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Chronic Wasting Disease
Bryan Richards
CWD Project Leader
USGS National Wildlife Health Center
Chronic Wasting Disease (CWD), a member of the family of diseases referred to as
Transmissible Spongiform Encephalopathies (TSEs), is an always-fatal,
neurodegenerative illness occurring in North American deer, elk and moose. Since its
discovery in 1967, CWD has continued to spread geographically and increase in
prevalence locally. Managing CWD in free-ranging populations is extremely difficult;
therefore preventative measures designed to reduce the chance for disease introduction
and spread are critically important.
History
Chronic Wasting Disease was first documented in a Colorado research facility in 1967.
During the next decade, additional cases were documented in Colorado and Wyoming
research facilities. In 1978, Dr. Elizabeth Williams, after identifying spongiform lesions
in brain material from affected animals, determined that CWD was a Transmissible
Spongiform Encephalopathy (TSE). The first detection of CWD in a free-ranging
population was in Rocky Mountain National Park (Colorado) in 1981. The first detection
of CWD in the captive cervid industry was in Saskatchewan in 1996 (trace-outs
confirmed the source as a South Dakota facility; CWD was confirmed there in 1997).
CWD was likely present in the zoo industry during the 1970s – the Toronto Zoo reported
losses consistent with CWD. This zoo had received animals from the Denver Zoo, which
had received animals from one of the infected research facilities. Prior to 2000, CWD
had been documented in only a handful of counties in southeastern Wyoming and
adjacent northeastern Colorado. Since 2000 and after significant increases in surveillance
efforts, CWD has been detected in many additional locations. Currently, CWD has been
documented in free-ranging populations in 11 states, Alberta and Saskatchewan, and in
over 80 individual captive cervid facilities in nine states, Alberta and Saskatchewan (see
map).
Transmissible Spongiform Encephalopathies (TSEs)
TSEs are a family of transmissible diseases, characterized by spongiform lesions in the
brain, that affect various groups of mammals. Humans TSEs include Creutzfeldt-Jakob
disease (CJD), Kuru, Fatal Familial Insomnia (FFI), Gerstmann-Straussler-Scheinker
Disease (GSS) and variant CJD (vCJD). TSEs in domestic livestock include scrapie in
sheep, Bovine Spongiform Encephalopathy (BSE) in cattle and Transmissible Mink
Encephalopathy (TME) in farmed mink. The only TSE recognized to-date in freeranging wildlife is Chronic Wasting Disease (CWD) in North American mule deer,
white-tailed deer, elk and moose. A TSE has also been recognized in both domestic and
large cats: Feline Spongiform Encephalopathy (FSE). BSE also apparently spilled over
into numerous ungulate species maintained in UK zoos. Some of the TSEs are spread via
aberrant feeding behavior within a species: Kuru and BSE. Some TSEs result from
feeding on infectious protein between species: TME, FSE, BSE in other ungulates and
vCJD. Some of the TSEs are of genetic or familial origin: GSS, FFI, some forms of CJD.
CJD and vCJD have been shown to been accidentally transmissible (iatrogenic). All
TSEs have been shown to be experimentally transmissible. Only two of the TSEs are
considered to be contagious: Scrapie and CWD.
Origin of CWD
The true origin of CWD probably will never be known. One hypothesis is that sheep
scrapie crossed the “species barrier” into deer or elk, either in the wild or inside the
Colorado research facility where it was first described. An alternative is that CWD arose
sporadically one or more times in free-ranging deer or elk. A third hypothesis is that
CWD arose from some other undocumented TSE.
Causative Agent
Although debate still occurs, the vast majority of research indicates that the causative
agent of TSEs (including CWD) is a misfolded protein called a prion. All mammals
produce normal cellular prion protein (abbreviated PrPC). PrPC is a small (approximately
250 amino acid chain), soluble, relatively unstable cell surface protein that is produced by
a variety of cell types, but especially within lymphoid and neural cell lines. Although
their function has not been completely characterized, normal prions are used by cells,
then degraded and eliminated or recycled within the body. An alternative tertiary form of
prion protein is associated with TSE. This disease-associated isoform (abbreviated PrPSc,
PrPRes, PrPTSE, PrPCWD) is insoluble, highly resistant to breakdown, and unusually stable
(may persist years to decades in the environment). Although the precise mechanism has
not been elucidated, post-translational conversion from PrPC to PrPCWD appears to occur
when disease-associated prions (PrPCWD) come into close physical contact with normal
prions, somehow causing them to refold into their own infectious isoform. Recent
evidence suggests that additional molecules (chaperones, co-factors) may facilitate this
process. Disease-associated prions tend to accumulate within lymphatic and neural
tissues. When PrPCWD accumulates in the brain, it results in a sponge-like appearance
and is associated with neuronal death.
Clinical Signs
CWD has an extended incubation period – some 18-24 months on average between
infection and the onset of clinical signs. The length of clinical phase disease varies from
days to months, but once clinical signs appear, death is certain. The most obvious
clinical sign of CWD is progressive weight loss – thus the name Chronic Wasting
Disease. Numerous behavioral changes have also been reported, including decreased
social interaction, loss of awareness and loss of fear of humans. Clinically-diseased
animals may also exhibit increased drinking, urination and excessive salivation.
Diagnosis
CWD is typically diagnosed by post-mortem examination of brain or lymphoid tissue.
Spongiform lesions may be detected through histopathological examination of brain
tissue. A variety of assays, including immunohistochemistry (IHC), immuno-blotting,
and ELISA techniques are currently in use for post-mortem examination of brain and
lymphoid tissues. These same techniques have been successfully used to test biopsies of
tonsillar or rectal tissue collected from live animals. Available assays work quite well for
detecting CWD in hunter-killed samples or within captive facilities. They are, however,
too insensitive to detect prion protein in other than lymphoid or neural tissues, where
PrPCWD concentrations are lower, but may still contain infectivity. Bioassays (challenge
studies in cervids or transgenic cervidized mouse models) are required to test various
tissues and fluids for infectivity. Numerous researchers are working to develop
additional, more sensitive assays with the ultimate goal of being able to reliably test
animals within a short time frame (minutes). Even if new live tests are developed, it will
still be extremely difficult to test large numbers of free-ranging animals, because they
must be captured in order to test.
Tissues for diagnosis
Preferred tissues for diagnosis include retropharyngeal lymph nodes, tonsils, and obex.
Retropharyngeal lymph nodes, in mule deer and white-tailed deer, reliably detect PrPCWD
concentrations relatively early in the course of disease, earlier than in obex. Lymphoid
involvement in elk is not as reliable as in deer; collection and testing of lymph nodes and
obex is therefore suggested for elk. Biopsies in live animals have primarily utilized
tonsillar tissue. Rectal biopsies are currently being evaluated as well.
Transmission
It has long been hypothesized that CWD is transmitted via direct (nose-to-nose) contact
between animals and that animals become infectious long before the onset of clinical
signs. It has now been demonstrated that CWD can also be transmitted indirectly –
diseased animals shed infectious prions into the environment where they reside and can
be ingested by healthy animals at a later date. Saliva collected from clinically-affected
deer has recently been shown to be infectious, helping to elucidate a potential mechanism
for both direct and indirect transmission. In areas where CWD has been established the
longest, trends in prevalence are clear. Prevalence continues to increase over time (>30%
prevalence has been reported in localized areas), is higher in adults than juveniles, and
may be 2-4 times higher in adult males than adult females. It is theorized that adult male
breeding behaviors may result in higher disease prevalence.
Environmental Reservoirs
The infectious isoform of prion protein has been shown to bind avidly to some soil
minerals. In this bound state infectious materials may remain available for uptake for
protracted periods. It has recently been shown that infectivity is greatly enhanced (~700
fold) when prions are bound to soil particles. Epidemiological studies imply that
environmental reservoirs and indirect transmission are important factors in CWD
dynamics.
Preventative Measures
Because CWD is nearly impossible to successfully manage in free-ranging populations,
disease prevention is critical. Many states have restricted or banned the importation
and/or movement of live cervids and are requiring whole-herd disease monitoring within
the captive cervid industry. Some states have banned hunters from bringing whole
carcasses into their home states (bringing home only processed and packaged meat,
devoid of lymphoid and neural tissues, greatly reduces the risk of disease spread). Some
states have banned feeding and baiting of wildlife to reduce artificial congregations of
animals and the consequent increased chances for disease spread (the recent confirmation
of infectiousness in saliva has served to reiterate the risk inherent in feeding and baiting).
Surveillance
Nearly every state and Canadian province is currently conducting some level of
surveillance for CWD. In areas where CWD has been detected, surveillance is used to
monitor for changes in disease distribution and prevalence. In areas where CWD has not
been detected, surveillance is used in attempts to find the disease and to determine the
likelihood that CWD is not present. Surveillance efforts include post-mortem
examination of hunter-killed animals, animals killed in collisions with vehicles, and live
animals displaying clinical signs of disease. In a few specialized situations, wildlife
researchers capture and test live animals using tonsillar biopsies.
Management
Disease management objectives may include limiting geographic spread, reducing
disease prevalence, or eliminating disease. Methods to manage CWD in free-ranging
populations are extremely limited. Several states have attempted to greatly reduce deer
populations, primarily through extended opportunities for hunters, in an effort to reduce
disease transmission. Agency sharpshooters have also been used to cull deer in disease
“hotspots.” At the current time, there is no instance where management has been clearly
successful. Management efforts are extremely difficult and expensive for states to
undertake. But the economic and social values associated with deer, elk and moose in
North America dictate that we continue efforts to detect and successfully manage CWD.
Domestic Livestock Risk
Risk of CWD transmission to domestic livestock (cattle) is apparently low. Cattle have
been housed in captive situations with CWD-infected elk and deer with no transmission
detected. Oral inoculations of cattle with CWD+ material have not been successful in
transmitting disease. Intracerebral inoculations have been successful, but with
incomplete penetrance and prolonged incubation periods.
Other Wildlife Risk
The potential risk of transmission to other species of wildlife is almost wholly
unexplored. Clearly, a tremendous variety of wildlife utilize deer carcasses, excreta, etc.
A small number of challenge studies are currently underway to examine the susceptibility
of other wildlife species. One such study has shown that meadow voles (Microtus
pennsylvanicus) are uniquely susceptible to intracerebral challenge.
Human Risk
The ever-increasing volume of scientific research continues to suggest that the risk of
CWD transmission to humans is remote. Scientists cannot, however, rule out the
possibility. Simple precautionary measures may help to reduce risk even further. Do not
harvest or consume obviously sick animals. If you hunt in areas where CWD is known to
exist, you may opt to have your animal tested. Avoid consuming internal organs, spinal
cord and lymph nodes. And wearing disposable gloves while field-dressing animals
helps reduce transmission risk, not only CWD, but for many other diseases as well.
Additional Information
For additional information on Chronic Wasting Disease and other wildlife health issues,
visit the USGS National Wildlife Health Center at http://www.nwhc.usgs.gov/ and the
Wildlife Disease Information Node of the National Biological Information Infrastructure
at http://wildlifedisease.nbii.gov.
Relevant Literature:
Angers R.C., Browning S.R., Seward T.S., Sigurdson C.J., Miller M.W., Hoover E.A. &
Telling G.C., 2006. Prions in skeletal muscles of deer with chronic wasting disease.
Science 311:1117.
Caughey B. & Baron G.S., 2006. Prions and their partners in crime. Nature 443:803810.
Johnson C.J., Phillips K.E., Schramm P.T., McKenzie D.I., Aiken J.M. & Pedersen J.A.,
2006. Prions adhere to soil minerals and remain infectious. PLoS Pathogens 2:296-302.
Johnson C.J., Pedersen J.A., Chappell R.J., McKenzie D. & Aiken J.M., 2007. Oral
transmissibility of prion disease is enhanced by binding to soil particles. PLos Pathogens
3(7):e93.
Mathiason C.K., Powers J.G., Dahmes S.J., Osborn D.A., Miller K.V., Warren R.J.,
Mason G.L., Hays S.A., Hayes-Klug J., Seelig D.M., Wild M.A., Wolfe L.L., Spraker
T.R., Miller M.W., Sigurdson C.J., Telling G.C. & Hoover, E.A., 2006. Infectious prions
in the saliva and blood of deer with chronic wasting disease. Science 314:133-136.
Miller M.W., Hobbs N.T. & Tavener S.J., 2006. Dynamics of prion disease transmission
in mule deer. Ecological Applications 16(6):2208-2214.
Miller M.W., Williams E.S., Hobbs N.T. & Wolfe L.L., 2004. Environmental sources of
prion transmission in mule deer. Emerging Infectious Diseases 10:1003-1006.
Raymond G.J., Bossers A., Raymond L.D., O’Rourke K.I., McHolland L.E., Bryant III
P.K., Miller M.W., Williams E.S., Smits M. & Caughey B., 2000. Evidence of a
molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting
disease. EMBO Journal 19:4425–4430.
Sigurdson C.J. & Miller M.W., 2003. Other animal prion diseases. British Medical
Bulletin 66:199-212.
Sigurdson C.J. & Aguzzi A., 2007. Chronic Wasting Disease. Biochimica et Biophysica
Acta 1772:610–618.
Watts J.C., Balachandran A. & Westaway D., 2006. The expanding universe of prion
diseases. PLoS Pathogens 2:152-163.
Williams E.S. & Young S., 1992. Spongiform encephalopathies in Cervidae. Revue
Scientifique et Technique 11:551–567.
Williams E.S., 2005. Chronic Wasting Disease. Veterinary Pathology 42:530-549.