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From: TSS ()
Date: March 16, 2007 at 9:09 am PST

Opinion of the Scientific Panel BIOHAZ on the Quantitative risk assessment
on the residual BSE risk in sheep meat and meat products [1]

Last updated: 15 March 2007 Publication Date: 15 March 2007

Adopted on 25 January 2007. (Question Nº EFSA-Q-2005-235)


The European Commission (DG SANCO) requested the Scientific Panel on
Biological Hazards (BIOHAZ) of the European Food Safety Authority (EFSA) for
an update on the risks posed by tissues of sheep to human health in the case
where Bovine Spongiform Encephalopathy (BSE) is confirmed in sheep and, more
particularly, on the feasibility of carrying out a Quantitative Risk
Assessment (QRA).

In replying to this mandate, the experts considered all necessary elements
needed to carry out a quantitative risk assessment of BSE transmission from
sheep to humans: (1) prevalence estimates of BSE infection in EU sheep (2)
the amount and distribution of infectivity in sheep tissues and body fluids
(3) the apparent barrier i.e. “species” barrier for transmission of BSE from
sheep to humans and (4) human consumption of sheep products. The experts
concluded that there are currently insufficient data for a QRA of the risks
posed by tissues of sheep to human health in the case where BSE is confirmed
in sheep.
However, they recognised that the prevalence of infection would have most
significant impact on any QRA. Using the latest Transmissible Spongiform
Encephalopathy (TSE) prevalence figures for Member States (MS) and the
results of BSE/scrapie discriminatory testing, the experts were able, with
certain assumptions, to estimate BSE prevalence in sheep. For example, they
calculated by one method that there is a 95% confidence that in the high
risk sub-group of countries there is less than 0.3-0.5 cases of BSE per
10,000 healthy-slaughtered animals.

In sheep experimentally infected with BSE, the distribution of the
infectious agent (prion) in tissues is wide-spread as the prion can be found
in secondary lymphoid tissue, skeletal muscle and blood. In considering more
recent attempts at quantifying the risk specifically from this experimental
ovine BSE, and in reviewing biochemical approaches to quantify titres in
affected animals, a major stumbling block to quantification was identified
to be the fact that the influence of age and genotype on the distribution of
BSE infectivity in sheep is only defined qualitatively. The BIOHAZ panel
agreed that absolute quantification of prions by biochemical methods was
difficult. However, in the absence of comprehensive infectivity data to
facilitate a QRA, it was concluded that Specified Risk Materials (SRM)
removal alone was unlikely to be sufficient to eliminate the residual BSE
risk to the consumer from a BSE-infected sheep carcass.

The experts further assumed that there is no intrinsic species barrier for
sheep BSE transmission to humans, which is in line with past opinions of the
Scientific Steering Committee. Human consumption levels of sheep meat and
other sheep products (domestic produced or imported) are high within the EU.
Data from two EU countries were used (Italy and GB) and gave intake
estimates that were broadly in agreement with the overall trade data for
sheep carcasses for these countries provided by Eurostat. This gave some
confidence in using Eurostat data as basis to estimate an average daily
intake of sheep meat or meat products in the EU of 8.4-9.3 g per person.

[1] For citation purposes: Opinion of the Scientific Panel on Biological
Hazards on a request from the European Commission on the quantitative risk
assessment on the residual BSE risk in sheep meat and meat products, The
EFSA Journal (2007) 442, 1-44



4.4.4 New types of BSE in cattle and the variable pathogenicity of scrapie

Discriminatory testing for BSE in sheep is based on immuno-histochemistry

and/or western blotting of brain (or lymphoid tissue) for abnormal prion
protein in animals

experimentally challenged with infectious material taken from cases of
cattle BSE defined as

“typical” or consistent with the original clinical and histopathological
case definition of the

disease (Wells et al., 1987). The methodologies have been evaluated, and
shown to be fit-forpurpose,

in an EU-wide ring trial using a variety of test materials covering oral and

(ic) challenged sheep of a limited range of PrP genotypes, and include cases

secondary ic transmission of sheep BSE to sheep (Stack et al., in
preparation). However, the

sample-set was necessarily restricted to what was available and no
meaningful estimate of the

sensitivity and specificity of these tests has been made. Nor were these
tests evaluated for

their ability to discriminate types of BSE (cattle TSE) now regarded, on
molecular and

histopathological criteria, to lie outside the original case definition of
BSE (Buschmann et al.,

2006; Beringue et al., 2006a; Baron et al., 2006a; Casalone et al., 2004;
Beringue et al.,

2006b; Baron et al., 2006b). These forms of cattle TSE have been dubbed
H-type BSE and Ltype

(or BASE) BSE. The significance, origin and transmissibility of these H- and
L-types of

BSE to sheep are only speculative at present and the BIOHAZ panel
recommended a

The EFSA Journal (2007) 442, 1-44

Opinion on the quantitative risk assessment on the residual BSE risk in

meat and meat products Page 21 of 44

watching brief on this area to monitor its relevance to the TSE risk of
human consumption of

ovine products. Similarly, the potential variable pathogenicity of scrapie
strains (such as

atypical scrapie) and their modification on transmission through a third
species which may

affect barriers to transmission to humans remain speculative and need
continual review.

4.4.5 Conclusion

The BIOHAZ panel considered that these data were not directly informative in
quantifying a

sheep-to-human species barrier particularly, as referenced in section 4.4.4,
since there are

many precedents for modification of TSE agents after passage through another
species. For

the purposes of a QRA for sheep products, the BIOHAZ panel confirmed the use
of the

previous assumption of a species barrier of 1 for putative sheep-to-human
transmissions of


4.5 Human consumption

There are few estimates of the level of consumption of sheep meat and meat
products in the

European Union and most surveys focusing on nutrition and diet (e.g. the
EPIC survey, ) include these foods under the cover of more general food

Exceptions have included two surveys in Italy and Great Britain and these
have been used to

check if Eurostat data on the production of ovine carcasses, import and
export in the EU15

countries since 1995 could be used to validate EU-wide per capita annual
intake data.

4.5.1 The Italian Survey

The Italian INN-CA survey covers the 1994-1996 period (Turrini et al.,
2001). It randomly

sampled 1,147 households and involved 1,978 individuals of all ages. A
self-compiled 7-day

food diary was used to gather data for analysis by sex and age categories.
Among the food

items “sheep meat” was specified. The percentage of (sheep meat) consumers
and daily food

intake by the total sample of individuals or by “consumers only” were
calculated. An overall

mean daily intake was calculated of 3.2 g (median 0.0g). Understandably,
consumption was

higher in the “consumers only” group (which represented 7.9% of the sample

with a mean and median intake of 40 and 25 g respectively.

4.5.2 The British Survey

The National Diet and Nutrition Survey of Great Britain is based on a

multistage random sample of 2,251 households in GB. One individual per
household, 19 to 64

years of age, was requested to compile a 7-day food diary which included the
category “lamb

and dishes”. As in the Italian survey the consumption figures were expressed
by the total

sample of individuals or by “consumers only” (22% of total). The mean 7-day
intakes were 51

g for the total sample and 226 g (median, 150 g) for “consumers only”.

The Italian and GB weekly intake were therefore comparable (22.4 g (Italy)
vs. 51 g (GB) in

the whole sample population, and 280 g (Italy) vs 226 (GB) in the “consumers
only” group).

(, accessed on
7th March




6.1 General

The BIOHAZ panel retains the view that there are insufficient data for a

assessment of the risks posed by tissues of sheep to human health in the
case where BSE is

confirmed in sheep. Moreover, even in the absence of quantitative
information, recent data on

the preclinical distribution of PrPSc and infectivity in skeletal muscle
tissues and blood

following experimental BSE challenge support their previous view that risk

strategies relying on SRM removal in sheep or goats will not be fully

The continuing lack of comprehensive quantitative data on species barrier
and infectious load

with respect to BSE in small ruminants prevents any meaningful quantitative
risk assessment

and precludes revision of the recommendations in the opinions of the
Scientific Steering

Committee (EC 2002a) on safe sourcing of small ruminant materials of April
2002 and its

complement of September 2002.


The EFSA Journal (2007) 442, 1-44

Opinion on the quantitative risk assessment on the residual BSE risk in

meat and meat products Page 28 of 44


1. More detailed evaluation of the screening and discriminatory TSE test
parameters are

recommended, in tandem with continued surveillance, in order to improve the

accuracy of the BSE in sheep prevalence estimates. To facilitate this, all
TSE positive

cases including secondary cases diagnosed in infected flocks should be

submitted for discriminatory testing.

2. Emerging data on the early accumulation of abnormal prion protein and
infectivity in

peripheral tissues of sheep exposed to natural scrapie and BSE before their

in the CNS re-inforce the value of maintaining current measures – especially

removal, and breeding for resistance15 - previously recommended to reduce

exposure to TSEs.

3. Further surveillance and multi-disciplinary investigation of all animal
TSEs, including

atypical types of scrapie and BSE, are recommended to evaluate their
implications for

human health. .......end

1: J Infect Dis 1980 Aug;142(2):205-8

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

Published online before print October 20, 2005

Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0502296102
Medical Sciences

A newly identified type of scrapie agent can naturally infect sheep with
resistant PrP genotypes

( sheep prion | transgenic mice )

Annick Le Dur *, Vincent Béringue *, Olivier Andréoletti , Fabienne Reine *,
Thanh Lan Laï *, Thierry Baron , Bjørn Bratberg ¶, Jean-Luc Vilotte ||,
Pierre Sarradin **, Sylvie L. Benestad ¶, and Hubert Laude *
*Virologie Immunologie Moléculaires and ||Génétique Biochimique et
Cytogénétique, Institut National de la Recherche Agronomique, 78350
Jouy-en-Josas, France; Unité Mixte de Recherche, Institut National de la
Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions
Hôte Agent Pathogène, 31066 Toulouse, France; Agence Française de Sécurité
Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels,
69364 Lyon, France; **Pathologie Infectieuse et Immunologie, Institut
National de la Recherche Agronomique, 37380 Nouzilly, France; and
¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway

Edited by Stanley B. Prusiner, University of California, San Francisco, CA,
and approved September 12, 2005 (received for review March 21, 2005)

Scrapie in small ruminants belongs to transmissible spongiform
encephalopathies (TSEs), or prion diseases, a family of fatal
neurodegenerative disorders that affect humans and animals and can transmit
within and between species by ingestion or inoculation. Conversion of the
host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a
misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission
and pathogenesis. The intensified surveillance of scrapie in the European
Union, together with the improvement of PrPSc detection techniques, has led
to the discovery of a growing number of so-called atypical scrapie cases.
These include clinical Nor98 cases first identified in Norwegian sheep on
the basis of unusual pathological and PrPSc molecular features and "cases"
that produced discordant responses in the rapid tests currently applied to
the large-scale random screening of slaughtered or fallen animals.
Worryingly, a substantial proportion of such cases involved sheep with PrP
genotypes known until now to confer natural resistance to conventional
scrapie. Here we report that both Nor98 and discordant cases, including
three sheep homozygous for the resistant PrPARR allele (A136R154R171),
efficiently transmitted the disease to transgenic mice expressing ovine PrP,
and that they shared unique biological and biochemical features upon
propagation in mice. These observations support the view that a truly
infectious TSE agent, unrecognized until recently, infects sheep and goat
flocks and may have important implications in terms of scrapie control and
public health.


Author contributions: H.L. designed research; A.L.D., V.B., O.A., F.R.,
T.L.L., J.-L.V., and H.L. performed research; T.B., B.B., P.S., and S.L.B.
contributed new reagents/analytic tools; V.B., O.A., and H.L. analyzed data;
and H.L. wrote the paper.

A.L.D. and V.B. contributed equally to this work.

To whom correspondence should be addressed.

Hubert Laude, E-mail:

Office Note


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

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

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



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;

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)


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.

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.

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


1: Eur J Epidemiol 1991 Sep;7(5):520-3

"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.

ISSUED 13/05/1999


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.
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: Received June 7, 2000;
revised July 3, 2000; accepted July 5, 2000.


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.


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.


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.

Transmission of Creutzfeldt-Jakob disease by handling of dura mater.
The Lancet Volume 341(8837) January 9, 1993 pp
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 ( 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
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