chronic wasting disease in deer and elk in north …...introduction chronic wasting disease (cwd) is...

IntroductionChronic wasting disease (CWD) is a naturally-occurring priondisease of native North American deer (Odocoileus spp.) andRocky Mountain elk (Cervus elaphus nelsoni). This is the onlyprion disease known to affect free-ranging species. Epidemicsof CWD are apparently self-sustaining in both captive and free-ranging populations, but the geographic distribution of the

disease is presently limited. The potential for movement ofCWD into the commercial cervid industry was raised as aconcern in a previous review of CWD (60). Unfortunately, therecent detection of CWD in the game farming industry ofNorth America raises the possibility that CWD will spreadacross the continent, and perhaps beyond, as was recentlyfound with the diagnosis of CWD in the Republic of Korea, viamarket-driven movements of infected cervids (members of thedeer family).

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Chronic wasting disease in deer and elk in North America

SummaryChronic wasting disease (CWD) has emerged as an important disease of wildlifein North America. The disease is a unique member of the transmissiblespongiform encephalopathies (TSEs) or prion diseases, which naturally affectonly a few species. Of the TSEs, CWD is the only one found in free-rangingspecies. However, interest in CWD has recently grown, by association with thebetter-known TSEs such as variant Creutzfeldt-Jakob disease of humans andbovine spongiform encephalopathy. Knowledge of the geographic distribution ofCWD, though still limited, has greatly improved since the mid-1990s as a result ofsurveillance in free-ranging deer and elk and in commercially owned RockyMountain elk (Cervus elaphus nelsoni), and the disease has now been found inmultiple areas of the plains and Rocky Mountain foothills of western NorthAmerica. Studies of the biology and natural history of CWD over recent yearshave resulted in a better understanding of the pathogenesis and epidemiology ofthe disease. Early involvement of the lymphoid tissues of the alimentary tractduring the incubation period of CWD suggests plausible routes for agent exit froman infected individual, such as in faeces or saliva. Chronic wasting disease islaterally transmitted and environmental contamination may play an important rolein local maintenance of the disease. Studies on the epidemiology of CWD haveled to the development of models to help explain the history of CWD and tosimulate future impacts on deer and elk populations. Diagnostic tests have beenimproved, allowing diagnosis early in the incubation period, long before theappearance of clinical disease. Surveillance techniques and programmes havebeen developed and instituted by wildlife management agencies for free-rangingdeer and elk and by state and federal agricultural agencies for privately-ownedelk. During the 1990s, perceptions of TSEs have altered dramatically; perhapsmost remarkably, the goal of global eradication of all prion diseases is now beingdiscussed.

KeywordsChronic wasting disease – Elk – Mule deer – North America – Prion diseases –Transmissible spongiform encephalopathies – White-tailed deer.

E.S. Williams (1) & M.W. Miller (2)

(1) Department of Veterinary Sciences, University of Wyoming, 1174 Snowy Range Road, Laramie, Wyoming 82070, United States of America(2) Colorado Division of Wildlife, Wildlife Research Center, 317 West Prospect Road, Fort Collins, Colorado80526, United States of America

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History and distributionAs with most infectious diseases, the precise timing andgeographic origin of the emergence of CWD cannot bedetermined with any certainty. A ‘chronic wasting disease’ wasfirst recognised in 1967 as a clinical syndrome of unknownaetiology among captive mule deer (Odocoileus hemionus) atwildlife research facilities in Colorado, United States of America(USA) (58), but deer in this facility originated from severalsources, including free-ranging populations and a wildliferesearch facility in Wyoming, USA. In 1978, ‘chronic wastingdisease’ was diagnosed as a spongiform encephalopathy byhistopathological examination of brains from affected animals.Shortly afterwards, CWD was recognised among captive muledeer in Wyoming (58). Diagnosis of CWD in elk from thesesame facilities followed rapidly (59). Deer and elk in a fewzoological gardens in the USA and Canada were identified withCWD in subsequent years (60). Apparently the disease did notpersist in these locations.

In 1981, CWD was recognised in a free-ranging elk inColorado (52). Subsequently, the disease was found in free-ranging elk in Wyoming, and in free-ranging mule deer andwhite-tailed deer (O. virginianus) in both states in 1985 and1990, respectively. However, surveillance data and epidemicmodelling suggest that CWD may have been present in somefree-ranging deer populations for two decades or more beforebeing detected (33).

Most recently, CWD has emerged as a disease of concern in thegame farm industry of North America. Following diagnosis ofthe disease in elk in Saskatchewan, Canada, in 1996, CWDsubsequently has been diagnosed in farmed elk from severallocations in the USA, namely: South Dakota, Nebraska,Oklahoma, Colorado and Montana, as well as from numerousfarms in Saskatchewan (8, 55). In Saskatchewan, occurrence ofCWD on elk farms has coincided with recognition of CWD ina local mule deer population (8). Based on initialepidemiological investigations, CWD appears likely to havebeen present in the farmed cervid industry of North Americafor over a decade, and perhaps much longer.

The known distribution of CWD currently includes endemicfoci in both free-ranging and captive cervids. ContemporaryCWD epidemics in free-ranging and farmed cervids appear tobe essentially independent entities with minimal geographicoverlap; if these epidemics share a common origin, it may dateback several decades. In free-ranging deer and elk, cases ofCWD have been diagnosed in contiguous portions of south-east Wyoming, north-east Colorado, and the extreme south-west corner of the panhandle of Nebraska, USA (Fig. 1a); thisendemic focus spans approximately 40,000 km2 of nativehabitats ranging from mountains and foothills to river bottomsand shortgrass prairie tablelands (33). Future geographicspread in this free-ranging endemic focus is relatively

predictable, and will most likely follow natural movements ofdeer and elk in affected areas (33). A geographically distinctfocus in western Saskatchewan, which is most likely a spilloverfrom ongoing epidemics in farmed elk in that province, wasonly recently discovered.

In the captive elk industry of North America, most infectedherds have been depopulated once detected, but infected gamefarms remain in Saskatchewan, Nebraska, Oklahoma andColorado (Fig. 1b); surveillance programmes may well uncovermore captive herds with CWD in the coming years. In contrastto the future geographic spread in free-ranging cervids, thespread of CWD in the cervid industry is highly unpredictablebecause animal movements are commercial, essentiallyrandom, and inadequately regulated in many locations.Undetected spread via trade of infected animals will probablycontinue until uniform surveillance programmes are adoptedand enforced.

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a) Free-ranging deer and elk

b) Captive, commercially-raised deer and elk

Depopulated herds

Herds in quarantine (or released without depopulation)

Fig. 1Known geographic distribution of chronic wasting disease,June 2001

Distribution of chronic wasting disease

Host rangeOnly three species, all members of the family Cervidae, areknown to be naturally susceptible to CWD, namely: mule deer,white-tailed deer and Rocky Mountain elk. Subspecies of thesecervids are probably also naturally susceptible.

Moose (Alces alces), pronghorn antelope (Antilocapraamericana), Rocky Mountain bighorn sheep (Ovis canadensiscanadensis), mouflon (Ovis musimon), mountain goats(Oreamnos americanus), and a blackbuck (Antilope cervicapra)which have been in contact with CWD-affected deer and elk orresided in premises in which CWD had occurred have notdeveloped the disease. Domestic livestock are not known to benaturally susceptible to CWD. A few cattle, sheep and goatshave resided in research facilities together with CWD-affectedanimals for prolonged periods without developing the disease.Cattle intensively exposed to CWD-affected deer and elk underexperimental conditions have remained healthy for over fouryears (E.S. Williams, M.W. Miller and T.J. Kreeger, unpublishedfindings). These observations of apparent cross-speciesresistance are supported by molecular studies (46).

Many species are experimentally susceptible to CWD byintracerebral inoculation, an unnatural but commonly usedroute for the study of prion diseases. Mink (Mustela vison),domestic ferret (Mustela putorius furo), squirrel monkey (Saimirisciureus), mule deer, domestic goats, domestic cattle, andlaboratory mice are susceptible to CWD by this route onprimary passage (6, 7, 27, 60). However, for some species otherthan mule deer, intracerebral transmission of CWD appears tobe inefficient on primary passage compared to that of scrapie orbovine spongiform encephalopathy (BSE) (7, 28).

AetiologyChronic wasting disease is a member of an unusual group ofneurological diseases called transmissible spongiformencephalopathies (TSEs). The TSEs are apparently caused byproteinaceous infectious agents called prions, which are devoidof nucleic acids (42). Although the debate continues (9, 15),the preponderance of data supports the hypothesis that TSEsare caused by abnormal, protease-resistant forms (PrPres) ofcellular proteins (PrPc) coded for and normally synthesised incentral nervous system (CNS) and lymphoid tissues (43). Theseabnormal proteins are thought to arise through post-translational modifications in the tertiary structure of PrPc,resulting in decreased α-helical content and increased amountsof β-sheet (44). In humans, PrPres may arise sporadicallythrough somatic mutations or spontaneous conversion of PrPc

to PrPres, as a result of germline mutations in the PrP gene(PRNP), resulting in familial disease, or via infection from anexogenous source (44). In animals, TSEs are infectious;spontaneous and familial forms have not been identified,although such forms may occur.

Distinct prion strains with specific molecular characteristicsand host affinities have been recognised (5, 6, 7, 45, 46, 47,48), although the nature of strain differences remainscontroversial. In addition, prions have remarkable resistance toenvironmental conditions and a range of treatments thattypically kill or inactivate conventional infectious agents (3, 14,34, 53, 54).

Characteristics of the agent causing CWD are poorlyunderstood, but the agent is presumed to be a prion. As withother details of the emergence of CWD, the origin of the prionstrain that now causes CWD (PrPCWD) is not known.Spontaneous somatic mutation of the PRNP gene may haveoccurred in mule deer, with subsequent transmission to otherdeer and to elk. An alternate explanation is that CWD is a strainof scrapie that has adapted to cervids. Chronic wasting diseasecould also have originated by infection with an as yetunrecognised prion strain. The CWD agent differs from the BSEagent, many strains of scrapie, and the TME agent based onmouse strain typing (6, 7). The marked similarity of CNSlesions and epidemiology strongly suggest that the CWD agentis the same in captive and free-ranging deer and elk. Whethermultiple strains of PrPCWD occur in nature remains under study.

Transmission and epidemiologyAlthough CWD is clearly an infectious disease, details oftransmission have not be determined. In contrast to BSE, CWDis not a food-borne disease associated with rendered ruminantmeat-and-bone meal (57). Cases of CWD among captive deerand elk, many of which were acquired as neonates, fawns, oradults from uninfected source populations, provide strongevidence of lateral transmission (31, 33, 60); recentexperimental and epidemic modelling data support theseanecdotal observations (19, 33). Maternal transmission mayalso occur, but appears to be relatively uncommon and cannotexplain most cases where complete epidemiological data areavailable (31, 33). Interspecies transmission is likely to occur;suspected cases of transmission have been documented frommule deer to elk, mule deer to white-tailed deer, and elk tomule deer and white-tailed deer.

The CWD agent, as demonstrated by immunohistochemistry, isfound in many lymphoid tissues, including those of thedigestive tract, tonsil and mesenteric lymph nodes (51; E.S. Williams and M.W. Miller, unpublished findings). Thisdistribution suggests that the agent may be shed through thealimentary tract; scrapie (the oldest recognised member of theTSEs) has a similar pattern of distribution in sheep and goattissues (1, 13, 25, 26, 56). As TSE agents are extremely resistantin the environment (3), transmission may be both direct andindirect. An increase in population density of deer and elk,either through keeping in captivity or artificial feeding, mayincrease the likelihood of transmission between individuals,whether direct or indirect. Contaminated pastures appear tohave served as sources of some CWD epidemics (31; E.S. Williams, T.R. Kreeger and W. Cook, unpublished

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findings), as has been suspected in some outbreaks of sheepscrapie (1, 18, 40). The apparent persistence of PrPCWD incontaminated environments represents a significant obstacle toeradication of CWD from either farmed or free-ranging cervidpopulations. Until effective cleaning and disinfectionprocedures are identified, prudent measures would be to refrainfrom reintroducing captive cervids into commercial facilitieswhere CWD has occurred, and to exclude free-ranging cervidsfrom previously-infected premises.

The youngest animal diagnosed with natural CWD wasseventeen months of age at death, suggesting sixteen toseventeen months as an approximate minimum incubation.However, without knowledge of when that animal wasinfected, an accurate determination of the overall disease courseis impossible. Under experimental conditions, minimumincubation was approximately fifteen months and mean timefrom oral infection to death was approximately twenty-threemonths (range: 20->25 months) in mule deer, and the range ofonset of clinical disease in orally infected elk was approximatelytwelve to thirty-four months (E.S. Williams, M.W. Miller andT.J. Kreeger, unpublished findings). The maximum diseasecourse is not known, but can exceed twenty-five months inexperimentally-infected deer and thirty-four months in elk.Most cases of CWD among deer and elk residing in facilitieswith a long history of CWD are in two- to seven-year-oldanimals, but elk over fifteen years of age have succumbed toCWD. The age of onset of clinical signs varies in animalsbrought into facilities as adults or among animals in herdsnewly recognised to be affected by CWD. The point at whichan animal may become infectious during the course of infectionis not known, but agent shedding appears likely to beprogressive through the course of the disease.

Chronic wasting disease can reach a high prevalence in highdensity captive cervid populations. In one study, more than90% of mule deer residing on a premises for more than twoyears died or were euthanised due to CWD (58). Chronicwasting disease was the primary cause of adult mortality (5 of7 [71%]; 4 of 23 [23%]) in two captive elk herds (31), and ahigh prevalence of CWD (59%) was detected byimmunohistochemistry in a group of seventeen elk slaughteredfrom a CWD-affected farm herd (41).

The epidemiology of CWD in free-ranging cervids has beenmore challenging to study. Distribution of CWD in free-rangingdeer and elk has been determined primarily through necropsyand examination of tissues from animals showing clinical signssuggestive of CWD (clinically-targeted surveillance); this is anefficient approach for detecting new foci of infection (33). Toestimate prevalence in infected populations, tissues from deerand elk harvested by hunters in CWD-endemic areas have beencollected and examined at random (34). Within endemic areas,prevalence of preclinical CWD, based on histopathology and/orimmunohistochemistry for PrPCWD, has been estimated at <1%-15% (34). With the exception of cases reported fromSaskatchewan in mule deer, no CWD-affected free-ranging

cervids have been detected outside the contiguous Wyoming-Colorado-Nebraska endemic area.

Epidemic models suggest that lateral transmission is necessaryto maintain CWD at the prevalence observed in infected free-ranging populations (19, 33). Maternal transmission mayoccur, but in the models, this route of transmission alone wasnot adequate to maintain the disease at observed levels (34).Models also failed to achieve a steady-state equilibrium ininfected deer populations, indicating that CWD may lead tolocal extinctions of infected deer populations (19).

Clinical signsThe most striking clinical features of CWD in deer and elk areloss of body condition (Fig. 2a) and changes in behaviour. Inelk, clinical signs of CWD may be more subtle and the clinicalcourse more prolonged than in deer (Fig. 2b). Affected animals


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a) Free-ranging, male mule deer showing emaciation and depressed demeanortypical of end-stage CWDThis deer was killed by coyotes a few hours after the photograph was taken

b) Captive female elk showing subtle reduction in body condition and modestbehavioural changesAt the time this photograph was taken, the animal had been classified as suspected of beinginfected with CWD for eight months, based on subtle but progressive behavioural changes

Fig. 2Clinical chronic wasting diseasePhotographs: M.W. Miller

may increase or decrease interaction with handlers or othermembers of the herd. Animals may show repetitive behaviourssuch as walking set patterns in the pen or pasture, show periodsof somnolence or depression from which they are easily roused,and may carry the head and ears lowered. Affected animalscontinue to eat but consume reduced amounts of feed, leadingto gradual loss of body condition. As the disease progresses,many affected animals display polydipsia and polyuria,increased salivation with resultant slobbering or drooling, aswell as inco-ordination, posterior ataxia, fine head tremors, anda wide-based stance. Oesophageal dilatation, hyperexcitabilityand syncope are occasionally observed. Death is inevitable.

In captive herds that are experiencing a new outbreak of CWD,animals frequently have a history that includes sporadic casesof prime aged animals losing condition, being unresponsive tosymptomatic treatment, and dying from pneumonia.Aspiration pneumonia, presumably caused by difficulty inswallowing and by ptyalism, may lead to misdiagnosis of thecondition if the brain is not examined microscopically. ‘Suddendeaths’ following handling also have been reported as the indexcases in some situations, as have unusual traumatic losses (e.g. an elk getting its head caught under a fence). Given thisvariety of index presentations of clinical CWD, carefullaboratory examinations of all adult cervid mortality on gamefarms appears prudent and has been required in somejurisdictions seeking to establish CWD surveillanceprogrammes in farmed cervids.

The clinical course of CWD varies from a few days toapproximately a year, with most animals surviving from a fewweeks to three to four months. Although protracted clinicaldisease is typical, occasionally acute death may occur in deer(M.W. Miller, unpublished findings). Caretakers familiar withindividual animals often recognise subtle changes in behaviourwell before abnormalities are detected by those unfamiliar withthe particular animal or before serious weight loss occurs. Inaddition, those who have seen clinically-affected animals aremore astute at detecting early behavioural changes than naiveobservers. Inspection of infected game farm herds by regulatoryanimal health officials often fails to detect evidence of clinicalCWD; therefore, surveillance based on microscopic evaluationof appropriate tissues from all mortalities represents the onlyreliable method of detecting CWD-affected populations at thecurrent time. In light of uncertain incubation periods andvariation in both clinical presentation and course, a minimumof five years of complete surveillance of all adult (over one-year-old) mortalities appears to be the minimum standard necessaryto assure farmed cervid herds are truly free of CWD.

The clinical course of CWD in free-ranging deer and elk isprobably somewhat shorter than that of animals kept incaptivity. Wild cervids must forage, find water, and aresusceptible to predation, all factors affecting the longevity ofdiseased animals in the wild.

PathogenesisThe pathogenesis of CWD has been studied in mule deer andelk which were experimentally infected via oral exposure tobrain homogenate from conspecific clinical cases. In bothspecies, this exposure route seemed to simulate naturalexposure conditions. In one study of experimentally-infectedmule deer fawns, PrPCWD was detected in retropharyngeal andileocaecal lymph nodes, tonsil and Peyer’s patches by forty-twodays post inoculation (p.i.) (51). In a separate study of orallyinoculated deer, consistent detection of PrPCWD in alimentaryassociated lymphoid tissue preceded consistent detection inbrain tissue by three months p.i. (E.S. Williams and M.W. Miller, unpublished findings). The parasympathetic vagalnucleus in the medulla oblongata of the brain was the initial siteof PrPCWD accumulation in brain tissue. Similarly, this siteyielded consistent spongiform lesions beginning sixteenmonths p.i.; PrPCWD accumulation preceded development ofspongiform changes by ten months. In experimentally-infectedelk, PrPCWD detection also occurred first at the vagal nucleus inthe medulla oblongata and preceded development ofspongiform lesions at this site by six months (E.S. Williams,T.R. Kreeger and W. Cook, unpublished findings).

In naturally-occurring cases of CWD, PrPCWD accumulation inalimentary tract associated lymphoid tissues, particularly tonsiland retropharyngeal lymph nodes, also precedes accumulationin brainstem. The parasympathetic vagal nucleus in themedulla oblongata is the site of the most severe and consistentlesions in naturally-infected deer (61), and is the site of PrPCWD

accumulation prior to development of spongiform changes (33;E.S. Williams and M.W. Miller, unpublished findings).Distribution of lesions in the brain (61) may explain clinicalsigns. Emaciation may be associated with hypothalamicdamage and polydipsia may reflect damage to theparaventricular and supraoptic nuclei, and subsequent diabetesinsipidus (60).

Based on similarities in clinical course, neuropathology, anddistribution of PrPCWD, pathogenesis of CWD in deer and elk isqualitatively similar to that of scrapie in sheep (25, 26, 56). TheCWD agent probably enters the animal by ingestion, perhapsfrom environmental contamination or direct interaction withanimals shedding the agent. Propagation and accumulation ofPrPCWD in the brain appears to compromise several physiologicalprocesses, ultimately leading to death in infected individuals.

PathologyAlterations in clinical chemistry and haematology may occur inCWD-affected animals, but are not diagnostic. In captive deer,low urine specific gravity (1.002-1.010) reflects polydipsia andpossibly the inability to concentrate urine (58). In free-ranginganimals, urine specific gravity may not be as low because theanimal may not have ready access to water and may be


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dehydrated at death. Other non-specific changes in clinicalpathology reflect emaciation or intercurrent diseases.

The gross lesions of CWD are non-specific. Carcasses may be inpoor nutritional state or emaciated, but may be in fair conditionif the animal died of aspiration pneumonia or after only a shortclinical course. Aspiration pneumonia with or withoutfibrinous pleuritis may be present in some animals. Rumencontents include excessive water in those animals displayingpolydipsia; sometimes the contents appear frothy; sand andgravel are often prominent.

Microscopic lesions of CWD have been described in mule deerand elk (61). The lesions are qualitatively typical of TSEs.Distribution of lesions is similar in deer and elk with someminor differences in degree. In all cases of clinical CWD, lesionsare in the parasympathetic vagal nucleus in the dorsal portionof the medulla oblongata at the obex (Fig. 3), in hypothalamusand thalamus, and in olfactory tracts and cortex. Other regionsof the brain, in particular thalamus and cerebellum, showtypical spongiform changes with varying degrees of severity.Lesions are usually mild in the cerebral cortex, hippocampusand basal ganglia. Scrapie-associated fibrils are found in the brain and spleen of

deer and elk with CWD (52, 60). The ultrastructural lesions ofCWD are typical of lesions found in animals with other TSEs(22, 23, 30).

DiagnosisClinical signs of CWD are not specific and currently diagnosisis based on examination of the brain for spongiform lesionsand/or accumulation of PrPCWD by immunohistochemistry. Theparasympathetic vagal nucleus in the dorsal portion of themedulla oblongata at the obex is the most important site to beexamined for diagnosis of CWD (61) and should be submittedfor histopathological examination on every animal suspected ofhaving CWD. The entire head or brain can be submitted to thediagnostic laboratory to ensure that the correct portion of thebrain is examined. Supplemental tests include negative stainelectron microscopy for scrapie-associated fibrils or Westernblotting for detection of PrPres in the brain (52, 60).

Demonstrating PrPCWD in tonsil (Fig. 5) and/or retropharyngeallymph nodes by immunohistochemistry appears to be bothsensitive and specific in detecting CWD in mule deer (M.W.Miller and E.S. Williams, unpublished findings). Appropriatetreatment of cervid lymphoid tissue (formic acid and proteases)is necessary to denature native PrPC which appears to benaturally abundant in cervids and may lead to false positivereactions because available antibodies cannot distinguishbetween the normal and abnormal PrP isoforms. Similarly,tonsil, lymph node and conjuctival lymphoid tissues are usefulin ante-mortem diagnosis of sheep scrapie (29, 38, 49, 50).Conjunctival lymphoid tissues are relatively sparse in deer, and consequently sampling these in deer often yields


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Fig. 3Typical spongiform encephalopathy in the parasympatheticvagal nucleus in a mule deer with clinical chronic wastingdiseaseNote the diffuse spongiform change and mild gliosis. Haematoxylin andeosin stain. Bar = 100 µmPhotomicrograph: E.S. Williams

Fig. 4Perineuronal (arrows) and extracellular deposition of PrP (redstained material) detected by immunohistochemistry in theparasympathetic vagal nucleus of a mule deer with clinicalchronic wasting diseaseImmunohistochemistry for PrP. Bar = 20 µmPhotomicrograph: E.S. Williams

Plaques composed of PrPCWD can be appreciated on routinehaematoxylin and eosin staining in most clinically-affectedwhite-tailed deer and in a few mule deer, but are not obviousin elk (2, 60). In white-tailed deer, plaques are oftensurrounded by vacuoles in the neuropil which allow easyvisualisation. The plaques are clearly stained byimmunohistochemistry for PrPCWD using a variety of polyclonaland monoclonal antibodies (20, 21, 30, 37, 60). Patterns ofimmunostaining in CWD include granularity and amorphousclumps on neuronal membranes (Fig. 4), perivascularaggregates, and large apparently extracellular accumulations ofPrPCWD.

non-diagnostic samples. Tonsillar biopsy is presently underevaluation as a technique for ante-mortem CWD diagnosis inmule deer.

unaffected elk (39). Resistance associated with PrP genotypehas not been recognised in deer, but this is still underinvestigation.

Control and treatmentNo treatment is currently available for animals affected withCWD, and the disease is considered invariably fatal onceclinical signs develop. If an affected animal developspneumonia, treatment with antibiotics might prolong thecourse of illness, but will not alter the fatal outcome.

Control of CWD is problematic. Given the long incubationperiods, subtle early clinical signs, absence of reliable ante-mortem diagnostic tests, extremely resistant infectious agent,possible environmental contamination, and incompleteunderstanding of transmission, designing methods for controlor eradication of CWD is extremely difficult. Managementcurrently involves quarantine or depopulation of CWD-affectedherds. Two attempts to eradicate CWD from captive cervidfacilities failed, although the cause of the failure was notdetermined; residual environmental contamination followingfacility clean-up was possible (31, 60). Attempts to eliminateCWD from farmed elk populations are relatively recent, andconsequently the efficacy of these attempts remains uncertain.Establishment of free-ranging reservoirs of infection in thevicinity of infected game farms could severely impair attemptsat eradication. The inherent difficulties in managing infectedherds and premises underscore the need for aggressivesurveillance to prevent movements of infected animals incommerce.

Management of CWD in free-ranging animals is even moreproblematic. Long-term active surveillance to determinedistribution and prevalence of CWD has been instituted toassist in evaluating both changes over time and effects ofmanagement intervention. To date, management programmeswhich have been established focus on containing CWD andreducing prevalence of the disease in endemic areas (32), buthave refrained from committing to eradication because thelatter appears unattainable in most circumstances.Translocation and artificial feeding of cervids in endemic areashave been banned in an attempt to limit range expansion andto decrease transmission of CWD. Selective culling of clinicalsuspects has been practised throughout endemic areas for anumber of years, but this approach alone appears insufficient toreduce prevalence in affected populations. Localised populationreduction in areas of high CWD prevalence has beenundertaken in Colorado, but efficacy remains to be determined.Lowered deer and elk densities may reduce both transmissionand the likelihood of emigration to adjacent areas, but historicallarge-scale migration patterns and social behaviourscharacteristic of some deer and elk populations may lessen theeffectiveness of density reduction on disease control. Models ofCWD epidemic dynamics suggest that early, aggressive


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Fig. 5Deposition of PrP detected by immunohistochemistry in thegerminal centre of a lymphoid follicle in the tonsil of a muledeer preclinically affected by chronic wasting diseaseImmunohistochemistry for PrP. Bar = 50 µmPhotomicrograph: E.S. Williams

Several rapid tests have been validated for use in diagnosis ofBSE in the European Union (35) and are currently being usedin slaughter houses on cattle over thirty months of age incontinental Europe. Some of these tests, as well as a rapidWestern blot and enzyme-linked immunosorbent assays (12)are being evaluated for use in cervids with CWD.

Differential diagnoses of CWD in deer and elk include a widevariety of diseases that cause CNS disease and/or emaciation.Animals with brain abscesses, traumatic injuries, encephalitis,meningitis, polioencephalomalacia, peritonitis, pneumonia,arthritis, starvation, nutritional deficiencies, haemorrhagicdisease, and dental attrition have been submitted to laboratoriesas CWD suspects. Aspiration pneumonia is often seen as aterminal event in deer and elk with CWD and when these signsare recognised in a prime aged cervid, CWD should beconsidered.

ImmunityNo antibody response to the CWD agent has been detected,although glial activation in the brain occurs in many TSEs (24)and evidence of an acute phase response in miceexperimentally infected with scrapie provides evidence of aninflammatory response to the TSE agents (10). The PrPgenotype plays a significant role in the development of naturaland experimental scrapie in sheep and mice (4, 28, 36).Whether particular PrP genotypes confer resistance or increasesusceptibility to CWD is not yet known; however, codon 132methionine homozygotes were over-represented among bothfree-ranging and captive CWD-affected elk when compared to

intervention via selective culling or more generalisedpopulation reduction show the greatest promise of preventingthe establishment of new endemic foci (19). Unfortunately,surveillance limitations (both cost and sensitivity) may hamperthe ability to detect newly infected free-ranging populationsuntil a decade or more after the introduction of CWD (33).Development of a practical ante-mortem test might aid controlefforts under some conditions, but large-scale applications tofree-ranging populations seem impractical.

Public health concernsNo cases of human disease have been associated with CWD(16, 62). In vitro studies demonstrated that PrPCWD inefficientlyconverts human PrPC to the abnormal isoform as compared tohomologous PrPCWD-cervid PrPC conversions, and that PrPCWD-human PrPC conversions were essentially equivalent toPrPSc-human PrPC and PrPBSE-human PrPC conversions (46).Uncertainty about interpreting these data and assessing thelevel of risk that CWD poses to humans is fostered by differingexperiences with two more common animal TSEs: humanexposure to scrapie through handling and eating sheep tissues,including brain, has occurred over a long period of time, yet noevidence has been found to suggest that this presents a risk tohuman health. In contrast, massive exposure (17) to the BSEagent in the United Kingdom and perhaps other countries ofEurope has resulted in approximately 100 cases of variantCreutzfeldt-Jakob disease to date.

In the absence of complete information and in light ofsimilarities of animal and human TSEs, public health officialsand wildlife management professionals recommend thathunters harvesting deer and elk in the endemic areas, as well asmeat processors and taxidermists handling cervid carcasses,should take some common sense measures to avoid exposureto the CWD agent and to known zoonotic pathogens (11).Advice includes avoiding harvest or consumption of diseaseddeer and elk; wearing latex or rubber gloves when dressing deeror elk from CWD-endemic areas; thoroughly washing knivesand other implements; and discarding the brain, spinal cord,lymph nodes, spleen, tonsils, and eyes because these organs

appear to contain the greatest amount of CWD agent ininfected animals. Since TSE agents have never beendemonstrated in skeletal muscle, boning game meat isrecommended as an effective way to further reduce thepotential for exposure. Similar recommendations appearappropriate for carcasses of farmed deer and elk. Because rawvelvet antler is a product unique to the farmed cervid industry,evaluation of the product for presence of PrPCWD may benecessary in order to preserve markets for this commodity.

Management implicationsThe presence of CWD in captive and free-ranging cervids is aserious management problem. Captive populations arequarantined, thus limiting the usefulness and value of theanimals for research or commerce. Indemnity for depopulatedcervids is not currently available in the USA; in Canada, themagnitude of infection in farmed elks has resulted in largeindemnity payments. Guidelines for management of captiveherds with CWD are being developed by state and provincialanimal health officials. A national programme has been adoptedin Canada, and a similar programme is currently under reviewin the USA. Spillover of CWD into local free-ranging cervidpopulations could establish new endemic foci and mightimpair the long-term viability of cervid farming in those areas.

Implications for free-ranging populations of deer and elk areequally significant. Deer and elk are not translocated fromCWD endemic areas, surveillance programmes are expensivefor wildlife management agencies, and the impact of the diseaseon the population dynamics of deer and elk are not currentlyknown. Modelling suggests that CWD could do substantialharm to infected cervid populations by lowering adult survivalrates and destabilising long-term population dynamics (19).Ultimately, public and agency concerns and perceptions abouthuman health risks associated with TSEs may erodeparticipation in sport hunting in endemic areas, and also mayhave a dramatic influence on management of herds of free-ranging cervids in those areas in which CWD is endemic.


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Cachexie chronique des cerfs et des wapitis en Amérique du Nord

E.S. Williams & M.W. Miller

RésuméLa cachexie chronique (ou maladie du dépérissement chronique) comptedésormais au nombre des maladies importantes de la faune sauvage enAmérique du Nord. Elle est la seule en son genre parmi les encéphalopathiesspongiformes transmissibles (EST) ou maladies à prion, qui n’affectent dans la

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Caquexia crónica en ciervos y wapitíes de América del Norte

E.S. Williams & M.W. Miller

nature que quelques espèces. De toutes les EST, la cachexie chronique est laseule observée chez les espèces vivant en liberté. Cependant, la cachexiechronique suscite depuis peu un intérêt accru du fait de ses liens avec des ESTplus connues, telles le nouveau variant de la maladie de Creutzfeldt-Jakob chezl’homme et l’encéphalopathie spongiforme bovine. La répartition géographiquede la cachexie chronique est encore méconnue mais beaucoup de progrès ontété accomplis depuis le milieu des années 1990 en raison de la surveillance descerfs et des wapitis vivant en liberté et des wapitis des montagnes Rocheuses(Cervus elaphus nelsoni) appartenant à des élevages privés, et la maladie adésormais été mise en évidence dans bon nombre de plaines et contreforts desmontagnes Rocheuses dans l’ouest de l’Amérique du Nord. Des études portantsur la biologie et l’évolution naturelle de la cachexie chronique, effectuées cesdernières années, ont permis de mieux comprendre la pathogénie etl’épidémiologie de la maladie. L’atteinte précoce des tissus lymphoïdes del’appareil digestif pendant la période d’incubation de la maladie laisse penser quel’agent de la cachexie chronique est sans doute excrété dans les matièresfécales ou la salive des animaux infectés. La cachexie chronique se transmet parvoie horizontale et la contamination de l’environnement pourrait jouer un rôleimportant dans la persistance locale de la maladie. Des études surl’épidémiologie de la cachexie chronique ont abouti à l’élaboration de modèlespermettant d’expliquer l’historique de la maladie et de simuler les conséquencesfutures sur les populations de cerfs et de wapitis. Les épreuves diagnostiques ontété améliorées afin de pouvoir réaliser un diagnostic au début de la périoded’incubation, bien avant l’apparition des signes cliniques. Des techniques etprogrammes de surveillance ont été élaborés et mis en place par les organismesresponsables de la protection de la faune sauvage, qui s’occupent des cerfs etdes wapitis vivant en liberté, ainsi que par l’État et les agences agricolesfédérales chargées des élevages privés de wapitis. Dans les années 1990,l’attitude à l’égard des EST a changé radicalement ; l’évolution la plussignificative est sans doute la réflexion conduite actuellement pour parvenir àl’éradication mondiale de toutes les maladies à prion.

Mots-clésAmérique du Nord – Cachexie chronique – Cerfs de Virginie – Cerfs-mulets –Encéphalopathies spongiformes transmissibles – Maladies à prion – Wapitis.�

ResumenEn Norteamérica, la caquexia crónica está adquiriendo una importanciacreciente como enfermedad de los animales salvajes. Se trata de una singularpatología del grupo de las encefalopatías espongiformes transmisibles, oenfermedades causadas por priones, que en condiciones naturales afectan sóloa unas pocas especies. De todas las encefalopatías transmisibles, la caquexiacrónica es la única que se ha observado en especies que viven en libertad. Noobstante, por asociación con otras encefalopatías más conocidas como laenfermedad de Creutzfeldt-Jakob en el hombre o la encefalopatía espongiformebovina, el interés por la caquexia crónica ha ido en aumento en los últimos años.

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Desde mediados de los años 1990, gracias a la vigilancia de ejemplares de ciervoy wapití en libertad así como de wapitíes de las Montañas Rocosas (Cervuselaphus nelsoni) de propiedad privada, se conoce mucho mejor, aunque todavíade manera imperfecta, la distribución geográfica de la enfermedad, cuyapresencia se ha detectado en muchos puntos de las llanuras del Oestenorteamericano y las estribaciones de las Rocosas. Gracias a una serie deestudios recientes sobre la biología y la historia natural de la caquexia, hoy seentienden mejor la patogénesis y la epidemiología de la enfermedad.Considerando la temprana afectación de los tejidos linfáticos del tracto digestivodurante el periodo de incubación, parece plausible que el agente etiológico salgadel individuo infectado por las heces o la saliva. La caquexia crónica se transmitelateralmente, y la contaminación ambiental podría ser un factor importante en elmantenimiento local de la enfermedad. A raíz de una serie de estudios decarácter epidemiológico se han elaborado modelos que ayudan a explicar lahistoria de la enfermedad y a simular los efectos que tendrá en el futuro sobre laspoblaciones de ciervos y wapitíes. Gracias al perfeccionamiento de las pruebasde diagnóstico es posible detectar la caquexia crónica al comienzo del periodode incubación, mucho antes de que se manifieste clínicamente. Existen hoy endía una serie de técnicas y programas de vigilancia, elaborados y aplicados porentes de gestión de la fauna salvaje (en el caso de los venados y wapitíes enlibertad) o por organismos de agricultura de ámbito estatal o federal (en el casode wapitíes de propiedad privada). Durante los años 1990, las ideas sobre lasencefalopatías espongiformes transmisibles experimentaron una radicaltransformación: lo más llamativo de la nueva situación reside quizá en el hechode que ahora se esté discutiendo el objetivo de erradicar todas las enfermedadescausadas por priones.

Palabras claveCaquexia crónica – Ciervos de Virginia – Ciervos mula – Encefalopatías espongiformestransmisibles – Enfermedades causadas por priones – Norteamérica – Wapitíes.�

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