Experimental Oral Transmission of Chronic Wasting Disease to Reindeer (Rangifer tarandus tarandus)
Experimental Oral Transmission of Chronic Wasting Disease to Reindeer
(Rangifer tarandus tarandus)
Gordon B. Mitchell1, Christina J. Sigurdson2,3, Katherine I. O’Rourke4,
James Algire1, Noel P. Harrington1, Ines Walther1, Terry R. Spraker5, Aru
Balachandran1*
1 National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food
Inspection Agency, Ottawa Laboratory – Fallowfield, Ottawa, Ontario,
Canada,
2 Departments of Pathology and Medicine, University of California, San
Diego, La Jolla, California, United States of America, 3 Department of
Pathology, Microbiology and Immunology, University of California, Davis,
California, United States of America, 4 Animal Disease Research Unit,
Agricultural Research Service, United States Department of Agriculture, Pullman,
Washington, United States of America, 5 Veterinary Diagnostic Laboratory,
Colorado State University, Fort Collins, Colorado, United States of
America
Abstract
Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of
cervids, remains prevalent in North American elk, white-tailed deer and mule
deer. A natural case of CWD in reindeer (Rangifer tarandus tarandus) has not
been reported despite potential habitat overlap with CWD-infected deer or elk
herds. This study investigates the experimental transmission of CWD from elk or
white-tailed deer to reindeer by the oral route of inoculation. Ante-mortem
testing of the three reindeer exposed to CWD from white-tailed deer identified
the accumulation of pathological PrP (PrPCWD) in the recto-anal mucosa
associated lymphoid tissue (RAMALT) of two reindeer at 13.4 months
post-inoculation. Terminal CWD occurred in the two RAMALT-positive reindeer at
18.5 and 20 months post-inoculation while one other reindeer in the white-tailed
deer CWD inoculum group and none of the 3 reindeer exposed to elk CWD developed
disease. Tissue distribution analysis of PrPCWD in CWD-affected reindeer
revealed widespread deposition in central and peripheral nervous systems,
lymphoreticular tissues, the gastrointestinal tract, neuroendocrine tissues and
cardiac muscle. Analysis of prion protein gene (PRNP) sequences in the 6
reindeer identified polymorphisms at residues 2 (V/M), 129 (G/S), 138 (S/N) and
169 (V/M). These findings demonstrate that (i) a sub-population of reindeer are
susceptible to CWD by oral inoculation implicating the potential for
transmission to other Rangifer species, and (ii) certain reindeer PRNP
polymorphisms may be protective against CWD infection.
snip...
The importance of Rangifer species to the culture of aboriginal peoples
cannot be underestimated with many components of hunted animals being consumed
as food. Although relatively limited in comparison to elk and deer industries in
North America, reindeer and caribou farming does occur, producing consumables
such as meat, hides and antler velvet. The human health risks of consuming meat
or other products derived from CWD-infected animals remain uncertain, although
epidemiological evidence indicates transmission has not yet occurred [30,31,32]
and transgenic mouse studies suggest the risk is remote in humans expressing
common PRNP sequences [33,34,35]. The finding that CWD can be transmitted to
squirrel monkeys by intracranial inoculation [36] raises concern for human
transmissibility, however a study in macaques failed to demonstrate transmission
after 70 months [37]. Since prion strains may undergo changes in transmission
characteristics following passage through different species and strain selection
pressures can be exerted by host genetic factors during passage within a species
[24,38,39,40], caution is warranted when predicting the risks of CWD
transmission from reindeer to other species.
This is the first evidence of CWD transmission to the sub-species Rangifer
tarandus tarandus, implicating the potential for transmission to others in this
genus. Current diagnostic tests, including antemortem RAMALT testing, appear
capable of detecting CWD in Rangifer species and increased surveillance would be
required to determine if natural transmission has indeed occurred. Additional
studies are ongoing to chart the distribution of infectivity during the course
of disease and determine the influence of PRNP polymorphisms in disease
susceptibility.
Citation: Mitchell GB, Sigurdson CJ, O’Rourke KI, Algire J, Harrington NP,
et al. (2012) Experimental Oral Transmission of Chronic Wasting Disease to
Reindeer (Rangifer tarandus tarandus). PLoS ONE 7(6): e39055.
doi:10.1371/journal.pone.0039055
Editor: Anthony E. Kincaid, Creighton University, United States of
America
Received May 4, 2012; Accepted May 15, 2012; Published June 18, 2012
This is an open-access article, free of all copyright, and may be freely
reproduced, distributed, transmitted, modified, built upon, or otherwise used by
anyone for any lawful purpose. The work is made available under the Creative
Commons CC0 public domain dedication.
Funding: This work was supported by the Canadian Food Inspection Agency and
Agriculture and Agri-Food Canada under C00233, the United States
Department of Agriculture Agricultural Research Service under CRIS
5348-32000-026-00-D and the United States National Institutes of Health under
NS069566 and U54AI0359. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests
exist.
* E-mail: Aru.Balachandran@inspection.gc.ca
THANK YOU PLOS FOR OPEN ACCESS FOR THE LAYPEOPLE, such as myself. ...TSS
natural cases of CWD in eight Sika deer (Cervus nippon) and five Sika/red
deer crossbreeds Korea and Experimental oral transmission to red deer (Cervus
elaphus elaphus)
SCWDS BRIEFS
A Quarterly Newsletter from the Southeastern Cooperative Wildlife Disease
Study College of Veterinary Medicine The University of Georgia Athens, Georgia
30602
Volume 27 January 2012 Number 4
Red deer susceptibility to CWD via oral inoculation was demonstrated in a
study conducted by collaborators from the U.S. and Canada. Red deer developed
clinical signs and had spongiform changes in the brain when euthanatized at 20
MPI. The CWD prion was detectable in neural and lymphoid tissues, endocrine
organs, cardiac muscle, nasal mucosa, and other tissues. Although field cases of
CWD in red deer have not been reported, results of this study indicate that it
could occur, which is not surprising given that elk and red deer are subspecies
of Cervus elaphus. The results of this study can be found in the Canadian
Veterinary Journal 51: 169-178.
In addition, it was reported in May 2011 that natural cases of CWD were
found in eight Sika deer (Cervus nippon) and five Sika/red deer crossbreeds
during epidemiological investigations of CWD cases in captive elk in Korea.
May 2011 natural cases of CWD were found in eight Sika deer (Cervus nippon)
and five Sika/red deer crossbreeds during epidemiological investigations of CWD
cases in captive elk in Korea
Friday, May 13, 2011
Chronic Wasting Disease (CWD) outbreaks and surveillance program in the
Republic of Korea Chronic Wasting Disease (CWD) outbreaks and surveillance
program in the Republic of Korea
Hyun-Joo Sohn, Yoon-Hee Lee, Min-jeong Kim, Eun-Im Yun, Hyo-Jin Kim,
Won-Yong Lee, Dong-Seob Tark, In- Soo Cho, Foreign Animal Disease Research
Division, National Veterinary Research and Quarantine Service, Republic of Korea
Chronic wasting disease (CWD) has been recognized as an important prion
disease in native North America deer and Rocky mountain elks. The disease is a
unique member of the transmissible spongiform encephalopathies (TSEs), which
naturally affects only a few species. CWD had been limited to USA and Canada
until 2000. On 28 December 2000, information from the Canadian government showed
that a total of 95 elk had been exported from farms with CWD to Korea. These
consisted of 23 elk in 1994 originating from the so-called “source farm” in
Canada, and 72 elk in 1997, which had been held in pre export quarantine at the
“source farm”.Based on export information of CWD suspected elk from Canada to
Korea, CWD surveillance program was initiated by the Ministry of Agriculture and
Forestry (MAF) in 2001. All elks imported in 1997 were traced back, however elks
imported in 1994 were impossible to identify. CWD control measures included
stamping out of all animals in the affected farm, and thorough cleaning and
disinfection of the premises. In addition, nationwide clinical surveillance of
Korean native cervids, and improved measures to ensure reporting of CWD suspect
cases were implemented. Total of 9 elks were found to be affected. CWD was
designated as a notifiable disease under the Act for Prevention of Livestock
Epidemics in 2002. Additional CWD cases - 12 elks and 2 elks - were diagnosed in
2004 and 2005. Since February of 2005, when slaughtered elks were found to be
positive, all slaughtered cervid for human consumption at abattoirs were
designated as target of the CWD surveillance program. Currently, CWD laboratory
testing is only conducted by National Reference Laboratory on CWD, which is the
Foreign Animal Disease Division (FADD) of National Veterinary Research and
Quarantine Service (NVRQS). In July 2010, one out of 3 elks from Farm 1 which
were slaughtered for the human consumption was confirmed as positive.
Consequently, all cervid – 54 elks, 41 Sika deer and 5 Albino deer – were culled
and one elk was found to be positive. Epidemiological investigations were
conducted by Veterinary Epidemiology Division (VED) of NVRQS in collaboration
with provincial veterinary services. Epidemiologically related farms were found
as 3 farms and all cervid at these farms were culled and subjected to CWD
diagnosis. Three elks and 5 crossbreeds (Red deer and Sika deer) were confirmed
as positive at farm 2. All cervids at Farm 3 and Farm 4 – 15 elks and 47 elks –
were culled and confirmed as negative. Further epidemiological investigations
showed that these CWD outbreaks were linked to the importation of elks from
Canada in 1994 based on circumstantial evidences. In December 2010, one elk was
confirmed as positive at Farm 5. Consequently, all cervid – 3 elks, 11
Manchurian Sika deer and 20 Sika deer – were culled and one Manchurian Sika deer
and seven Sika deer were found to be positive. This is the first report of CWD
in these sub-species of deer. Epidemiological investigations found that the
owner of the Farm 2 in CWD outbreaks in July 2010 had co-owned the Farm 5. In
addition, it was newly revealed that one positive elk was introduced from Farm 6
of Jinju-si Gyeongsang Namdo. All cervid – 19 elks, 15 crossbreed (species
unknown) and 64 Sika deer – of Farm 6 were culled, but all confirmed as
negative. : Corresponding author: Dr. Hyun-Joo Sohn (+82-31-467-1867, E-mail:
shonhj@korea.kr)
2011 Pre-congress Workshop: TSEs in animals and their environment 5
Friday, May 13, 2011
Chronic Wasting Disease (CWD) outbreaks and surveillance program in the
Republic of Korea
Research Project: TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES: THE ROLE OF
GENETICS, STRAIN VARIATION, AND ENVIRONMENTAL CONTAMINATION IN DISEASE CONTROL
Location: Animal Diseases Research
Title: Experimental oral transmission of chronic wasting disease to red
deer (Cervus elaphus elaphus): Early detection and late stage distribution of
protease-resistant prion protein
Authors
Balachandran, A - CANADIAN FOOD INSPCTN AG Harrington, Noel - CANADIAN FOOD
INSPCTN AG Algire, James - CANADIAN FOOD INSPCTN AG Souyrine, Andre - CANADIAN
FOOD INSPCTN AG Spraker, Terry - COLORADO ST UNIV Jeffrey, Martin - Gonzalez,
Lorenzo - Orourke, Katherine
Submitted to: Canadian Veterinary Journal Publication Type: Peer Reviewed
Journal Publication Acceptance Date: December 1, 2008 Publication Date: March
11, 2010 Repository URL: http://ddr.nal.usda.gov/dspace/bitstream/10113/40677/1/IND44334511.pdf
Citation: Balachandran, A., Harrington, N., Algire, J., Souyrine, A., Spraker,
T., Jeffrey, M., Gonzalez, L., Orourke, K.I. 2010. Experimental oral
transmission of chronic wasting disease to red deer (Cervus elaphus elaphus):
Early detection and late stage distribution of protease-resistant prion protein.
Canadian Veterinary Journal. Canadian Veterinary Journal. 51:169-178.
Interpretive Summary: Farmed cervids may be exposed to the prion disorder
chronic wasting disease through contact with free ranging or farmed infected
Rocky Mountain elk, white tailed deer, mule deer, or moose. This is the first
report of experimental transmission of chronic wasting disease to red deer, an
economically important agricultural commodity in parts of North America. Brain
tissue from infected Rocky Mountain elk was administered by the oral route of
red deer. Deer were examined at 18 months after infection for evidence of
abnormal prion protein, the marker for the disease. The abnormal protein was
found throughout the brain, spinal cord and lymphoid tissues, with variable
distribution in other organ systems. This finding confirms the potential
susceptibility of this species to disease under natural conditions and the
reliability of the current testing format for identifying the abnormal protein
in the tissues routinely collected in surveillance programs. The widespread
distribution of the abnormal protein in red deer indicates the potential for
shedding of the agent into the environment. Technical Abstract: Chronic wasting
disease CWD is the transmissible spongiform encephalopathy or prion disease of
wild and farmed cervid ruminants, including Rocky Mountain elk (Cervus elaphus
nelsoni), white tailed deer (Odocoileus virginianus), mule deer (Odocoileus
hemionus), or moose (Alces alces). Reliable data on the susceptibility of other
farmed cervid species, the distribution of the abnormal prion protein marker in
brain and lymphoid tissues collected in surveillance programs, and the role of
prion genotype are necessary for design of control programs for CWD in farmed
cervids. In this study, red deer (Cervus elaphus elaphus) were exposed to the
prion agent by oral administration of brain homogenates from infected Rocky
Mountain elk. Antemortem testing was performed at 7 months post infection and
the deer were euthanized when clinical disease was observed at approximately 18
months after infection. The abnormal prion protein was assayed by
immunohistochemistry, enzyme linked immunosorbent assay and western blot.
Abnormal prion protein was found in the spinal cord, brainstem, cerebellum,
midbrain, thalamus, and cerebrum in all 4 infected red deer. Most of the lymph
nodes throughout the body were positive for abnormal prion proteins. Abnromal
prion protein was observed in some additional peripheral tissues in some but not
all of the deer. In particular, most areas of the gastrointestinal tract were
positive for abnormal prions, although the salivary glands were rarely positive.
This study demonstrates the potential for oral transmission of chronic wasting
disease to red deer and confirms the usefulness of the current testing methods
for post mortem diagnosis of the disease in this species.
Project Team Orourke, Katherine Knowles, Donald - Don White, Stephen
Schneider, David
Publications Publications Related National Programs Animal Health (103)
Last Modified: 06/18/2012
Saturday, June 09, 2012
USDA Establishes a Herd Certification Program for Chronic Wasting Disease
in the United States
Wednesday, June 13, 2012
TAHC Modifies Entry Requirements Effective Immediately for Cervids DUE TO
CWD
FOR IMMEDIATE RELEASE
Tuesday, June 05, 2012
Captive Deer Breeding Legislation Overwhelmingly Defeated During 2012
Legislative Session
Sunday, January 22, 2012
Chronic Wasting Disease CWD cervids interspecies transmission
Thursday, May 31, 2012
CHRONIC WASTING DISEASE CWD PRION2012 Aerosol, Inhalation transmission,
Scrapie, cats, species barrier, burial, and more
Research Project: TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES: THE ROLE OF
GENETICS, STRAIN VARIATION, AND ENVIRONMENTAL CONTAMINATION IN DISEASE CONTROL
Location: Animal Diseases Research
2011 Annual Report
1a.Objectives (from AD-416) The project has 4 objectives: (1) Identify
conformational and biological correlates of strain variation in the
transmissible spongiform encephalopathies, (2) Identify genetic factors
associated with horizontal transmission efficiency and susceptibility to the
transmissible spongiform encephalopathies (3) Characterize the influence of
genetics, strain, and multiple births on placental transmission of small
ruminant TSEs; and (4) Devise a model system for assessing methods to reduce
persistent environmental contaminations by prions.
1b.Approach (from AD-416) The current proposal addresses methods for
characterizing and controlling classical and novel transmissible spongiform
encephalopathies (TSEs)of domestic sheep and of farmed and free ranging deer and
elk. The project includes discovery of unique identifiers for the North American
TSE strain of small and wild ruminants and development of standardized methods
suitable for use by the federal diagnostic reference laboratory and federally
approved diagnostic laboratories. The genetic basis for relative transmission
efficiency between and within the affected species, a critical element in design
of control programs, will be is addressed through identification of haplotypes
associated with naturally occurring disease. Allelic frequencies and disease
associations are determined from tissue samples of naturally infected sheep,
goats, deer, and elk. Genomic DNA is analyzed for the sequence of genomic
regions including Prnp, Prnd, and Prnp' (when applicable). Samples of brain from
infected animals are evaluated for relatively large changes in the apparent
molecular weight of the proteinase K resistant core and for changes in the
relative abundance of the variously glycosylated isoforms. The distribution and
processing of disease associated PrP will be examined with a panel of monoclonal
antibodies using single and double label immunohistochemistry assay. Samples
with novel genotypes or prion protein isoforms will be evaluated in vivo when
applicable. If novel strains are identified by these methods, standardized
reagents and protocols for rapid strain typing of field samples will be
developed and transferred to the national reference laboratory and the federally
approved veterinary diagnostic laboratories. The role of the shed placenta and
other environmental factors in TSE transmission and prion persistence will be
examined.
3.Progress Report The project (1) addresses critical gaps in our
understanding of the distribution of abnormal prion proteins in the tissues of
sheep, goats, deer, elk, and small carnivores; (2) determines whether the
current diagnostic methods are suitable for animals in each genotype; (3)
identifies the limits of genetic resistance to the prion diseases; and (4)
identifies environmental reservoirs of the infectious agent. This project
provided reagents and methods for the first generation live animal test in sheep
and participated in two international collaborations to extend those methods to
diagnosis of bovine spongiform encephalopathy by assay of brain tissue. The
methods were used to characterize atypical (Nor98) scrapie in Canada and the US.
In association with Colorado State University, we described the distribution of
the abnormal prion protein in the tissues of Rocky Mountain elk; this work
contributed to our understanding of disease transmission and early diagnosis of
prion disease in captive elk. In collaboration with the Canadian Food Inspection
Agency, we reported the experimental transmission of prion disease from elk to
red deer. The project provided information on the role of prion genotype in
disease transmission in sheep and information on the effects of chimerism on
genotype testing. In collaboration with the Canadian Food Inspection Agency, we
described the prion genotypes of scrapie infected Canadian sheep and reported
that the susceptibility patterns are similar to those observed in the US sheep.
We provided baseline information on prion gene variation in US goats. In
collaboration with the Veterinary Genetics Laboratory, we developed methods for
determining relatedness in captive herds of white tailed deer with prion
disease. In addition, we described the association between tissue mineral levels
and prion disease in Rocky Mountain elk. Taken together, studies provided
information being used by the regulatory agencies of the US and Canada in
developing scrapie eradication programs. New project 5348-32000-030-00D to start
10-1-11.
4.Accomplishments 1. Association analysis of prion gene region sequences
with chronic wasting disease in Rocky Mountain elk. Genetic resistance to ovine
scrapie is a cornerstone of the current control program and a similar approach
to chronic wasting disease (CWD) would be beneficial to the industry. In
association with Colorado State University and USDA APHIS, ARS scientists in
Pullman, WA, analyzed prion gene sequences in a sample of 559 captive and free
ranging Rocky Mountain elk, of which 120 were considered positive for CWD. The
previously reported mutation at codon 132 cut the odds of CWD by half but no
association with CWD was found for any additional variants in the PRNP region (P
> 0.05). This finding supports the current control programs, which consider
that all elk exposed to CWD must be considered at risk of CWD.
2. Prion genotypes of scrapie-infected Canadian sheep. Selection for
genetic resistance to scrapie is a critical element in the North American
scrapie control programs although data supporting this approach are derived
largely from European studies. The Canadian Food Inspection Agency and ARS
collaborated on a retrospective study of the prion genotypes of a sample of 249
sheep with confirmed classical scrapie infection representing 98 flocks from 6
provinces and a further case-control analysis of 3 of these flocks comparing the
genotypes between infected sheep (n = 72) and those of their healthy flockmates
(n = 1990). The incidence of classical scrapie in the Canadian sheep population
was highly associated with a single haplotype (91.8%), findings similar to those
reported by USDA APHIS for US scrapie-infected sheep. This finding supports the
current control program that specifies removal or permanent quarantine of all
scrapie-exposed sheep homozygous for that genotype.
3. The effects of autolysis on detection of abnormal prion proteins.
Diagnosis and characterization of scrapie strains is made by a combination of
biochemical tests for the abnormal prion protein PrP-Sc. Tissues submitted for
analysis are often of poor quality, with varying levels of autolysis noted but
the effect of autolysis on detection and characterization of the prion protein
is not known. The Canadian Food Inspection Agency, in collaboration with ARS,
completed a study of experimentally autolyzed tissues to address this knowledge
gap. This study showed that the amount of PrP-Sc in lymphoid and central nervous
system (CNS) tissues from elk and sheep decreased gradually as a result of
autolysis, but PrP-Sc was still detectable after 5 and 15 d incubation at 37°C
using either of two detection methods. The study demonstrated that the western
blot technique can be used for diagnosis of scrapie using autolyzed samples.
4. Scrapie control program. The scrapie control program is based on the
observations that ovine scrapie is transmitted effectively at the time of
lambing and that transmission by unbred ewes or males rarely occurs. Similar
data on transmission of scrapie in goats is lacking. In this study, ARS
scientists in Pullman, WA examined the placentas of goats with naturally
acquired scrapie and determined that the levels of abnormal prion protein are
significantly lower than those observed in infected sheep, although the progeny
of these goats were shown to develop the disease. This finding suggests that
control programs specific for goats may be warranted, with attention to
alternative modes of transmission.
5. Resistance of fallow deer to chronic wasting disease under field
conditions. Chronic wasting disease in farmed cervids is managed on a species
basis by a coordinated series of state and federal regulations. The regulations
were written for the most commonly affected species (mule deer, white tailed
deer and Rocky Mountain elk). The susceptibility of fallow deer, another
commonly held species, to experimental infection by the intracerebral route has
been established but the susceptibility of the species to natural challenge is
not known. ARS contributed to a study conducted by USDA APHIS and the Colorado
Division of Wildlife, in which fallow deer were held in pens with mule deer; all
mule deer in the study died with evidence of CWD infection and none of the
fallow deer showed either clinical disease or evidence of abnormal prions in any
of the examined tissues. This finding suggests that the species is relatively
resistant to natural transmission and may represent the only naturally resistant
deer species reported to date.
Review Publications White, S.N., Spraker, T.R., Reynolds, J.O., Orourke,
K.I. 2010. Association analysis of PRNP gene region with chronic wasting disease
in Rocky Mountain elk. BMC Research Notes. 3:314.
Orourke, K.I., Zhuang, D., Truscott, T.C., Yan, H., Schneider, D.A. 2011.
Scant PrP-Sc accumulation in the placentas of goats with naturally acquired
scrapie. BioMed Central (BMC) Veterinary Research. 7(1):7.
Huang, H., Soutyrine, A., Rendulich, J., Orourke, K.I., Balachandran, A.
2011. Investigation of the effects of experimental autolysis on the detection of
abnormal prion protein in lymphoid and central nervous system tissues from elk
and sheep using the Western blotting method. Canadian Journal of Veterinary
Research. 75(1)69-72.
Harrington, N., Orourke, K.I., Feng, Y., Rendulich, J., Difruscio, C.,
Balachandran, A. 2010. Prion genotypes of scrapie-infected Canadian sheep
1998-2008. Canadian Journal of Veterinary Research. 74(3):228-232.
Rhyan, J.C., Spraker, T.R., Mccollum, M., Nol, P., Wolfe, L., Miller, M.W.,
Davis, T., Creekmore, L., Orourke, K.I. 2009. Resistance of fallow deer (dama
dama) to chronic wasting disease under natural exposure in a heavily
contaminated environment. Journal of Wildlife Diseases. 47(3):739-744.
Project Team Orourke, Katherine Knowles, Donald - Don White, Stephen
Schneider, David Project Annual Reports FY 2011 FY 2010 FY 2009 FY 2008 FY 2007
Publications Publications Related National Programs Animal Health (103)
Last Modified: 06/18/2012
Monday, June 18, 2012
natural cases of CWD in eight Sika deer (Cervus nippon) and five Sika/red
deer crossbreeds captive Korea and Experimental oral transmission to red deer
(Cervus elaphus elaphus)
TSS
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