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From: TSS (216-119-143-222.ipset23.wt.net)
Subject: CHRONIC WASTING DISEASE IN UK DEER SEAC 85/2
Date: November 27, 2004 at 2:15 pm PST

-------- Original Message --------
Subject: CHRONIC WASTING DISEASE IN UK DEER SEAC 85/2
Date: Sat, 27 Nov 2004 16:07:38 -0600
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@LISTSERV.KALIV.UNI-KARLSRUHE.DE


##################### Bovine Spongiform Encephalopathy #####################

1
SEAC 85/2
CHRONIC WASTING DISEASE IN UK DEER
ISSUE
1. The FSA have asked SEAC to consider the current knowledge
on, and comment on the possible public and animal health
implications of, CWD in UK deer.
BACKGROUND
2. Over the past few decades, chronic wasting disease (CWD) has
emerged as an endemic transmissible spongiform
encephalopathy (TSE) in a number of captive and free-ranging
cervid species (mule and white-tailed deer and Rocky Mountain
elk) in some areas of North America. To date, CWD has not
been detected elsewhere in the world. CWD is naturally
transmissible from infected to susceptible cervids. The primary
route(s) of infection are unclear but it is possible that it may be
transmitted via contaminated environments. The origins of the
disease are unknown. CWD is the only known TSE to occur
naturally in cervids.
3. CWD is experimentally transmissible to non-cervid species by
intracerebral inoculation. Very few studies have investigated
experimental transmission to non-cervid species by oral routes
that may mimic the possible natural route(s) of infection. In these
studies, oral transmission of CWD has only been successful to
North American cervid species. Thus, it is unclear whether CWD
could be naturally transmitted to other cervid and non-cervid
species.
4. There is very limited epidemiological data on the possible
transmission of CWD to humans as a result of consumption of
infected venison. No definitive or suspected cases of
transmission of CWD to humans have been reported. Thus, it is
not known whether CWD can be transmitted to humans from
consumption of venison.
2
5. It is likely, prior to the reinforced mammalian meat and bone meal
(MMBM) ban in 1996, that both captive and free-ranging deer
species in the UK, and possibly elsewhere in Europe, were
exposed to contaminated feed. Studies investigating
experimental transmission of BSE to cervids have not been
completed. Although no TSEs have been detected in deer
populations in the UK (or elsewhere in Europe), surveillance data
are limited. Thus, it is possible that BSE may have been
transmitted to, and could be present in, UK deer. If present, deer
infected with BSE could present a risk to consumers of venison.
SEAC CONSIDERATION
6. SEAC has not considered CWD previously. The committee is
asked to consider the possible public and animal health
implications of CWD in UK deer with a view to producing a SEAC
position statement. The literature on CWD is extensive. It is
therefore, envisaged that this consideration could be conducted
over two consecutive meetings. The first meeting (SEAC 85)
would consider the current knowledge on TSEs in deer. A list of
possible areas for discussion is given at the end of the paper with
a view to formulating a draft position statement and identifying
key issues and questions for further discussion at the next
meeting (SEAC 86). If SEAC require, it may be possible to invite
an expert on CWD to SEAC 86 to provide additional expertise for
consideration of the key issues identified.
7. This paper provides the following information:
" Two recent scientific reviews on CWD from the Wildlife
Information Network (October 2004) and the EU Scientific
Steering Committee (March 2003).
" An overview of the UK deer industry (2002).
" A summary of current TSE surveillance in deer in the UK and
elsewhere in Europe as well as an EFSA opinion on TSE
surveillance in deer.
" A summary of current FSA research on the susceptibility of UK
red deer to BSE infection.
" Possible exposure of UK deer to TSEs as well as sources and
consumption of venison in the UK.
3
REVIEWS OF CWD
Wildlife Information Network
8. A review of available scientific literature (up to October 2004) on
CWD has been prepared by the Wildlife Information Network
(Annex 1). It covers current knowledge in the following areas:
" Distribution and host range
" Diagnosis and detection
" Epidemiology
" Susceptibility and routes of transmission
" Public and animal health implications
Scientific Steering Committee
9. The TSE/BSE ad hoc group of the EU Scientific Steering
Committee (SSC) conducted a review of the scientific literature
on CWD in March 2003 (Annex 2). The SSC concluded that:
A theoretical risk for prion transmission to humans consuming
products of CWD affected-cervids of all ages in countries where
CWD exists cannot be excluded. Similarly, a transmission risk of
prions to domestic animals cannot be excluded. There is
therefore, a scientific basis on which to exclude tissues from
animals that carry a CWD risk from the human and animal feed
chains.
However, the early and widespread involvement of tissues in
CWD infected animals does not allow a SRM list, neither to define
any lower age cut-off as has been defined for cattle in relation to
BSE. Neither is there sufficient knowledge to define exclusions or
amendment of any SRM rule of the basis of relative genetic
resistance to infection as has been proposed for sheep and goats
in the event that evidence indicates the probable natural
occurrence of BSE in these species.
Although available information indicates imports of live Cervidae
from North America to EU and trade in meat products from cervid
species as being negligible, it is important to reach certainty that
no transfer of risk takes place through trade of live cervids and its
derived products.
At present, there is no scientific data that CWD is occurring in
Cervidae elsewhere than in those countries from which it has
previously been reported. However, systematic TSE surveillance
4
of cervid populations has either been absent or has only just
started in European countries. Until the results of such
surveillance become available no conclusion can be drawn with
regard to the occurrence of CWD or similar TSE in the cervid
population of Europe.
REPORT ON THE UK DEER INDUSTRY
10. Information on the deer industry and venison trade in the UK is
limited. A 2002 report by Professor Ranald Munro (Royal (Dick)
School of Veterinary Studies, Edinburgh) provides an overview of
the type (wild, farmed, park or zoo), size and geographical
distribution of the five main deer species in the UK (Annex 3).
Information on trading and slaughter practices, routes of supply of
venison into the food chain and disposal of fallen stock and byproducts
is also provided. The report was commissioned by
Defra and FSA to inform surveys of TSEs in UK.
11. In the report, Professor Munro makes a number of observations
about the possibility of TSEs in UK deer (pages 43 and 48-50):
" Although surveillance is limited, as yet, CWD has not been
found in deer populations in the UK.
" Prior to the reinforced MMBM ban in 1996, deer were exposed
to feed potentially contaminated with MMBM.
" Red deer, a deer species prevalent in the UK, are closely
related to Rocky Mountain elk (a North American species
known to be susceptible to CWD). Thus, of the five principal
UK deer species (red, roe, fallow, sika and muntjac), red deer
may be the UK species with the greatest potential to develop
TSEs.
" Early in the BSE epidemic, cases of BSE occurred in
zoological collections of a number of species (antelope,
Ankole cattle, bison, eland, oryx, gemsbok, kudu and nyala)
presumably from the use of feed concentrates contaminated
with MMBM. Although deer in zoos were fed similar
concentrates, there are no reports of BSE cases in these
animals.
SURVEILLANCE OF TSEs IN EUROPEAN DEER
12. Limited surveys have been carried out for TSEs in European deer
populations but, to date, these programmes have not reported
5
TSE cases. A summary of TSE surveys of deer in the UK and
other EU Member States is given at Annex 4.
13. The European Food Safety Authority (EFSA) recently published
an opinion on proposals for an EU surveillance programme for
TSEs in deer (2004) (Annex 5). The opinion is under
consideration by the EU.
FSA RESEARCH ON TSEs IN DEER
14. A FSA funded study is underway to investigate if UK red deer (a
species closely related to Rocky Mountain elk) are susceptible to
BSE infection by oral or intracerebral challenge (Annex 6). The
study is in its early stages and is due to complete in 2007. To
date, there are no clinical or pathological signs of BSE in orally or
intracerebrally challenged animals at 12 or 6 months postadministration,
respectively. Please note that Annex 6 has not
been circulated outside the committee as it contains new
scientific data that has not yet been published in a scientific
journal.
ANIMAL EXPOSURE AND VENISON CONSUMPTION
Potential exposure of UK deer to TSEs
CWD
15. No live cervids from North America have been imported into the
EU (see Annex 2, page 38). In addition, HM Customs and Excise
have no record of imports of live cervids from North America into
the UK. Thus, opportunities for natural transmission of CWD from
infected animals imported from North America into the UK or
Europe have not been available.
BSE
16. There are no quantitative data that would allow an estimation of
past exposure of wild, farmed or park (and zoo) deer to animal
feed containing MMBM. However, it appears likely that each of
these deer populations consumed MMBM to some extent (see
Annex 3 page 10).
6
Sources and consumption of deer and elk products in the UK
17. In the UK, much of the venison from wild deer is exported (see
Annex 3, pages 29-33). However, most venison from UK farmed
deer is sold in the UK (see Annex 3, pages 38-39).
18. Specific figures for imports of edible deer and elk products from
North America into the EU are not available. However, figures for
game meat (excluding rabbits, hares and swine) suggest that a
very limited quantity of deer and/or elk meat may have been
imported from North America into the EU, including the UK, over
the period 1988-2001 (see Annex 2, pages 51-52). More recent
information (2001-2004) from HM Customs and Excise supports
this conclusion.
19. There are few data on consumption of UK produced or imported
venison. National Diet and Nutrition Surveys1,2,3 provide profiles
of eating habits in the UK. An analysis of the surveys indicates
that venison is rarely consumed in comparison with beef and
lamb (of the combined total of 5608 consumers in the surveys,
2064 (37%) had consumed lamb, 4819 (86%) had consumed
beef and 12 (0.2%) had consumed venison). Data on venison
consumption from the surveys suggest a trend towards increased
venison consumption (0.14% versus 0.41% of consumers ate
venison in the years 1986/7 and 2000/1, respectively). However,
the data are too limited to allow a quantitative assessment of
venison consumption.
ADVICE SOUGHT FROM THE COMMITTEE
20. The committee is asked to consider the possible public and
animal health implications of TSEs in UK deer with a view to
producing a SEAC position statement. The FSA have asked that
SEAC address the following question in the position statement:
" What is the level of risk posed to consumers from
eating meat from a CWD infected animal?
21. To help its consideration the committee may wish to consider the
following areas:
1J Gregory, K Fisher, H Tyler & M Wiseman. Dietary and Nutritional
Survey of British Adults, HMSO, 1990.
2S Finch, W Doyle, S Lowe, C Bates, A Prentice, G Smithers & P Clarke.
National Diet and Nutritional Survey;
People 65 Years and Over. Volume 1: Report of the Diet and Nutrition
Survey, TSO 1998.
3L Henderson, J Gregory & G Swan. National Diet and Nutritional Survey;
Adults Aged 19 to 65 years. Volume 1:
Types and Quantities of Foods Consumed, TSO 2002.
7
" possible origins of CWD.
" possible routes of intra- and inter-species transmission of
CWD.
" potential susceptibility of UK cervid and non-cervid
(livestock) species to CWD.
" likelihood of the presence of TSEs in UK deer.
" possible human and animal health risks of TSEs in UK
deer.
Are members aware of any other data that can add to the
information in this paper?
Would the committee wish to invite an expert on CWD to the next
meeting and, if so, could members suggest a particular expert?

http://www.seac.gov.uk/papers/tsesdeer-%20final.pdf

CWD Review / Dr Debra Bourne / October 2004 / For SEAC / Page 1 of 66
CHRONIC WASTING DISEASE REVIEW
Written by Dr Debra Bourne, Wildlife Information Network, October 2004,
for SEAC
[Wildlife Information Network (WIN) is a UK Registered Charity (No.
1048059) WINs aim
is to "disseminate information on the health and management of
free-ranging and captive
animals and their environments, together with emerging infectious
diseases, to professionals
and decision-makers worldwide." The main way in which WIN achieves this
is through
development of the WildPro® Electronic Encyclopaedia, which is made
available through a
website (www.wildlifeinformation.org) and as CD-ROM volumes.]
CWD Review / Dr Debra Bourne / October 2004 / For SEAC / Page 2 of 66
RESOURCES USED IN WRITING THIS REVIEW
This review was based on a peer-reviewed Wildlife Information Network CD-ROM
(Wildpro v5.0 Chronic Wasting Disease in Deer and Elk (Bourne, D.C.,
Dein, F.J. &
Boardman, S.I. (eds.). Wildlife Information Network, Twycross, UK. ISBN
0-9547185-4-
2. This volume of Wildpro is accessible at www.wildlifeinformation.org
and was based
on references found by the following methods:
" Searches on PubMed using various keywords including CWD, Chronic
Wasting
Disease and transmissible spongiform encephalopathy, together with other
keywords (transmissible mink encephalopathy/TME, feline spongiform
encephalopathy/FSE etc.) for comparative data. Searches were also
carried out using
names of key authors, e.g. ORourke and Williams, ES.
" Searches on Agricola, Biological Abstracts, CAB Abstracts, Wildlife
Worldwide and
Zoological Record. Keywords used included chronic wasting disease, CWD,
transmissible spongiform encephalopathies, bovine spongiform encephalopathy,
scrapie, transmissible mink encephalopathy, fatal familial insomnia,
kuru, Gerstmann-
Straussler-Scheinker, feline spongiform encephalopathy and nvCJD.
" Abstracts of papers found from database searches were read and
relevant papers (all
papers on CWD plus key and review papers on other TSEs/general prion
science)
were then examined in more detail.
" For key journals such as Emerging Infectious Diseases and Journal of
General
Virology, the contents list of every volume was checked, or keyword
searches were
performed on the website of the individual journal.
" Reference lists of papers on CWD were traced backwards, particularly
those from
both recent and early review articles on the topic. Similar tracing back
was performed
for papers on other TSEs and general papers on TSEs/prion science, where
this was
felt appropriate.
" Key proceedings were checked, e.g. proceedings of conferences on
CWD/TSEs and
certain other conferences such as the Proceedings of the Wildlife
Disease Association
and the US Animal Health Association.
" Reference lists on CWD/TSEs compiled by other organisations were checked,
particularly that of the National Wildlife Health Center, USGS
" ProMED-Mail was utilised as a means of detecting emerging information,
for example
initial reports of findings of CWD in new geographical areas.
" For data on geographical range and incidence, relevant federal and
state/provincial
websites were searched, e.g. CFIA, APHIS, Colorado Fish & Game, Wisconsin
Department of Natural Resources. Such sites also provided additional
material such as
the Wisconsin DNRs Environmental Impact Statement and An Analysis of
Risks
Associated with the Disposal of Deer from Wisconsin in Municipal Solid Waste
Landfill.
" Published data from journals, books, proceedings and Websites was
supplemented by
personal communications from people working on CWD in Wisconsin and
elsewhere
in the USA
In addition, for this report, data specifically concerning CWD was
updated by searches on
PubMed, tracking back from recent papers, checking key websites and key
journals and using
some more general web searches (on Google) using carefully chosen
keyword combinations.
Very recent findings were confirmed or expanded, where required, by
contacting key
researchers.
CWD Review / Dr Debra Bourne / October 2004 / For SEAC / Page 3 of 66
CONTENTS
1)
INTRODUCTION................................................................................................................
5
2) EMERGENCE, AETIOLOGY AND POSSIBLE ORIGINS
.......................................... 5
Emergence/History.................................................................................................................
5
Aetiology...............................................................................................................................
6
Strains of CWD?
................................................................................................................
6
Possible Origins of
CWD.......................................................................................................
7
Scrapie...............................................................................................................................
7
Development from a spontaneous or genetic SE in mule deer
.......................................... 8
Unknown
source.................................................................................................................
9
Alternative suggestions considered and rejected
............................................................... 9
Familial or genetic
association.......................................................................................
9
Animal protein fed to the
deer........................................................................................
9
3) KNOWN GEOGRAPHICAL DISTRIBUTION AND TIMELINES OF SPREAD...... 9
In captive cervids
...................................................................................................................
9
In research facilities
.........................................................................................................
10
In farmed
cervids..............................................................................................................
10
Canada.........................................................................................................................
10
USA.............................................................................................................................
11
Outside North America
................................................................................................
12
In free-ranging cervids
.........................................................................................................
12
USA.................................................................................................................................
12
Canada.............................................................................................................................
16
Outside North America
....................................................................................................
16
4) HOST
RANGE...................................................................................................................
16
Known natural
hosts.............................................................................................................
16
Experimental transmission by intracerebral
inoculation...................................................... 16
Experimental transmission by oral
inoculation....................................................................
18
Experimental transmission by
contact..................................................................................
19
Natural transmission by contact/environmental contamination
........................................... 19
5) CWD IN THE KNOWN NATURAL
HOSTS................................................................. 19
Clinical signs in cervids
.......................................................................................................
19
Clinical signs in Cervus elaphus
nelsoni..........................................................................
20
Clinical signs in Odocoileus hemionus
............................................................................
20
Clinical signs in Odocoileus virginianus
......................................................................... 21
Incubation period in
cervids.................................................................................................
21
Morbidity/mortality in cervids
.............................................................................................
22
Pathological
findings............................................................................................................
22
Gross
pathology................................................................................................................
22
Histopathology
.................................................................................................................
23
Electron
microscopy.........................................................................................................
23
PrP deposition
..................................................................................................................
24
Pathogenesis
.........................................................................................................................
25
Early lymphoid
tropism....................................................................................................
25
Changes in distribution of PrP and lesions with time during
infection............................ 26
Variations between species
..............................................................................................
26
Individual variation
..........................................................................................................
27
6) DIAGNOSIS
.......................................................................................................................
27
Histopathology
.....................................................................................................................
27
Immunohistochemistry.........................................................................................................
28
Electron
microscopy.............................................................................................................
29
Other
tests............................................................................................................................
29
CWD Review / Dr Debra Bourne / October 2004 / For SEAC / Page 4 of 66
ELISA..............................................................................................................................
30
Immunoblotting................................................................................................................
30
Conformation-dependent immunoassay (CDI)
................................................................ 31
Limitations of rapid
tests......................................................................................................
31
Choice of tissues for testing
.................................................................................................
32
7) EPIDEMIOLOGY AND
TRANSMISSION....................................................................
32
Potential sources and transmission
routes............................................................................
33
Contact
.............................................................................................................................
34
From enclosures previously used by infected
animals..................................................... 34
From carcasses
.................................................................................................................
34
Problems of eradication/environmental
contamination........................................................ 35
Epidemiology and spread in captive and farmed
cervids..................................................... 35
Epidemiology and spread in free-ranging
cervids................................................................ 36
8) SUSCEPTIBILITY WITHIN THE KNOWN NATURAL
HOSTS.............................. 38
Genetics in Cervus elaphus nelsoni
.....................................................................................
38
Genetics in Odocoileus hemionus
........................................................................................
38
Genetics in Odocoileus virginianus
.....................................................................................
39
Age specific
susceptibility?..................................................................................................
40
Effect of sex on susceptibility?
............................................................................................
41
9) ANIMAL HEALTH CONCERNS
...................................................................................
42
Potential risk to other
Cervidae............................................................................................
42
Surveillance
studies..........................................................................................................
42
Reindeer (caribou)  Rangifer
tarandus.......................................................................
43
Common European deer species  red deer Cervus elaphus elaphus, roe deer
Capreolus capreolus and fallow deer Dama
dama...................................................... 43
Potential risk to domestic cattle & sheep
.............................................................................
44
Potential risk to other
species...............................................................................................
44
10) HUMAN HEALTH CONCERNS
..................................................................................
44
Epidemiological investigations
............................................................................................
45
Laboratory studies
................................................................................................................
47
Potential risk from consuming cervid
products....................................................................
48
Velvet antler
.....................................................................................................................
48
Consumption of venison and other parts of the
animal.................................................... 48
Potential risk from handling and processing cervids
........................................................... 48
Potential risk from disposal of carcasses and subsequent contamination
of ground/water/air
.............................................................................................................................................
48
TABLES.................................................................................................................................
49
Table 1: Summary of results of CWD transmission
experiments........................................ 49
Table 2: Summary of PRNP gene differences between species and
polymorphisms within
species for the known natural hosts of
CWD.......................................................................
52
Table 3: Comparison of PRNP sequence variations from some North American and
European cervid species
.......................................................................................................
53
REFERENCES......................................................................................................................
54

snip...

CWD Review / Dr Debra Bourne / October 2004 / For SEAC / Page 44 of 66
Potential risk to domestic cattle & sheep
211. To date, no transmission of CWD has been reported in domestic
species living in
CWD endemic areas or in research facilities with CWD. Monitoring is
ongoing (Gould et al.,
2003; Williams & Miller 2002; Belay et al., 2004). It has been possible
to infect domestic
cattle, goats and sheep by intracerebral inoculation, although not in
all inoculated individuals
(Hamir et al., 2003a; Hamir et al., 2004a); see paragraphs 66-67. Data
from intracerebral
inoculation experiments show that diagnostic methods currently in use
for BSE surveillance
would detect the CWD agent in cattle and sheep if it were present (Hamir
et al., 2003a).
212. Data from in vitro experiments suggests that there may be a
considerable species
barrier limiting transmission of CWD from cervids to domestic cattle
and, to a lesser extent,
to domestic sheep. In a cell-free conversion system, PrPCWD from elk,
mule deer or whitetailed
deer showed 5-to-12-fold lower conversion efficiency of bovine PrP-sen
than for intercervid
conversion reactions; conversion efficiency of ovine PrP-sen (ovine
PrP-AQ) was also
less than half as efficient as for homologous cervid reactions (Raymond
et al., 2000).
213. There is a theoretical risk than CWD could be transmitted to cattle
via incorporation of
infected tissue from Cervidae into meat and bone meal. The risk for this
occurring in the USA
was considered [in 1992] to be small because CWD is believed to be rare
and localized, and
the proportion of harvested Cervidae whose offal is rendered is probably
small [in the USA]
(Saunders, 1994). The feeding of ruminant-derived protein to ruminants
has been banned in
Canada and the USA since 1997 (Kahn et al., 2004). The US Food and Drug
Administration
(FDA) has, since November 2002, banned the use of material from Chronic
Wasting Disease
(CWD)-positive animals, or animals at high risk for CWD, to be used as
an ingredient in feed
for any animal species. Animals considered to be at high risk for CWD
were stated to
include animals from CWD-positive captive herds, free-ranging animals
from the CWDendemic
area in Colorado and Wyoming, deer from the CWD eradication zone in
Wisconsin
and also deer from any areas designated around any new foci of CWD
infection that might
be identified through surveillance or hunter harvest testing (FDA,
2002). Such policies
should minimise the potential oral exposure of domestic ruminants to
CWD-agent in feed.
Potential risk to other species
214. Since BSE appears to have been transmitted orally to various
Felidae (Kirkwood et
al., 1995; Bourne, 2004b), the possibility of CWD being transmitted to
carnivores must be
considered.
215. Experimentally, CWD has been successfully transmitted by
intracerebral inoculation
to domestic ferrets (Mustela putorius fero) and to American mink
(Mustela vison), but not to
common raccoons (Procyon lotor) (Williams, Young & Marsh 1982; Williams
& Young,
1992; Williams et al., 1992; Hamir et al., 2003c; Sigurdson et al.,
2003). Since raccoons are
highly adaptable carnivores which may include carrion in their diet
(Hamir et al., 2003c), the
lack of success in transmission of CWD to raccoons even by intracerebral
inoculation is
encouraging.
216. There is no published data on transmission or attempted
transmission of CWD to
felids or canids.
10) HUMAN HEALTH CONCERNS
217. To date there are no known cases of human prion disease
attributable to CWD
transmitted to humans (Belay et al., 2004). While limited
epidemiological investigations to
date have not shown any links between CWD and humans with spongiform
encephalopathies
CWD Review / Dr Debra Bourne / October 2004 / For SEAC / Page 45 of 66
this data must be considered along with a caveat: because CWD is a
relatively new TSE, it is
unlikely that enough people have consumed enough CWD-affected cervids to
result in a
clinically or pathologically recognizable disease attributable to CWD,
especially considering
the very long incubation periods characteristic of TSE diseases. (Race
et al., 2002)
Epidemiological investigations
218. Epidemiological investigations have failed to show any links
between cases of prion
disease in unusually young people or in hunters in the USA and CWD (CDC,
2003). Two
major epidemiological investigations have been carried out, one on cases
of CJD in unusually
young individuals in the USA, the second on a group of men from
Wisconsin who developed
neurological diseases.
219. The first study (Belay et al., 2001) focused on three individuals,
two 28 years of age
and the third 30 years old, diagnosed with CJD in the USA between 1st
January 1997 and 31st
May 2000, and without any established risk factors for CJD (family
history, receipt of human
growth hormone, receipt of grafts of dura mater or cornea, or previous
neurological surgery)
and concluded that there was no strong evidence for a causal link with
CWD. None of the
individuals had travelled to Europe (therefore a link with BSE was
unlikely). Two of the
individuals were hunters who regularly consumed game meat while the
third (case 1) had, as a
young child, regularly consumed venison from animals hunted by family
members and on two
occasions from a family friend. Two of the individuals (cases 1 and 2)
had undergone tonsillar
surgery as children; the third had never received any surgical
treatment. One individual (case
1) had eaten venison mainly hunted in Maine, occasionally hunted in New
Jersey, and, on two
occasions at about six years old, elk meat which had probably been
harvested in Wyoming.
The second person (case 2) had hunted cervids mainly in Utah, but had
harvested an elk in
southwestern Wyoming on one occasion (less than three years before onset
of clinical signs)
and had hunted in British Columbia on one occasion nine years before
onset of illness. The
third person (case 3) had hunted close to home and never in Colorado or
Wyoming although
the plant where he took his carcasses for processing did also process
some elk from Colorado
each year. The clinical signs, duration of illness and histopathological
findings for the three
individuals showed no obvious similarities to one another. One
individual was
methionine/methionine homozygous at codon 129 of the PRNP (case 1), one was
homozygous for valine at this gene (case 2) and the third (case 3) was
heterozygous
methionine/valine. Immunohistochemistry revealed strong staining with a
synaptic pattern
in the first individual and weak staining with a synaptic pattern in
the second case; in case
3, based on a brain biopsy sample obtained at an early point in the
illness, staining was
questionable and possibly showed a synaptic pattern. Cases 2 and 3
showed a Type 1
immunoblot pattern, this test had not been carried out for case 1. It
was noted that none of
these three individuals had a definite history of consumption of venison
from the geographical
areas in which CWD was known to be endemic in Colorado and Wyoming, and
no CWD had
been identified in 299 deer and sampled from the area in which most of
the venison consumed
by patient 1 had originated, nor in 404 deer and 196 elk sampled from
the area in which most
of the venison consumed by patient 2 had originated, nor in 138 deer
samples from the area in
which most of the venison consumed by patient 1 had originated.
Additionally, there was no
homogeneity in phenotypic expression of the disease and all three
possible options for coding
at codon 129 of the PRNP gene were represented. Since a survey had
indicated that
approximately 40% of blood donors in the USA consumed venison from wild
cervids, it was
considered most likely that coincidence explained why three of the four
young (30 years old
or younger) individuals with sporadic CJD reported in the USA after
March 1996 had
consumed such meat (Belay et al., 2001).
CWD Review / Dr Debra Bourne / October 2004 / For SEAC / Page 46 of 66
220. The second major epidemiological investigation centred around three
men from
Wisconsin and Minnesota who had died from degenerative neurological
illnesses and who
had participated in wild game feasts in northern Wisconsin. Full
investigation including
examination of fixed brain tissue confirmed CJD in only one of the three
individuals. Wild
game eaten during the feasts was harvested mainly in Wisconsin but also
in areas of
Colorado, Wyoming and Montana; CWD was not known to be endemic in the
areas where the
game was hunted at the time that the game was harvested. Further
investigations of other
possible attendees of the feasts revealed 34 participants, all male, of
whom a total of seven
were deceased, including the three individuals in the initial
investigation. Causes of death in
the other four deceased individuals were not attributed to nor
associated with any
degenerative neurological disorder and no signs or symptoms associated
with a degenerative
neurological disorder were noted for any of the remaining living
participants of the feasts. It
was noted that only one case of CJD had occurred among known
participants at the feasts,
that this case was consistent with the commonest form of sporadic CJD,
that this individual
had only participated in one feast and that it was unlikely that he had
consumed CWDinfected
venison at the feasts because venison and other game from outside
Wisconsin that
was served at these feasts did not originate from known CWD-endemic
areas. Limitations of
the investigations were noted to include reliance on recall of events
from up to 25 years
previously and the fact that not all participants in the feasts could be
contacted and
interviewed. However, those who were interviewed agreed in their recall
of events (CDC,
2003).
221. It is important to recognise that the limited epidemiological
investigations that have
been carried out are not able to rule out the possibility that CWD might
play a role in causing
illness in humans (CDC, 2003).
222. Three further cases of prion disease in young humans in the USA
have been
investigated for possible links to CWD (Belay et al., 2004). The first
case was a 25-year-old
man who died in 2001 after about 22 months of illness. Gerstmann-
Sträussler-Scheinker
syndrome (GSS) was diagnosed by analysis of the prion gene, with a P102L
mutation
together with valine at codon 129 in the mutant allele. It was noted
that the disease had
occurred at an unusually young age, even for GSS, and the possibility
that exposure to CWDinfected
venison contributed to early onset of the disease could not be ruled
out; the patients
grandfather had regularly hunted in southeastern Wyoming, around the
known CWD-endemic
area, and had given venison to the patients family. Two other cases of
prion disease occurred
in individuals of 26 and 28 years of age, from adjacent counties, and
with onset of illness only
months apart, therefore an environmental source of infection was
investigated. However,
these two individuals were finally diagnosed with different prion
diseases: sporadic CJD in
one case and GSS in the other, indicating that a common cause was
unlikely. In the first case
CJD was confirmed from autopsy samples (by histopathology,
immunohistochemistry and
immunoblotting); the individual had no history of hunting nor of regular
consumption of
venison, and although he may have eaten venison originating from the
Upper Peninsula of
Michigan while at college CWD has never been detected in deer from Michigan.
Phenotypically this individual fit the MM2 sporadic CJD phenotype
described by Parchi et
al. (1999). In the other case post mortem immunohistochemistry revealed
prion deposition
which was consistent with GSS and a GSS P102L mutation was detected in a
blood sample
from one parent (appropriate samples were not available from the
affected patient); this
individual may possibly have eaten venison from Michigan on one occasion
at about two
years of age (Belay et al., 2004).
223. A further three cases of CJD in individuals of 54 to 66 years old
who were deer and
elk hunters (two individuals) or ate wild-harvested venison (one
individual) have been
CWD Review / Dr Debra Bourne / October 2004 / For SEAC / Page 47 of 66
investigated. There was no evidence that any of these individuals had
hunted in known CWDendemic
areas; information available indicated hunting or eating venison from
Washington
State and Pennsylvania. Two individuals were V/V at codon 129 the third
was M/M; they
were considered to fit known subtypes of sporadic CJD (MM1, VV1 and VV2
subtypes as
described by Parchi et al. (1999)). Further investigations were also
made on the only two
nonfamilial cases of CJD in individuals with a history of eating venison
from the known
CWD-endemic areas. One was reported to have eaten venison from two deer
harvested in an
area with endemic CWD, but both deer had been tested and not found to be
CWD-positive;
the patients illness was consistent with the CJD subtype MM1. The other
individual grew up
in a CWD-endemic area and ate locally-harvested venison; her disease fit
the MM1 CJD
phenotype and no atypical neurological features were noted (Belay et
al., 2004).
224. Additional epidemiological notes are that the incidence and age
distribution of CJD in
Colorado and Wyoming, where CWD is thought to have been endemic for
decades, are
similar to those found in other areas of the USA. In Wyoming, seven
cases of CJD have been
reported between 1979 and 2000 with an average annual age-adjusted CJD
death rate of 0.8
per million and no cases reported in humans less than 55 years old. In
Colorado in the same
period 67 cases of CJD have been reported, with an average annual
age-adjusted CJD death
rate of 1.2 per million (Belay et al., 2004).
225. In summary, there is no evidence of an increase in incidence of CJD
in Colorado and
Wyoming, nor have epidemiological investigations carried out so far
found any evidence of a
link between CWD and cases of CJD in persons in the USA (Belay et al.,
2001; CDC, 2003;
Belay et al., 2004).
Laboratory studies
226. There is evidence from an in vitro cell-free system that there may
be a considerable
species barrier reducing the probability that CWD will affect humans.
It was shown that
PrPres associated with chronic wasting disease (PrPCWD) from elk, mule
deer or white-tailed
deer was able to readily induce substantial conversion of recombinant
cervid PrPsen
molecules form any of these three species to the protease-resistant
state. In the same system,
CWD-associated PrPres was shown to convert human PrPsen but at a much
lower efficiency:
more than 14-fold lower efficiency than inter-cervid conversion
reactions and more than fivefold
lower than conversion of human PrPsen by PrPres from the brains of
humans with CJD
(Raymond et al., 2000). While encouraging, interpretation of this study
is complicated by the
fact that conversion of human PrPC by PrPBSE and PrPSc from sheep were
of similar efficacy,
both being more than 10-fold less efficient compared with corresponding
homologous
conversions) and one of these appears to be orally transmissible to
humans (BSE) while the
other (scrapie) appears not to be (Raymond et al., 2000). In previous
experiments PrPBSE had
showed 10-fold greater conversion efficacy for bovine PrPsen than for
human codon 129-M
(methionine) PrPsen and 30-fold greater conversion efficacy than for
human codon 129-V
(valine) PrPsen, while ovine PrPSc showed five-fold greater conversion
efficacy for ovine
PrPsen than for human 129-M PrPsen and eight-fold greater conversion
than for human 129-
V PrPsen (Raymond et al., 1997).
227. Results of recent work in transgenic mice expressing human PrP (see
paragraph 71), in
which transmission of CWD from elk by intracerebral inoculation failed,
was considered to
strongly suggest a species barrier to transmission of elk CWD to
humans (Kong et al.,
2004).
CWD Review / Dr Debra Bourne / October 2004 / For SEAC / Page 48 of 66
Potential risk from consuming cervid products
Velvet antler
228. Limited studies to date indicate risk from this product may be very
low. No CWDspecific
PrP accumulation was detected in a sample of velvet from an elk stag which
developed clinical CWD about three months later; there were severe brain
lesions and
extensive CWD-specific PrP staining in both the brain and peripheral
lymphoid tissue of the
stag (Kahn et al., 2004).
Consumption of venison and other parts of the animal
229. PrPCWD has not been detected in muscle tissue from infected cervids
(Spraker et al.,
2002c). However, it has been recommended by the World Health
Organisation that no parts or
products of any animal know to be CWD-positive should be consumed (WHO,
2000). Public
health authorities in the USA and Canada have indicated agreement with
this (Canadian Food
Inspection Agency, 2003; Chronic Wasting Disease Alliance, 2004). It has
been suggested
that if a harvested cervid is being tested for CWD, the test results
should be awaited before
the meat is eaten (Wisconsin Department of Agriculture, Trade and
Consumer Protection,
2002). Authorities in North America have widely advised that (a) tissues
likely to contain the
greatest amount of CWD agent in infected cervids, including the brain,
spinal cord, lymph
nodes, spleen, tonsils and eyes, should not be consumed from any
harvested deer; (b) meat
should be boned out and fat and connective tissue removed (which would
also remove lymph
nodes); and (c) hunters should avoid eating meat from deer or elk which
look sick or which
test positive for CWD (Buege, 2002; Chronic Wasting Disease Alliance,
2004; Williams et
al., 2002; Wisconsin Department of Agriculture, Trade and Consumer
Protection, 2002;
Belay et al., 2004).
Potential risk from handling and processing cervids
230. In order to minimise any potential risk from exposure to the agent
of CWD, hunters,
meat processors and taxidermists handling cervid carcasses are advised
to wear latex or
rubber gloves when handling or dressing cervids from CWD-endemic areas,
to minimise
handling of brain and spinal cord, and to thoroughly wash knives and
other implements after
use on deer or elk carcasses (Belay, 2004; Williams et al., 2002). It
has been suggested that
the risk of build-up of infectious CWD agent in a venison processing
plant would be
unlikely (Buege, 2002).
Potential risk from disposal of carcasses and subsequent contamination of
ground/water/air
231. In 2002 a risk analysis was produced on disposal of deer from
Wisconsin in municipal
solid landfills. It was noted that it is not known how much infected
material a human (or
animal) must consume or be exposed to in order to be infected with CWD.
The report took
into account the probable species barrier for transmission to humans
(Raymond et al., 2000).
It was noted that the CWD agent is hydrophobic and likely to adhere to
organic materials
within a landfill, taking several months to move through the landfill,
and that any infectivity
exiting the landfill would be captured in the landfill effluent. If
effluent was transferred to a
wastewater plant (rather than recirculated in the landfill) the agent
would be expected to
partition with the sludge fraction, which would be diluted greatly with
other solids and mixed
with nine inches (22.5 cm) of topsoil, providing an extremely large
dilution factor. It was
concluded that there was no significant risk to human health from
disposing of deer infected
with CWD in properly constructed landfill sites (Olander, 2002).

snip...

FULL TEXT 66 PAGES ;

http://www.seac.gov.uk/papers/cwdiseaseannex1.pdf

1
Chronic wasting disease
AND TISSUES THAT MIGHT CARRY A RISK
FOR HUMAN FOOD AND ANIMAL FEED CHAINS
REPORT
2
1
MANDATE..........................................................................................................................................4
2
PREAMBLE........................................................................................................................................4
3 CWD IN NORTH AMERICA
............................................................................................................5
3.1 HISTORICAL PERSPECTIVE OF OCCURRENCE
......................................................................5
3.1.1 CWD in captive and farmed
cervidae......................................................................................5
3.1.2 CWD in free-ranging cervidae
................................................................................................6
3.2 NATURAL HOST
RANGE..............................................................................................................7
3.3 EXPERIMENTAL
TRANSMISSIBILITY.......................................................................................8
3.3.1 Transmissibility of
CWD..........................................................................................................9
3.3.1.1 Intracerebral inoculation
studies:.......................................................................................................
9
3.3.1.2 Oral and other natural exposure route studies
.................................................................................
10
3.3.2 Susceptibility of deer and elk to other TSEs
..........................................................................11
3.4
EPIDEMIOLOGY..........................................................................................................................11
3.4.1 Descriptive Epidemiological Features
..................................................................................11
3.4.1.1 Chronology of distribution in the USA
...........................................................................................
11
3.4.1.2 Chronology of distribution in CANADA
........................................................................................
12
3.4.2 Evidence for lateral transmission
..........................................................................................13
3.4.3 The origin of
CWD.................................................................................................................15
3.5
PATHOGENESIS..........................................................................................................................16
3.5.1 Distribution of lesions / PrPCWD in clinically affected animals
..........................................17
3.5.2 Studies of PrPCWD in pre-clinically infected
animals..........................................................18
3.5.2.1 Studies of PrPCWD in naturally exposed
animals...........................................................................
18
3.5.2.2 Studies of PrPCWD in experimentally infected animals
................................................................. 18
3.5.3 Conclusions
...........................................................................................................................19
3.6 DIAGNOSIS
..................................................................................................................................19
3.6.1 Clinical diagnosis of
CWD....................................................................................................19
3.6.2 Laboratory
Diagnosis............................................................................................................21
3.6.3 Laboratory diagnosis in live animals
....................................................................................22
Mule deer and white-tailed
deer......................................................................................................................
22
Elk..................................................................................................................................................................
22
3.7
SURVEILLANCE..........................................................................................................................23
3.7.1 Type and organisation of surveillance in free-ranging cervids
.............................................23
3.7.1.1
USA................................................................................................................................................
23
3.7.1.2
Canada............................................................................................................................................
24
3.7.1.3 Planned surveillance on free ranging Cervidae in
NA..................................................................... 24
3.7.2 Surveillance in farmed cervids
..............................................................................................25
3.7.2.1
USA................................................................................................................................................
25
3.7.2.2
Canada............................................................................................................................................
26
3.8 CONTROL
STRATEGIES.............................................................................................................26
3.8.1 In the
USA.............................................................................................................................26
3.8.2 In Canada
..............................................................................................................................28
3.8.3 Economic impact
...................................................................................................................29
4 TSES IN CERVIDS IN
EUROPE...................................................................................................30
4.1 THE HISTORICAL AND CURRENT SITUATION IN GREAT BRITAIN IN RELATION TO
BSE 30
4.2 PAST AND CURRENT SURVEILLANCE IN EUROPE
.............................................................31
5 POSSIBLE GLOBAL OCCURRENCE OF TSES IN FARMED CERVIDAE
...........................33
6 FOOD AND FEED SAFETY AND HUMAN AND ANIMAL RISK
...........................................34
6.1 FOOD
SAFETY.............................................................................................................................35
6.2 FEED SAFETY AND ANIMAL HEALTH
...................................................................................36
6.3 CJD IN THE USA AND POSSIBLE RELEVANCE TO
CWD.....................................................36
7 RISK OF SPREAD TO
EUROPE....................................................................................................38
8 SUMMARY AND
CONCLUSIONS.................................................................................................39
8.1
SUMMARY...................................................................................................................................39
8.2
CONCLUSIONS............................................................................................................................40
9
BIBLIOGRAPHY.............................................................................................................................41
10 ANNEXES
.........................................................................................................................................48

snip...

36
6.3 CJD IN THE USA AND POSSIBLE RELEVANCE TO CWD
Recently, the Center for Disease Control (CDC) has issued a new statement
concerning CWD and possible human infection: Although it is generally
prudent to
avoid consuming food derived from any animal with evidence of a TSE, to
date, there is
no evidence that CWD has been transmitted or can be transmitted to
humans under
natural conditions. However, the CDC has renewed surveillance efforts
in order to rule
out a link between CWD and vCJD. While, to date there has been one case
of vCJD
reported in US (contracted in the UK), the CDC is working with ongoing
investigations
in Wyoming and Colorado to track cases of CJD or suspected CJD.
37
CDC reported on the epidemiological investigations carried out on three
patients
who died of degenerative neurological illness during the period
1993-1999 and who were
hunter and/or had a history of consuming venison during wild game
feasts. All three
patients were aged over 55 and developed neurological symptoms prior to
death.
Sporadic CJD was confirmed in one case as the cause of death (CDC, 2003).
Belay et al., (2001) Recent reports on of 3 unusually young CJD patients
(aged 28,
28 and 30 years) who regularly consumed deer or elk meat, which created
concern about
the zoonotic transmission of CWD. Investigations, however, by CDC found
that these
were all cases of sporadic CJD of different types. In the USA the
occurrence of CJD in
persons 30 years or younger is rare (during 1979-1996, only 12 such CJD
cases were
reported to the CDC and 8 of these resulted from the use of contaminated
growth
hormone or dura maters grafts). Against the background of the occurrence and
recognition of vCJD in 1996 it is difficult to make an epidemiological
distinction between
an increased incidence of CJD that might represent an indication of a
novel exogenous
source of infection and an increased ascertainment of CJD cases in young
patients due to
better surveillance. Belay et al., (2001), from the National Centre for
Infectious Diseases
have examined the hypothesis that a causal link could be made between
the disease in
these 3 patients and CWD. They reviewed medical records and interviewed
family
members and state wildlife and agriculture officials. Brain tissue
samples were examined
using histopathologic, immunohistochemical, immunoblotting, or prion
gene analysis
methods. The investigation assessed the presence or absence of CJD risk
factors,
associations with deer and elk hunting in CWD- enzootic areas and
comparison of the
evidence from the 3 patients with that of a zoonotic link between vCJD
and bovine
spongiform encephalopathy. None of the patients had established CJD risk
factors or a
history of travel to Europe. Two of the patients hunted game animals and
one was a
daughter of a hunter. Unlike patients with vCJD, the 3 patients did not
express a common
phenotype of the disease, which did not suggest a causal link between
CWD and CJD
(there was also heterogeneity among the three patients on the codon 129
: Met/Met,
Val/Val and Met/Val respectively). Molecular phenotyping characteristics
for the 2
patients studied gave type 1 on Western Blot according to Parchi et
al.(1997), which
differs from that of vCJD.
In conclusion, the CDC report on the CJD in the patients aged over 55
years and
the investigation of Belay et al. (2001) related to the young CJD
patients found no strong
evidence for a causal link between CWD and CJD. Both, however, concluded
as well
that ongoing national surveillance for CJD and other neurological cases
will remain
important for continuing to assess the risk, if any, of CWD transmission
to humans.
Race et al., (2002) described abnormal PrP glycoforms of CWD in
comparison to
PrP from scrapie and BSE. Analysis of these abnormal PrP glycoform
patterns from
CWD affected deer and elk, scrapie-affected sheep and cattle and cattle
with BSE failed
to identify patterns capable of reliably distinguishing these
transmissible spongiform
encephalopathy diseases. However, PrP-res patterns sometimes differed among
individual animals, suggesting the possibility of multiple CWD strains.

snip...

40
8.2 CONCLUSIONS
With regard to the initial question of the mandate, a theoretical risk
for prion
transmission to humans consuming products of CWD affected-cervids of all
ages in
countries where CWD exists cannot be excluded. Similarly, transmission
risk of prions to
domestic animals cannot be excluded. There is therefore a scientific
basis on which to
exclude tissues from animals that carry a CWD risk, from human or animal
feed chains.
However, the early and widespread involvement of tissues in CWD infected
animals
does not allow to define a SRM list, neither to define any lower age cut
off as has been
defined for cattle in relation to BSE. Neither is there sufficient
knowledge to define
exclusions or amendment of any SRM rule on the basis of relative genetic
resistance to
infection as has been proposed for sheep and goats in the event that
evidence indicates
the probable natural occurrence of BSE in these species 5.
Although available information indicates imports of live Cervidae from
NA to EU
and trade in meat products from cervid species as being negligible, it
is important to
reach certainty that no transfer of risk takes place through trade of
live cervids and its
derived products.
At present, there are no scientific data that CWD is occurring in
Cervidae elsewhere
than in those countries from which it has been previously reported.
However, systematic
TSE surveillance of cervid populations has either been absent or has
only just started in
European countries. Until results of such surveillance become available
no conclusion
can be drawn with regard to the occurrence of CWD or similar TSE in the
cervid
population of Europe.

snip...

http://europa.eu.int/comm/food/fs/sc/ssc/out324_en.pdf

Report on the Deer Industry in
Great Britain, 2002

http://www.seac.gov.uk/papers/munrodeerrptannex3.pdf

TSE SURVEILLANCE IN DEER
Background
1. Prior to the reinforced mammalian meat and bone meal ban, it is
likely that deer in the UK and elsewhere in Europe were exposed to
contaminated feed. Therefore, the possibility that BSE may be
present in deer cannot be ruled out. Additionally, some deer
species in North America are known to be affected by chronic
wasting disease (CWD) a naturally occurring TSE.
2. Although there has been no reported evidence of TSE infection
among deer in the EU, active surveillance is necessary to
determine whether or not it is present. There is no current EU
requirement for TSE surveillance in deer. However, it is likely that
Member States may be required to initiate surveillance
programmes in the future. In advance of this possible requirement,
the VLA has conducted some small surveys to evaluate the tests.
Other Member States have also conducted some TSE surveillance
in deer.
UK surveys
3. In 2002, VLA obtained samples of whole carcases and viscera from
304 wild deer (189 roe, 66 fallow, 22 red and 13 muntjac deer as
well as 14 samples from undetermined deer species). Most had
been shot for human consumption but there were also some road
kills. All had been submitted for TB testing. Samples, including
brain, spleen, lymph node and Peyers Patch, from these cases
were examined by immunohistochemistry using antibodies known
to be able to detect CWD as well as those used in the UK for the
detection of BSE and scrapie. Positive control samples of CWD
from US deer and BSE from UK cattle were also included.
4. In 2003, a further 99 samples were collected from 52 roe, 33 fallow,
5 muntjac and 9 undetermined species of deer. In addition, to the
immunohistochemical examination, these samples were also tested
using the Biorad ELISA. No evidence of TSE was detected in any
of the 403 deer examined in this survey.
5. A further survey of 1249 deer culled from Royal Parks (856 red and
393 fallow deer) was conducted from September to December
2003. All the samples were examined by immunohistochemistry
using antibodies that recognise CWD and BSE and by the Biorad
ELISA. No evidence of any TSE was detected.
6. A further survey of deer culled from the New Forest is now in
progress.
Surveys in other Member States
7. A number of other EU Member States have conducted surveys for
TSEs in deer. The programmes vary considerably in their size and
scope and, although the surveillance is limited, none have detected
any evidence of TSE in deer. The available information from these
surveillance studies is summarised in Table 1.
TABLE 1 Surveys of TSEs in deer in other EU Member States
Country Period Number of animals
(type/species)
Test methods
Germany 2001 1000 (Wild deer) Biorad, IHC
2002-
2004
> 4000 (Roe, red and fallow) Biorad, IHC
2004-
2005
Testing of 6000 planned Biorad, IHC
Belgium 1997-
2003
38 (unknown) Histopathology,
IHC, SAF.
Biorad since
2001
Denmark 1999-
2002
6 (farmed fallow),
7 (wild roe),
3 (exotic)
Italy 1999-
2004
18 (wild) Histopathology,
IHC and
western blot
Finland 1999-
2002
5 (white tailed)
4 (unknown)
2003 900 (healthy reindeer)
3 (fallen reindeer)
Biorad
Sweden 2002-
2003
6 (moose)
2 (roe)
IHC,
histopathology.
Biorad since
2003

http://www.seac.gov.uk/papers/deersurvannex4.pdf

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