion infection in humans and other animals. of the bovine spongiform encephalopathy agent to primatesand comparison with Creutzfeldt- Jakob disease: Implications forhuman healthTHE findings from Corinne Ida Lasmézas*, [dagger] , Jean-Guy Fournier*,Virginie Nouvel*,Hermann Boe*, Domíníque Marcé*, François Lamoury*, Nicolas Kopp [Dagger] , Jean-Jacques Hauw§, James Ironside¶, Moira Bruce [||] , DominiqueDormont*, and Jean-Philippe Deslys* et al, that The agent responsiblefor French iatrogenic growth hormone-linked CJD taken as a control isvery different from vCJD but is similar to that found in one case ofsporadic CJD and one sheep scrapie isolate; recent discoveries of previously unidentified strains ofScrapie such as 221C44 and the Nor9845;2.5.2 The existence of distinct strains was recognised when sources ofsheep scrapie were serially transmitted to mice. A single inbred line of mice, in which allindividuals make the same PrPC, can propagate several different strains of scrapie, each withits own distinctive incubation period, pattern of damage in the brain and PrPScproperties42, 43. Strain variation also occurs in natural scrapie, and the recent discoveries ofpreviously unidentified strains, such as 221C44 and Nor9845, suggests that thespectrum of different strains may change with time. Since different strains can have verydifferent patterns of pathology and distribution of PrPSc, their presence may be missed by theapplication of standard sampling and testing protocols used for surveillance45.Although a single strain of BSE appears to be responsible for the vast majority of cases around theworld46, 47, evidence is emerging that suggests that there may be other strains whichhave different properties when transmitted to mice48 or result in different pathologyor properties of PrPSc in infected cattle49, 50.FULL TEXT APPRX. 91 PAGESUK Strategy for Research andDevelopment on Human and AnimalHealth Aspects of TransmissibleSpongiform Encephalopathies2004-2007 in fact, the findings from Marsh and the findings atMISSION, TEXAS support even further evidence that thereare furthers strains of TSE in the USA besides that oneaccidently documented BSE case in Washington onDec. 23, 2003;In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - Report of a visit to the USA - April-May 1989 - G A H Wells [head of England's main veterinary lab]2. Meeting with USDA, BSE Task ForceThis group comprises Alex Thierman (USDA-APHIS, International Programs)(Chairman), Roger Breeze (USDA-ARS Director, Plum Island), Bill Hadlow(Neuropathologist - retired, formerly of NIH Rocky Mountain Laboratory, Hamilton, Montana), John Gorhan and Mark Robinson (USDA-ARS, Pullman, Washington) and Dick Marsh (Dept. Vet. Science, Univ Wisconsin - Madison). The objectives of the group are to assess the implications of the occurrence of BSE for US cattle particularly the risk of BSE occurrence in the US in relation to endemic scrapie agent.The purpose of my invitation to this meeting was to discuss aspects ofresearch which are of common interest and to identify a tentative USDAresearch programme including any potential collaborative projects. Thediscussions were informal and there was no agenda. The general opinionof those present was that BSE, as an overt disease phenomenon, couldexist in the USA but if it did it was very rare. The need for improvedand specific surveillance methods to detect it was recognised. Clinicalsimilarities between BSE and rabies suggested one means of sampling thecattle population which might increase the probability of detection ofBSE. It was clear that the bovine rabies negative rate would varygreatly between States but initially this should be determined and as itwould inevitably be high relative to positive cases, some differentialdiagnosis carried out.The work of Wilbur Clarke at Mission, Texas was discussed briefly. theresults of this study in which 10 calves were inoculated with scrapiehas not been published and perhaps would not be published. USDA aresensitive regarding publicity of the results of the study which remainfar from conclusive. Apparently only 3 of the inoculated animalsdeveloped neurological signs. The neuropathology of the affected cattlehas not been examined in any depth but Hadlow has the material. Marshindicated the requirement to obtain the fresh brain material from thisstudy in order to perform PrP extractions.Because of the successful transmission of the Brecke (Stetsonville)isolate of TME to cattle and the subsequent passage history in mink itwas generally considered important that comparisons be made with BSEisolates in mink. Is BSE like scrapie in mink? Is BSE like the Breckeisolate of TME?Very little was said about CWD but some present considered that itsoccurrence may indicate a sylvatic origin of agent. It was also agreedthat the role of possible subclinical infection in theepidemiology of transmissible spongiform encephalopathies could wellbe important but was unknown. Marsh remarked on the possibility thatBSE was due to an extremely thermostable strain of agent. Hisexperience in the past with one particular Wisconsin isolate of TME(Hayward strain) suggested that i/c biopsy needles could not beeffectively "scrapie sterilised", even employing an experimentalautoclave system capable of 60 psi and 300"C+ for 5 hours. Thisexperience led him to the policy that in scrapie or TME transmissionstudies re-use of instruments or glassware that had contained agent wasan unacceptable protocol.I was given confidential access to sections from the Clarke scrapie- cattle transmission experiment. Details of the experimental design were as supplied previously by Dr Wrathall (copy of relevant informationappended). Only 3 animals (2 inoculated with 2nd pass Suffolk Scrapieand 1 inoculated with Angora goat passaged scrapie) show clinical signs.Clinical signs were characterised by weakness, "a stilted hindlimb gait", disorientation, ataxia and, terminally,lateral recumbency. The two cattle from which I examined material wereinoculated at 8 months of age and developed signs 36 months pi (goatscrapie inoculum) and 49 months pi (one of the Suffolk scrapieinoculated) respectively. This latter animal was killed at 58 monthsof age and so the clinical duration was only 1 month. The neuropathologywas somewhat different from BSE or the Stetsonville TME in cattle.Vacuolar changes were minimal, to the extent that detection requiredcareful searching. Conversely astrocyte hypertrophy was a widespread andprominent feature. The material requires detailed neuropathologicalassessment but whether or not this will be done remains in question.Appendix IVISIT TO USA - DR A E WRATHALL - INFO ON BSE AND SCRAPIE1. Dr Clark lately of the Scrapie Research Unit, Mission Texas hassuccessfully transmitted ovine and caprine scrapie to cattle. Theexperimental results have not been published but there are plans to dothis. This work was initiated in 1978. A summary of it is:-Expt A 6 Her x Jer calves born in 1978 were inoculated as follows with a2nd Suffolk scrapie passage:-i/c 1ml i/m, 5ml; s/c 5ml; oral 30ml.1/6 went down after 48 months with a scrapie/BSE-like disease.Expt B 6 Her or Jer or HxJ calves were inoculated with angora Goat virus2/6 went down similarly after 36 months.Expt C Mice inoculated from brains of calves/cattle in expts A & B were resistant, only 1/20 going down with scrapie and this was the reason given for not publishing.Diagnosis in A, B, C was by histopath. No reports on SAF were given.Dr Warren Foote indicated success so far in eliminating scrapie inoffspring from experimentally (and naturally) infected sheep by ET. Hehad found difficulty in obtaining emhryos from naturally infected sheep (cf SPA).3. Prof. A Robertson gave a brief account of BSE. The US approach was toaccord it a very low profile indeed. Dr A Thiermann showed the picturein the "Independent" with cattle being incinerated and thought this wasa fanatical incident to be avoided in the US at all costs. BSE was notreported in USA.4. Scrapie incidents (ie affected flocks) have shown a dramatic increasesince 1978. In 1953 when the National Control Scheme was started there were 10-14 incidents, in 1978 - 1 and in 1988 so far 60.5. Scrapie agent was reported to have been isolated from a solitary fetus.6. A western blotting diagnostic technique (? on PrP) shows some promise.7. Results of a questionnaire sent to 33 states on the subject ofthe national sheep scrapie programme survey indicated;17/33 wished to drop it6/33 wished to develop it8/33 had few sheep and were neutralInformation obtained from Dr Wrathall's notes of a meeting of the U.S.Animal Health Association at Little Rock, Arkansas Nov. 1988.CONFIDENTIAL TRANSMISSION (Day 4)6.1 BSE to pigssnip...endfull text ; be published in the Proceedings of theFourth International Scientific Congress inFur Animal Production. Toronto, Canada,August 21-28, 1988Evidence That Transmissible Mink EncephalopathyResults from Feeding Infected CattleR.F. Marsh* and G.R. Hartsough"Department of Veterinary Science, University of Wisconsin-Madison, Madison,Wisconsin 53706; and ^Emba/Creat Lakes Ranch Service, Thiensville, Wisconsin 53092ABSTRACTEpidemiologic investigation of a new incidence oftransmissible mink encephalopathy (TME) in Stetsonville, Wisconsinsuggests that the disease may have resulted from feeding infectedcattle to mink. This observation is supported by the transmission ofa TME-like disease to experimentally inoculated cattle, and by therecent report of a new bovine spongiform encephalopathy inEngland.INTRODUCTIONsnip...Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died fromTME.Since previous incidences of TME were associated with common or shared feedingpractices, we obtained a careful history of feed ingredients used over the past 12-18months. The rancher was a "dead stock" feeder using mostly (>95%) downer or dead dairycattle and a few horses. Sheep had never been fed.Experimental Transmission. The clinical diagnosis of TME was confirmed byhistopaihologic examination and by experimental transmission to mink after incubationperiods of four months. To investigate the possible involvement of cattle in this diseasecycle, two six-week old castrated Holstein bull calves were inoculated intracerebrallywith a brain suspension from affected mink. Each developed a fatal spongiformencephalopathy after incubation periods of 18 and 19 months.DISCUSSIONThese findings suggest that TME may result from feeding mink infected cattle andwe have alerted bovine practitioners that there may exist an as yet unrecognizedscrapie-like disease of cattle in the United States (Marsh and Hartsough, 1986).snip...full text; the question has again been brought up as to whetherscrapie is transmissible to man. This has followed reports that thedisease has been transmitted to primates. One particularly luridspeculation (Gajdusek 1977) conjectures that the agents of scrapie,kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy ofmink are varieties of a single "virus". The U.S. Department ofAgriculture concluded that it could "no longer justify or permitscrapie-blood line and scrapie-exposed sheep and goats to be processedfor human or animal food at slaughter or rendering plants" (ARC 84/77)"The problem is emphasised by the finding that some strains of scrapieproduce lesions identical to the once which characterise the humandementias"Whether true or not. the hypothesis that these agents might betransmissible to man raises two considerations. First, the safetyof laboratory personnel requires prompt attention. Second, actionsuch as the "scorched meat" policy of USDA makes the solution of theacrapie problem urgent if the sheep industry is not to suffergrievously.snip...76/10.12/4.6 TO PIGThe neuropathology of experimental bovine spongiform encephalopathyin the pig.Ryder SJ, Hawkins SA, Dawson M, Wells GA.Veterinary Laboratories Agency Weybridge, Woodham Lane, New Haw,Addlestone, Surrey, KT15 3NB, UK.In an experimental study of the transmissibility of BSE to the pig,seven of 10 pigs, infected at 1-2 weeks of age by multiple-routeparenteral inoculation with a homogenate of bovine brain fromnatural BSE cases developed lesions typical of spongiformencephalopathy. The lesions consisted principally of severe neuropilvacuolation affecting most areas of the brain, but mainly theforebrain. In addition, some vacuolar change was identified in therostral colliculi and hypothalamic areas of normal control pigs. PrPaccumulations were detected immunocytochemically in the brains ofBSE-infected animals. PrP accumulation was sparse in many areas andits density was not obviously related to the degree of vacuolation.The patterns of PrP immunolabelling in control pigs differedstrikingly from those in the infected animals.PMID: 10684682 [PubMed - indexed for MEDLINE] >new FDA/Center for Food Safety and Applied Nutrition BSE-food safety rules, >FDA again is missing the bigger picture, ALL TSEs! THE BSE/nvCJD only theory should be trashedonce and for all. the name should read;new FDA/Center for Food Safety and Applied Nutrition TSE-food safety rules>and>labeling claims for TSE clearance studies for plasma derivative>products. >>The committee will then discuss and make recommendations>regarding presumptive transfusion transmissions of variant Creutzfeldt>Jakob Disease (vCJD) and current FDA-recommended safeguards.>ONE of the things i have been most worried about and will continue to bring to the attention of theTSE advisory committee is the continued denial of the potential of transmission of sporadic CJDvia blood and blood products. THERE are studies showing infectivity in the blood of sporadic CJD,and just how many phenotypes there are of sporadic CJD is anyone's guess at this point in time.WE have already documented transmission of sporadic CJD via tissues and organs.TO continue the BSE/nvCJD only theory will only continue to spread this agent. WE must moveaway from this mentality and move on with all TSEs and treat all TSEs as one, until proven otherwise,not the other way around. with 6,000 'DEAR nvCJD LETTERS' due to blood and blood products so far,i can only imagine the number, once sporadic CJD is documented to have transmitted via blood, what thatnumber will be when those 'DEAR SPORADIC CJD LETTERS' go out and how many will becomeclinical once exposed, a frightening thought;It is possible to transmit BSE to a sheepby transfusion with whole blood taken fromanother sheep during the symptom-free phaseof an experimental BSE infection'It is well known that variant Creutzfeldt-Jakobdisease (vCJD) is caused by the same strain ofagent that causes bovine spongiform encephalopathy(BSE) in cattle. F Houston and colleaguesreport the preliminary findings of transfusingblood from 19 UK Cheviot sheep fed with 5 gBSE-affected cattle brain into Cheviot sheep fromscrapie-free flock of New Zealand-derivedanimals. The investigators found BSE clinicalsigns and pathology in one recipient of blood takenfrom a BSE infected animal. Immunocytochemistry ontissues taken from the transfused sheepshowed widespread PrPSC deposition throughout thebrain and the periphery. This findingsuggests that blood donated by symptom-freevCJD-infected human beings could transmitinfection to recipients of blood transfusions.In a Commentary, Paul Brown states that theseobservations are consistent with previous reportsin experimentally infected rodents.==================Research lettersVolume 356, Number 9234 16 September 2000Transmission of BSE by blood transfusion in sheepLancet 2000; 356: 999 - 1000Download PDF (1 Mb)F Houston, J D Foster, Angela Chong, N Hunter, C J BostockSee CommentaryWe have shown that it is possible to transmitbovine spongiform encephalopathy (BSE)to a sheep by transfusion with whole bloodtaken from another sheep during thesymptom-free phase of an experimental BSEinfection. BSE and variantCreutzfeldt-Jakob disease (vCJD) in humanbeings are caused by the same infectiousagent, and the sheep-BSE experimental modelhas a similar pathogenesis to that ofhuman vCJD. Although UK blood transfusionsare leucodepleted--a possible protectivemeasure against any risk from bloodtransmission--this report suggests that blooddonated by symptom-free vCJD-infected humanbeings may represent a risk of spreadof vCJD infection among the human populationof the UK.The demonstration that the new variant ofCreutzfeldt-Jakob disease (vCJD) is caused by thesame agent that causes bovine spongiformencephalopathy (BSE) in cattle1 has raised concernsthat blood from human beings in the symptom-freestages of vCJD could transmit infection torecipients of blood transfusions. There is noevidence that iatrogenic CJD has ever occurred as aresult of the use of blood or blood products,but vCJD has a different pathogenesis and couldpresent different risks. CJD is one of thetransmissible spongiform encephalopathies (TSEs)characterised by the deposition of an abnormalform of a host protein, PrPSc; the normalisoform (PrPC) is expressed in many body tissues.Available evidence, based on detection ofinfectivity in blood in rodent models, and absenceof infectivity in naturally occurring TSEs, addsto the uncertainty in risk assessments of thesafety of human blood. PrPSc has been reported inblood taken from preclinical TSE-infected sheep,2but it does not follow that blood is infectious.Bioassays of human blood can only be carried outin non-human species, limiting the sensitivityof the test. One way of avoiding such a speciesbarrier is to transfer blood by transfusion in anappropriate animal TSE model. BSE-infected sheepharbour infection in peripheral tissues3 andare thus similar to humans infected with vCJD.4BSE infectivity in cattle does not havewidespread tissue distribution.We report preliminary data from a studyinvolving blood taken from UK Cheviot sheepchallenged orally with 5 g BSE-affected cattlebrain and transfused into Cheviot sheep from ascrapie-free flock of New Zealand-derived animals(MAFF/SF flock). MAFF/SF sheep do notdevelop spontaneous TSE and the transfusedanimals are housed separately from other sheep.All sheep in the study have the PrP genotypeAA136QQ171 which has the shortest incubationperiod of experimental BSE in sheep.5 19 transfusions fromBSE-challenged sheep have beendone, mostly with whole blood. Sheep havecomplex blood groups and only simplecross-matching can be done by mixing recipientserum and donor erythrocytes and vice versa.Therefore single transfusions only were madebetween sedated cross-matched animals tominimise the risk of severe reactions. Negativecontrols were MAFF/SF sheep transfused withblood from uninfected UK Cheviot sheep. As apositive control, MAFF/SF sheep wereintravenously injected with homogenised BSE-affectedcattle brain.We have seen BSE clinical signs and pathologicalchanges in one recipient of blood from aBSE-infected animal, and we regard this findingas sufficiently important to report now ratherthan after the study is completed, several yearshence. The blood donation resulting intransmission of BSE to the recipient was 400 mLof whole blood taken from a healthy sheep318 days after oral challenge with BSE. BSE subsequentlydeveloped in this donor animal 629days after challenge, indicating that blood was takenroughly half way through the incubationperiod. 610 days after transfusion, the transfusedsheep (D505) itself developed typical TSEsigns: weight loss, moderate pruritus, tremblingand licking of the lips, hind-limb ataxia, andproprioceptive abnormalities. This is the firstexperimental transmission of BSE from sheep tosheep and so we have nothing with which to comparethis incubation period directly. Incross-species transmissions, bovine BSE injectedintracerebrally gives incubation periods ofabout 450 days in these sheep,5 and the donor animalhad an oral BSE incubation period of 629days (see above). There are no similar dataavailable on other infection routes.Immunocytochemistry with the antibody BG4 on tissuestaken from sheep D505 showedwidespread PrPSc deposition throughout the brain andperiphery. Western blot analysis of braintissue with the antibody 6H4 showed that the PrPScprotein had a glycoform pattern similar tothat of experimental BSE in sheep and unlike thatof UK natural scrapie (figure), indicating thatthe TSE signs resulted from transmissionof the BSE agent. All other recipients of transfusionsand positive and negative controls arealive and healthy. The positive controls, which involve aspecies barrier, are expected to havelengthy incubation periods. With one exception, alltransfused animals are at earlier stagespost-transfusion than was D505. The exception is asheep which is healthy 635 days after transfusionwith BSE-blood donated at less than 30% ofthe BSE incubation period of the donor sheep.PrPSc (proteinase K treated) analysed by SDS-PAGE,immunoblotted with 6H4, andvisualised with a chemiluminescent substrateAll lanes are from the same gel with differentexposure times. Size markers are to the left oflane 1. Lane1: natural scrapie sheep brain,3 min exposure. Lane 2: as lane 1, 10 min exposure.Lane 3: sheep D505, blood-transfusionrecipient, 10 min exposure. Lane 4: experimentalBSE-affected sheep brain, 30 s exposure.Lane 5: as lane 4, 10 min exposure. Each laneloaded with amount of protein extracted from0·1 g wet weight of brain, except lane 3 whichwas extracted from 0·2 g brain.Although this result was in only one animal, itindicates that BSE can be transmitted betweenindividuals of the same species by whole-bloodtransfusion. We have no data on blood fractionsor on levels of infectivity in blood of preclinicalvCJD cases, but whole blood is not now used inUK transfusions. The presence of BSE infectivityin sheep blood at an early stage in theincubation period suggests that it should bepossible to identify which cells are infected, to testthe effectiveness of leucodepletion, and todevelop a diagnostic test based on a blood sample.We thank Karen Brown, Moira Bruce, CalumMcKenzie, David Parnham, Diane Ritchie, andthe Scottish Blood Transfusion Service. Theproject is funded by the Department of Health.1 Bruce ME, Will RG, Ironside JW, et al.Transmissions to mice indicate that 'new variant' CJDis caused by the BSE agent. Nature 1997;389: 488-501 [PubMed].2 Schmerr MJ, Jenny A, Cutlip RC. Use ofcapillary sodium dodecyl sulfate gel electrophoresisto detect the prion protein extracted fromscrapie-infected sheep. J Chromatogr B BiomedAppl 1997; 697: 223-29 [PubMed].3 Foster JD, Bruce M, McConnell I, Chree A,Fraser H. Detection of BSE infectivity in brainand spleen of experimentally infected sheep.Vet Rec 1996; 138: 546-48 [PubMed].4 Hill AF, Zeidler M, Ironside J, Collinge J.Diagnosis of new variant Creutzfeldt-Jakob diseaseby tonsil biopsy. Lancet 1997; 349: 99-100.5 Goldmann W, Hunter N, Smith G, Foster J,Hope J. PrP genotype and agent effects inscrapie: change in allelic interaction withdifferent isolates of agent in sheep, a natural host ofscrapie. J Gen Virol 1994; 75: 989-95 [PubMed].Institute for Animal Health, Compton, Newbury,UK (F Houston PhD, CJ BostockPhD); and Institute for Animal Health, Neuropathogenesis Unit,Edinburgh, EH93JF, UK (N Hunter PhD, JD Foster BSc, Angela Chong BSc)Correspondence to: Dr N HunterALSO;Transmission of prion diseases by blood transfusionNora Hunter,1 James Foster,1 Angela Chong,1 Sandra McCutcheon,2 DavidParnham,1 Samantha Eaton,1 Calum MacKenzie1 and Fiona Houston2see full text; 356, Number 9234 16 September 2000BSE and transmission through bloodLancet 2000; 356: 955 - 956Download PDF (55 Kb)snip...Blood from four of 37 human beings withclinically evident sporadic CJD has been reportedto transmit the disease after intracerebral inoculation into guineapigs,mice, or hamsters. But eachsuccess has been questioned on technical groundsand has not been reproducible;snip...Is it appropriate to publish an experimentalresult from a single animal in a study that is not farenough along even to have validated its positivecontrols? Especially a result that does not in anyfundamental way change our current thinking aboutBSE and vCJD and which would not seemto have any practical consequences for publichealth? The UK National Blood TransfusionService has already implemented leucodepletionof donated blood, and imports all plasma andplasma derivatives from BSE-free countries. Nofurther measures would seem possible--shortof a draconian decision to shut down the wholeUK blood-donor system. What, therefore, is therationale for this publishing urgency? Theanswer, evidently, is a perceived need to "defuse", byan immediate and accurate scientific report,public reaction to possibly inaccurate mediaaccounts. The full study, when it appears, willbe an important addition to our knowledge ofTSEs, but science should not be driven to whatin certain medical quarters might be termed apremature emission through fear of media misrepresentation.Paul BrownLaboratory of Central Nervous System Studies,National Institutes of Health, Bethesda,MD 20892, USA> What, therefore, is the> rationale for this publishing urgency? Wonder what Dr. Paul Brown would think of this stupid statement now?SEEMS the urgency was and is a long time coming. HOW many moredo we expose with 'rationale' such as Paul Browns?Transmission of Creutzfeldt-Jakob Disease from Blood and Urine Into MiceThe Lancet, November 9, 1985Sir,--Professor Manuelidis and his colleagues (Oct 19, p896) reporttransmission to animals of Creutzfeldt-Jakob disease (CJD) from thebuffy coat from two patients. We also transmitted the disease fromwhole blood samples of a patient (and of mice) infected with CJD.1Brain, Cornea, and urine from this patient were also infectious, andthe clinicopathological findings2 are summarised as follows.A 70-year-old man was noted to have a slowing of speech and writingand some disorientation, all of which progressed rapidly. Decorticaterigidity, forced grasping, positive snout reflex, and myoclonusappeared within 2 months. Electroencephalogram revealed typicalperiodic synchronous discharge, and he died of pneumonia and uppergastrointestinal haemorrhage, about 3 months after onset of thesymptoms. The Brain weighed 1290g and showed severe histologicalchanges diagnostic of CJD, including spongiform change, loss ofnerve cells, and diffuse proliferation of astrocytes. There were noinflammatory cells, microglia, neurofibrillary tangles, andamyloid plaques, although virus-like particles were detected byelectron microscopy.Results of innoculation in MiceInocula NO* Incubation period (days)+Brain 7/10 (4) 789 (+ or - 112)Cornea 1/6 (0) 1037Blood 2/13 (0) 1080 (+ or - 69)Urine 5/10 (1) 880 (+ or - 55)CSF 0/10* Number of mice with CJD change/number examined histologically.Number with amyloid plaques shown in parentheses.+ means + or - SDSamples were taken aseptically at necropsy. 10% crude homogenatesof brain and cornea in saline, whole blood (after crushing a clot),and untreated CSF and urine were innoculated intracerebrally intoCF1 strain mice (20 ul per animal). Some mice showed emaciation,bradykinesia, rigidity of the body and tail, and sometimes tremorafter long incubation periods. Tissues obtained after the animaldied (or was killed) were studied histologically (table). Animalsinfected by various inocula showed common pathological changes,consisting of severe spongiform changes, glial proliferation, anda moderate loss of nerve cells. A few mice inoculated with braintissue or urine had the same amyloid plaques found in patients andanimals with CJD.3In our long-term experiments, inoculating materials taken fromtwenty patients with CJD or Gerstmann-Straussler-Scheinker'sdisease (GSS) into rodents, positive results were obtained inseventeen cases, including this patient. Brain tissue transmittedthe disease most frequently within the shortes incubation period,except for one case where the lymph node was the most infectious.Transmission through the cornea has been noted in man4 and inguineapigs.5 Whole blood samples taken from three patients wereinoculated and a positive transmission occured only in the caserecorded here. Mouse-to-mouse transmission through bloodinoculation was successful after a mean incubation period of 365days.1 Transmission through urine was positive in this patientonly, and negative in one other patient and in many infected animals.Transmission through the CSF from eight patients was negative, yettransmission via the CSF of infected rats was positive.1As viraemia has been proved in guineapigs,6 mice,1,7 and latelyin patients with CJD, blood for transfusion or blood products formedical use must be tested for unconventional pathogens. For thispurpose, we inoculated blood products inot rodents.8 The CJDpathogen was not found in the products examined. However, thisapproach takes too long to be of practical value. More efficientmethods must be developed to detect pathogens and to eliminatethem from blood. One proposal9 is to apply membrane filtration tothe pruification protocol of human growth hormone suspected ofbeing contaminated with CJD. Similar methods are needed for bloodcontamination.Department of Neuropathology,Neurological Institute,Faculty of Medicine,Kyushu University,Fukuoka812, JapanJUN TATEISHI1. Tateishi J, Sato Y, Kaga M. Doi H, Ohta M. Experimental transmissionof human subacute spongiform encephalopathy to smallrodents 1: Clinical and histological observations.Acta Neuropathol (Berl) 1980; 51: 127.2. Shibayama Y, Sakaguchi Y, Nakata K, et al, Creutzfeldt-Jakobdisease with demonstration of virus-like particles.Acta pathol Jpn 1982;32: 695.3. Tateishi J, Nagara H, Hikita K, Sato Y. Amyloid plaques in thebrains of mice with Creutzfeldt-Jakob disease.Ann Neurol 1984; 15: 278.4. Duffy P, Wolf J, Colings G, DeVoe AG, Streeten B, Cowen D.Possible person-to-person transmission of Creutzfeldt-Jakob disease.N Engl J Med 1974; 290: 692.5. Manuelidis EE, Angelo JN, Gorgacz EJ, Kim JH, Manuelidis L.Experimental Creutzfeldt-Jakob disease transmitted via the eyewith infected cornea. N Engl J Med 1977; 296: 1334.6. Manuelidis EE, Gorgacz EJ, Manuelidis L. Viremia in experimentalCreutzfeldt-Jakob disease. Science 1978: 200: 1069.7. Kuroda Y, Gibbs CJ Jr, Amyx HL, Gajdusek DC.Creutzfeldt-Jakob disease in mice. Persistent viremiam andpreferential replication of virus in low-density lymphocytes.Infect Immun 1983; 41: 154.8. Tateishi J, Tsuji S. Unconventional pathogens causing spongiformencephalopathis absent in blood products. J Med Virol 1985; 15: 11.9. Tateishi J, Kitamoto T, Hiratani H. Creutzfeldt-Jakob diseasepathogen in growth hormone preparations is eliminatable.Lancet (in press).============ TransfusionVolume 42 Issue 5 Page 513 - May 2002doi:10.1046/j.1537-2995.2002.00098.x Brain and buffy coat transmission of bovine spongiform encephalopathy to the primate Microcebus murinusNöelle Bons, Sylvain Lehmann, Nadine Mestre-Francès, Dominique Dormont, and Paul BrownBACKGROUND: More than 100 cases of variant CJD resulting from infections with bovine spongiform encephalopathy (BSE) have accumulated in the United Kingdom since 1995. Concern about the possibility of secondary transmissions via blood and blood components donated by infected individuals has prompted a variety of international donor deferral policies that will continue until laboratory and epidemiologic evidence provides a consensus about potential risk.STUDY DESIGN AND METHODS: BSE was passaged through macaque monkeys andthen adapted to the prosimian microcebe (Microcebus murinus ). Brainhomogenate and buffy coat from an affected microcebe were separatelyinoculated intracerebrally into three healthy microcebes (two animalsreceived brain and one received buffy coat).RESULTS: All three inoculated microcebes became ill after incubationperiods of 16 to 18 months. Clinical, histopathologic, andimmunocytologic features were similar in each of the recipients.CONCLUSION: Buffy coat from a symptomatic microcebe infected 17 monthsearlier with BSE contained the infectious agent. This observationrepresents the first documented transmission of BSE from the blood of anexperimentally infected primate, which in view of rodent buffy coatinfectivity precedents and the known host range of BSE is neitherunexpected nor cause for alarm. Prions in skeletal musclePatrick J. Bosque*,dagger ,Dagger , Chongsuk Ryou*, Glenn Telling*,§,David Peretz*,dagger , Giuseppe Legname*,dagger , Stephen J.DeArmond*,dagger ,¶, and Stanley B. Prusiner*,dagger ,||,*** Institute for Neurodegenerative Diseases and Departments of daggerNeurology, ¶ Pathology, and || Biochemistry and Biophysics, Universityof California, San Francisco, CA 94143Contributed by Stanley B. Prusiner, December 28, 2001Considerable evidence argues that consumption of beef products fromcattle infected with bovine spongiform encephalopathy (BSE) prionscauses new variant Creutzfeldt-Jakob disease. In an effort to preventnew variant Creutzfeldt-Jakob disease, certain "specified offals,"including neural and lymphatic tissues, thought to contain high titersof prions have been excluded from foods destined for human consumption[Phillips, N. A., Bridgeman, J. & Ferguson-Smith, M. (2000) in The BSEInquiry (Stationery Office, London), Vol. 6, pp. 413-451]. Here wereport that mouse skeletal muscle can propagate prions and accumulatesubstantial titers of these pathogens. We found both high prion titersand the disease-causing isoform of the prion protein (PrPSc) in theskeletal muscle of wild-type mice inoculated with either the Me7 orRocky Mountain Laboratory strain of murine prions. Particular musclesaccumulated distinct levels of PrPSc, with the highest levels observedin muscle from the hind limb. To determine whether prions are producedor merely accumulate intramuscularly, we established transgenic miceexpressing either mouse or Syrian hamster PrP exclusively in muscle.Inoculating these mice intramuscularly with prions resulted in theformation of high titers of nascent prions in muscle. In contrast,inoculating mice in which PrP expression was targeted to hepatocytesresulted in low prion titers. Our data demonstrate that factors inaddition to the amount of PrP expressed determine the tropism of prionsfor certain tissues. That some muscles are intrinsically capable ofaccumulating substantial titers of prions is of particular concern.Because significant dietary exposure to prions might occur through theconsumption of meat, even if it is largely free of neural and lymphatictissue, a comprehensive effort to map the distribution of prions in themuscle of infected livestock is needed. Furthermore, muscle may providea readily biopsied tissue from which to diagnose prion disease inasymptomatic animals and even humans. Dagger Present address: Departmentof Medicine, Denver Health Medical Center, Denver, CO 80204.§ Present address: Department of Microbiology and Immunology, Universityof Kentucky, Lexington, KY 40536-0230.** To whom reprint requests should be addressed. E-mail: FULL TEXT;
Extraneural Pathologic Prion Protein in Sporadic Creutzfeldt-Jakob DiseaseMarkus Glatzel, M.D., Eugenio Abela, Manuela Maissen, M.S., and Adriano Aguzzi, M.D., Ph.D.snip...Conclusions Using sensitive techniques, we identified extraneural depositionof PrPSc in spleen and muscle samples from approximately one third of patientswho died with sporadic Creutzfeldt-Jakob disease. Extraneural PrPSc appearsto correlate with a long duration of disease. reports AOP Published online: 11 April 2003Widespread PrPSc accumulation in muscles of hamsters orally infected with scrapieAchim Thomzig, Christine Kratzel, Gudrun Lenz, Dominique KrÒ¼ger & MichaelBeekes Robert Koch-Institut, P26, Nordufer 20, D-13353 Berlin, GermanyReceived 13 February 2003; Accepted 13 March 2003; Published online 11April 2003.Abstract :Scrapie, bovine spongiform encephalopathy and chronic wasting diseaseare orally communicable, transmissible spongiform encephalopathies(TSEs). As zoonotic transmissions of TSE agents may pose a risk to humanhealth, the identification of reservoirs for infectivity in animaltissues and their exclusion from human consumption has become a matterof great importance for consumer protection. In this study, a variety ofmuscles from hamsters that were orally challenged with scrapie wasscreened for the presence of a molecular marker for TSE infection, PrPSc(the pathological isoform of the prion protein PrP). Sensitive westernblotting revealed consistent PrPSc accumulation in skeletal muscles fromforelimb and hindlimb, head, back and shoulder, and in tongue.Previously, our animal model has provided substantial baselineinformation about the peripheral routing of infection in naturallyoccurring and orally acquired ruminant TSEs. Therefore, the findingsdescribed here highlight further the necessity to investigate thoroughlywhether muscles of TSE-infected sheep, cattle, elk and deer containinfectious agents. previous data on TSE in muscle;J69CVO BSE 1 5SCRAPIE AGENT IN MUSCLE - PATTISON I A (1990) VETERINARY RECORD, 20JANUARY 1990, p.68Background1 Dr Pattison, a retired but eminent worker on scrapie for many years inthe AFRC, has pointed out that in one of his experimental studies ofscrapie in goats he found scrapie agent in the biceps femoris (rump)muscle of one animal with clinical disease but not in 2 others withclinical disease and in none with pre-clinical disease. MAFF have basedtheir policy on BSE in regard to meat (beef) on the results of studiesof natural scrapie (ie disease occurring under farm conditions) in bothsheep and goats by Hadlow 1979, 80, 81.Other Infectivity Studies2. These studies on 52 animals by equally eminent scrapie workers(Hadlow et al) revealed no evidence whatever of infectivity in skeletalmuscle from these natural cases either in the pre-clinical or evenclinical stages of disease.It is clear that the pathogenesis of experimental (Pattison) and natural(Hadlow) scrapie may be different and it was therefore considered wiseto base present policy on knowledge of the natural disease.3. Pattison exposed his 14 goats to intracerebral inoculation of thricepassaged scrapie virus (in goats). This may have resulted in strainselection and/or mutation of the natural agent. In contrast Hadlow'sstudy involved natural strains (probably multiple) in a flock with ahigh incidence of disease in which exposure would almost certainly havebeen by the mouth.4. The fact that Hadlow identified no infectivity in muscle by mouseinoculation (whereas some other tissues not normally consumed haddetectable infectivifcy) shows that cross contamination of his tissuesdid not occur. Pattison's experiments were reported about 20 yearsearlier when much less was known about Scrapie. In the interveningperiod the knowledge available to Hadlow on the insensitivity of scrapieagent to heat became available. There is therefore at least thepossibility that Pattison's instruments were not sterilised effectively,thus possibly giving the false positive result for muscle.5. Pattison used a more sensitive model for the detection ofinfectivifcy, namely goats, whereas Hadlow used mice ie necessitatingcrossing the species barrier and possibly reducing the test sensitivity.90/1.19/9.1CVO BSE 1 56. In regard to the choice of species for agent assay, mice (Hadlow),these would be guaranteed free of pre-existing Scrapie infection.Pattison could offer no such guarantee that this was the case in theanimal to which muscle was passaged and disease could have developedfrom exposure from a source other than muscle.7. Pattison did not report that his recipient animals, including the oneinoculated with muscle, were examined by histopathology to confirm thepresence of disease. This is a significant deficit. Clinical diagnosisalone is not acceptable as adequate evidence for the existence of scrapie.8. Even in Pattison's studies only in 1 out of 14 goats was infectivitydetected in muscle and that was in a CLINICAL case. In BSE all clinicalcases are notified and do not enter any food chain.9. The last paragraph of Pattison's letter is illogical. Furthermore,this is no evidence whatsoever that scrapie or BSE is a danger to man.W A WATSON 19 January 1990Private Offices Mr K C Meldrum Mrs E Attridge Mr R Lowson Ms L Austin MrR Bradley90/1.19/9.2
CONSIDER the fact non-documented TSEs have been circulating in the US bovine for decades.CWD in deer and elk for decades and spreading.Scrapie in sheep and goats for decades and spreading.TME in the USA as well.ALL rendered for human/animal consumption for decades in the USA(don't think too much mink have been rendered due to musk gland?)THE lack of TSE surveillance in both animals and MAN.4.5 MILLION ALZHIEMER'S a year with a projected 20 million by 2050.4 studies showing from 3 to 33 percent of those diagnosed with Alzheimer'safter autopsy, actually had CJD (Yale, Duke, PA and a Mexican study).one-in-a-million?amplfication via medical/surgical arena?NOW, the important question would be, how many of those new atypical TSE showing up in cattle and sheepthat are very similar to sporadic CJD, how those tissues, blood and blood products infectivity studies might comeout and IF BSE propagates as both nvCJD and sporadic CJDs, then the blood ban is not complete. either way,the public looses. FOR this reason the damn BSE/nvCJD only theory is more dangerous than the agent itself.YOUR missing 85%+ of all cases, and the agent (however many different phenotypes there maybe)continues to spread and expose. NOW, for a final thought;-------- Original Message --------Subject: TSE REPORT USA September 14, 2004Date: Tue, 14 Sep 2004 14:54:52 -0500From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy To: BSE-L@UNI-KARLSRUHE.DEPrepared by National Center for Animal Health Programs Eradication and Surveillance Team July 31, 2004 SCRAPIE INFECTED AND SOURCE FLOCKS AS of July 31, 2004, there were 71 scrapie infected and source flocks (figure 3). There were 4 new infected and source flocks reported in July (figure 4) with a total of 90 flocks reported for FY 2004 (figure 5). The total infected and source flocks that have been released in FY 2004 are 62 (figure 6), with 15 flocks released in July. The ratio of infected and source flocks released to newly infected and source flocks for FY 2004 = 0.69 : 1. IN ADDITION, AS OF JULY 31, 2004, 282 SCRAPIE CASES HAVE BEEN CONFIRMED and reported by the National Veterinary Services Laboratories (NVSL) in FY 2004, OF WHICH 42 WERE RSSS CASES (figure 7). This includes 60 NEWLY CONFIRMED CASES IN JULY 2004 (figure 8). THIRTEEN cases of scrapie in GOATS have been reported since 1990 (figure 9). ONE NEW GOAT CASE WAS REPORTED IN FY 2004. New infected flocks, source flocks, and flocks released or put on clean-up plans for FY 2004 are depicted in figure 10... snip... Emergency Programs * Imported Belgium/Netherlands Sheep Test Results APRIL 2002 snip... The Western-blot test however cannot differentiate between scrapie and BSE. The only known validated method to differentiate between these two diseases requires a series of mouse bioassay systems, which take at least 23 years for completion. snip... -------- Original Message -------- Subject: Re: AW: [BSE-L] USDA did not test possible mad cows - Dr. Detwiler, what about those sheep? Date: Sun, 13 Jun 2004 11:27:24 -0500 From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy Greetings list members, Thought I should let the list know that Dr. Detwiler kindly replied to my question about the delayed 'atypical' TSE testing in the Vermont sheep and tried to explain what caused the delay. If I interpreted it correctly, seems it was the fault of the U.K. ; -------- Original Message -------- Subject: Sheep Date: Sat, 12 Jun 2004 14:26:04 EDT From: To: Mr. Singeltary. I hope this finds you well. As you are aware I left the USDA last year. I can only update you on the sheep before that time. Contact was established with the UK on doing the bioassay studies. They agreed. However, we were prioritized after their own needs, hence the delay. I am aware that there are now additional labs in Europe running the mouse bioassay strain typing. You will have to contact USDA for further word. Linda Detwiler ========= My reply to Dr. Detwiler; -------- Original Message -------- Subject: Re: Sheep Date: Sat, 12 Jun 2004 13:53:57 -0500 From: "Terry S. Singeltary Sr." To: References: <> hello Dr. Detwiler, thanks for your kind reply. > However, we were prioritized after their own needs, hence the delay. not sure i understand that? > You will have to contact USDA for further word. already done that, and there answer was; >5/20/04 > >Dear Mr. Singeltary, > >The Western blot tests on these animals were completed in April of this >year. That means that we can begin the mouse inoculations. To get the >results of the Western blot tests, you will need to submit a Freedom of >Information Act request through our FOIA office. The FAX number there is >301-734-5941. > >Have a nice day, > >Jim Rogers >APHIS LPA > and with my previous attempts for information via the FOIA through this administration (as you are probably very well aware of) they have all been ignored/refused. so any further attempts would be fruitless i am sure. thanks anyway... kindest regards, Terry wrote: > Mr. Singeltary. snip... TSS ============================================= 12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY snip... A The Present Position with respect to Scrapie A] The Problem Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries. The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep. It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible. Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias" Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously. snip... 76/10.12/4.6 CHRONIC WASTING DISEASE MULTI-STATE GUIDLELINES FOR CHRONIC WASTING DISEASE MANAGEMENT IN FREE-RANGING WHITE-TAILED DEER, MULE DEER AND ELK April 2004 LANCET INFECTIOUS DISEASE JOURNAL Volume 3, Number 8 01 August 2003 Newsdesk Tracking spongiform encephalopathies in North America Xavier Bosch snip... Norman Foster, director of the Cognitive Disorders Clinic at the University of Michigan (Ann Arbor, MI, USA), says that current surveillance of prion disease in people in the USA is inadequate to detect whether CWD is occurring in human beings; adding that, the cases that we know about are reassuring, because they do not suggest the appearance of a new variant of CJD in the USA or atypical features in patients that might be exposed to CWD. However, until we establish a system that identifies and analyses a high proportion of suspected prion disease cases we will not know for sure. The USA should develop a system modelled on that established in the UK, he points out. Ali Samii, a neurologist at Seattle VA Medical Center who recently reported the cases of three hunterstwo of whom were friendswho died from pathologically confirmed CJD, says that at present there are insufficient data to claim transmission of CWD into humans; adding that [only] by asking [the questions of venison consumption and deer/elk hunting] in every case can we collect suspect cases and look into the plausibility of transmission further. Samii argues that by making both doctors and hunters more aware of the possibility of prions spreading through eating venison, doctors treating hunters with dementia can consider a possible prion disease, and doctors treating CJD patients will know to ask whether they ate venison. CDC spokesman Ermias Belay says that the CDC will not be investigating the [Samii] cases because there is no evidence that the men ate CWD-infected meat. He notes that although the likelihood of CWD jumping the species barrier to infect humans cannot be ruled out 100% and that [we] cannot be 100% sure that CWD does not exist in humans& the data seeking evidence of CWD transmission to humans have been very limited. snip... From: "Belay, Ermias" To: Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias" Sent: Monday, September 30, 2002 9:22 AM Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS Dear Sir/Madam, In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD. That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091). Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated. Ermias Belay, M.D. Centers for Disease Control and Prevention > > -----Original Message----- > > From: > > Sent: Sunday, September 29, 2002 10:15 AM > > To:;; ebb8@CDC.GOV > > Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG > > HUNTERS continued...tss Chronic Wasting Disease and Potential Transmission to Humans Ermias D. Belay,*Comments Ryan A. Maddox,* Elizabeth S. Williams, Michael W. Miller,! Pierluigi Gambetti,§ and Lawrence B. Schonberger* *Centers for Disease Control and Prevention, Atlanta, Georgia, USA; University of Wyoming, Laramie, Wyoming, USA; !Colorado Division of Wildlife, Fort Collins, Colorado, USA; and §Case Western Reserve University, Cleveland, Ohio, USA Environmental Sources of Prion Transmission in Mule Deer Michael W. Miller,*Comments Elizabeth S. Williams, N. Thompson Hobbs,! and Lisa L. Wolfe* *Colorado Division of Wildlife, Fort Collins, Colorado, USA; University of Wyoming, Laramie, Wyoming, USA; and !Colorado State University, Fort Collins, Colorado, USA Suggested citation for this article: Miller MW, Williams ES, Hobbs NT, Wolfe LL. Environmental sources of prion transmission in mule deer. Emerg Infect Dis [serial on the Internet]. 2004 Jun [date cited]. Available from: PAGE 25 Transmission Studies Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculam (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in all of these species with the shortest incubation period in the ferret. snip... The occurrence of CWD must be viewed against the context of the locations in which it occurred. It was an incidental and unwelcome complication of the respective wildlife research programmes. Despite its subsequent recognition as a new disease of cervids, therefore justifying direct investigation, no specific research funding was forthcoming. The USDA viewed it as a wildlife problem and consequently not their province! [figures...TSS] snip... VISIT TO USA - DR A E WRATHALL - INFO ON BSE AND SCRAPIE 1. Dr Clark lately of the Scrapie Research Unit, Mission Texas has successfully transmitted ovine and caprine scrapie to cattle. The experimental results have not been published but there are plans to do this. This work was initiated in 1978. A summary of it is:- snip... Gerald Wells: Report of the Visit to USA, April-May 1989 Aguzzi warns of CWD danger The TSE family of diseases also includes chronic wasting disease (CWD) in deer, a condition that has spread in the US in recent years (Nature 416, 569; 2002). Speaking at the Days of Molecular Medicine conference in La Jolla in March, prion expert Adriano Aguzzi issued a strong warning against underestimating this form of TSE. "For more than a decade, the US has by-and-large considered mad cows to be an exquisitely European problem. The perceived need to protect US citizens from this alien threat has even prompted the deferral of blood donors from Europe," he said. "Yet the threat-from-within posed by CWD needs careful consideration, since the evidence that CWD is less dangerous to humans than BSE is less-than-complete. Aguzzi went on to point out that CWD is arguably the most mysterious of all prion diseases. "Its horizontal spread among the wild population is exceedingly efficient, and appears to have reached a prevalence unprecedented even by BSE in the UK at its peak. The pathogenesis of CWD, therefore, deserves a vigorous research effort. Europeans also need to think about this problem, and it would be timely and appropriate to increase CWD surveillance in Europe too." Aguzzi has secured funding from the National Institutes of Health to investigate CWD, and the effort will be lead by Christina Sigurdson in his department at the University of Zurich. KAREN BIRMINGHAM, LONDON This quote from Dr. Gambetti is especially significant since he is the rather cautious TSE researcher under contract with the Centers for Disease Control to examine the brains of individuals who have died of CJD. ----------------- Pierluigi Gambetti, director of the National Prion Disease Pathology Surveillance Center at Case Western Reserve University in Cleveland, said all deer should be tested for chronic wasting disease before any processing is done. "There is no way around it," he said. "Nobody should touch that meat unless it has been tested." -------------------------------------- TRANSMISSIBLE MINK ENCEPHALOPATHY Transmissible Mink Encephalopathy Transmissible mink encephalopathy (TME) is a rare illness that affects the central nervous system of ranch-raised mink. It was first detected in the United States in 1947. Since then, TME outbreaks have been reported in numerous locations worldwide, including the United States, Canada, Finland, Germany, and the republics of the former Soviet Union. snip... The first documented TME outbreak in the United States occurred in 1947 on one ranch in Wisconsin and then on a ranch in Minnesota that had received mink from the Wisconsin ranch. In 1961, TME outbreaks occurred on five ranches in Wisconsin. In 1963, outbreaks occurred in Idaho, Minnesota, and Wisconsin. Epidemiologic data from the Minnesota and Wisconsin outbreaks trace the cases in those States to one common purchased food source. The 1985 Stetsonville Outbreak The most recent TME outbreak occurred on one mink ranch in Stetsonville, WI, in 1985. In the herd of 7,300 adult mink, 60 percent of the animals died. Clinical signs included tail arching, incoordination, and hyperexcitability. At the most advanced stages of the disease, the animals were in trancelike states and eventually died. The outbreak lasted 5 months. Microscopic examination of sections of the brain confirmed the spongelike changes characteristic of TME. Diagnostic tests identified the prion protein. The following year, mink born during the outbreak showed no signs of TME. The late Richard Marsh, a veterinary virologist at the University of Wisconsin who studied the transmission of TME and other TSEs, investigated this outbreak. Marsh learned that the mink were fed a diet composed of fresh meat products from downer cattle and commercial sources of fish, poultry, and cereal. Downer cattle are nonambulatory and cannot rise because they are affected with a condition such as a metabolic disease, broken limbs, or a central nervous system disorder. Marsh theorized that the meat from these downer cattle introduced a TSE agent to the mink in which TME resulted. Although Marshs hypothesis is based on speculation and anecdotal evidence, in 1993 APHIS adjusted its national BSE surveillance program to include testing downer cattle for evidence of a TSE. The brains of more than 20,141 cattle have been examined at APHIS National Veterinary Services Laboratories and other State diagnostic laboratories. Not a single tissue sample has revealed evidence of BSE or another TSE in cattle... snip... BOVINE SPONGIFORM ENCEPHALOPATHY No mad cow results for nearly 500 cows By Steve Mitchell United Press International Published 8/11/2004 11:23 AM WASHINGTON, Aug. 11 (UPI) -- The U.S. Department of Agriculture failed to test for mad cow disease or collect the correct portion of the brain on nearly 500 suspect cows over the past two years -- including some in categories considered most likely to be infected -- according to agency records obtained by United Press International. The testing problems mean it may never be known with certainty whether these animals were infected with the deadly disease. Department officials said these animals were not included in the agency's final tally of mad cow tests, but the records, obtained by UPI under the Freedom of Information Act, indicate at least some of them were counted... snip... -- Steve Mitchell is UPI's Medical Correspondent. E-mail Copyright © 2001-2004 United Press International July 13, 2004 IG Audit Finds Multiple Flaws in Mad Cow Surveillance Plan Rep. Waxman raises questions about the effectiveness and credibility of USDA's response to mad cow disease, citing an audit by the USDA Inspector General that finds systemic deficiencies in the Department's surveillance plan and new evidence that USDA misled the public in the wake of the detection of an infected cow in Washington State. - Letter to USDA IG Draft Audit May 13, 2004 Failure To Test Staggering Cow May Reflect Wider Problems Rep. Waxman raises concerns that the recent failure of USDA to test an impaired cow for BSE may not be an isolated incident, citing the failure of USDA to monitor whether cows condemned for central nervous system symptoms are actually tested for mad cow disease. - Letter to USDA EFSA Scientific Report on the Assessment of the Geographical BSE-Risk (GBR) of the United States of America (USA) Adopted July 2004 (Question N° EFSA-Q-2003-083) [20 August 2004] From: Terry S. Singeltary Sr. [] Sent: Tuesday, July 29, 2003 1:03 PM To: Cc:;; BSE-L Subject: Docket No. 2003N-0312 Animal Feed Safety System [TSS SUBMISSION TO DOCKET 2003N-0312] Greetings FDA, snip... PLUS, if the USA continues to flagrantly ignore the _documented_ science to date about the known TSEs in the USA (let alone the undocumented TSEs in cattle), it is my opinion, every other Country that is dealing with BSE/TSE should boycott the USA and demand that the SSC reclassify the USA BSE GBR II risk assessment to BSE/TSE GBR III 'IMMEDIATELY'. for the SSC to _flounder_ any longer on this issue, should also be regarded with great suspicion as well. NOT to leave out the OIE and it's terribly flawed system of disease surveillance. the OIE should make a move on CWD in the USA, and make a risk assessment on this as a threat to human health. the OIE should also change the mathematical formula for testing of disease. this (in my opinion and others) is terribly flawed as well. to think that a sample survey of 400 or so cattle in a population of 100 million, to think this will find anything, especially after seeing how many TSE tests it took Italy and other Countries to find 1 case of BSE (1 million rapid TSE test in less than 2 years, to find 102 BSE cases), should be proof enough to make drastic changes of this system. the OIE criteria for BSE Country classification and it's interpretation is very problematic. a text that is suppose to give guidelines, but is not understandable, cannot be considered satisfactory. the OIE told me 2 years ago that they were concerned with CWD, but said any changes might take years. well, two years have come and gone, and no change in relations with CWD as a human health risk. if we wait for politics and science to finally make this connection, we very well may die before any decisions or changes are made. this is not acceptable. we must take the politics and the industry out of any final decisions of the Scientific community. this has been the problem from day one with this environmental man made death sentence. some of you may think i am exaggerating, but you only have to see it once, you only have to watch a loved one die from this one time, and you will never forget, OR forgive...yes, i am still very angry... but the transmission studies DO NOT lie, only the politicians and the industry do... and they are still lying to this day...TSS EFSA Scientific Report on the Assessment of the Geographical BSE-Risk (GBR) III of the United States of America (USA) Adopted July 2004 (Question N° EFSA-Q-2003-083) [20 August 2004] THE MAD COW DOWNER THAT WALKED Dave Louthan - Killed the Mad Cow Stanley Prusiner ''nobody has ever ask us to comment'' ''they don't want us to comment'' ''they never ask'' i tried to see Venemon, after Candian cow was discovered with BSE. went to see lyle. after talking with him... absolute ignorance... then thought i should see Venemon... it was clear his entire policy was to get cattle boneless beef prods across the border... nothing else mattered... his aids confirmed this... 5 times i tried to see Venemon, never worked... eventually met with carl rove the political... he is the one that arranged meeting with Venemon... just trying to give you a sense of the distance... healh public safety... was never contacted... yes i believe that prions are bad to eat and you can die from them...END Dr. Stan bashing Ann Veneman - 3 minutes On September 13, 2004, no positive or inconclusive test results were reported. Weekly Summary Cumulative Total from June 1, 2004: 57,064 Research Project: Bovine Spongiform Encephalopathy and Other Transmissible Spongiform Encephalopathies Location: Virus and Prion Diseases of Livestock Title: Experimental Inoculation of Tme, Scrapie, and Cwd to Raccoons (Procyon Lotor) and the Utilization of Raccoons for Strain-Typing of Unknown Tses in the United States Authors item Hamir, Amirali item Miller, Janice item Cutlip, Randall item Stack, M - VSA, WEYBRIDGE, UK item Chaplin, M - VSA, WEYBRIDGE, UK item Bartz, J - CREIGHTON UNIVERSITY item Jenny, A - USDA, APHIS item Williams, E - UNIVERSITY OF WYOMING Submitted to: American Association Of Veterinary Laboratory Diagnosticians Publication Acceptance Date: April 29, 2002 Publication Date: October 17, 2002 Abstract only Technical Abstract: Raccoons (Procyon lotor) are omnivorous and their diet may include carrion. It is, therefore, possible that in the wild they may get exposed to carcasses of animals with transmissible spongiform encephalopathies (TSEs). To determine the susceptibility of raccoons to transmissible mink encephalopathy (TME), scrapie, and chronic wasting disease (CWD), each of these agents was inoculated intracerebrally into a group of 4 kits. Three uninoculated kits served as controls. All raccoons in the TME-inoculated group developed neurologic signs and were euthanized within 6 months post inoculation (PI). In the scrapie-inoculated group, 3 animals became sick and were euthanized between 18 and 22 PI. Although the fourth raccoon in this group did not show any clinical signs, it was euthanized at 24 months PI. At present, 3 years PI, all CWD-infected raccoons are alive and apparently healthy. At necropsy all clinically affected raccoons had extensive microscopic lesions of spongiform encephalopathy and protease-resistant prion protein (PrPres) was detected in the CNS by immunohistochemistry and Western blot. These preliminary findings demonstrate that TME and scrapie can be transmitted to raccoons within 6 months and 2 years, respectively, whereas CWD cannot. Based on these incubation periods, it may be possible to differentiate these 3 TSEs. Such a laboratory model would be relatively simple, fast and inexpensive for strain-typing of unknown TSEs in the United States. CJD/TSE SURVEILLANCE HUMANS USA THE PATHOLOGICAL PROTEIN CHAPTER 14 LAYING ODDS Answering critics like Terry Singeltary, who feels that the U.S. under- counts CJD, Schonberger conceded that the current surveillance system has errors but stated that most of the errors will be confined to the older population. INTRODUCTION CJD screening may miss thousands of cases By Steve Mitchell UPI Medical Correspondent Published 7/21/2003 3:00 PM View printer-friendly version WASHINGTON, July 21 (UPI) -- The federal government's monitoring system for cases of Creutzfeldt-Jakob disease, a fatal human brain illness, could be missing tens of thousands of victims, scientists and consumer advocates have told United Press International. Creutzfeldt-Jakob disease or CJD can be caused by eating beef contaminated with mad cow disease, but the critics assert without a better tracking system it might be impossible to determine whether any CJD cases are due to mad cow or obtain an accurate picture of the prevalence of the disorder in the United States. Beginning in the late 1990s, more than 100 people contracted CJD in the United Kingdom and several European countries after eating beef infected with bovine spongiform encephalopathy -- the clinical name for mad cow disease. No case of mad cow has ever been detected in U.S. cattle and the Centers for Disease Control and Prevention's monitoring system has never detected a case of CJD due to eating contaminated American beef. Nevertheless, critics say, the CDC's system misses many cases of the disease, which currently is untreatable and is always fatal. The first symptoms of CJD typically include memory loss and difficulty keeping balance and walking. As the disease destroys the brain, patients rapidly progress in a matter of months to difficulty with movement, an inability to talk and swallow and, finally, death. Spontaneously-occurring or sporadic CJD is a rare disorder. Only about 300 cases appear nationwide each year, but several studies have suggested the disorder might be more common than thought and as many as tens of thousands of cases might be going unrecognized. Clusters of CJD have been reported in various areas of the United States -- Pennsylvania in 1993, Florida in 1994, Oregon in 1996, New York in 1999-2000 and Texas in 1996. In addition, several people in New Jersey developed CJD in recent years, including a 56 year old woman who died on May 31, 2003. Although in some instances, a mad cow link was suspected, all of the cases ultimately were classified as sporadic. People who develop CJD from eating mad-cow-contaminated beef have been thought to develop a specific form of the disorder called variant CJD. But new research, released last December, indicates the mad cow pathogen can cause both sporadic CJD and the variant form. "Now people are beginning to realize that because something looks like sporadic CJD they can't necessarily conclude that it's not linked to (mad cow disease)," said Laura Manuelidis, section chief of surgery in the neuropathology department at Yale University, who conducted a 1989 study that found 13 percent of Alzheimer's patients actually had CJD. Several studies, including Manuelidis', have found that autopsies reveal 3 percent to 13 percent of patients diagnosed with Alzheimer's or dementia actually suffered from CJD. Those numbers might sound low, but there are 4 million Alzheimer's cases and hundreds of thousands of dementia cases in the United States. A small percentage of those cases could add up to 120,000 or more CJD victims going undetected and not included in official statistics. Experiences in England and Switzerland -- two countries that discovered mad cow disease in their cattle -- have heightened concerns about the possibility some cases of sporadic CJD are due to consuming mad-cow-tainted beef. Both countries have reported increases in sporadic CJD since mad cow was first detected in British herds in 1986. Switzerland discovered last year its CJD rate was twice that of any other country in the world. Switzerland had been seeing about eight to 11 cases per year from 1997 to 2000. Then the incidence more than doubled, to 19 cases in 2001 and 18 cases in 2002. The CDC says the annual rate of CJD in the United States is one case per million people, but the above studies suggest the true prevalence of CJD is not known, Manuelidis told UPI. Diagnosing CJD or Alzheimer's is difficult because no test exists that can identify either disease in a living patient with certainty. So physicians must rely on the patient's symptoms to determine which illness might be present. Sometimes, however, the symptoms of one disease can appear similar to the other disorder. The only way to determine the disease conclusively is to perform an autopsy on the brain after death. Unfortunately, although autopsies once were performed on approximately half of all corpses, the frequency has dropped to 15 percent or less in the United States. The National Center for Health Statistics -- a branch of the CDC -- stopped collecting autopsy data in 1995. "If we don't do autopsies and we don't look at people's brains ... we have no idea about what is the general prevalence of these kinds of infections and (whether) it is changing," Manuelidis said. At the same time autopsies have been declining, the number of deaths attributed to Alzheimer's has increased more than 50-fold since 1979, going from 857 deaths then to nearly 50,000 in 2000. Though it is unlikely the dramatic increase in Alzheimer's is due entirely to misdiagnosed CJD cases, it "could explain some of the increase we've seen," Manuelidis said. "Neurodegenerative disease and Alzheimer's disease have become a wastebasket" for mental illness in the elderly that is difficult to diagnose conclusively, she said. "In other words, what people call Alzheimer's now is more broad than what people used to call it, and that has the possibility of encompassing more diseases -- including CJD." The autopsy studies that found undiagnosed CJD cases raise the question of whether the United States "already has an undetected epidemic here," Jeff Nelson, director of, a vegetarian advocacy Web site, told UPI. "What's the source of that?" Nelson asked. "Could it be the same source of encephalitis we saw in minks?" Nelson referred to an outbreak of a mad-cow-type disorder in minks in Wisconsin in the 1980s. The origin was traced back to the animals' diet, which included parts of so-called downer cattle -- sick cows that are unable to stand, which often indicates a neurological disease, including mad cow. The mink disease raised concerns about whether U.S. cattle were carrying a mad-cow-like pathogen even prior to the U.K. epidemic that began in 1986. Andrew Monjan, chief of the neuropsychology of aging program at the National Institute of Aging -- part of the National Institutes of Health in Bethesda, Md. -- acknowledged there has been an increase in U.S. Alzheimer's cases. However, he told UPI, this probably is due to the aging of the population -- as people grow older, they develop a higher risk of developing Alzheimer's. "There's been no change in the number of CJD cases in the country and there has been clearly a tracking of the unusual cases of CJD" that could be due to mad cow disease, Monjan said. However, Terry Singletary, coordinator of CJD Watch -- an organization founded to track CJD cases -- says efforts to track the disease have been close to nonexistent. For example, only 12 states require such reports. Therefore, many cases might be going undetected, unreported or misdiagnosed. If more states made CJD a reportable illness, there would be more clusters detected across the United States, said Singletary, who became involved with CJD advocacy after his mother died from a form of CJD known as Heidenhain variant. In the 18-year period between 1979 and 1996, he noted, the country saw a jump from one case of sporadic CJD in people under the age of 30 -- a warning sign for a link to mad cow because nearly all of the U.K. victims were 30 years of age or younger -- to five cases in five years between 1997 and 2001. "That represents a substantial blip," he told UPI. Singletary also said there have been increases in sporadic CJD in France, Germany and Italy, all of which have detected mad cow disease in their cattle. So far, the CDC has refused to impose a national requirement that physicians and hospitals report cases of the disease. The agency has not chosen to make CJD a reportable disease because "making it reportable is not necessarily directly helpful in surveillance because in some states where it's reportable you may not get the physician to report it," said Dr. Ermias Belay, CDC's medical epidemiologist working on CJD. Instead, the agency relies on other methods, including death certificates and urging physicians to send suspicious cases to the National Prion Disease Pathology Surveillance Center at Case Western Reserve University in Cleveland, which is funded by the CDC. However, because autopsies generally are not done, if a CJD case is misdiagnosed as Alzheimer's or dementia, a correct diagnosis might never be determined and therefore the cause of death listed on a death certificate might be inaccurate. Belay told UPI he discounted this possibility. It is unlikely to happen, he said, because it is easy to distinguish CJD from Alzheimer's -- the two conditions display different symptoms. Manuelidis disagreed. It can be quite difficult to determine accurately if a patient has CJD, as evidenced by her study, in which respected and competent neurologists and psychiatrists at Yale originally diagnosed patients with Alzheimer's, yet were wrong at least 13 percent of the time. Another study conducted at the University of Pennsylvania, which found 6 percent of dementia patients actually were suffering from CJD, supports the difficulty in distinguishing the illnesses correctly. The U. Penn. researchers concluded: "These results show that in patients with a clinical diagnosis of dementia, the etiology (cause) cannot be accurately predicted during life." In addition, the NPDPSC sees less than half of all the CJD cases each year, so the CDC's investigational system not only is missing many of the misdiagnosed CJD cases, it also is not conducting autopsies on most of the detected cases. Belay said the CDC follows up on all cases of CJD that occur in people under age 55, as these could be linked to variant -- mad-cow-related -- CJD. But so far, all have turned out to be sporadic forms of the disease. About 30 cases of the disorder occur each year in the United States in this age group, while the remaining 270 or so are older. The case of Carrie Mahan -- a Philadelphia woman who developed a brain disorder that appeared to be CJD and died from it in 2000 at the age of 29 -- illustrates just how difficult it can be to diagnose the disease. Mahan's physician, Dr. Peter Crinos of the University of Pennsylvania Medical Center, ruled out other disorders and felt certain the young woman had died of CJD, a concern that raised the possibility of a link to mad cow disease because of her young age. When neuropathologist Nicholas Gonatas, who had seen CJD before, examined Mahan's brain after her death, he, likewise, was confident he detected the microscopic, sponge-like holes caused by the disease. But when he sent brain samples to the NPDPSC, the results came back negative. Gonatas, convinced the surveillance center's finding was erroneous, sent off two more samples, only to have them both come back negative. Subsequent research, however, has shown the test used by the surveillance center cannot rule out CJD, said Crinos, an assistant professor of neurology. "There's no question that Carrie had a spongiform encephalopathy," Crinos said, but added although it appeared to be CJD, it is difficult if not impossible to say if it was due to mad cow disease. Crinos told UPI until the CDC implements a better tracking system, a lot of questions will remain about CJD and cases like Carrie Mahan's. One central question: Why are cases of what is presumed to be a rare disease popping up in clusters in certain areas of the country? Crinos said the clustering suggests an environmental or food-borne cause, but so far, "No one knows the answer to that." Copyright © 2001-2003 United Press International THE EPIDEMIOLOGY OF CJD RG WILL 1984 (182 PAGES) snip... One reason for this was the _inaccuracy_ in coding of cases correctly certified as CJD Coding is carried out by staff who are not medically qualified and it is not surprising that coding errors occur in the processing of large numbers of certificates. In 1982, 12,000 certificates per week were processed at the office of population censuses and surveys bu 15 coders and 6 checkers (Alderson et al., 1983). The occurrence of both inter- and intra-observer coding errors has been described (Curb et al., 1983) and the _inaccuracies_ of BOTH certification and coding discovered in this study _support_ the introduction of a more accurate system of death certificates and a more detailed and specific coding system... snip... RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States Email Terry S. Singeltary: I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc? 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 deer and elk, or any of the 20+ strains of Scrapies in sheep or goats? i get dizzy thinking of the different scenerio's. what would the human TSEs from these species look like?HOUND STUDY AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease. snip... FINAL important factor, the recent finding of the incubation period of 38 years from a _small_ dose of human growth hormone; snip... 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). snip...Creutzfeldt-Jakob disease 38 years after diagnostic use of human growth hormone SO my quesion is, how low is 'low' in quantifing the infectious dose in vCJD, comparing to _all_ sporadic CJDs, from the many different potential routes, sources, and infectivity dose? HOW many more do we expose while waiting for confirmation? Thank You, I am sincerely, Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
Docket No, 04-047-l Regulatory Identification No. (RIN) 091O-AF46 NEW BSE SAFEGUARDS (comment submission) No. 03-080-1 -- USDA ISSUES PROPOSED RULE TO ALLOW LIVE ANIMAL

Docket No. 2003N-0312 Animal Feed Safety System [TSS SUBMISSION]

Docket Management Docket: 02N-0273 - Substances Prohibited From Use in

Animal Food or Feed; Animal Proteins Prohibited in Ruminant Feed

Comment Number: EC -10

Accepted - Volume 2



File Format: PDF/Adobe Acrobat -

Page 1. J Freas, William From: Sent: To: Subject: Terry S. Singeltary

Sr. [] Monday, January 08,200l 3:03 PM freas ...

Asante/Collinge et al, that BSE transmission to the 129-methionine

genotype can lead to an alternate phenotype that is indistinguishable

from type 2 PrPSc, the commonest _sporadic_ CJD;

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

[PDF] Appendices to PL107-9 Inter-agency Working Group Final Report 1-1
File Format: PDF/Adobe Acrobat - View as HTML
Agent, Weapons of Mass Destruction Operations Unit Federal Bureau of
those who provided comments in response to Docket No. ...
Meager 8/18/01 Terry S. Singeltary Sr ...

Docket No. 2003N-0312 Animal Feed Safety System [TSS SUBMISSION
TO DOCKET 2003N-0312]

# Docket No: 02-088-1 RE-Agricultural Bioterrorism Protection Act of
TSS 1/27/03 (0)

Docket Management

Docket: 02N-0276 - Bioterrorism Preparedness; Registration of Food Facilities, Section 305
Comment Number: EC-254 [TSS SUBMISSION]

Dockets Entered On October 2, 2003 Table of Contents, Docket #,
Title, 1978N-0301,

OTC External Analgesic Drug Products, ... EMC 7, Terry S. Singeltary Sr.
Vol #: 1, ...

Daily Dockets Entered on 02/05/03

DOCKETS ENTERED on 2/5/03. ... EMC 4 Terry S. Singeltary Sr. Vol#: 2.
... Vol#: 1.

03N-0009 Federal Preemption of State & Local Medical Device Requireme. ...

Docket Management

Docket: 02N-0370 - Neurological Devices; Classification of Human Dura Mater

Comment Number: EC -1

Accepted - Volume 1

Daily Dockets - 04/10/03

... 00D-1662 Use of Xenotransplantation Products in Humans.
EMC 98 Terry S. Singeltary Sr. Vol#: 3. 01F ... - 05-20-2003
- Cached

Guidance for Industry: Use of Material From Deer and Elk In Animal Feed

Terry S. Singeltary Sr.
Vol #:

Guidance for Industry: Use of Material From Deer and Elk In Animal Feed

Terry S. Singeltary Sr.
Vol #:

Guidance for Industry: Use of Material From Deer and Elk In Animal Feed

Terry S. Singeltary Sr.
Vol #:

01N-0423 Substances Prohibited from use in animal food/Feed Ruminant

APE 5 National Renderers Association, Inc. Vol#: 2

APE 6 Animal Protein Producers Industry Vol#: 2

APE 7 Darling International Inc. Vol#: 2

EMC 1 Terry S. Singeltary Sr. Vol#: 3


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