Chronic Wasting Disease and Potential Transmission to Humans
Ermias D. Belay,*Comments
Ryan A.
Maddox,* Elizabeth S. Williams, Michael W. Miller,! Pierluigi
Gambetti,§ and Lawrence B. Schonberger*
*Centers for Disease Control and Prevention, Atlanta, Georgia, USA;
University of Wyoming, Laramie, Wyoming, USA; !Colorado Division of
Wildlife, Fort Collins, Colorado, USA; and §Case Western Reserve
University, Cleveland, Ohio, USA
Suggested citation for this article: Belay ED, Maddox RA, Williams
ES, Miller MW, Gambetti P, Schonberger LB. Chronic wasting disease
and potential transmission to humans. Emerg Infect Dis [serial on
the Internet]. 2004 Jun [date cited]. Available from:
http://www.cdc.gov/ncidod/EID/vol10no6/03-1082.htm
------------------------------------------------------------------------
Chronic wasting disease (CWD) of deer and elk is endemic in a
tri-corner area of Colorado, Wyoming, and Nebraska, and new foci of
CWD have been detected in other parts of the United States. Although
detection in some areas may be related to increased surveillance,
introduction of CWD due to translocation or natural migration of
animals may account for some new foci of infection. Increasing
spread of CWD has raised concerns about the potential for increasing
human exposure to the CWD agent. The foodborne transmission of
bovine spongiform encephalopathy to humans indicates that the
species barrier may not completely protect humans from animal prion
diseases. Conversion of human prion protein by CWD-associated prions
has been demonstrated in an in vitro cell-free experiment, but
limited investigations have not identified strong evidence for CWD
transmission to humans. More epidemiologic and laboratory studies
are needed to monitor the possibility of such transmissions.
Chronic wasting disease (CWD) is classified as a transmissible
spongiform encephalopathy (TSE), or prion disease, along with other
animal diseases, such as scrapie and bovine spongiform encephalopathy.
The only known natural hosts for CWD are deer (Odocoileus species) and
Rocky Mountain elk (Cervus elaphus nelsoni) (1,2
). CWD and other
TSEs are believed to be caused by a pathogenic effect on neurons of an
abnormal isoform of a host-encoded glycoprotein, the prion protein. The
pathogenic form of this protein appears to be devoid of nucleic acids
and supports its own amplification in the host. TSEs in animals
primarily occur by transmitting the etiologic agent within a species,
either naturally or through domestic husbandry practices. In contrast,
most such encephalopathies in humans occur as a sporadic disease with no
identifiable source of infection or as a familial disease linked with
mutations of the prion protein gene (3
). A notable
exception among the human TSEs is the variant form of Creutzfeldt-Jakob
disease (vCJD), which is believed to have resulted from the foodborne
transmission of bovine spongiform encephalopathy (BSE) to humans (4,5
).
CWD was first identified as a fatal wasting syndrome of captive mule
deer in the late 1960s in research facilities in Colorado and was
recognized as a TSE in 1978 (6,7
). Subsequently,
this wasting disease was identified in mule deer in a research facility
in Wyoming and in captive elk in both the Colorado and Wyoming
facilities (68 ).
The disease was first recognized in the wild in 1981 when a free-ranging
elk from Colorado was diagnosed with the disease (1,9
). By the
mid-1990s, CWD had been diagnosed among free-ranging deer and elk in a
contiguous area in northeastern Colorado and southeastern Wyoming, where
subsequent surveillance studies confirmed it to be endemic (10
). Epidemic
modeling suggested that this wasting disease might have been present
among free-ranging animals in some portions of the disease-endemic area
several decades before it was initially recognized (10
). On the basis of
hunter-harvested animal surveillance, the overall prevalence of the
disease in this area from 1996 through 1999 was estimated at
approximately 5% in mule deer, 2% in white-tailed deer, and <1% in elk
(10 ). In 2000,
surveillance data indicated that the disease-endemic focus extended
eastward into adjacent areas of Nebraska (1
,11
), and ongoing
surveillance continues to redefine the limits of this focus.
Clinical manifestations of CWD include weight loss over weeks or months,
behavioral changes, excessive salivation, difficulty swallowing,
polydipsia, and polyuria (1,68
). In some
animals, ataxia and head tremors may occur. Most animals with the
disease die within several months of illness onset, sometimes from
aspiration pneumonia. In rare cases, illness may last for ?1 year. In
captive cervids, most cases occur in animals 27 years of age; however,
the disease has been reported in cervids as young as 17 months and as
old as >15 years of age (1
). This disease
can be highly transmissible within captive deer and elk populations. A
prevalence of >90% was reported among mule deer in facilities where the
disease has been endemic for >2 years (2,6,7
,12
). The mode of
transmission among deer and elk is not fully understood; however,
evidence supports lateral transmission through direct animal-to-animal
contact or as a result of indirect exposure to the causative agent in
the environment, including contaminated feed and water sources (12
).
Geographic Distribution of Chronic Wasting Disease
Figure
Figure.
Click to view enlarged image
Figure. Chronic wasting disease among free-ranging deer and elk by
county, United States.
The geographic extent of CWD has changed dramatically since 1996 (2
). Two largely
independent and simultaneous epidemics, one in free-ranging deer and elk
and another in the captive elk and deer industry, appear to represent
the main framework for explaining the disease's current distribution (2
). More extensive
and coordinated surveillance has provided a clearer picture of its
distribution over the last few years. Since 2000, the disease in
free-ranging cervids has been increasingly identified outside of the
original CWD-endemic areas of Colorado and Wyoming (Figure
). The
observed distribution seems to be related in part to natural movement of
deer and elk and to commercial movement of infected animals to areas far
from the disease-endemic zone. Considerable attention has been given to
recent increases in the geographic spread of the disease, which in some
areas is likely a result of increased surveillance rather than evidence
of explosive geographic spread.
No single original event or source links all wasting disease foci
documented to date. Given the disease's insidious nature and the
apparent duration (at least several decades) of epidemics among captive
and free-ranging cervids, gaps in knowledge about its spread and
distribution are not surprising, particularly within the captive deer
and elk industry. However, our current knowledge cannot explain some of
the distinct foci of CWD among free-ranging animals (e.g., in New Mexico
and Utah). Thus, unidentified risk factors may be contributing to the
occurrence of CWD among free-ranging and captive cervid populations in
some areas.
Chronic Wasting Disease in Free-ranging Deer and Elk
In 2000, surveillance of hunter-harvested deer first detected the
occurrence of CWD in counties in southwestern Nebraska, adjacent to the
previously recognized areas of Colorado and Wyoming that are endemic for
this disease (Figure
) (1
,11
). It was
reported subsequently in other Nebraska counties, including among deer
and elk in a commercial, large enclosure surrounded by a fence in
northwestern Nebraska, where the prevalence of CWD was >50% (11
). Free-ranging
deer from areas surrounding the enclosure also tested positive for the
disease but at substantially lower rates. In 2001, CWD in a free-ranging
deer was identified in the southwestern part of South Dakota along the
Nebraska border close to an area where the disease had been reported
among captive elk (13
). Since then,
additional CWD-positive free-ranging deer and elk have been identified
in southwestern South Dakota.
CWD in free-ranging cervids was first reported east of the Mississippi
River in Wisconsin among white-tailed deer harvested in the 2001 hunting
season (14 ).
Subsequent surveillance indicated that this CWD epidemic focus was
limited to several counties in the south-central region of Wisconsin,
although a second focus spanning the Illinois border was also detected
(15 ). The
absence of evidence for a widespread occurrence of CWD and its low
prevalence, despite a highly dense deer population, indicate that the
disease probably was recently introduced into Wisconsin. Because the
distance from the CWD-endemic area of Colorado-Wyoming effectively
precludes eastward migration of animals as a logical source of
infection, CWD in Wisconsin was more likely introduced by an imported
infected cervid or some other unidentified source (14
). The proximity
of the Wisconsin-Illinois focus to a white-tailed deer farm with
infected animals appears to support this explanation, as highlighted by
the report of CWD in a previously captive white-tailed deer
approximately 7 months after it escaped into the wild in southern
Wisconsin (14 ).
The disease among the captive deer herd from which the white-tailed deer
escaped was demonstrated earlier, when a still-captive deer tested
positive for the disease. The captive source herd was held in a facility
?3050 km from the Illinois location where CWD was recently identified
in a free-ranging deer (16
). In 2002, the
Wisconsin Department of Natural Resources launched an ambitious culling
program by providing special hunting permits to eliminate the disease in
a designated "eradication zone" around the areas where it was detected
(15,17 ). Whether
such aggressive management will succeed in eliminating free-ranging foci
of CWD remains to be determined.
In Colorado, the Continental Divide initially appeared to have prevented
natural expansion of CWD into the western part of the state. However, in
2002, the disease was confirmed for the first time in several
free-ranging deer harvested in western Colorado in an area surrounding a
commercial enclosure, where entrapped mule deer tested positive for CWD.
Aggressive culling of deer and elk surrounding the enclosure was
initiated to prevent further spread of the disease in the western slope
of Colorado. Through the 2002 hunting season, CWD-positive deer and elk
continued to be identified outside of the previously defined
disease-endemic area, primarily in northwestern Colorado (18
). This
northwestern focus appears to be discontinuous from the previously
identified CWD-endemic area, although surveys conducted in 2002
demonstrated that the western and southern boundaries of that area were
wider than previously believed. The ultimate source of this wasting
disease in northwestern Colorado remains unidentified.
In 2002, samples from an emaciated, free-ranging mule deer found in
White Sands, New Mexico, tested positive for CWD (1
,19
). No cervids
have been held in captivity close to the area where the New Mexico deer
was found, and the origin of the disease in this deer remains unknown.
In addition, CWD-positive, free-ranging deer have been identified in
Wyoming to the west over the Continental Divide from the known
CWD-endemic zone (20
). In 2003, a
mature buck deer harvested in the fall of 2002 in northeastern Utah
tested positive for the disease (21
); additional
cases have since been found in central and eastern Utah (Figure
). These
cases provide additional evidence for the potential spread of this
wasting disease in the wild.
In Canada, CWD was first detected in free-ranging cervids (two mule
deer) in 2001 in Saskatchewan; a few additional deer tested positive in
2002 and 2003 (22
). Saskatchewan
Environment has implemented a herd-reduction program using "control
permits" to prevent further spread of the disease among free-ranging
cervids.
Chronic Wasting Disease in Captive Deer and Elk
CWD was first recognized in the captive elk industry in Saskatchewan in
1996, but subsequent investigations indicated that the most likely
source of Canadian cases was captive elk imported from South Dakota
prior to 1989 (2
,22
). Since 1996,
surveillance has detected infected animals on more than 25 elk farms in
Colorado, Kansas, Minnesota, Montana, Nebraska, Oklahoma, South Dakota,
and Alberta, Canada, and the Republic of Korea (1
,14
,23,24
). CWD in most of
these farms was identified in the past 5 years. In 2002, the disease was
detected in white-tailed deer on farms in Alberta and Wisconsin (23,25
). More extensive
and uniform surveillance in captive white-tailed deer is needed to
determine the full extent of the disease in this industry.
Captive herds with a CWD-infected cervid are often depopulated both in
Canada and the United States. Carcasses of depopulated animals are
incinerated or buried in accordance with local regulations. Meat from
depopulated animals has not been allowed to enter the human food and
animal feed supply.
Transmission to Other Animals
Concerns have been raised about the possible transmission of the CWD
agent to domestic animals, such as cattle and sheep, which may come in
contact with infected deer and elk or CWD-contaminated environments. If
such transmissions were to occur, they would potentially increase the
extent and frequency of human exposure to the CWD agent. In addition,
passage of the agent through a secondary host could alter its infectious
properties, increasing its potential for becoming more pathogenic to
humans. This phenomenon may have occurred with BSE when a strain of
scrapie, a possible original source of the BSE outbreak, changed its
pathogenic properties for humans after infecting cattle. However, the
exact origin of BSE remains unknown.
Although CWD does not appear to occur naturally outside the cervid
family, it has been transmitted experimentally by intracerebral
injection to a number of animals, including laboratory mice, ferrets,
mink, squirrel monkeys, and goats (1
,26
). In an
experimental study, the CWD agent was transmitted to 3 of 13
intracerebrally injected cattle after an incubation period of 22 to 27
months (27 ). The
susceptibility of cattle intracerebrally challenged with the agent of
this disease was substantially less than that observed after
intracerebral scrapie challenge: nine of nine cattle succumbed to
scrapie challenge after intracerebral injection (28
). In ongoing
experimental studies, after >6 years of observation, no prion disease
has developed in 11 cattle orally challenged with the CWD agent or 24
cattle living with infected deer herds (E.S. Williams and M.W. Miller,
unpub. data) (1 ).
In addition, domestic cattle, sheep, and goat residing in research
facilities in close contact with infected cervids did not develop a
prion disease.
Analysis by immunohistochemical studies of the tissue distribution of
prions in CWD-infected cervids identified the agent in the brain, spinal
cord, eyes, peripheral nerves, and lymphoreticular tissues (Table 1
) (29,30
). Distribution
of the CWD agent outside of the brain seems to be less widespread in elk
than in deer (2 ).
Involvement of the tonsils and peripheral nerves early in the course of
experimental and natural prion infection suggests the possible
involvement of the lymphoreticular and peripheral nervous systems in the
pathogenesis and transmission of the disease (2
,12
,30
,31
).
Risk for Transmission to Humans
Epidemiologic Studies
The increasing detection of CWD in a wider geographic area and the
presumed foodborne transmission of BSE to humans, resulting in cases of
vCJD, have raised concerns about the possible zoonotic transmission of
CWD (32 ). In the
late 1990s, such concerns were heightened by the occurrence of CJD among
three patients ?30 years of age who were deer hunters or ate deer and
elk meat harvested by family members (Table 2
). However,
epidemiologic and laboratory investigations of these case-patients
indicated no strong evidence for a causal link between CWD and their CJD
illness (33 ).
None of the patients were reported to have hunted deer or eaten deer
meat harvested in the CWD-endemic areas of Colorado and Wyoming. Such a
history in unusually young CJD patients, if present, would have
supported a causal link with CWD. Moreover, the testing of brain tissues
from >1,000 deer and elk harvested from areas where the patients hunted
or their venison originated did not show any evidence of CWD (33
). In addition,
the lack of homogeneity in the clinicopathologic manifestation and codon
129 of the prion protein gene among the three patients suggested that
their illnesses could not be explained by exposure to the same prion
strain. In vCJD, homogeneity of the genotype at codon 129 and the
clinical and pathologic phenotype were attributed to the patients'
exposure to the same prion strain, the agent of BSE.
In 2001, the case of a 25-year-old man who reportedly died of a prion
disease after an illness lasting ?22 months was investigated (Table 2
). Although
this man had hunted deer only rarely, his grandfather hunted deer and
elk throughout much of the 1980s and 1990s and regularly shared the
venison with the case-patient's family. The grandfather primarily hunted
in southeastern Wyoming, around the known CWD-endemic area. The
case-patient's illness began with a seizure and progressed to fatigue,
poor concentration, and depression. Memory loss, ataxia, speech
abnormalities, combative behavior, and recurrent seizures also
developed. Histopathologic, immunohistochemical, and Western blot
testing of brain autopsy samples confirmed a prion disease diagnosis.
Analysis of the prion protein gene indicated a P102L mutation coupled
with valine at the polymorphic codon 129 in the mutant allele,
confirming a diagnosis of Gerstmann-Sträussler-Scheinker syndrome (GSS).
This case-patient was unusually young even for a person with a GSS P102L
mutation. It remains unknown whether the possible exposure of the
case-patient to CWD-infected venison potentially contributed to the
early onset of his prion disease.
In 2001, two additional CJD patients 26 and 28 years of age were
reported from a single state (Table 2
) (34
). The patients
grew up in adjacent counties and had illness onset within several months
of each other. As a result of this fact and their unusually young age, a
possible environmental source of infection, including exposure to
CWD-infected venison, was considered. One of the patients died after an
illness lasting 56 months that was characterized by progressive
aphasia, memory loss, social withdrawal, vision disturbances, and
seizure activity leading to status epilepticus and induced coma.
Histopathologic, immunohistochemical, and Western blot testing of brain
biopsy and autopsy samples confirmed a CJD diagnosis. The patient's
disease phenotype corresponded to the MM2 sporadic CJD subtype reported
by Parchi et al. (35
). This patient
did not hunt, and family members provided no history of regularly eating
venison. The patient may have occasionally eaten venison originating
from the Upper Peninsula of Michigan while away from home during his
college years. However, ongoing surveillance has not detected CWD in
Michigan deer (36 ).
The second patient died from an illness lasting <16 months. The
patient's illness began with behavioral changes, including unusual
outbursts of anger and depression. Confusion, memory loss, gait
disturbances, incontinence, headaches, and photophobia also developed.
Western blot analysis of frozen brain biopsy tissue confirmed a prion
disease diagnosis. Immunohistochemical analysis of brain tissue obtained
after the patient's death showed prion deposition consistent with GSS. A
prion protein gene analysis could not be performed because appropriate
samples were lacking. However, prion protein gene analysis of a blood
sample from one of the patient's parents indicated a GSS P102L mutation.
The patient did not hunt but may have eaten venison from Michigan once
when he was 12 years old. The GSS diagnosis greatly reduced the
likelihood that the two patients reported from adjacent counties had
disease with a common origin.
Recently, rare neurologic disorders resulting in the deaths of three men
who participated in "wild game feasts" in a cabin owned by one of the
decedents created concern about the possible relationship of their
illnesses with CWD (Table 2
) (37
). Two of the
patients reportedly died of CJD, and the third died from Pick's disease.
More than 50 persons were identified as possibly participating in these
feasts; the three patients were the only participants reported to have
died of a degenerative neurologic disorder. Reanalysis of autopsy brain
tissues from the three patients at the National Prion Disease Pathology
Surveillance Center indicated that two of them had no evidence of a
prion disease by immunohistochemical analysis. CJD was confirmed in the
third patient, who had clinicopathologic, codon 129, and prion
characteristics similar to the most common sporadic CJD subtype
(MM1/MV1) (35 ).
This patient participated in the feasts only once, perhaps in the
mid-1980s. In addition, the investigation found no evidence that the
deer and elk meat served during the feasts originated from the known
CWD-endemic areas of Colorado and Wyoming.
In 2003, CJD in two deer and elk hunters (54 and 66 years of age) was
reported (38 ).
The report implied that the patients had striking neuropathologic
similarities and that their illness may represent a new entity in the
spectrum of prion diseases. A third patient (63 years of age), who was
also purported to have been a big game hunter, was subsequently reported
from the same area. However, none of the three patients were reported to
have eaten venison from the CWD-endemic areas of the western United
States. The 66-year-old patient hunted most of his life in Washington
State. Although information about the 54-year-old patient was limited,
there was no evidence that he hunted in CWD-endemic areas. The third
patient was not a hunter but ate venison harvested from Pennsylvania and
Washington. The neuropathologic changes, Western blot profile, and
genotype at codon 129 of the three patients each fit the MM1, VV1, or
VV2 sporadic CJD subtype, indicating absence of phenotypic similarity
among the cases or atypical neuropathologic features (35
).
To date, only two nonfamilial CJD cases with a positive history of
exposure to venison obtained from the known CWD-endemic areas have been
reported. One of the patients was a 61-year-old woman who grew up in an
area where this disease is known to be endemic, and she ate venison
harvested locally. She died in 2000, and analysis of autopsy brain
specimens confirmed that the patient's CJD phenotype fit the MM1
subtype, with no atypical neuropathologic features. The second patient
was a 66-year-old man who was reported to have eaten venison from two
deer harvested in a CWD-endemic area. Both deer tested negative for CWD,
and the patient's illness was consistent with the MM1 CJD phenotype.
Despite the decades-long endemicity of CWD in Colorado and Wyoming, the
incidence of CJD and the age distribution of CJD case-patients in these
two states are similar to those seen in other parts of the United
States. From 1979 to 2000, 67 CJD cases from Colorado and 7 from Wyoming
were reported to the national multiple cause-of-death database. The
average annual age-adjusted CJD death rate was 1.2 per million persons
in Colorado and 0.8 in Wyoming. The proportion of CJD patients who died
before age 55 in Colorado (13.4%) was similar to that of the national
(10.2%). The only CJD case-patient <30 years of age in Colorado had
iatrogenic CJD linked to receipt of human growth hormone injections. CJD
was not reported in persons <55 years of age in Wyoming during the
22-year surveillance period.
Laboratory Studies
The possible interspecies transmission of prions can be assessed with
laboratory methods. In BSE and vCJD, several laboratory studies provided
crucial evidence that helped establish a causal link between the two
diseases (3941
). These studies
characterized the molecular similarities of the agents causing BSE and
vCJD and determined the lesion profile and incubation period patterns of
different panels of mice inoculated by the two agents. Limited
laboratory studies have been performed to molecularly characterize
CWD-associated prions and to compare them with prions from human
case-patients and other species. Strain typing studies involving
wild-type inbred mice indicated that the CWD agent from a mule deer
produced incubation-period and brain-lesion profiles different from
those produced by the agents causing BSE and scrapie (39
,42
). These same
strain-typing techniques had identified the similarities of the
etiologic agents of BSE and vCJD, providing strong laboratory evidence
for a link between the two diseases.
In human prion diseases, two major types of the proteinase-Kresistant
prion protein fragment have been identified on the basis of their
molecular size by one-dimensional immunoblot analysis: type 1 migrating
at 21 kDa and type 2 at 19 kDa (35
). N-terminal
protein sequencing indicated that the cleavage site of the type 1
fragment is generally at residue 82 and that of type 2 is at residue 97
(43 ). Prion
strain diversity is believed to be encoded in the three-dimensional
conformation of the protein, which determines the cleavage site and
molecular size of proteinase-Ktreated prion fragment, indicating that
the difference in molecular size may correlate with strain differences.
However, one-dimensional immunoblot analysis may not identify more
subtle differences that may influence the conformation of different
prion strains. Analysis of the glycoform ratios of prion fragments and
application of a two-dimensional immunoblot may help further identify
these subtle differences. On one-dimensional immunoblot analysis, the
prion fragment from several CWD-infected deer and elk migrated to 21
kDa, corresponding to the type 1 pattern. This specific type has been
identified in most cases of sporadic CJD in the United States. However,
the deer and elk prion fragment differs from that in sporadic CJD cases
in the glycoform ratio. In the CWD-associated prion fragment, the
diglycosylated form was predominant, but in the CJD-associated prions,
the monoglycosylated form was predominant. Preliminary analysis using
two-dimensional immunoblot indicated that the CWD-associated prion
fragment exhibited patterns different from that of the CJD-associated
prion fragment from a human patient with the type 1 pattern (S. Chen,
pers. comm.). Although analysis of more samples from cervids and humans
is needed before meaningful conclusions can be made, these molecular
techniques could potentially be used to study the similarities or
differences in prion strains from cervids and humans with possible
exposure to CWD.
The likelihood of successful interspecies transmission of prion diseases
is influenced by the degree of homology of the infecting prion with that
of the host endogenous prion protein. Such observations have given rise
to the concept of a "species barrier," which would need to be overcome
before an infecting prion strain caused disease in a recipient host. In
vitro cell-free conversion reaction experiments have been developed to
assess the degree of molecular compatibility of disease-associated
prions from one species with normal prion protein obtained from a
different species (44,45
). Such
experiments specifically assess the likelihood that an infecting prion
would potentially initiate the formation and propagation of pathogenic
prions if it came in contact with normal prion protein. A cell-free
conversion experiment indicated that CWD-associated prions can convert
human prion protein into its abnormal conformer, albeit at a very low
rate (44 ). The
efficiency of this conversion was >14-fold weaker than the homologous
conversion of cervid prion protein and >5-fold weaker than the
homologous conversion induced by CJD-associated prions. A similar low
efficiency conversion of human prion protein by bovine- and
scrapie-associated prions was also reported (44,45
). Although a
high level of compatibility of prions in in vitro conversion reactions
is believed to correlate with in vivo transmissibility of the agents,
the threshold of compatibility efficiency below which no natural
transmission should be anticipated is unknown. A low level of
compatibility of infecting prions and host prion protein does not
necessarily rule in or out natural interspecies transmission of prion
diseases. However, the comparably low-level in vitro conversion of
bovine prion protein by CWD-associated prions is consistent with the
relative in vivo resistance of cattle to CWD under all but the most
extreme experimental challenges. In addition, several other factors may
determine the in vivo transmission of disease-associated prions,
including dose, strain of the agent, route of infection, stability of
the agent inside and outside the host, and the efficiency of agent
delivery to the nervous system (44,46
).
Conclusions
The lack of evidence of a link between CWD transmission and unusual
cases of CJD, despite several epidemiologic investigations, and the
absence of an increase in CJD incidence in Colorado and Wyoming suggest
that the risk, if any, of transmission of CWD to humans is low. Although
the in vitro studies indicating inefficient conversion of human prion
protein by CWD-associated prions raise the possibility of low-level
transmission of CWD to humans, no human cases of prion disease with
strong evidence of a link with CWD have been identified. However, the
transmission of BSE to humans and the resulting vCJD indicate that,
provided sufficient exposure, the species barrier may not completely
protect humans from animal prion diseases. Because CWD has occurred in a
limited geographic area for decades, an adequate number of people may
not have been exposed to the CWD agent to result in a clinically
recognizable human disease. The level and frequency of human exposure to
the CWD agent may increase with the spread of CWD in the United States.
Because the number of studies seeking evidence for CWD transmission to
humans is limited, more epidemiologic and laboratory studies should be
conducted to monitor the possibility of such transmissions. Studies
involving transgenic mice expressing human and cervid prion protein are
in progress to further assess the potential for the CWD agent to cause
human disease. Epidemiologic studies have also been initiated to
identify human cases of prion disease among persons with an increased
risk for exposure to potentially CWD-infected deer or elk meat (47
). If such cases
are identified, laboratory data showing similarities of the etiologic
agent to that of the CWD agent would strengthen the conclusion for a
causal link. Surveillance for human prion diseases, particularly in
areas where CWD has been detected, remains important to effectively
monitor the possible transmission of CWD to humans. Because of the long
incubation period associated with prion diseases, convincing negative
results from epidemiologic and experimental laboratory studies would
likely require years of follow-up. In the meantime, to minimize the risk
for exposure to the CWD agent, hunters should consult with their state
wildlife agencies to identify areas where CWD occurs and continue to
follow advice provided by public health and wildlife agencies. Hunters
should avoid eating meat from deer and elk that look sick or test
positive for CWD. They should wear gloves when field-dressing carcasses,
bone-out the meat from the animal, and minimize handling of brain and
spinal cord tissues. As a precaution, hunters should avoid eating deer
and elk tissues known to harbor the CWD agent (e.g., brain, spinal cord,
eyes, spleen, tonsils, lymph nodes) from areas where CWD has been
identified.
Acknowledgments
We thank Claudia Chesley for editorial assistance and state and
local health departments for facilitating and participating in the
investigation of individual case-patients.
Dr. Belay is a medical epidemiologist at the Division of Viral and
Rickettsial Diseases, Centers for Disease Control and Prevention
(CDC); he coordinates the CDC prion disease surveillance and
research activities. His research areas of interest include the
interspecies transmission of prion diseases, Kawasaki syndrome, and
Reye syndrome.
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Table 1. Deer tissues tested for the CWD agent by animal bioassay or
immunohistochemical studiesa
------------------------------------------------------------------------
Tissues positive for CWD agent
Brain
Pituitary gland
Spinal cord
Eyes (optic nerve, ganglion cells, retina)
Tonsils
Lymphoid tissues (e.g., gut-associated, retropharyngeal, posterior nasal
septum)
Spleen
Pancreas
Peripheral nerves (e.g., brachial plexus, sciatic nerve, vagosympathetic
trunk)
Tissues negative for CWD agent
Dorsal root ganglia
Parotid and mandibular salivary glands, tongue, esophagus, small
intestine, colon
Thymus
Liver
Kidneys, urinary bladder, ovary, uterus, testis, epididymis, placentomes
Myocardium, Purkinje fibers, arteries, veins
Trachea, bronchi, bronchioles, aleveolar parenchyma
Bone marrow
Thyroid gland, adrenal gland
Skeletal muscle
Skin
------------------------------------------------------------------------
aCWD, chronic wasting disease.
Table 2. Creutzfeldt-Jakob disease patients investigated for a possible
causal link of their illness with chronic wasting disease of deer and
elk, United Statesa
------------------------------------------------------------------------
Case no.
Age at death (y)
Year of death
Codon 129
Western blot
Final diagnosis
Eating of venison from
CWD-endemic area
------------------------------------------------------------------------
1
25
2001
M/V
Type 1
GSS 102
Yes
2
26
2001
M/M
Type 2
CJD
No
3b
28
2002
nd
nd
GSS 102
No
4
28
1997
M/M
nd
CJD
No
5
28
2000
M/V
Type 1
CJD
No
6
30
1999
V/V
Type 1
CJD
No
7
54
2002
V/V
Type 2
CJD
No
8c
55
1999
M/M
Type 1
CJD
No
9d
61
2000
M/M
Type 1
CJD
Yes
10
63
2002
V/V
Type 1
CJD
No
11e
64
2002
M/M
Type 1
CJD
Yes
12
66
2001
M/M
Type 1
CJD
No
------------------------------------------------------------------------
aCWD, chronic wasting disease; GSS, Gerstmann-Sträussler-Scheinker
syndrome; CJD, Creutzfeldt-Jakob disease; nd, not done.
bImmunohistochemical analysis of postmortem brain tissue was consistent
with GSS, and a GSS 102 mutation was confirmed in the family.
cInvestigated as part of a cluster of three case-patients who
participated in "wild game feasts" in a cabin owned by one of the
decedents.
dPatient grew up in an area known to be endemic for CWD and ate venison
harvested locally; however, the CJD phenotype fits the most common form
of sporadic CJD.
ePatient may have been successful in harvesting two deer since 1996 from
a CWD-endemic area, but both deer tested negative for CWD.
http://www.cdc.gov/ncidod/EID/vol10no6/03-1082.htm
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