also, there is just as much need to be concerned with sheep scrapie as with BSE and or BASE in cattle. the myth that sheep scrapie will not transmit to humans is just that, a myth. ..........
----- Original Message -----
From: "Terry S. Singeltary Sr." <
[email protected]>
To: "Jim Woodward" <
[email protected]>; "'Shu Chen'" <
[email protected]>
Sent: Sunday, December 18, 2005 9:51 AM
Subject: Re: Human resistance to scrapie?
> Greetings Jim and Dr. Chen,
>
>
> as far as amplification and transmission, this is not rocket science, just
> junk science and or denial $ ;-)
> there are plenty of references in science 'sound science' to show that
> indeed the potential for scrapie transmission
> to man (who knows which strain of scrapie or all of them) is as real is as
> BSE or CWD. to continue with the myth
> that scrapie will not transmit to humans, under the pretence of 200 years of
> scrapie and no documented transmision
> to humans, is like saying that we have never had BSE/TSE in USA cattle herds
> until Dec. 2003. it's simply not true.
> the truth is they never looked until then, thus it was never documented. two
> different things, not here and not documented.
>
>
> but just look at the science just off the top of my head here, and then try
> referencing scrapie transmission studies to
> humans and or primates to dispute it. ......TSS
>
>
> Gerald Wells: Report of the Visit to USA, April-May 1989
>
> snip...
>
> The general opinion of those present was that BSE, as an
> overt disease phenomenon, _could exist in the USA, but if it did,
> it was very rare. The need for improved and specific surveillance
> methods to detect it as recognised...
>
> snip...
>
> It is clear that USDA have little information and _no_ regulatory
> responsibility for rendering plants in the US...
>
> snip...
>
> 3. Prof. A. Robertson gave a brief account of BSE. The US approach
> was to accord it a _very low profile indeed_. Dr. A Thiermann showed
> the picture in the ''Independent'' with cattle being incinerated and thought
> this was a fanatical incident to be _avoided_ in the US _at all costs_...
>
> snip...
>
> http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf
>
> To be published in the Proceedings of the
> Fourth International Scientific Congress in
> Fur Animal Production. Toronto, Canada,
> August 21-28, 1988
>
> Evidence That Transmissible Mink Encephalopathy
> Results from Feeding Infected Cattle
>
> R.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
> 53092
>
> ABSTRACT
> Epidemiologic investigation of a new incidence of
> transmissible mink encephalopathy (TME) in Stetsonville, Wisconsin
> suggests that the disease may have resulted from feeding infected
> cattle to mink. This observation is supported by the transmission of
> a TME-like disease to experimentally inoculated cattle, and by the
> recent report of a new bovine spongiform encephalopathy in
> England.
>
> INTRODUCTION
>
> Transmissible mink encephalopathy (TME) was first reported in 1965 by
> Hartsough
> and Burger who demonstrated that the disease was transmissible with a long
> incubation
> period, and that affected mink had a spongiform encephalopathy similar to
> that found in
> scrapie-affecied sheep (Hartsough and Burger, 1965; Burger and Hartsough,
> 1965).
> Because of the similarity between TME and scrapie, and the subsequent
> finding that the
> two transmissible agents were indistinguishable (Marsh and Hanson, 1969), it
> was
> concluded that TME most likely resulted from feeding mink scrapie-infecied
> sheep.
> The experimental transmission of sheep scrapie to mink (Hanson et al., 1971)
> confirmed the close association of TME and scrapie, but at the same time
> provided
> evidence that they may be different. Epidemiologic studies on previous
> incidences of
> TME indicated that the incubation periods in field cases were between six
> months and
> one year in length (Harxsough and Burger, 1965). Experimentally, scrapie
> could not be
> transmitted to mink in less than one year.
> To investigate the possibility that TME may be caused by a (particular
> strain of
> scrapie which might be highly pathogenic for mink, 21 different strains of
> the scrapie
> agent, including their sheep or goat sources, were inoculated into a total
> of 61 mink.
> Only one mink developed a progressive neurologic disease after an incubation
> period of
> 22 mon..s (Marsh and Hanson, 1979). These results indicated that TME was
> either caused
> by a strain of sheep scrapie not yet tested, or was due to exposure to a
> scrapie-like agent
> from an unidentified source.
>
> OBSERVATIONS AND RESULTS
>
> A New Incidence of TME. In April of 1985, a mink rancher in Stetsonville,
> Wisconsin
> reported that many of his mink were "acting funny", and some had died. At
> this time, we
> visited the farm and found that approximately 10% of all adult mink were
> showing
> typical signs of TME: insidious onset characterized by subtle behavioral
> changes, loss of
> normal habits of cleanliness, deposition of droppings throughout the pen
> rather than in a
> single area, hyperexcitability, difficulty in chewing and swallowing, and
> tails arched over
> their _backs like squirrels. These signs were followed by progressive
> deterioration of
> neurologic function beginning with locomoior incoordination, long periods of
> somnolence
> in which the affected mink would stand motionless with its head in the
> corner of the
> cage, complete debilitation, and death. Over the next 8-10 weeks,
> approximately 40% of
> all the adult mink on the farm died from TME.
> Since previous incidences of TME were associated with common or shared
> feeding
> practices, we obtained a careful history of feed ingredients used over the
> past 12-18
> months. The rancher was a "dead stock" feeder using mostly (>95%) downer or
> dead dairy
> cattle and a few horses. Sheep had never been fed.
>
> Experimental Transmission. The clinical diagnosis of TME was confirmed by
> histopaihologic examination and by experimental transmission to mink after
> incubation
> periods of four months. To investigate the possible involvement of cattle in
> this disease
> cycle, two six-week old castrated Holstein bull calves were inoculated
> intracerebrally
> with a brain suspension from affected mink. Each developed a fatal
> spongiform
> encephalopathy after incubation periods of 18 and 19 months.
>
> DISCUSSION
> These findings suggest that TME may result from feeding mink infected cattle
> and
> we have alerted bovine practitioners that there may exist an as yet
> unrecognized
> scrapie-like disease of cattle in the United States (Marsh and Hartsough,
> 1986). A new
> bovine spongiform encephalopathy has recently been reported in England
> (Wells et al.,
> 1987), and investigators are presently studying its transmissibility and
> possible
> relationship to scrapie. Because this new bovine disease in England is
> characterized by
> behavioral changes, hyperexcitability, and agressiveness, it is very likely
> it would be
> confused with rabies in the United Stales and not be diagnosed. Presently,
> brains from
> cattle in the United States which are suspected of rabies infection are only
> tested with
> anti-rabies virus antibody and are not examined histopathologically for
> lesions of
> spongiform encephalopathy.
> We are presently pursuing additional studies to further examine the possible
> involvement of cattle in the epidemiology of TME. One of these is the
> backpassage of
> our experimental bovine encephalopathy to mink. Because (here are as yet no
> agent-
> specific proteins or nucleic acids identified for these transmissible
> neuropathogens, one
> means of distinguishing them is by animal passage and selection of the
> biotype which
> grows best in a particular host. This procedure has been used to separate
> hamster-
> adapted and mink-udapted TME agents (Marsh and Hanson, 1979). The
> intracerebral
> backpassage of the experimental bovine agent resulted in incubations of only
> four months
> indicating no de-adaptation of the Stetsonville agent for mink after bovine
> passage.
> Mink fed infected bovine brain remain normal after six months. It will be
> essential to
> demonstrate oral transmission fiom bovine to mink it this proposed
> epidemiologic
> association is to be confirmed.
>
> ACKNOWLEDGEMENTS
> These studies were supported by the College of Agricultural and Life
> Sciences,
> University of Wisconsin-Madison and by a grant (85-CRCR-1-1812) from the
> United
> States Department of Agriculture. The authors also wish to acknowledge the
> help and
> encouragement of Robert Hanson who died during the course of these
> investigations.
>
> REFERENCES
> Burger, D. and Hartsough, G.R. 1965. Encephalopathy of mink. II.
> Experimental and
> natural transmission. J. Infec. Dis. 115:393-399.
> Hanson, R.P., Eckroade, R.3., Marsh, R.F., ZuRhein, C.M., Kanitz, C.L. and
> Gustatson,
> D.P. 1971. Susceptibility of mink to sheep scrapie. Science 172:859-861.
> Hansough, G.R. and Burger, D. 1965. Encephalopathy of mink. I.
> Epizoociologic and
> clinical observations. 3. Infec. Dis. 115:387-392.
> Marsh, R.F. and Hanson, R.P. 1969. Physical and chemical properties of
> the
> transmissible mink encephalopathy agent. 3. ViroL 3:176-180.
> Marsh, R.F. and Hanson, R.P. 1979. On the origin of transmissible mink
> encephalopathy. In Hadlow, W.J. and Prusiner, S.P. (eds.) Slow
> transmissible
> diseases of the nervous system. Vol. 1, Academic Press, New York, pp
> 451-460.
> Marsh, R.F. and Hartsough, G.R. 1986. Is there a scrapie-like disease in
> cattle?
> Proceedings of the Seventh Annual Western Conference for Food Animal
> Veterinary
> Medicine. University of Arizona, pp 20.
> Wells, G.A.H., Scott, A.C., Johnson, C.T., Cunning, R.F., Hancock, R.D.,
> Jeffrey, M.,
> Dawson, M. and Bradley, R. 1987. A novel progressive spongiform
> encephalopathy
> in cattle. Vet. Rec. 121:419-420.
>
> MARSH
>
> http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf
>
>
>
>
> 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
>
> http://www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf
>
>
> Like lambs to the slaughter
> 31 March 2001
> Debora MacKenzie
> Magazine issue 2284
> What if you can catch old-fashioned CJD by eating meat from a sheep infected
> with scrapie?
> FOUR years ago, Terry Singeltary watched his mother die horribly from a
> degenerative brain disease. Doctors told him it was Alzheimer's, but
> Singeltary was suspicious. The diagnosis didn't fit her violent symptoms,
> and he demanded an autopsy. It showed she had died of sporadic
> Creutzfeldt-Jakob disease.
>
> Most doctors believe that sCJD is caused by a prion protein deforming by
> chance into a killer. But Singeltary thinks otherwise. He is one of a number
> of campaigners who say that some sCJD, like the variant CJD related to BSE,
> is caused by eating meat from infected animals. Their suspicions have
> focused on sheep carrying scrapie, a BSE-like disease that is widespread in
> flocks across Europe and North America.
>
> Now scientists in France have stumbled across new evidence that adds weight
> to the campaigners' fears. To their complete surprise, the researchers found
> that one strain of scrapie causes the same brain damage in ...
>
> The complete article is 889 words long.
>
> full text;
>
> http://www.newscientist.com/article.ns?id=mg16922840.300
>
>
>
> Neurobiology
> Adaptation of the bovine spongiform encephalopathy agent to primates and
> comparison with Creutzfeldt- Jakob disease: Implications for human health
> Corinne Ida Lasmézas*,, Jean-Guy Fournier*, Virginie Nouvel*, Hermann Boe*,
> Domíníque Marcé*, François Lamoury*, Nicolas Kopp, Jean-Jacques Hauw§, James
> Ironside¶, Moira Bruce, Dominique Dormont*, and Jean-Philippe Deslys*
> * Commissariat à l'Energie Atomique, Service de Neurovirologie, Direction
> des Sciences du Vivant/Département de Recherche Medicale, Centre de
> Recherches du Service de Santé des Armées 60-68, Avenue du Général Leclerc,
> BP 6, 92 265 Fontenay-aux-Roses Cedex, France; Hôpital Neurologique Pierre
> Wertheimer, 59, Boulevard Pinel, 69003 Lyon, France; § Laboratoire de
> Neuropathologie, Hôpital de la Salpêtrière, 83, Boulevard de l'Hôpital,
> 75013 Paris, France; ¶ Creutzfeldt-Jakob Disease Surveillance Unit, Western
> General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom; and
> Institute for Animal Health, Neuropathogenesis Unit, West Mains Road,
> Edinburgh EH9 3JF, United Kingdom
>
> Edited by D. Carleton Gajdusek, Centre National de la Recherche
> Scientifique, Gif-sur-Yvette, France, and approved December 7, 2000
> (received for review October 16, 2000)
>
>
> Abstract
> Top
> Abstract
> Introduction
> Materials and Methods
> Results
> Discussion
> Conclusions
> References
> There is substantial scientific evidence to support the notion that bovine
> spongiform encephalopathy (BSE) has contaminated human beings, causing
> variant Creutzfeldt-Jakob disease (vCJD). This disease has raised concerns
> about the possibility of an iatrogenic secondary transmission to humans,
> because the biological properties of the primate-adapted BSE agent are
> unknown. We show that (i) BSE can be transmitted from primate to primate by
> intravenous route in 25 months, and (ii) an iatrogenic transmission of vCJD
> to humans could be readily recognized pathologically, whether it occurs by
> the central or peripheral route. Strain typing in mice demonstrates that the
> BSE agent adapts to macaques in the same way as it does to humans and
> confirms that the BSE agent is responsible for vCJD not only in the United
> Kingdom but also in France. The agent responsible for French iatrogenic
> growth hormone-linked CJD taken as a control is very different from vCJD but
> is similar to that found in one case of sporadic CJD and one sheep scrapie
> isolate. These data will be key in identifying the origin of human cases of
> prion disease, including accidental vCJD transmission, and could provide
> bases for vCJD risk assessment.
>
>
> http://www.pnas.org/cgi/content/full/041490898v1TSS
>
>
> 1: Cent Eur J Public Health 2003 Mar;11(1):19-22
>
> Analysis of unusual accumulation of Creutzfeldt-Jakob disease cases
> in Orava and Liptov regions (northern Slovak focus) 1983-2000.
>
> Mad'ar R, Maslenova D, Ranostajova K, Straka S, Baska T.
>
> Institute of Epidemiology, Jessenius Faculty of Medicine, Comenius
> University, Sklabinska 26, Martin, 037 53 Slovakia.
[email protected]
>
> While familial cases of Creutzfeldt-Jakob disease are extremely rare
> all over the world, 3 familial clusters were observed between
> 1983-2000 in a relatively small area situated in the North of
> Slovakia. Prevalence of CJD in this area exceeded the overall
> prevalence in Slovakia more than 8 times. The majority of CJD
> patients admitted consuming sheep brain. Most patients lived in
> small secluded villages with rather common familial intermarriage.
> CJD affected both sexes equally. All patients were prior to the
> disease mentally normal individuals. Shortly after the onset of CJD
> their mental status deteriorated remarkably with an average survival
> rate of 3.6 months.
>
> PMID: 12690798
>
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ui
> ds=12690798&dopt=Abstract
>
> ------------------------------------------------------------------------
>
> 1: Eur J Epidemiol 1991 Sep;7(5):520-3
> <http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?db=PubMed&cmd=Display&dopt
> =pubmed_pubmed&from_uid=1761109>
>
>
> "Clusters" of CJD in Slovakia: the first laboratory evidence of scrapie.
>
> Mitrova E, Huncaga S, Hocman G, Nyitrayova O, Tatara M.
>
> Institute of Preventive and Clinical Medicine, Bratislava.
>
> Epidemic-like occurrence of Creutzfeldt-Jakob disease was observed in
> 1987 in Slovakia (Orava). Search for the cause of CJD focus indicated a
> coincidence of genetic and environmental risks in clustering patients.
> Since Spongiform Encephalopathies might be transmitted orally, (Bovine
> Spongiform Encephalopathy), the possibility of zoonotic source of CJD
> cases in Orava was also considered. A deficient knowledge about the
> occurrence of scrapie in Slovakia stimulated an examination of sheep
> with signs of CNS disorders in two flocks of Valasky breed in Orava. In
> one flock, neurohistopathological examination revealed in sheep brains
> lesions characteristic for scrapie. Frozen brain tissue of these animals
> were used for the detection of scrapie associated fibrils. They were
> found in 2 animals from the same flock. This is the first laboratory
> confirmation of scrapie in Czecho-Slovakia. The possible epidemiological
> and economical implications are emphasized.
>
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ui
> ds=1761109&dopt=Abstract
>
>
> STATEMENT OF DR HELEN GRANT MD FRCP
> ISSUED 13/05/1999
>
> BSE INQUIRY
>
> http://www.bseinquiry.gov.uk/files/ws/s410.pdf
> http://www.bseinquiry.gov.uk/files/ws/s410x.pdf
>
> http://www.bseinquiry.gov.uk/evidence/ws/ws8.htm
>
> CWD to CJD in humans (why not?), as easy as BSE/Scrapie;
>
> The EMBO Journal, Vol. 19, No. 17 pp. 4425-4430, 2000
> © European Molecular Biology Organization
>
> Evidence of a molecular barrier limiting
> susceptibility of humans, cattle and sheep to
> chronic wasting disease
>
> G.J. Raymond1, A. Bossers2, L.D. Raymond1, K.I. O?Rourke3,
> L.E. McHolland4, P.K. Bryant III4, M.W. Miller5, E.S. Williams6, M.
> Smits2
> and B. Caughey1,7
>
> 1NIAID/NIH Rocky Mountain Laboratories, Hamilton, MT 59840,
> 3USDA/ARS/ADRU, Pullman, WA 99164-7030, 4USDA/ARS/ABADRL,
> Laramie, WY 82071, 5Colorado Division of Wildlife, Wildlife Research
> Center, Fort Collins, CO 80526-2097, 6Department of Veterinary Sciences,
> University of Wyoming, Laramie, WY 82070, USA and 2ID-Lelystad,
> Institute for Animal Science and Health, Lelystad, The Netherlands
> 7Corresponding author e-mail:
[email protected] Received June 7, 2000;
> revised July 3, 2000; accepted July 5, 2000.
>
> Abstract
>
> Chronic wasting disease (CWD) is a transmissible
> spongiform encephalopathy (TSE) of deer and elk,
> and little is known about its transmissibility to other
> species. An important factor controlling
> interspecies TSE susceptibility is prion protein (PrP)
> homology between the source and recipient
> species/genotypes. Furthermore, the efficiency with which
> the protease-resistant PrP (PrP-res) of one
> species induces the in vitro conversion of the normal PrP
> (PrP-sen) of another species to the
> protease-resistant state correlates with the cross-species
> transmissibility of TSE agents. Here we
> show that the CWD-associated PrP-res (PrPCWD) of cervids
> readily induces the conversion of recombinant cervid PrP-sen
> molecules to the protease-resistant state in accordance
> with the known transmissibility of CWD between cervids. In contrast,
> PrPCWD-induced conversions of human and bovine PrP-sen were
> much less efficient, and conversion of ovine PrP-sen was
> intermediate. These results demonstrate a barrier at the
> molecular level that should limit the susceptibility of these non-cervid
> species to CWD.
>
> snip...
>
> Clearly, it is premature to draw firm conclusions about CWD
> passing naturally into humans, cattle and sheep, but the present
> results suggest that CWD transmissions to humans would be as
> limited by PrP incompatibility as transmissions of BSE or sheep
> scrapie to humans. Although there is no evidence that sheep
> scrapie has affected humans, it is likely that BSE has caused variant
> CJD in 74 people (definite and probable variant CJD cases to
> date according to the UK CJD Surveillance Unit). Given the
> presumably large number of people exposed to BSE infectivity,
> the susceptibility of humans may still be very low compared with
> cattle, which would be consistent with the relatively inefficient
> conversion of human PrP-sen by PrPBSE. Nonetheless, since
> humans have apparently been infected by BSE, it would seem prudent
> to take reasonable measures to limit exposure of humans
> (as well as sheep and cattle) to CWD infectivity as has been
> recommended for other animal TSEs.
>
> snip...
>
> http://www.emboj.org/current.shtml
>
> Scrapie to Humans USA?
>
>
> 1: Neuroepidemiology. 1985;4(4):240-9.
>
> Sheep consumption: a possible source of spongiform encephalopathy in humans.
>
> Davanipour Z, Alter M, Sobel E, Callahan M.
>
> A fatal spongiform encephalopathy of sheep and goats (scrapie) shares many
> characteristics with Creutzfeldt-Jakob disease (CJD), a similar dementing
> illness of humans. To investigate the possibility that CJD is acquired by
> ingestion of contaminated sheep products, we collected information on
> production, slaughtering practices, and marketing of sheep in Pennsylvania.
> The study revealed that sheep were usually marketed before central nervous
> system signs of scrapie are expected to appear; breeds known to be
> susceptible to the disease were the most common breeds raised in the area;
> sheep were imported from other states including those with a high frequency
> of scrapie; use of veterinary services on the sheep farms investigated and,
> hence, opportunities to detect the disease were limited; sheep producers in
> the area knew little about scrapie despite the fact that the disease has
> been reported in the area, and animal organs including sheep organs were
> sometimes included in processed food. Therefore, it was concluded that in
> Pennsylvania there are some 'weak links' through which scrapie-infected
> animals could contaminate human food, and that consumption of these foods
> could perhaps account for spongiform encephalopathy in humans. The weak
> links observed are probably not unique to Pennsylvania.
>
>
>
> http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list
> _uids=3915057&dopt=Abstract
>
>
> Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to
> nonhuman primates.
>
> Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
>
> Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of
> sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that
> were exposed to the infectious agents only by their nonforced consumption of
> known infectious tissues. The asymptomatic incubation period in the one
> monkey exposed to the virus of kuru was 36 months; that in the two monkeys
> exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months,
> respectively; and that in the two monkeys exposed to the virus of scrapie
> was 25 and 32 months, respectively. Careful physical examination of the
> buccal cavities of all of the monkeys failed to reveal signs or oral
> lesions. One additional monkey similarly exposed to kuru has remained
> asymptomatic during the 39 months that it has been under observation.
>
> PMID: 6997404
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ui
> ds=6997404&dopt=Abstract
>
>
>
>
> Approved-By: tom <
[email protected]>
> Message-ID: <v0401170fb3b92015c5cd@[12.7.122.68]>
> Date: Mon, 19 Jul 1999 11:21:25 -0800
> Reply-To: Bovine Spongiform Encephalopathy <
[email protected]>
> Sender: Bovine Spongiform Encephalopathy <
[email protected]>
> From: tom <
[email protected]>
> Subject: iatrogenic scrapie from sheep dura mater?
> Someone kindly sent me the full text of a very curious 1993 Lancet article.
> This is available from the Ovid service -- Lancet itself ironically does not
> offer an electronic version this far back.
>
> An orthopaedic surgeon employed by the lyodura company [Braun Melsungen]
> extracted dura mater from sheep and human cadavers and came down with fast
> CJD 22 years later. The ratio of sheep to human dura mater he collected
> was150 sheep to 12 humans. Apparently the surgeon and the sheep were German.
> Scrapie has long been present in Germany but reported levels are very low,
> about a flock a year has to be destroyed. I am not aware of any high
> sensitivity tests or random screening every being used in Germany to assess
> the levels of preclinical animals.
>
> This raises the question, what did the lyodura company do with so much dura
> mater from sheep? The market for specialty surgical products was
> overwelmingly in humans in 1968. The Lancet article only says it was for
> research -- but in what species? Perhaps dura mater gives an immune
> response across species after processing, ruling out its use in humans.
> But as far as I know, blood type or other genetic differences do not matter
> within humans, ie, there is no tissue matching with dura mater.
>
> I always wondered how CJD could show up from a handful of human dura mater
> donations with sporadic CJD supposedly so rare -- on the other hand, there
> would be no surprise at all if a case of subclinical scrapie showed up in
> 150 sheep.
>
> This raises the question, have dura mater recipients or the surgeon
> subsequently been strain-typed? This might give a very different outcome
> than other forms of iatrogenic CJD or simply co-classify with pituitary
> growth hormone if route of infection (injected, oral, hereditary, etc.) is
> more important than strain source.
>
> Otherwise, iatrogenic scrapie (like cwdCJD) is somwhat unpredictable in its
> gel pattern (though strains of scrapie in other primate species might be
> re-examined). The original scrapie strain is not be identifiable directly
> because material was not likely retained. Strain-typing was not available
> at the time of the article -- but Collinge was one of the authors.
>
> There is little doubt that scrapie could be transfered to humans by
> intracerebral injection (based on lack of species barrier in primates) and
> that processed pooled (human?) dura mater can carry sufficient infectivity
> to cause CJD. I am not aware of animal experiments that specifically used
> sheep dura mater as experimental dose source.
>
>
> tom
>
> -=-=-=-=-=-=-
>
>
> Transmission of Creutzfeldt-Jakob disease by handling of dura mater.
> The Lancet Volume 341(8837) January 9, 1993 pp
> 123-124
> Weber, Thomas; Tumani, Hayrettin; Holdorff, Bernd; Collinge, John; Palmer,
> Mark; Kretzschmar, Hans A.; Felgenhauer, Klaus
>
>
> Sir,- Creutzfeldt-Jakob disease (CJD) can be transmitted iatrogenically by
> human pituitary growth hormone, corneal transplants, and dura mater grafts
> (1). Possible accidental transmission has been reported in only four
> people-a neurosurgeon (2), a pathologist (3), and two laboratory technicians
> (4,5) . We have encountered an unusually rapid case of CJD probably acquired
> through handling of sheep and human dura mater.
> In May, 1992, a 55-year-old orthopaedic surgeon developed paraesthesia of
> the left arm. A few days later he had spatial disorientation, apraxia, and
> gait ataxia. In June he was admitted and a neurologist suspected CJD on the
> basis of the clinical signs, typical electroencephalogram (EEG) pattern, and
> history. An EEG in June revealed a typical pattern of periodic biphasic and
> triphasic sharp wave complexes. We saw the patient in July, 1992. He was
> awake and oriented, with dyscalculia, dysgraphia, disturbed vision, apraxia
> mainly of the left side, rigidity of wrists, spasticity of all muscles,
> myoclonus of the left arm, increased tendon reflexes, ataxia of limbs and
> trunk, and incoordination of left arm. Within 3 weeks he had impaired
> consciousness and attention, mildly impaired memory, and threatening visual
> hallucinations with restless turning. He had periodic states with movements
> of his head and eye-bulbs resembling tonic adversive seizures. During sleep
> these motor disturbances stopped. 2 1/2 months later the patient died.
>
> This patient had worked with sheep and human dura mater from 1968 to 1972.
> He handled about 150 specimens of ovine origin and at least a dozen human
> preparations for research. Handling involved opening skulls with a band saw,
> removing dura, and testing them either fresh (usually), preserved, or
> lyophilised for mechanical qualities. These specimens were sent to a company
> that has sold dura mater preparations by which CJD was transmitted in six
> instances. No information was available from the company about a possible
> connection with this patient's disease and the earlier cases of transmitted
> CJD. Brain biopsy was consistent with diagnosis of CJD. Cerebrospinal fluid
> obtained in July showed neuron-specific enolase (NSE) at 82.0 ng/mL,
> compared with 16.7 ng/mL in serum of other cases (6). Proton magnetic
> resonance spectroscopy of parieto-occipital and temporal grey matter,
> parietal white matter, and thalamus revealed a 20-30% reduction of
> N-acetylaspartate, as described (7). DNA was genotyped with allele-specific
> oligonucleotides (8) and was homozygous for methionine at the polymorphic
> codon 129. Subsequent direct DNA sequencing for the PrP gene open-reading
> frame demonstrated normal sequence on both alleles, excluding known or novel
> pathogenic PrP mutations.
>
> It is tempting to speculate that prions were transmitted to this patient
> from sheep or human dura mater through small lacerations of his skin, but
> the patient and his wife did not remember any significant injury during his
> four years of working with these samples. It cannot be excluded that this
> was a case of sporadic CJD although this assumption is unlikely in view of
> the clinical course which was similar to iatrogenic CJD transmitted by
> peripheral inoculation, such as with human pituitary growth hormone or
> gonadotropin or to kuru (1). Iatrogenic cases resulting from intracerebral
> inoculation with the transmissible agent, for instance following dura mater
> grafts (2-5), present with a dementing picture, as is usual in sporadic CJD,
> rather than with ataxia as in this case.
>
>
> 1. Brown P, Preece MA, Will RG. "Friendly fire" in medicine: hormones,
> homografts, and Creutzfeldt-Jakob disease. Lancet 1992; 340: 24-27. [Medline
> Link] [Context Link]
>
> 2. Schoene WC, Masters CL, Gibbs CJ Jr, et al. Transmissible spongiform
> encephalopathy (Creutzfeldt-Jakob Disease): atypical clinical and
> pathological findings. Arch Neurol 1981; 38: 473-77. [Medline Link] [Context
> Link]
>
> 3. Gorman DG, Benson DF, Vogel DG, Vinters HV. Creutzfeldt-Jakob disease in
> a pathologist. Neurology 1992; 42: 463. [Medline Link] [Context Link]
>
> 4. Miller DC. Creutzfeldt-Jakob disease in histopathology technicians. N
> Engl J Med 1988; 318: 853-54. [Medline Link] [Context Link]
>
> 5. Sitwell L, Lach B, Atack E, Atack D, Izukawa D. Creutzfeldt-Jakob disease
> in histopathology technicians. N Engl J Med 1988; 318: 854. [Medline Link]
> [Context Link]
>
> 6. Wakayama Y, Shibuya S, Kawase J, Sagawa F, Hashizume Y. High
> neuron-specific enolase level of cerebrospinal fluid in the early stage of
> Creutzfeldt-Jakob disease. Klin Wochenschr 1987; 65: 798-801. [Medline Link]
> [Context Link]
>
> 7. Bruhn H, Weber T, Thorwirth V, Frahm J. In-vivo monitoring of neuronal
> loss in Creutzfeldt-Jakob disease by proton magnetic resonance spectroscopy.
> Lancet 1991; 337: 1610-11. [Medline Link] [Context Link]
>
> 8. Collinge J, Palmer MS, Dryden AJ. Genetic predisposition to iatrogenic
> Creutzfeldt-Jakob disease. Lancet 1991; 337: 1444-42. [Medlin
>
> Issues raised by a subsequent comment letter seem dubious at best in the
> case of this surgeon:
>
>
> Ridley: Lancet, Volume 341(8845).Mar 6, 1993.pp 641-642.
> The Lancet Volume 341(8845) Mar 6, 1993 pp 641-642
>
> Occupational risk of Creutzfeldt-Jakob disease.
> [Letters to the Editor]
> Ridley, R.M.; Baker,H.F.
> Division of Psychiatry, Clinical Research Centre, Harrrow, Middlesex HA1
> 3UJ, UK.
>
>
> Sir,- Readers should be cautious about Dr Weber and colleagues' (Jan 9, p
> 123) suggestion that occupational transmission of Creutzfeldt-Jakob disease
> (CJD) may have taken place in a neurosurgeon, a pathologist, 2 histology
> technicians, and an orthopaedic surgeon. Large epidemiological surveys
> (1,2) have failed to find a link between occupation and CJD. This disease
> has been reported in several people working in occupations in which exposure
> to neural tissue could have happened (eg, butchers, farmers, and various
> health professionals (3) ) but the number of these cases is not in excess
> of that which would be expected by random association. In the absence of a
> clear excess of cases, as has occurred in the iatrogenic transmission of
> spongiform encephalopathy by exposure to human derived growth hormone (4),
> the occurrence of CJD in people from the medical and paramedical professions
> is no more remarkable than its occurence in people of any other profession.
> Brown et al (1) rep!
> orted six cases among clerics, but this does not necessarily implicate their
> occupation in their ultimate demise.
>
> The notion that CJD is always acquired (as opposed to idiopathic) and that
> the existence of any hypothetical risk factor must therefore be the cause of
> the disease led to the much cited claim that the high incidence of CJD among
> Libyan Jews was due to their consumption of sheep's eyeballs (5), despite a
> lack of evidence that their dietary habits differed from their ethnic
> neighbours in whom no increased incidence of this disease was recorded. The
> high frequency of CJD in the Libyan Jews is now known to be due to a codon
> 200 mutation in the PrP gene in affected families in that ethnic group (6).
>
> CJD is a peculiar disease that does not fit into any single pattern of
> distribution. The great majority of cases cannot be attributed to
> environmental exposure. Very particular precautions are required to prevent
> transmission from cases of human and animal spongiform encephalopathy since,
> when this does occur, a major outbreak of disease can arise. Under these
> circumstances it is especially important that the occurrence of CJD is
> viewed from an epidemiological rather than an anecdotal perspective.
>
> REFERENCES
>
> 1. Brown P, Cathala F, Raubertas RF, et al. The epidemiology of
> Creutzfeldt-Jakob: conclusion of a 15-year investigation in France and a
> review of the world literature. Neurology 1987; 37: 895-904. [Medline
> Link] [Context Link]
>
> 2. Harries-Jones R, Knight R, Will RG, et al. Creutzfeldt-Jakob disease in
> England and Wales, 1980-1984; a case control study of potential risk
> factors. J Neurol Neurosurg Psychiatry 1988; 51: 1113-19. [Medline Link]
> [Context Link]
>
> 3. Masters CL, Harris JO, Gajdusek C, et al. Creutzfeldt-Jakob disease:
> patterns of worldwide occurrence and the significance of familial and
> sporadic clustering. Ann Neurol 1978; 5: 177-88. [Medline Link] [Context
> Link]
>
> 4. Brown P, Gajdusek C, Gibbs CJ, Asher DM. Potential epidemic of
> Creutzfeldt-Jakob disease from human growth hormone therapy. N Engl J Med
> 1985; 313: 728-31. [Medline Link] [Context Link]
>
> 5. Kahana E, Alter M, Braham J, Sofer D. Creutzfeldt-Jakob disease: focus
> among Libyan Jews in Israel. Science 1974; 183: 90-91. [Medline Link]
> [Context Link]
>
> 6. Hsiao K, Meiner Z, Kahana E, et al. Mutation of the prion protein in
> Libyan Jews with Creutzfeldt-Jakob disease. N Engl J Med 1991; 324: 1091-97.
>
>
> ----------------------------------------------------------------------------
> ----
>
>
>
>
> Approved-By: "Roland Heynkes @ T-Online" <
[email protected]>
> Message-ID: <006a01bed26b$d48e9400$31be9ec1@pentium>
> Date: Mon, 19 Jul 1999 23:28:00 +0200
> Reply-To: Bovine Spongiform Encephalopathy <
[email protected]>
> Sender: Bovine Spongiform Encephalopathy <
[email protected]>
> From: "Roland Heynkes @ T-Online" <
[email protected]>
> Subject: Re: iatrogenic scrapie from sheep dura mater?
> Dear Tom,
>
> >An orthopaedic surgeon employed by the lyodura company [Braun Melsungen]
> >extracted dura mater from sheep and human cadavers and came down with
> >fast CJD 22 years later.
> >
> the article does not say that he was an employee of Braun Melsungen, but
> sent et least some of the lyodoras to the company. Do you have additional
> information from one of the authors and do you know if the company got
> the ovine dura maters too?
>
> >Scrapie has long been present in Germany but reported levels are very
> >low, about a flock a year has to be destroyed. I am not aware of any
> >high sensitivity tests or random screening every being used in Germany
> >to assess the levels of preclinical animals.
> >
> I don't know if the Groschup group in Tuebingen does use a sensitive
> scrapie test like the dutch test in order to perform a random screening
> program. When I asked last time a few years ago, they "only" tested animals
> with unclear neurological symptoms.
> Scrapie still occurs in Germany, but we have less than one recorded case
> per year.
>
> >This raises the question, what did the lyodura company do with so much
> >dura mater from sheep? The market for specialty surgical products was
> >overwelmingly in humans in 1968. The Lancet article only says it was for
> >research -- but in what species?
> >
> Are you sure that this research with the ovine dura mater has been done
> at Braun Melsungen?
>
> best regards
>
> Roland Heynkes
>
> Erkwiesenstr. 19
> D-52072 Aachen (Germany)
> Tel.: +49 (0)241/932070
> Fax: +49 (0)241/932071
> email:
[email protected].
> http://home.t-online.de/home/Roland.Heynkes
>
>
> ----------------------------------------------------------------------------
> ----
>
>
>
>
> Approved-By: tom <
[email protected]>
> Message-ID: <v04011712b3ba63ee05b6@[12.7.122.68]>
> Date: Tue, 20 Jul 1999 11:48:17 -0800
> Reply-To: Bovine Spongiform Encephalopathy <
[email protected]>
> Sender: Bovine Spongiform Encephalopathy <
[email protected]>
> From: tom <
[email protected]>
> Subject: Re: iatrogenic scrapie from sheep dura mater?
> In-Reply-To: <006a01bed26b$d48e9400$31be9ec1@pentium>
>
> >
> >>An orthopaedic surgeon employed by the lyodura company [Braun Melsungen]
> >>extracted dura mater from sheep and human cadavers and came down with
> >>fast CJD 22 years later.
> >>
> >the article does not say that he was an employee of Braun Melsungen, but
> >sent et least some of the lyodoras to the company. Do you have additional
> >information from one of the authors and do you know if the company got
> >the ovine dura maters too?
>
> I really do not know any more at this time than what was in the article.
> The way I read it, he was not an internal employee but an independent
> orthopaedic surgeon who had a contract to supply dura mater to the company.
> The victim's wife may be able to supply details, however the family name is
> not given.
>
> >
> >>Scrapie has long been present in Germany but reported levels are very
> >>low, about a flock a year has to be destroyed. I am not aware of any
> >>high sensitivity tests or random screening every being used in Germany
> >>to assess the levels of preclinical animals.
> >>
> >I don't know if the Groschup group in Tuebingen does use a sensitive
> >scrapie test like the dutch test in order to perform a random screening
> >program. When I asked last time a few years ago, they "only" tested animals
> >with unclear neurological symptoms.
> >Scrapie still occurs in Germany, but we have less than one recorded case
> >per year.
>
> Sure. According to this, it was a bit of extraordinary bad luck that any of
> 150 sheep + 12 humans could have carried the disease, but we know not to
> equate recorded cases with incidence. Portugal had very few recorded cases
> per year of BSE too.
>
> In your opinion, how exactly has it been possible for scrapie to persist in
> Germany for all these decades at this vanishingly small level? Cases are
> probably not geographically or farm-exchange linked. Surely the
> authorities don't allow live imports from England.
>
> >
> >>This raises the question, what did the lyodura company do with so much
> >>dura mater from sheep? The market for specialty surgical products was
> >>overwelmingly in humans in 1968. The Lancet article only says it was for
> >>research -- but in what species?
> >>
> >Are you sure that this research with the ovine dura mater has been done
> >at Braun Melsungen?
>
> I would guess that they did not do the research there but sold it to the
> marketplace. Perhaps you could give the German authors a call (Weber,
> Thomas; Tumani, Hayrettin; Holdorff, Bernd all in Hamburg I think) I will
> shop around on Internet catalogues, see which companies today sell sheep
> dura mater for research (my guess is no one).
>
> It is annoying that so many details relevent to interpretation were left out
> of the paper. Still, any forward tracing of the dura mater will soon hit a
> brick wall at the company, Braun Melsungen- B. Carl-Braun-Str. 1
> D-34212 Melsungen Germany Tel: ++49 5661 - 71-1739, Fax: ++49 5661 -
> 71-1632. If any humans received sheep dura mater, I doubt that this will be
> disclosed or that specific recipients will be identified to their doctors.
> It is probably better to trace backwards from affected recipients -- see if
> they strain-type out to be sheep.
>
> Japan has been particularly hard hit by dura mater CJD (curious in itself)
> and researchers there might be motivated to find out what happened. I am
> not aware of agricultural agencies that would impede research over there.
>
> tom
>
> P.S. The US would never think of pooling dura mater in the same container.
> However, even after the lyodura experience, apparently we thought it safe to
> use the same rinse water on 26 consecutive dura mater donations:
>
> Creutzfeldt-Jakob Disease (CJD) in a Recipient of a U.S.-Processed Dura
> Mater Graft: Cause or Coincidence? Belay E.D.1, Dobbins, J.G.1, Malecki,
> J.2, Buck, B.E.3, Bell, M.1, Cobb, J.2, Schonberger, L.B.1, 1Centers for
> Disease Control and Prevention (CDC), Atlanta, GA; 2Palm Beach County Health
> Department, West Palm Beach, FL; 3Department of Orthopedics and
> Rehabilitation, University of Miami School of Medicine, Miami, FL.
> http://www.life.umd.edu/jifsan/tse/belay.htm
>
> In 1997, CDC was notified about a 72-year-old man who developed CJD 54
> months after he received a dura mater graft during removal of a meningioma.
> CDC confirmed that CJD diagnosis was based on standard clinical criteria,
> including typical electroencephalographic changes. Investigation of patients
> who underwent craniotomy within 4 months before or after the case-patient's
> surgery revealed no evidence for nosocomial transmission of CJD. The dura
> donor was a previously healthy 34-year-old man with no known risk factors
> fore CJD who had died in a motor vehicle collision. The dura was processed
> in the United States with no direct contact with other dura. However,
> possible indirect contact through water used to rinse dural grafts from
> about 25 other donors simultaneously could not be ruled out; tracing of
> recipients of these grafts is in progress. If this case-patient remains the
> only recipient of a U.S.-processed dural graft with CJD, then this graft-CJD
> association is more likely to be coincidental than causal. This report
> underscores the potential importance of recent recommendations to minimize
> the risk of CJD transmission by such grafts, including neuropathologic
> screening of all donors and removal of opportunities for cross-contamination
> among grafts.
>
>
>
> IA#84-03 --- 6/27/87
> http://www.fda.gov/ora/fiars/ora_import_ia8403.html
>
> BACKGROUND
>
> A recent reported case of Creutzfeldt-Jakob Disease (CJD) in a 28 year-old
> patient who had received a human dura mater graft indicates that the graft
> may
> have been the source of this always fatal disease. The woman died 22 months
> after receiving the lyophilized, irradiated human cadaveric dura mater
> graft.
> The dura mater used in the graft was packaged in October 1982 under lot
> #2105
> by B. Braun Melsungen AG of West Germany, shipped to Tri Hawk International,
> Inc., Montreal, Quebec, Canada and sold to Saint Francis Hospital, Hartford,
> Connecticut, on April 4, 1985.
>
> This is the first known case of CJD transmission associated with a dura
> mater
> graft. Present methods of sterilizing the dura mater do not completely
> inactivate the CJD agent.
>
> The dura mater is manufactured by the West German firm under the trade name
> Lyodura. Although the material is primarily used in neurosurgery, it is
> also
> used in orthopedic, otologic, dental, urologic, gynecologic, and cardiac
> surgical procedures.
>
> We have been unable to determine the total number of packages of Lyodura
> that
> were imported into the United States because the Canadian distributor failed
> to maintain adequate records of distribution for all lots which may have
> been
> distributed by mail to hospitals in the United States and Canada.
>
> As stated in the FDA Safety Alert which issued April 28, 1987, we strongly
> recommend that users of dura mater choose only products from known sources
> which retrieve, process and handle the material according to guidelines such
> as those of the American Association of Tissue Banks.
>
> To report cases or for further information, please contact:
>
> Gordon C. Johnson, M.D.
> Center for Devices and Radiological Health
> Food and Drug Administration
> 8757 Georgia Ave,
> Silver Spring, Maryland 20910
>
>
> GUIDANCE
>
> Alert your local Customs office to be aware of this import alert and to
> monitor mail shipments for this product.
>
> Detain all shipments of Lyodura (dura mater) received from Tri Hawk
> International, Inc., Montreal, Quebec, Canada or from B. Braun Melsungen AG
> of
> West Germany. Charge: "The article is subject to refusal of admission
> pursuant to section 801(a)(1) in that it appears to be adulterated under
> section 501(h), because the methods and controls used for the storage and
> distribution of Lyodura (dura mater) are not in conformance with current
> good
> manufacturing practice requirements under section 520(f)(1)."
>
> -=-=-=-=-
>
> DR. MARTIN ZEIDLER:
> http://www.life.umd.edu/jifsan/tse/zeidler.htm
> 8 June 1998
>
> Thank you very much and I'd like to start this by thanking JIFSAN for kindly
> inviting me here today.
>
> I became involved in the whole issue of Creutzfeldt-Jakob disease and dura
> mater grafts about a year ago when I had the good fortune to be working with
> the World Health Organization. It was at this time that WHO had a
> consultation addressing the issue of safety of medicinal and other products
> in relation to human and animal TSEs. This meeting recommended that dura
> mater grafts could no longer be used, which caused some controversy and I
> was involved in the debate which ensued with various dura mater
> manufacturers....
>
> So, what is dura mater? Well, it's the outer covering of the meninges, this
> is the fibrous sheath which encircles the central nervous system. It really
> has two functions, first, to keep the spinal fluid in, and, second, to stop
> infection from getting into the central nervous system. Surgical procedures
> or trauma that broach the dura mater may result in a hole, that because of
> the fibrous, inelastic nature of dura, may not be possible shut by primary
> closure. If the defect is to be filled, perhaps the obvious tissue to do
> this is a dural graft.
>
> Since the 1950s, dura mater grafts have been utilised ; some of the first
> grafts came from the U.S. Navy's Medical School here in the United States.
> The popularity of dural grafts came to the fore in the 1970s and 1980s when
> they were commercially produced. It appeared that surgeons were actually
> very happy with these particular materials - they provided a good barrier to
> infection and stopped the leakage of CSF.
>
> It was in 1987 that the first case was reported of a person with CJD who
> had previously been known to have received a dura mater graft. The patient
> was a 28-year-old woman who had an operation 18 months previously to remove
> a cholesteatoma and she subsequently developed histologically confirmed CJD.
> To date I've managed to find a total of 83 case reports of dura mater
> related CJD cases, and I am grateful Dr Paul Brown for providing me with
> data. There are 3 additions to the number which Paul mentioned during his
> talk earlier, although these three cases are slightly questionable. Two of
> these were reported from France, and both had undergone embolisation
> procedures with dura mater rather than receiving a conventional graft. The
> third case is from Thailand and has not yet been pathologically confirmed.
>
> The clinical phenotype of patients with dura mater-associated CJD is similar
> to that seen in the classical sporadic form of CJD: rapidly progressive
> dementia, myoclonus, and in the majority of patients a characteristic EEG.
> However, there are some differences: dura-associated cases tend to have more
> prominent early cerebellar symptoms and a somewhat more prolonged clinical
> course. In sporadic CJD the median illness duration is 4 1/2 months and this
> is doubled on average in dura mater cases. The age at onset is about 10-15
> years younger on average than we see with sporadic CJD.
>
> I think the youngest dura mater case documented was 16 or 17. The average
> incubation period from the time the patient received their graft to onset of
> their illness is approximately 6 years, but ranges from 16 months to 16
> years. Although most of these cases have arisen through the use of dura
> mater for cranial surgery, there are some cases which have been known to
> have resulted from ear, nose and throat surgery or from spinal surgery. Two
> cases from France, as mentioned, followed embolism procedures, in one case
> the patient had a nasopharyngeal tumor and dura mater was cut up into lots
> of little pieces and injected into the external carotid artery to embolise
> this, and in the other case the dura mater was inoculated into an artery in
> the chest to embolise an area of infection.
>
> I would like to just go back and show you the countries which are known to
> have had dura mater cases of CJD. Most of the reports come from Japan, and
> we were rather surprised at the WHO consultation last year in Geneva, to
> hear reports from Dr Tateishi of a recent study conducted in Japan which had
> shown the presence of 43 cases of dura mater CJD.
>
> I think you will agree looking at the slide that the other cases have been
> reported really quite widely throughout the world. Virtually all of these
> patients received one particular form of dura mater graft that was
> commercially manufactured by a single German company. The product was called
> Lyodura, and most of the patients had received grafts that had been
> manufactured during a 4 year period between 1983 and 1987. Lyodura was
> pooled during this time, so there was a potential for cross contamination
> and the sterilization procedures used involved 10% hydrogen peroxide for 24
> hours and ionizing radiation. Subsequent animal experiments have shown that
> this is not an adequate form of sterilization.
>
> An important question is whether any of the dura mater cases were recipients
> of grafts that were treated with more thorough and adequate sterilisation.
> By this, I mean treatment with 1N sodium hydroxide, which is in the standard
> step which was introduced in the treatment of Lyodura after 1987. There are
> four cases out of this series of 83 which perhaps I'll talk about in a
> little bit more detail. Two cases were clearly not Lyodura. These were
> locally procured grafts, one from Italy and the other from the United
> Kingdom - these were used between 1969 and 1981.
>
> Furthermore, there was the a recently reported case from America which we
> heard about yesterday. Perhaps the case of most interest is one from the
> Japanese series. This was a lady in her mid-60s who received a graft in 1991
> and later developed clinically probable CJD, but this was not histologically
> confirmed. The hospital records did not note whether or not her graft was
> Lyodura or the other form of dura used in that hospital at that time. It was
> concluded in the report of the Japanese cases that it was unlikely that this
> patient had received Lyodura produced before 1987.
>
> So the possibility exists that this patient had received a form of dura
> which was considered to be adequately sterilised. It is important to note
> two points, first, as this case did not undergo histological examination the
> diagnosis of CJD is not 100% certain, and second, we can not be absolutely
> sure that in this or some of the of other 82 cases that the history of
> receiving a dural mater graft is coincidental. In none of these cases is
> there data which tells if the graft donor had CJD.
>
> Following the announcement of the first case here in the United States,
> doctors in the United Kingdom, Australia and New Zealand decided that they
> were going to use alternatives to cadaveric dura homografts, and here in the
> States I believe there was an importation ban on Lyodura.
>
> So what alternatives are there to cadaveric-derived dura? There are
> several - I'll just run through these. One of the most popular is fascia
> lata, this is the fibrous covering of the lateral thigh muscle. The removal
> of this can add about 30 minutes to the length of the operation and of
> course leaves a wound which, as with all wounds, can potentially become
> infected or have other complications.
>
> Other alternatives include pericranium (the covering of the skull bone),
> temporalis fascia (the membrane which surrounds the temporalis muscle at the
> side of the head) and synthetic materials - a number of such materials have
> been tried over the years including gold foils, cellophane, and dacron
> grafts. However, there has been some concern about the safety of synthetic
> materials and neurosurgeons have felt that these were rather inferior,
> although I think with the newer materials that's not so clearly the case. I
> should note that there is no controlled trial that has ever been conducted
> to answer the question as to whether or not these substitutes are better or
> worse than cadaveric-derived dura.
>
> I think there are two key questions that need to be addressed, first, are
> there situations where cadaveric dura is better than available alternatives?
> If the answer is no then we need to question why we are using cadaveric
> dural grafts at all. If the answer is yes, then the next question is how can
> dura be made as safe as possible? I'd like to show you some of the report
> from the WHO meeting over a year ago. I'll read it to you.
>
> "Because over 50 cases of CJD have resulted from cadaveric dura mater
> grafts, the group strongly recommended that dura mater no longer be used,
> especially in the case of neurosurgery, unless no alternative is available.
> If dura mater is to be used, only material which is from non-pooled sources
> originating from carefully screened donors subjected to validated
> inactivated treatment should be considered."
>
> Following this recommendation the Japanese authorities decided that they
> were no longer going to issue a license for the use of dura mater and the
> TSE Advisory Committee here in the States met again to discuss the issue of
> dura mater. I just want to run through their recommendations, there were
> some differences from WHO's: although they also discouraged use of dura
> mater, the final decision on its usage was left up to the individual
> physicians, but certain additional safeguards were put into place.
>
> For instance, it was felt mandatory that for every donor a full brain
> autopsy should be performed and examined histologically and with
> immunocytochemistry, which is probably the most sensitive method that we
> have, other than transmission studies. It was further recommended that a
> sample of the dura and the brain should be kept for further testing as
> needed.
>
> Additionally, standard protocols for determining donors eligibility and
> tissue procurement were recommended, and dura should be collected before the
> brain at autopsy - which obviously makes sense to avoid contamination of the
> graft. Furthermore, decontamination with 1N sodium hydroxide for one hour
> should be used. This had previously been confirmed by Paul Brown and
> colleagues to be an effective decontamination procedure. There should be no
> pooling of grafts, to prevent cross-contamination and there should be
> documentation to allow tracking from the donor to the recipient and from the
> recipients to the donor. I think there can be little doubt that if these
> recommendations are adopted, then the safety of dura mater grafts will be
> dramatically improved.
>
> However, I would like to just play the devil's advocate here and to mention
> a few cautions. We know from animal experiments that infectivity can predate
> any pathological changes and this includes immunocytological changes as
> well. We also know that standard decontamination procedures using sodium
> hydroxide, as David Taylor mentioned yesterday, may not completely be
> effective. I think we have to remember that dura is a potentially high-risk
> material, and that studies also performed by David Taylor