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From: TSS ()
Date: May 30, 2005 at 12:51 pm PST

Last Updated: Monday, 30 May, 2005, 17:38 GMT 18:38 UK

Medics trace patients in CJD fear

Lyodura patches were used to seal wounds after brain surgery
Doctors in Edinburgh are trying to track down up to 50 patients who could be at risk from Creutzfeldt-Jakob Disease (CJD).
The former patients each underwent brain surgery at the city's Western General between 1982 and 1992.

Four or five patients a year could have been exposed to CJD via contaminated Lyodura grafts, used to seal wounds after neurosurgery.

The alert follows an English coroner's verdict linking the patches to CJD.

The verdict of medical misadventure was recorded in April against the death of 34-year-old Simon Stratford.

The Cambridgeshire inquest said the Lyodura patch used on the father-of-four during surgery in 1987 later led to his death from CJD.

There is no cause for concern

Dr Charles Swainson
NHS Lothian

Coroner David Morris said the evidence showed that neither the patch manufacturers nor surgeons could have been aware of its dangers at the time.

During the case, experts added that Mr Stratford was likely to be the last person in the UK to come to light who had contracted CJD in this way.

The Lyodura patches, made by the German company B. Braun Melsungen AG, were commonly used until their withdrawal in 1996.

It is thought certain batches of the patches became contaminated with CJD during their manufacture.

NHS Lothian has been unable to trace the patients concerned because their medical records have been destroyed.

The health board is currently seeking advice from the CJD Incidents Panel about notifying the people concerned.

The London-based panel was set up 2000 to offer advice on how to manage incidents involving CJD.

A coroner linked Simon Stratford's death from CJD to Lyodura patches

The National CJD Surveillance Unit, which is based at the Western General, has also been monitoring the situation since the concerns arose.

The situation in Scotland was disclosed by Dr Charles Swainson, medical director of NHS Lothian, in a report to the board.

Dr Swainson said: "There is no cause for concern. Following the death of a patient in England I reported that the CJD Incidents Panel has been notified of the case, and their advice has been sought about notification to patients who may have received a contaminated graft.

"The CJD Surveillance Unit is monitoring the situation and providing evidence to the coroner."

In the past, experts have agreed with Dr Swainson's assessment and insist the risk of infection is extremely low.

One study calculated the chances to stand at one in 2,000.

1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8

Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery.

Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.

Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.

PMID: 8006664 [PubMed - indexed for MEDLINE]

Surgical treatment and risk of sporadic Creutzfeldt-Jakob disease: a
case-control study.

Collins S, Law MG, Fletcher A, Boyd A, Kaldor J, Masters CL.

Australian National Creutzfeldt-Jakob Disease Registry, Department of
Pathology, The University of Melbourne, Parkville, Victoria.

BACKGROUND: Apart from the small number of iatrogenic and familial
cases, the cause of most cases of Creutzfeldt-Jakob disease (CJD) is not
known. We aimed to identify risk factors for sporadic CJD. METHODS: In a
case-control study, we compared the medical history and selected
demographic characteristics of 241 definite (neuropathologically
confirmed) and probable (clinically likely) patients with CJD,
ascertained from the Australian National Creutzfeldt-Jakob Disease
Registry between Jan 1, 1970, and October 31, 1997, and of 784 controls,
recruited from the community by random telephone interview in August,
1997. Standard logistic regression was used for the comparisons.
FINDINGS: Surgical procedures were significantly associated with the
development of sporadic CJD. This risk progressively increased with the
number of surgical treatments to a maximum for three procedures (odds
ratio 2.13 [95% Cl 1.34-3.41], p=0.002). There was also a significant
association between risk of CJD and residence or employment on a farm
(p<0.001) or market garden (p=0.002) for longer than 10 years. We found
no significant risk associated with a history of blood transfusion,
organ transplantation, major dental work, or occupation. INTERPRETATION:
Our findings accord with the hypothesis that a range of surgical
treatments may serve as unrecognised contamination events and account
for a proportion of cases of sporadic CJD. Possible biases in different
methods and times for the acquisition of data on cases and controls
suggest our findings need to be replicated in independent studies with
community controls.

PMID: 10073510 [PubMed - indexed for MEDLINE]

Lancet. 1999 Feb 27;353(9154):693-7.


Small, unexplained ‘clusters’ of sporadic CJD have been reported in
Italy, Japan, and Canada,13–
but rigorous
statistical analyses of these clusters have not generally been
performed. Geographical clustering of sporadic CJD cases, if it occurs,
might reflect case-to-case transmission of the agent, common exposure to
an environmental source or, perhaps, a shared genetic susceptibility
lying outside the PrP coding region.


We examined the records of the cases involved in the two most likely
clusters detected by Kulldorff's method. Some characteristics of the
cases are summarized in Table 2
. In the
South-West cluster, three cases aged 60–84 years at onset lived at the
time of disease onset in two small rural parishes less than 5 km apart.
Two had lived in the same parish throughout life. The third case was
born about 100 km from his place of residence at the time of disease
onset, but his residential history throughout life was not recorded. Two
cases were methionine homozygotes, the third case was not genotyped.
Detailed information on medical history and other possible exposures
were available for only two cases. One case with onset in 1996 had a
history of five surgical procedures between 1959 and 1996 including
vertebral column surgery in 1991. The other case, with onset in 1997,
had ocular surgery in 1994 and had had other surgical treatments in 1977
and 1993. The two patients had been operated on in the same hospitals,
but not within a one-year period of each other. They had both undergone
dental treatment by the same dentist who practised in the area. One case
was reported to eat brain of veal or lamb at least once per month, while
the other reportedly ate brain occasionally. Both ate veal thymus
several times per year and venison occasionally and both had lived on


A case-control study performed in Australia reported an increased risk
of sporadic CJD associated with surgery, though the methodological
limitations of the study prevent any firm conclusions being drawn with
regard to this association.11
In the
present study, we found that some of the cases belonging to two possible
clusters had undergone several episodes of surgery. One possible
explanation for the presence of these clusters is, therefore, that some
of these cases were iatrogenically infected, although we could not
identify any clear surgical links between any of the cases. We should
note that cluster analyses based on place of residence at onset might
miss clusters of unrecognized iatrogenic CJD if the surgery took place
relatively far away from the place of residence of individuals at onset.

In summary, we used three methods to investigate the geographical
distribution of sporadic CJD cases in France. Each of these methods
found some evidence of clustering, though the extent of that clustering
differed between approaches. The strongest evidence, statistically,
related to three cases living in a small rural area in South-West
France. Two of the three cases lived in the same area throughout life
and could have shared an environmental exposure to the infectious agent.
They had also both undergone surgery on several occasions. Little
information is available on the third case. The precise mechanism
underlying this cluster of cases remains, therefore, unclear. ...

snip... Subject: Occupational risk factors for the sporadic form of
Creutzfeldt-Jakob disease (FULL TEXT)
Date: Sat, 29 Nov 2003 13:09:20 -0600
From: "Terry S. Singeltary Sr."

{please note, scanned, copied, and corrected, could be errors..TSS)

La Medicina del Lavoro
Med Lav 2003; 94,4:353-363

Occupational risk factors for the sporadic form of
Creutzfeldt-Jakob disease


Dipardmento di Sanita Pubblica, Sezione di Medicina del Lavoro,
Universita di Cagliari
* Isdtuto di Medicina del Lavoro, Facolta di Medicina e Chirurgia A.
Gemelli, Universita Cattolica del Sacro Cuore, Roma


Creutzfeldt-Jakob disease; epidemiology; occupational health


Some case reports among European farmers and a few case-control
studies suggested the hypothesis of an increased risk of the
sporadic form of CJD (sCJD) associated with livestock farming or
work as a butcher. Also, the discovery of the possibility of
transmission of the disease via blood or by contact following
corneal or dura madre transplant suggested that health
occupations might also run higher sCJD risks. However, a
meta-analysis of three case-control studies and a multicentre
European study did not find any positive association between
sCJD and health-related jobs or occupational contact with
livestock, such as cattle and sheep, or animal products. To
explore possible occupational risk factors for Creutzfeldt-Jakob
disease (CJD), we used a publicly available US database including
about 6 million deaths in 24 states during 1984-95. Cases were
636 deaths (300 men and 336 women) with CJD (ICD-9 code 046.1)
as the underlying cause of death. Controls were 3,180 deaths
randomly selected from among those who died from all other
diseases except those affecting the central nervous system.
CJD cases represented a wide variety of occupations (159) and
industries (147). Among occupations and industries, for which
previous reports suggested potential exposure to a transmissible
spongiform encephalopathy (TSE) agent, the OR for CJD was
significantly increased among butchers (OR=6.8, 95% C.I. 1.5,
30.1, based on 4 cases and 3 controls), and persons working in
offices of physicians (OR=4.6, 95% C.I. 1.2, 17.6 based on 5
cases and 4 controls). Nine other occupations and seven other
industries, for which no previous suggestion existed in the
literature, also showed significant associations. Overall, our
results suggest that occupational exposures are not an important
source of sCJD infection. However, as the excess among butchers
and some workers in health occupations was consistent with
previous reports, more indepth research is warranted to address
the hypothesis.


«Fattori di rischio professlonale per la forma sporadica della
malattia di CreutzfeIdt-Jakob». L'epidemia delta cosiddetta
"nuova variante" della malattia di Creutzfeldt-Jakob (CJD) in
Gran Bretagna, e la sua dimostrata associazione con l'epidemia
di encefalopatia spongiforme bovina (BSE) in quello stesso Paese,
hanno ridestato l'in-

Pervenuto il 28.11.2002 - Accettato il 15.1.2003

Corrispondenza: Diparrimento di Sanita Pubblica, Sezione di
Medicina del Lavoro, Universita di Cagliari, via San Giorgio 12,

09124 Cagliari - Tel. 070-60285278 - Fax 070654350 -

Comunicazione orale alia XXV Riunione Annuale dell'Associazlone
Italiana di Epidemioloeia, Venezia 4 Ottobre 2001



teresse nei confronti di tutte leforme di questa rara malattia e
del suo possibile rapporto con alcune esposizioni in amblto
lavorativo. La descrizione di alcuni casi di CJD in contadini
europeifece ipotizzare che attivita quail l'all-evamento di
bovini o l'abbattimento degli stessi in mattatoi potessero
comportare un aumento del rischio di CJD. Inoltre, la possibility
di una trasmissione per via ematica o per contatto con materiali
biologici, successivamente ai trapianfi di dtira madre o di
cornea, fece sospettare che anche le professioni sanitane potessero
comportare un aumento del rischio di CJD. Tuttavia, una
meta-analisi di tre studi caso-controllo non dimostro una
associazione tra forma sporadica di CJD ed attivita sanitarie o
contatto con bovini ed ovini, ed uno studio multicentrico Europeo
non trovb akuna associazione con I'esposizione professionale ad
animali o pelli, mentre itrischio risultava elevato perfrequents
esposizlone a cuoio ed esposizione a fertilizzanti contenenti
zoccoli e coma. La dispombilita di un data-base pubblicamente
accessible, contenente i dati di circa 6 milioni di certificati
di morte in 24 Stati degli Stati Uniti nel periodo 1984-95, ha
consentito I'esplorazione dei rischi occupazionali di CJD in
questo Paese. Sono stati individual in tutto 636 casi (300 uomini
e 336 donne) di decessi per CJD (ICD-9 046.1). Come controlli
sono stati selezionati 3180 soggetti deceduti per altre patologie,
ad esclusione di quelle a carico del sistema nervoso centrale,
accoppiati in rapporto di 5:1 ai casi per area geografica'di
residenza, sesso, razza edeta. Tra le occupaziom sospettate a
priori di un'associazione, i macellai mostravano un OR di 6,8
(I.F. 95% 1,5, 30,1, basato su 4 casi e 3 controlli), ma un
risultato simile veniva osservato anche in altre nove occupazioni
non sospettate a priori di un'associazione. Il rischio non
risultava elevato per Ie attivita agricole nel complesso, o nelle
Industrie alimentan, mentre un OR di 4,6 (I.F. 95% 1,2, 17,6,
basato su 5 casi e 4 controlli) era associate al lavoro in
ambulaton medici, ma non in ospedali o altri servizi sanitari.
Altre sette attivita industriali, non sospettate a priori di
un'associazione, mostravano un significative aumento del rischio
di CJD. La dispersione dei casi di CJD in una grande varieta di
occupazioni induce a ritenere che le esposizioni professionali
contribuiscano scarsamente all'eziologia della forma sporadica di
CJD. D'altro canto, i risultati positivi potrebbero essere genera
ti dal caso data la molteplicita di con-fronti effettuati.
Tuttavia, appare opportuna la pianificazione di indagini
multicentriche piu approfondite che testino l'ipotesi del ruolo di
esposizioni professionali nell 'attivita di abbattimento degli
animali, insieme ad altri possibili fattori di rischio,
nell'eziologia di questa rara malattia.


The UK epidemics of the new variant form of
Creutzfeldt-Jakob disease (nvCJD), and its link
with bovine spongiform encephalopathy (BSE)
(46, 47) has raised interest in searching for etiolog-
ical clues for the more commonly seen, classic
forms of CJD. Classic CJD is a neurological disor-
der, classified in the group of transmissible spongi-
form encephalopathies (TSEs), that has been esti-
mated to affect approximately 1x10-6 persons per
year worldwide. It is invariably fatal, with a mean
illness duration of 5 months (47), and a median age
at death of 68 years (20). Some TSEs in humans
have been shown to be associated with mutations
in the prion protein (PrP) gene (PRNP) on chro-
mosome 20 (32), and a few are classified as familial
CJD. In patients affected by the non-familial spo-
radic form of classic CJD (about 85% of CJD cas-
es), a significantly increased prevalence of homozy-

gosity for methionine or valine at PrP codon 129
has been reported (25, 28, 37, 40). Based on the
scarce geographical variation in the occurrence of
sporadic CJD over long time periods, it has been
proposed that there is no environmental source of
infection (16, 31) and that the vast majority of cas-
es rather result from de novo spontaneous genera-
tion of a transmissible agent consisting of an ab-
normal form of a host-encoded glycoprotein (31).
This transmissible agent was given the name of
"prion" in 1982 (30). However, a 5-fold inter-re-
gional variation in the crude CJD mortality rate
occurred within Italy in 1993-99 (8). Also, the pro-
portion of polymorphism at codon 129 among
sCJD cases is more similar to that observed among
persons with iatrogemc CJD, than to that in the
general population, which suggested that simple
stochastic events would not fully explain SCJD
(33). Also, sCJD cases are tipically elderly, with
cortical symptoms, and abnormal PrP, but not



amyloid, deposits in the synapses, On the other
hand, nvCJD typically affects young people; it is
not associated with codon 129 polymorphism and
it does present amyloid plaques in the brain (47).

A substantial body of evidence supports the hy-
pothesis of blood transmission of the sCJD agent
in various animal species (41), depending on the
tissue level of PrP infectivity, the species barrier,
and the route of administration (33). However, the
risk of CJD transmission by transfusion remains
theoretical, since no confirmed cases have ever
been causally attributed to the receipt of a blood
transfusion, nor has any case developed in recipi-
ents of clotting factor concentrates, or pooled plas-
ma derivatives, to which a donor, who subsequently
developed CJD, had contributed (15, 27, 41). Also,
no known cases of CJD were attributable to the
reuse of percutaneous transluminal coronary angio-
plasty (PTCA) equipment contaminated by blood
(15). While the potential exists for blood transmis-
sion of the disease, thus far human epidemiological
evidence suggests that such an occurrence would be
rare, as only a small fraction of the general popula-
tion carrying codon 129 and codon 200 polymor-
phisms might be susceptible to infection, and most
transfusions might not contain infective doses suf-
ficient to cause the disease (33). On the other
hand, the hypothesis of a transmissible agent, pos-
sibly with blood, is supported by numerous clinical
reports of iatrogenic CJD consistently identifying
surgical procedures as a risk factor. Although such
a possibility was ruled out in an early study among
French cases occurring in 1968-77 (4), CJD cases
have been described after dura madre or corneal
transplants from infected donors (14, 21, 24, 26,
27, 29), neurosurgery of stereotactical encephalog-
raphy with contaminated instruments (3, 49), use
of GH hormonal extracts from cadavers (2), and
three epidemiological studies showed a higher
sCJD risk following general surgery (9, 22, 43).
However, while Australian authors interpreted the
evidence as an indication of the possibility of dis-
ease transmission (9), German authors suggested
stress as the relevant risk factor (22). Due to the
exceptional resistance of the infecting agent to
common sterilising agents, autoclave and sodium
hypochloride or hydroxide treatment, or formic

acid treatment of infected materials and instru-
ments has been suggested to prevent occupational
and/or iatrogenic transmission of the disease (34,
36), while formadehyde was not effective in pre-
venting transmission (33).

If blood transmission were important, occupa-
tional contact with animal blood, organs, and other
animal products would be a plausible co-factor in
sCJD etiology. In the pre-nvCJD-epidemic era, the
hypothesis of CJD as a zoonotic disease was raised
(23). As early as 1986, such a hypothesis was again
raised in a small French study (11). Occupational
contact with animals such as deer, monkeys, and
squirrels was associated with a non-significant 9-
fold increase in risk, while the excess risk of similar
degree associated with non occupational contact
with deer or rabbits was statistically significant.
Exposure to animal organs was also significantly
associated with CJD (OR=20.9; p<0.005) (11).
Following the nvCJD epidemics in the UK, clinical
reports of sCJD cases among livestock farmers and
butchers have been repeatedly published (17, 35,
44, 48), further suggesting that - if the link were to
be confirmed in analytical studies — transmission
via the blood or skin contact through skin lesions
with infected materials and/or instruments would
be important (19). Analytical studies have been less
numerous, and they are reported in table 1. A
meta-analysis of three case-control studies on
sCJD published at that time concluded that a non
significant association existed with livestock farm-
ing and with health related occupations (45). The
study of 662 sCJD deaths in 1970-96 in the Unit-
ed Kingdom found a significant excess risk among
livestock farmers (6 observed deaths versus 2.4 ex-
pected), although the interpretation was limited to
the absence of any link with the nvCJD epidemics
(10). All the observed cases were livestock farmers,
four of whom (0.6 expected) occurred in farms
where BSE cases had been reported. No cases were
observed among veterinarians (0.03 expected), or
butchers. (0.15 expected). A matched case-control
study of 206 sCJD cases and controls did not iden-
tify any association with a priori suspected occupa-
tions (38). However, 21 cases (10%) e 14 controls
(7%) occurred in subjects with occupational contact
with animal products (p=0.17). The authors did



Fable 1 - Studies of sCJD and occupation


Type of study Health Raising Butchers,

occupations cattle/sheep abattoir workers

Wientjens et al, 1996

Cousens et al, 1997

UK Nat CJD Surv Unit, 1997

Van Duijn et al, 1998

Aylin et al, 1999

UK Nat CJD Surv Unit, 2001**




Trend in proportional mortality


snip...not available...tss

* contact with animal products; ** combining nvCJD and sCJD cases

not explore this finding in detail. We conducted a
crude calculation based on the published data, and
we found instead an Odds Ratio of 1.6 (95% confi-
dence interval 1.18,2.15).

A European case-control study was conducted
by interviewing next-of-kins of 405 CJD cases and
405 hospital controls, excluding patients suffering
from dementia (42) .The authors reported a signifi-
cant excess risk associated with the use of fertilizers
containing substances derived from hoofs and
horns, and with contact with skin and fur not as
garments. Among individual occupations, only
butchers showed a non-significant increase in the
Odds Ratio. A proportional mortality analysis of
deaths from dementia in England and Wales dur-
ing 1979-96 did not find a consistently increasing
temporal trend in occupations suspected a priori of
being at risk, such as farmers, butchers and abattoir
workers, and veterinarians (1). Another prelimi-
nary combined case-control analysis of 102 nvCJD
cases and 197 sCJD cases, compared to 195 con-
trols, found no excess risk among health related oc-
cupations, butchers and abattoir workers, and other
occupations involving contact with animal products
(39). Eight out of 114 identified cases in Slovakia
had health related occupations (25).The authors
excluded a link between occupational factors and
CJD risk, although no formal analysis was con-
ducted in this regard, nor any information was pro-
vided on which were the occupations of the other
106 cases.

It is possible that, in the studies conducted thus
far, the small number of subjects in the occupations
at risk limited the exposure assessment to ever hav-
ing held a job considered a priori at risk, indepen-
dently of the period in the lifetime, duration, type
of animals, and actual job content. The methods
section of these papers do not explain whether
complete work histories were included in the ques-
tionnaire, or whether only one or more main occu-
pational titles or the last were collected. A further
problem in these studies is that information for
cases always relied on next-of-kin reporting, whilst
the same study subjects provided the information
in about half the hospital controls and in all popu-
lation controls.

Overall, the results of the studies conducted thus
far stress the fundamental requirement of having
experts in occupational epidemiology, agricultural
work technology and veterinarian hygiene par-
ticipating in planning and analyzing occupational

To examine the possible association of CJD with
occupational risk factors, we accessed a large pub-
licly available database, including death certificate
from 24 US states in 1984-95, to analyze the occu-
pations of the 636 deaths due to CJD therein re-
ported in comparison to 3,180 controls deceased
from other selected causes of death, in a country
thus far not affected by the nvCJD epidemics.


The 24 US states death certificates database we
used consists of several million coded death certfi-
cates from 24 US states, covering the years 1984-
95. The 24 states are: Colorado, Georgia, Idaho
(from 1988), Indiana (from 1986), Kansas, Ken-
tucky, Missouri (in 1984-86), Maine, Nebraska (in



1984-85), Nevada, New Hampshire, New Jersey
(from 1988), New Mexico (from 1986), North
Carolina (from 1987), Ohio (from 1985), Okla-
homa, Rhode Island, South Carolina, Tennessee
(in 1985-88), Utah (from 1985), Vermont, West
Virginia (from 1988), Washington (from 1989),
and Wisconsin. In addition to standardized coding
procedures, information on usual occupation and
kind of business or industry, reported in the death
certificate for each decedent, was included in the
database provided to the National Center for
Health Statistics (NCHS) (7). The information on
occupation and industry was coded according to
the 1980 US Bureau of the Census classification
(6). The underlying cause of death was coded ac-
cording to the International Classification of Dis-
eases - 9th revision. No further details, such as du-
ration of employment or concurrent diseases, are
available from this database. Among subjects 25
years of age or more at death, 636 cases of CJD
(ICD-9 code 046.1) were identified. Table 2 shows
the case distribution by age, and gender. Only 22
subjects were indicated as non-whites in the data
base. As we did not see any reason why a gross def-
inition of genetic background, such as the demo-
graphic concept of "race", should affect sCJD risk,
we included all subjects in the analysis. Eligible
controls were subjects who died from all other dis-
eases, except mental disorders (ICD-9 codes
290.0-319.9), diseases of the central nervous sys-
tem (ICD-9 codes 320.0-349.9), cerebrovascular
diseases (ICD-9 codes 430.0-438.9), unspecified
atherosclerosis (ICD-9 code 440.9), and ill defined
conditions and symptoms involving the central
nervous system (ICD-9 codes 780.0-781.9). We

Table 2 - Deaths from Creutzfeldt-Jakob disease in 24 US
states in 1984-95 by age, and gender

Age group Men Women
25-39 3 4
40-49 11 16
50-59 47 46
60-69 126 121
70-79 92 117
80 + 21 32
All ages 300 336

randomly selected five controls per each case with-
in the set of controls with the same geographic re-
gion, race, gender, 5-year age group, and year of
death as the index case. The Odds Ratio (OR) as-
sociated with a given occupation or industry cate-
gory was expressed relative to an unexposed refer-
ence group including all other occupation or indus-
try categories.

Odds Ratios (ORs) and their 95% confidence
intervals (95% C.I.) were derived from the respec-
tive log odds obtained with logistic regression
modeling, using the GMBO feature of the Epi-
cure® software. ORs were calculated for selected
demographic variables. We first calculated OR for
those occupations and industries for which litera-
ture reports suggested a potential association with
CJD. For occupations, these prior hypotheses were
livestock farmers, veterinarians, butchers and other
food-related occupations, pathologists and other
health professionals. For industries, those consid-
ered as prior hypotheses were livestock tanning,
slaughterhouses and meat processing plants, hospi-
tals and other health facilities. Secondly, we calcu-
lated OR for all occupations and industries for
which there were three or more exposed cases. Co-
variates in the logistic regression model for occupa-
tion and industry were age (5-year age categories),
marital status (never-married versus ever-married),
and socioeconomic status (SES) (five categories).
The SES indicator was obtained by categorizing
the Greens Standardized Scores for Specific Occu-
pations (13,18), as follows:

- low SES (score 21-39);

- medium-low SES (score 40-49);

- medium SES (score 50-59); 4. medium-high
SES (score 60-64);

- high SES (score >65).
Introducing gender as a covariate in the logistic
regression model did not change the risk estimates.


In the present study population, female cases are
more numerous than male, and more than 94 per-
cent of the cases died at age 50 or older (table 2).
Subjects who died from CJD were less likely to have


never been married and to have lived in the South,
and slightly more likely to have resided in metropol-
itan areas (not shown in the tables). The OR for
CJD increased with higher SES (test for trend,
p<0.001). This association persisted within strata of
latitude, geographic region, race (although numbers
were very small among African Americans), gender,
age, and marital status (not shown in the tables).

Overall, 159 occupation and 147 industry cate-
gories were represented among CJD cases, with 52
of the occupation and 54 of the industry categories
composed of at least three cases. A statistically sig-
nificant association with CJD was observed for
10/52 occupation categories (19%) and 8/54 indus-
try categories (15%), including disparate activities
such as financial managers, mechanical engineers,
teachers, military personnel, and persons working
in manufacture of toys, amusement, and sporting
goods, telephone utility companies, beauty shops,
and financial services (table 3). These associations
varied very little after limiting the analysis to sub-
jects aged 40 years or older.

Among food handling occupations, a prior hy-
pothesis in this study, a statistically significant asso-
ciation was observed for butchers (OR=6.8, 95%
C.I. 1.5, 30.1, based on 4 cases and 3 controls). The
OR was non-significantly elevated for miscella-
neous food preparation occupations (Census code
444: OR=3.2, 95% C.I. 0.9, 10.7, based on 4 cases
and 9 controls), a heterogeneous category which in-
corporates food preparation occupations other than
those with specific codes (such as cooks, waiters, or
bartenders). When we combined all food prepara-
tion occupations, no association was observed
(OR=1.1; 95% C.I. 0.5,2.3, based on 9 cases and 41
controls), suggesting that the observed excesses
were restricted to butchers and miscellaneous food
preparation occupations. No cases or controls were
coded as non-farm animal caretakers. One case and
no controls were classified as a hunter or trapper.
When examined by industry grouping (table 3) the
ORs were non significantly elevated in the meat
products industry (OR=3.8, 95% C.I. 0.8, 17.3,
based on 3 cases and 4 controls).

CJD was not associated with agricultural work.
The occupation of non horticultural farmer showed
a non significant 20% increase in risk. Among in-
dustries, a similar result was observed for crop pro-
duction (OR=1.2; 95% C.I. 0.6, 2.4, based on 12
cases and 73 controls), and livestock farming
(OR=1.2, 95% C.I. 0.3, 4.2, based on 3 cases and
17 controls).

Health-related occupations and industries were
also a prior hypothesis in this study. The excess ob-
served among physicians was not statistically sig-
nificant (OR=4.6, 95% C.I. 0.7, 29.0, based on 3
cases and 2 controls). No excess was observed for
nurses (occupational codes 095 and 207 combined:

OR=0.8, 95% C.I. 0.4, 1.5; based on 12 cases and
55 controls), or for all health related occupations
combined (OR=0.8; 95% C.I. 0.5, 1.5, based on 13
cases and 72 controls). No pathologists were re-
ported among cases. No veterinarians were report-
ed among cases versus one among controls.

Among health-related industries, a significant
association was observed for persons working in
offices of physicians (OR=4.6, 95% C.I. 1.2, 17.6,
based on 5 cases and 4 controls), but not for those
working in hospitals (OR=1.0, 95% C.I. 0.6, 1.7,
based on 22 cases and 95 controls), or health ser-
vices not elsewhere classified (OR=1.1, 95% C.I.
0.3, 3.8, based on 3 cases and 13 controls).

For the occupations and industries shown in
table 3, being a prior hypothesis of this study did not
increase the likelihood of a significant association
with CJD (1/6 or 17% significant findings among
prior hypotheses versus 9/46 or 20% among the other
occupations, and 1/7 or 14% among prior hypotheses
compared with 7/47 or 15% among the other in-


In this death certificate based case-control study,
we observed a statistically significant association of
CJD with work as a butcher and with employment
in the office of a physician, occupation and indus-
try categories for which previous literature reports
suggested potential exposure to a TSE agent.
However, other occupations and industries for
which the same hypothesis was raised, such as
work on a livestock farm, were unassociated with
CJD. The positive associations with the occupation


of butcher and employment in physician's offices
cannot be conclusively interpreted because of the
small numbers and lack of information on the type
and extent of exposure to potentially infectious
material. Also, other generally smaller studies of
CJD in Europe have not found specific associa-
tions with livestock farming or other specific occu-
pations, including health care workers (1,42).

In our study, significant associations were found
for CJD with 19 percent of the occupations and 15
percent of the industries composed of at least three
cases, and these proportions did not vary according
to being a prior hypothesis in this study or not. A
proportion of positive findings (about 5%) would
be expected to occur by chance. Relative differences
in ascertainment may also have contributed to pos-
itive findings for some high SES employment cate-
gories, such as financial managers, engineers,
teachers, drafting occupations, or work in insurance
firms and financial industries. In this data set, risk
for other neurological diseases, including
amyothrophic lateral sclerosis, multiple sclerosis,
and Parkinson's disease, also showed this pattern
(data not shown), suggesting a generalized diag-
nostic bias related to SES in diseases requiring a
more sophisticated diagnostic evaluation. The pos-
sible under-ascertainment of CJD deaths in the
lower SES categories may also explain some of the
deficit in CJD mortality previously reported among
African Americans compared to whites in the USA
(20). Therefore, as described in the methods sec-
tion, we adjusted by SES all risk estimates. The in-
crease in CJD risk for butchers and employees in
physicians offices persisted in the unadjusted
analysis or when the analysis was restricted to the
SES category they belonged.

An important limitation in our study is that it
was based on the one occupation and industry
combination on the death certificate of study sub-
jects, and no further details, such as duration of
employment, were available. This should be con-
sidered when interpreting our findings. One
strength of our study is the large number of CJD
deaths available for analysis (636 cases), as we uti-
lized the largest database possible to evaluate the
relationship of CJD with occupational risk factors.
Still, the numbers for specific occupations and in-
dustries are quite small, and chance could account
for the increases in risk observed in our study.

Disease misclassification was likely to be a mi-
nor problem in this study, as death certificates have
been shown to be a reasonably specific source for
ascertaining CJD cases (5, 12), and control subject;

were selected after excluding deaths linked to diag-
nostic codes conceivably including misdiagnosed
CJD cases. However, as it is not possible to distin-
guish familial from non-familial CJD cases within
a data base of coded death certificates, we cannot
assess whether and to what extent individual find-
ings may have been biased by poor diagnostic in-

While chance could account for the associations
we observed, their consistency with other pub-
lished clinical and epidemiological reports indicate
that further in-depth studies are warranted to eval-
uate the findings among butchers and employees in
physician's offices before concluding for a CJD ex-
cess in these jobs. The rarity of the sCJD has pre-
vented substantial progress in the knowledge of its
etiological factors. The international multicentre
approach, and a detailed occupational exposure as-
sessment performed by experts, would be crucial in
successfully identifying candidate risk factors...


Table 3 - Odds Ratio for Creutzfeldt-Jakob disease associated with
selected industries
and occupations (at least 3 exposed cases)


007 - Financial managers 6/5 4.2 (1.2-14.8)
019 - Managers and administrators, n.e.c. 36/151 0.9 (0.5-1.3)
023 - Accountants and auditors 6/24 0.9 (0.4-2.4)
056 - Industrial engineers 3/3 3.0 (0.6-15.6)
057 - Mechanical engineers 7/4 6.0(1.6-22.2)
084 - Physicians 3/2 4.6 (0.7-29.0)
095 + 207 - Registered nurses & licensed practical nurses 12/55 0.8
156 - Teachers, elementary school 16/63 1.0(0.5-1.8)
157 - Teachers, secondary schools 3/4 2.8 (0.6-12.8)
159 - Teachers, n.e.c. 5/6 3.5 (1.0-11.8)
176 - Clergy 3/14 1.1 (0.3-3.9)
185 - Designers 3/8 1.4 (0.4-5.5)
217 - Drafting occupations 3/4 3.8 (0.8-17.2)
243 - Supervisors and proprietors, sales occupations 22/97 1.1 (0.7-1.8)
253 - Insurance sales occupations 5/11 1.8 (0.8-5.3)
254 - Real estate occupations 3/9 1.3 (0.3-4.8)
259 - Sales representatives, mining, manufacturing, wholesale 7/16 1.7
263 - Sales workers, motor vehicles and boats 4/9 2.2 (0.7-7.0)
274 - Sales workers, other commodities 8/59 0.7 (0.3-1.4)
313 - Secretaries 14/73 1.0 (0.5-1.7)
337 - Bookkeepers, accounting, and auditing clerks 8/30 1.3 (0.6-2.9)
379 - General office clerks 10/30 1.7 (0.8-3.4)
407 - Private household cleaners and servants 9/39 1.7 (0.8-3.8)
417 - Firefighting occupations 3/7 2.1 (0.5-8.1)
435 - Walters and waitresses 4/22 1.1 (0.4-3.4)
436 - Cooks, except short order 5/30 1.1 (0.4-2.8)
444 - Miscellaneous food preparation occupations 4/9 3.2 (0.9-10.7)
447 - Nursing aides, orderlies, and attendants 3/39 0.5 (0.1-1.6)
449 - Maids and housemen 3/7 2.8 (0.7-11.0)
453 - Janitors and cleaners 5/50 0.7(0.3-1.7)
458 - Hairdressers and cosmetologists 6/8 3.7 (1.3-10.7)
473 - Farmers, except horticultural 14/87 1.2 (0.6-2.3)
518 - Industrial machinery repairers 3/3 5.2 (1.0-26.1)
529 - Telephone installers and repairers 3/2 7.2 (1.2-43.4)
558 - Supervisors, n.e.c. 3/17 0.9 (0.2-2.9)
563 - Bnckmasons and stonemasons 3/4 5.0(1.1-22.7)
567 - Carpenters 4/41 0.6 (0.2-1.7)
575 - Electricians 4/15 1.3 (0.4-4.0)
633 - Supervisors, production occupations 10/40 1.2 (0.6-2.5)
637 - Machinists 6/22 1.3 (0.5-3.3)
653 - Sheet metal workers 3/4 3.8 (0.8-17.2)
686 - Butchers 4/3 6.8 (1.5-30.1)
744 - Textile sewing machine operators 5/28 1.2 (0.4-3.1)
757 - Separating, filtering &, clarifying machine operators 3/2 7.2
779 - Machine operators, not specified 10/25 2.0 (0.9-4.2)
783 - Welders and cutters 3/20 0.9 (0.3-3.2)
785 - Assemblers 9/31 1.9 (0.9-4.2)
804 - Truck drivers, heavy 7/62 0.7(0.3-1.5)
844 - Operating engineers 3/7 2.1 (0.5-8.1)
877 - Stock handlers and baggers 3/8 2.0 (0.5-7.6)
889 - Laborers except construction 16/93 1.3 (0.7-2.5)
905 - Military 10/23 2.2 (1.0-4.6)

Table 3 - continued

Census/Code Cases/Controls OR (95% C.I.)


010 - Agricultural production, crops 12/73 1.2 (0.6-2.4)
O11 - Agricultural production, livestock 3/17 1.2 (0.3-4.2)
060 - Construction 26/179 0.8 (0.5-1.2)
100 - Meat products 3/4 3.8 (0.8-17.3)
142 - Yarn, thread and fabric mills 10/49 1.2 (0.6-2.4)
151 - Apparel and accessories, except knit 3/23 0.8 (0.2-2.6)
160 - Pulp, paper, and paperboard mills 4/12 1.7 (0.5-5.3)
172 - Printing and publishing, except newspapers 4/20 0.9 (0.3-2.8)
181 - Drugs manufacturing 3/5 3.0 (0.7-12.7)
192 - Industrial and miscellaneous chemicals 3/14 1.1 (0.3-3.9)
200 - Petroleum refining 3/11 1.2 (0.3-4.6)
270 - Blast furnaces, steelworks, rolling, and finishing 9/27 1.7 (0.8-3.7)
280 - Other primary metal industries 3/6 2.6 (0.6-10.3)
320 - Metal working machinery manufacturing 3/4 3.6 (0.8-16.4)
331 - Machinery except electrical, n.e.c. 5/20 1.1 (0.4-3.0)
342 - Electrical machinery, equipment and supplies 4/24 0.8 (0.3-2.4)
351 - Motor vehicles and motor vehicle equipment 13/43 1.7(0.9-3.1)
352 - Aircrafts and parts 6/16 1.8 (0.7-4.5)
371 - Scientific and controlling instruments 3/7 1.9 (0.5-7.5)
390 - Toys amusement, and sporting goods 3/1 18.3 (1.9-177)
392 - Not specified manufacturing industries 11/57 1.1 (0.6-2.1)
400 - Railroads 4/31 0.6 (0.2-1.8)
410 - Trucking service 9/51 1.0 (0.5-2.0)
441 - Telephone (wire and radio) 10/17 2.7 (1.2-5.9)
552 - Wholesale trade of petroleum products 3/4 3.8 (0.8-17.1)
601 - Grocery stores 4/33 0.6 (0.2-1.8)
612 - Motor vehicle dealers 9/25 1.8 (0.8-3.9)
620 - Auto and home supply stores 3/5 2.9 (0.7-12.1)
621 - Gasoline service stations 6/12 2.8 (1.0-7.4)
630 - Apparel and accessories stores, except shoe 4/17 1.1 (0.4-3.3)
641 - Eating and drinking places 13/70 1.0(0.5-1.8)
682 - Miscellaneous retail stores 3/13 1.1 (0.3-3.9)
691 - Not specified retail trade 3/25 0.6 (0.2-1.9)
700 - Banking 6/14 1.7 (0.7-4.6)
710 - Security, commodity brokerage, & invest, companies 3/4 3.5 (0.8-15.8)
711 - Insurance 17/29 2.6 (1.4-4.7)
712 - Real estate 9/30 1.3 (0.6-2.7)
742 - Business services, n.e.c. 3/18 0.8 (0.2-2.6)
751 - Automotive repair shops 4/18 1.3 (0.4-3.9)
760 - Miscellaneous repair services 3/15 1.1 (0.3-3.7)
761 - Private households 9/46 1.4 (0.7-3.1)
772 - Beauty shops 6/10 3.0(1.1-8.3)

812 - Offices of physicians 5/4 4.6 (1.2-17.6)
831 - Hospitals 22/95 1.0(0.6-1.7)
832 - Nursing and personal care facilities 3/21 0.8 (0.2-2.6)
840 - Health services, n.e.c. 3/13 1.1 (0.3-3.8)
842 - Elementary and secondary schools 34/128 1.2(0.8-1,8)
880 - Religious organizations 3/23 0.7 (0.2-2.3)
890 - Accounting, auditing, and bookkeeping services 4/9 1.9 (0.6-6.1)
901 - General government, not elsewhere classified 6/37 0.8 (0.3-1.8)
910 - Justice, public order, and safety 8/34 1.1 (0.5-2.5)
921 - Public finance, taxation, and monetary policy 4/3 5.5 (1.2-24.8)
931 - Administration and economic programs 3/10 1.4(0.4-5.0)
942 - Armed Forces 10/22 2.3 (1.1-4.9)

Note: N.e.c. = not elsewhere classified


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WHAT about humans exposed to animal TSEs, then operated on, and the agent passed as sporadic CJD VIA THE SURGICAL ARENA. ...TSS

Article Preview

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 mice as sCJD.

"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie,"

says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris.Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.Brain damageScrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.

Deslys and colleagues were originally studying vCJD, not sCJD. They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases:

a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain.As expected, they all affected the brain in a different way from BSE and vCJD. But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology.Multiple strains

"The main evidence that scrapie does not affect humans has been epidemiology,"

says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys.

"You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie," she says.

In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar.

But there are more than 20 strains of scrapie, and six of sCJD.

"You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys.

Bruce is cautious about the mouse results, but agrees they require further investigation. Other trials of scrapie and sCJD in mice, she says, are in progress.

Deformed proteins

People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD.

But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD.

"If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar,

"that could mean they were caused by infection."

There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain.Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.

Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.

More at: Proceedings of the National Academy of Sciences (vol 98, p 4142)

Correspondence about this story should be directed to letters@newscientist.com1900 GMT, 28 March 2001* New Scientist
Then follow up with PNAS studies from which new scientist article written from;

Published online before print March 20, 2001 Proc. Natl. Acad. Sci. USA, 10.1073/pnas.041490898 Abstract of this Article Reprint (PDF) Version of this Article Similar articles found in: PNAS Online PubMed PubMed Citation Search Medline for articles by: Lasmézas, C. I. || Deslys, J.-P. Alert me when: new articles cite this article Download to Citation Manager Neurobiology

Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt- Jakob disease: Implications for human health

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 [||] , 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; [Dagger ] 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.

Introduction Top Abstract Introduction Materials and Methods Results Discussion Conclusions References

The recognition of a variant of the human transmissible spongiform encephalopathy (TSE) Creutzfeldt-Jakob Disease (vCJD) in the U.K. in 1996 raised the major concern that it would correspond to human infection with the agent responsible for bovine spongiform encephalopathy (BSE; ref. 1). Transmission of BSE to macaques provided the first experimental evidence as it produced a disease close to vCJD in humans (2). Strain typing in inbred mice (consisting of measuring the incubation period and establishing lesion profiles corresponding to the strain-specific distribution of brain vacuolation) allows reliable identification of TSE strains (3). This method, together with biochemical methods, has revealed a single phenotype for the agents of BSE and the British cases of vCJD (4-6). Mice expressing only the bovine prion protein (PrP) were highly susceptible to vCJD and BSE, which induced the same disease (7). Thus, it is now well established that BSE has caused vCJD, probably by alimentary contamination. In this respect, the finding of abnormal PrP labeling in the gastrointestinal tract and lymphatic tissues of orally BSE-contaminated lemurs shows that the BSE agent can infect primates by the oral route (8). About 1 million contaminated cattle may have entered the human food chain, and the future number of vCJD cases could range from 63 to 136,000 depending on the incubation period of BSE in humans (9). Unlike sporadic CJD (sCJD) and iatrogenic CJD (iCJD) linked to the administration of contaminated growth hormone extracted from human hypophyses, in vCJD, the infectious agent seems to be widely distributed in lymphoid organs, as pathological PrP (PrPres) can be detected in tonsils, lymph nodes, spleen, and appendix even in the preclinical phase of the disease (10, 11). This raises a public health issue with regard to the risk of iatrogenic transmission of vCJD through surgical instruments, grafts, blood transfusion, or parenteral administration of biological products of human origin. However, this risk is difficult to assess, because it largely depends on factors such as the virulence of the BSE agent adapted to primates and the efficiency of secondary transmission to humans by a peripheral route such as the i.v. one. A further issue is whether vCJD accidentally acquired from humans would be recognized. The latter poses the question of a phenotypic variation of the BSE agent after successive transmissions in humans: does it retain its strain characteristics, and does it induce a pathology similar to that observed in the previous host? A 9-year history of transmission of BSE to primates and mice enables us today to clarify a number of these important points. Although BSE has mainly affected the U.K., two definite cases and one probable case of vCJD have now been reported in France in people who have never resided in the U.K. (12, 13). We strain-typed the first of these cases to establish its origin. Strain typing in C57BL/6 mice of BSE, French, and British vCJD was compared with that of BSE passaged in nonhuman primates, thus allowing us to study the effect of serial passages in primates. Comparisons were also made with French cases of sCJD and iCJD and two strains of scrapie (one of French and one of U.S. origin). Our findings provide experimental demonstration that the same agent, namely that responsible for the cattle disease BSE, has caused vCJD both in France and in the U.K., in line with biochemical data and with the fact that, until 1996, about 10% of the beef consumed in France was imported from the U.K. We found that the BSE agent in nonhuman primates is similar to that causing vCJD in humans and tends to evolve rapidly toward a primate-adapted variant. Furthermore, we showed that the strain responsible for iCJD is closely related to that of one patient with sCJD, and, more unexpectedly, that these agents were similar to the French scrapie strain studied (but different from the U.S. scrapie strain). This finding requires a cautious interpretation for several reasons, not least because of the inevitably limited number of TSE strains that can be studied by such a cumbersome method as strain typing. Nonetheless, it also prompts reconsideration of the possibility that, in some instances, sheep and human TSEs can share a common origin.



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: 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. 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.


Scrapie to Humans?

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


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