CWD - The Disease in Deer and Elk

Incubation Period, Time Course and Persistence of Disease

1) INCUBATION PERIOD:

• The exact incubation period for natural CWD in cervids is not known and may vary between species. However the youngest clinically affected free-living elk (Cervus elaphus nelsoni - Rocky Mountain Elk (Cervus elaphus - Red deer)) was 21 months old, the youngest captive elk was 17 months. In Odocoileus hemionus - Mule deer the youngest naturally infected individual with clinical signs was 18 months old. In Odocoileus virginianus - White-tailed deer the youngest individual with clinical signs was 1.5 years old. Data from two outbreaks in a wildlife research facility in Colorado suggested an incubation period of 18-36 months. An incubation period of 17-24 months was seen following experimental infection by intracerebral inoculation. With experimental oral infection the incubation period was 12-34 months in elk while in mule deer the earliest onset of clinical signs occurred at 15 months after oral inoculation.
• Experimental infection by intracerebral inoculation of infectious material into other species has produced incubation periods of six years in a goat, 22-27 months in calves of domestic cattle (Bos taurus - Domestic cattle), 17-21 months in ferrets (Mustela putorius fero - Domestic ferret (Mustela putorius - Polecat)), reduced to 8-9 months on the first serial passage and five months on the second and subsequent passages, 100-239 days in hamsters (Mesocricetus auratus - Golden Hamster (Syrian hamster)) inoculated with ferret-passaged agent, reducing to about 53-58 days on subsequent passage in hamsters, and more than 500 days in mice.

2) DISEASE DURATION (FROM FIRST SIGNS TO DEATH) IN INDIVIDUAL ANIMALS:

• In cervids the duration of the clinical course ranges from days to about a year and is generally a few weeks to a few months; it has been reported as two weeks to eight months in captive mule deer (Odocoileus hemionus - Mule deer), one to twelve months in captive elk (Cervus elaphus nelsoni - Rocky Mountain Elk (Cervus elaphus - Red deer)). It has been suggested that the time course in free-living animals is generally shorter than that seen in captive animals. In white-tailed deer (Odocoileus virginianus - White-tailed deer) the time course is similar to that in mule deer but may tend to be shorter; a much shorter time course of only a few days, or even acute death, has been seen in some individuals of this species.
• Experimental infection by intracerebral inoculation of infectious material into other species has produced in domestic cattle (Bos taurus - Domestic cattle) calves disease with a clinical course lasting two to three months to recumbency and euthanasia, and in ferrets (Mustela putorius fero - Domestic ferret (Mustela putorius - Polecat)) one to six weeks from the first clinical signs to death or euthanasia in extremis, reduced to one to four weeks on the first serial passage and one to three weeks on subsequent passages. 

3) TIME COURSE / PERSISTENCE OF DISEASE IN A SUSCEPTIBLE POPULATION:

• CWD is both contagious and self-sustaining in both captive and free-living deer and elk populations in North America.
• The course of CWD within a population may be best described as an extended epidemic with a time scale of years (for confined populations) to decades or longer for free-living populations.
• Historically, natural expansion of CWD within free-living cervid populations appears to have been slow, and has probably been due mainly to dispersal and/or migratory movements of wild populations. 
• During 2002 CWD was detected in free-living populations in several areas in which it had not previously been recorded. It is not known whether the new areas have become infected due to natural movements of free-living cervids or as an expansion from the disease in captive populations or whether there are other unknown factors; some cases (e.g. in Saskatchewan) are considered highly likely to be extensions from the disease in captive cervids.
• Data from 2002 to 2003 from Colorado and Wyoming suggests the possibility of more rapid movement out of the core endemic areas to distant locations.
• In captive cervids within-herd spread of the disease is likely to be faster than in free-living populations, due to the greater density of animals and the associated increased opportunities for disease transmission by both direct and indirect transmission routes.
• Within the larger captive population, the epidemic is likely to be driven by between-herd movements of (undiagnosed) infected cervids.

• CWD Literature Reports: Incubation Period (Disease Reports)
• CWD Literature Reports: Disease Duration (to Death) in Individual Animals (Disease Reports)
• CWD Literature Reports: Time Course/Persistence of Disease in a Susceptible Population (Disease Reports)

Mortality / Morbidity / Susceptibility / Life stage affected

1) NUMBER OF DEATHS

• It is expected that 100% of clinically affected individuals will die from CWD.

2) NUMBER OF ANIMALS AFFECTED

• In captive deer morbidity (and mortality) rates as high as 80-90% have been recorded for deer spending more than two years at certain wildlife research facilities.
• In free-ranging cervids estimated prevalence in core endemic areas has varied from year to year. Recent data suggests prevalence in mule deer in the endemic area of northeastern Colorado of about 5% and in elk less than 1% (2001 data). For the core endemic area of Wyoming the estimated prevalence (from 1997 onwards) is 12% in mule deer, 16% in white-tailed deer and less than 3% in elk. For Wisconsin prevalence in the core area is about 7%.

3) EFFECTS OF AGE, SEX AND REPRODUCTIVE STATUS

• Male, female (including pregnant individuals) and castrated male cervids have all been affected. Recent data from Colorado, Wisconsin and Wyoming suggests that in adult deer there is a higher prevalence in males than in females.

• All ages older than the apparent minimum incubation period have been reported to be affected including individuals as young as 17 months and as old as 15 years. Most cases have been reported in young adults, two to five years old. In 2001 four Odocoileus virginianus - White-tailed deer fawns aged only eight months were found to be CWD-positive when wild deer fenced in on an elk farm were tested. 

4) EFFECTS OF OTHER FACTORS (SEASON, GENOTYPE)

• External Acquired Factors (Concurrent Disease, Immunosupression)
  • Cases of terminal clinical disease in both captive (research facilities) and free-living deer and elk have been noted more frequently during the winter months. This may be due to the stressful climatic conditions and, in the free-living animals, by the fact that this is the time of year when wild herd of cervids are closest to human populations and are most visible.
• Inherited Susceptibility Factors (Genetics)
  • Genotype may not be important in the susceptibility of cervids to CWD. 
  • In both free-ranging and captive elk individuals homozygous for methionine at PrP cervid codon 132 were over-represented among individuals with CWD when compared to unaffected individuals.
  • In white-tailed deer in Wisconsin the QGS allele tended to be over-represented in CWD-positive deer however positives have been detected in all genotypes.

• CWD Literature Reports: Mortality Rate (Percentage of the Species Population that die) (Disease Reports)
• CWD Literature Reports: Morbidity Rate (Percentage of the Species Population that develop clinical disease) (Disease Reports)
• CWD Literature Reports: Life Stage Affected (Age, Sex, Physiological Status) (Disease Reports)
• CWD Literature Reports: Susceptibility Factors (Concurrent Disease, Immunosupression) (Disease Reports)

Human Health Considerations

• A World Health Organization Report (WHO Consultation on Public Health and Animal Transmissible Spongiform Encephalopathies: Epidemiology, Risk and Research Requirements) noted that "there is currently no evidence that CWD in Cervidae is transmitted to humans" but recommended that "no part or product of any animal with evidence of CWD or other TSEs should be fed to any species (human, or any domestic or captive animal)." (W244.09Apr2002.CWD1)
• One study indicated that PrP^CWD was relatively inefficient in converting human PrP^C prions to the protease resistant form. The efficiency of conversion was similar to that produced by either bovine PrP^BSE or sheep PrP^Sc;  BSE causes disease in humans (new-variant CJD) while scrapie has never been linked to disease in humans. (J227.19.w1)

Information on recommended laboratory biosafety levels is provided in: Prion Protein (Complex Chemical) - Degree of Hazard (Risk to Humans / other Species)

Clinical Signs (by physiological system)

• In deer and elk generally CWD presents as a disease of insidious onset, with gradual weight loss and behavioural changes which may be extremely subtle initially and include reduced interaction with conspecifics as well as changes in responses to humans; nervousness, hyperexcitability and/or hyperaesthesia may be seen. 
• Listlessness, drooping ears, lowered head, blank facial expression, periods of somnolence (easily roused) and repetitive walking in set patterns have all been recorded, also excessive salivation and tooth grinding. Fine tremors and mild ataxia may be seen late in the disease. 
• In Odocoileus spp. deer polyuria and polydipsia are common; these are less obvious in elk. 
• Terminally the disease progresses to emaciation, recumbency and death.
• Death may be due to due to aspiration pneumonia, dehydration or hypothermia associated with cold weather.

• CWD Literature Reports: Detailed Clinical Signs (Disease Reports)

Clinical Pathology (Testing Samples incl. Serology)

• BLOOD SAMPLES
  • Blood samples of cervids with CWD generally show no haematological or biochemical abnormalities; in some individuals changes may be seen reflecting emaciation or intercurrent disease.
  • There is no known detectable immune response to the TSE diseases, therefore there are no serological tests for these diseases.
  • In laboratory mice experimentally infected with scrapie, sheep with clinical signs of scrapie and cattle with early clinical signs of BSE, it has been shown that levels of a blood protein called erythroid differentiation-related factor (EDFR) are lower than in normal individuals of these species. The relevance of this finding to testing deer for CWD is not yet known.
  • A test has been described, using capillary electrophoresis and fluorescent labeled peptides, which suggested the possibility of detecting abnormal prion proteins in the blood of elk with CWD.
• URINE SAMPLES
  • Urine specific gravity may be lowered in cervids with CWD.
• CEREBROSPINAL FLUID
  • Cerebrospinal fluid samples from captive cervids with CWD have been normal except for changes associated with the method of euthanasia or with intercurrent disease.
• TONSILLAR BIOPSY
  • In biopsy samples, preferably containing several follicles, from the tonsils of mule deer (Odocoileus hemionus - Mule deer) and white-tailed deer (Odocoileus virginianus - White-tailed deer) PrP^CWD can be detected by immunohistochemistry in both clinically affected individuals and in individuals which have not yet shown clinical signs.  In elk however the tonsils do not contain PrP^CWD until much later in the course of the disease.
    • Failure to detect PrP^CWD in a tonsillar biopsy specimen cannot be taken as proof of absence of infection because an affected follicle may not have been present in the sample (particularly if only one or a few follicles were present in the sample), very early in infection PrP^CWD accumulation in lymphoid tissues is not detectable, and occasionally an individual deer does not accumulate PrP^CWD in the tonsils despite widespread infection in the brain.

See: CWD Individual Techniques: Tonsillar Biopsy in Deer (Cervidae) for Diagnosis of CWD (Techniques)

• CWD Literature Reports: Detailed Clinical-Pathological Test Findings - Samples (Disease Reports)

• Prion Protein Literature Reports: Detection and Identification Techniques (Chemical Reports)

Pathological Findings (by anatomical system)

GROSS PATHOLOGY

• The main gross pathological finding in deer and elk which have died of CWD or have been euthanased late in the course of the disease, is emaciation, with total loss of body fat, serous atrophy of fat and even severe muscular atrophy in terminal cases. The bone marrow may be yellow and gelatinous.
• Other findings may include lesions of aspiration pneumonia. 
• Particularly in Odocoileus hemionus - Mule deer the rumen contents may be excessively liquid or frothy, and sand or gravel may be notable in the rumen.

HISTOLOGY

• The main lesions of CWD are found within the central nervous system. Typically there are changes of spongiform encephalopathy, characterized by microcavitation of grey matter and/or white matter, intraneuronal vacuolation and neuronal degeneration. Lesions are basically bilaterally symmetrical and characteristically affect some areas of the brain to a greater extent than other areas.
  • Lesions are detectable first in the dorsal motor nucleus of the vagus nerve (DMNV).
• Amyloid plaques are readily detected by immunohistochemistry (IHC) as scrapie amyloid-immunoreactive plaques and in mule deer may be visible with specific stains e.g. Congo red.
• Scrapie-associated Fibrils may be present in the brain and the spleen of clinically affected individuals. 
• Immunohistochemistry and Western blotting can detect the presence of PrP^res in the brain and in lymphoid tissue; in elk (Cervus elaphus nelsoni - Rocky Mountain Elk (Cervus elaphus - Red deer)) PrP^res is detected in lymphoid tissue only relatively late in the course of the disease while in Odocoileus spp. deer it may be detected in individuals which have not shown any clinical signs of the disease.
• PrP^CWD accumulation is detectable in the CNS by IHC prior to the development of vacuolar lesions.
• Immunohistochemistry has detected PrP^CWD in the pituitary (pars nervosa and pars intermedia), adrenal medulla and the islets of Langerhans in the pancreas.
• Secondary lesions such as bronchopneumonia, serous atrophy of fat, gastric ulceration and adrenal cortical hypertrophy may be seen also.

• CWD Literature Reports: Detailed Pathological Findings - (Necropsy/Post Mortem) (Disease Reports)

Diagnostic Criteria

• CWD may be suspected in Odocoileus spp. deer and elk showing classical signs such as weight loss/emaciation and/or neurological signs.
• Loss of body condition is the most obvious sign but this is highly non-specific and is more commonly due to other causes such as malnutrition.
• Early behavioural signs are most likely to be recognised by observers who have previously seen clinically-affected individuals
• Early behavioural changes are frequently subtle and detection requires knowledge of the individual animals affected. 
• Experienced observers may be able to recognise behavioural signs in most Odocoileus spp. deer late in the course of clinical disease, but signs in elk may sometimes be more subtle.
• Individuals may be found close to a water source and be in the same general location day after day

Other TSE Diseases

Scrapie:

Ovis aries - Domestic sheep:

• Suggestive clinical signs combined with histopathological findings. Characteristic histopathological findings are: neuronal vacuolation, degeneration of neurons and neuronal loss, vacuolation of the grey matter neuropil, astrocytosis and (not in all cases) the presence of amyloid plaques. Although occasional vacuolated neurons may be found in brain tissue from apparently normal sheep these are not accompanied by the other histopathological changes characteristically seen with scrapie and are few in number. (J64.11.w4)

Transmissible Mink Encephalopathy:

Mustela vison - American mink:

• Diagnosis confirmed by histopathological lesions of the brain, transmission experiments (to neonatal and adult mink) and demonstration of PrP^res. (J223.72.w1)
• Diagnosed on the basis of the clinical findings of a progressive neurological disease combined with the histopathological lesions of spongiform encephalopathy. (J64.11.w5)

Bovine Spongiform Encephalopathy (BSE):

• In non-domestic mammals: "The disease may be ly suspected in animals that show progressive behavioural changes or ataxia, postural abnormalities, and abnormal muscle movements; the suspect animals reside in or were imported from the United Kingdom or other European countries with endemic BSE; and where there is potential exposure to BSE-contaminated feeds. (B209.17.w17)
• [In non-domestic animals in zoos] Suspicious clinical signs in the absence of another explanation for such signs, particularly in an individual with a history of exposure to potentially infectious tissues. (B23.101.w4, J3.135.w1)

• Definitive diagnosis of CWD depends on the detection of typical histopathological lesions in the brain and/or the detection by immunohistochemistry (IHC) of PrP^res in the brain or lymphoid tissues. In Odocoileus hemionus - Mule deer and Odocoileus virginianus - White-tailed deer PrP^CWD may be detected in the lymph nodes and tonsils of preclinically infected individuals. In Cervus elaphus nelsoni - Rocky Mountain Elk (Cervus elaphus - Red deer) PrP^CWD may be detected in the lymph nodes. (J40.66.w1, J40.66.w2, J84.9.w1, J212.15.w2, P10.67.w1, P40.1.w18, B336.78.w78)

Histopathology:

• The dorsal motor nucleus of the vagus (DMNV) is the area of the CNS most consistently and severely affected by vacuolar lesions in CWD-infected cervids. (P46.1.w4, J40.66.w1, P10.67.w1)

Immunohistochemistry:

• The "gold standard" test for detection of prions associated with CWD is immunohistochemistry (IHC), particularly of the parasympathetic vagal nucleus in the dorsal portion of the medulla oblongata at the obex. (J40.66.w1, P10.67.w1)
  • Monoclonal antibody F99/97.6.1 is used most commonly in detection of CWD in the USA and Canada. (B336.78.w78)
  • The dorsal motor nucleus of the vagus (DMNV) is the area of the brain in which PrP^Sc is first detectable by IHC. (P46.1.w4, J40.66.w1, P10.67.w1)
  • IHC of the obex allows staining (detection of abnormal PrP) in association with specific tissue architecture for high confidence of diagnosis. (P50.1.w7)
• Recent studies have shown that abnormal prions are usually detectable by immunohistochemistry in the retropharyngeal lymph nodes of both deer and elk, and in the tonsils of deer, earlier in infection than they are detectable in the obex. However on rare occasions a deer may be positive by IHC in the obex but not in lymphoid tissues. (P10.67.w1, J3.151.w3, J212.15.w2)

Other tests:

• ELISA and Western blot tests developed for BSE detection have been tested for use in detection of CWD in cervids. Various commercially-available tests have now been approved for use and ELISA is now [end 2003] being used extensively for for screening large numbers of animal with the diagnosis of individuals which test positive then being confirmed by immunohistochemistry. (W30.09Jun03.CWD1, V.w48, V.w49)

See:

• CWD Individual Techniques: Removal of the Retropharyngeal lymph nodes and tonsillar tissue from dead Deer (Cervidae) for CWD Diagnosis (Techniques)
• CWD Individual Techniques: Removal of the Obex from Deer and Elk (Cervidae) for CWD Diagnosis (Techniques)

In live animals:

• In Odocoileus spp. deer live animals may be positively diagnosed by the immunohistochemical (IHC) staining of tonsillar tissue biopsies; however a negative result may be found very early in the course of infection and the test is not suitable for diagnosis of live or preclinically infected elk ((Cervus elaphus nelsoni - Rocky Mountain Elk (Cervus elaphus - Red deer)) as they do not consistently develop tonsillar PrP^CWD. (J40.66.w2, J223.83.w1, P10.67.w1, P40.1.w18, B336.78.w78)
  • Testing of conjunctival lymphoid tissue (used in sheep) is not useful in deer as only sparse lymphoid tissue is present in this area so that samples are often non-diagnostic. (J64.21.w17)

See: CWD Individual Techniques- Tonsillar Biopsy in Deer (Cervidae) for Diagnosis of CWD (Techniques)

(J40.66.w1, J40.66.w2, J223.83.w1, J64.21.w17, J84.9.w1, P10.67.w1, P46.1.w4, W30.09Jun03.CWD1, V.w48, V.w49)

• Prion Protein Literature Reports: Detection and Identification Techniques (Chemical Reports)

• CWD Literature Reports: Detailed Clinical-Pathological Test Findings - Samples (Disease Reports)

• CWD Literature Reports: Detailed Pathological Findings - (Necropsy/Post Mortem) (Disease Reports)

• The main signs of CWD are weight loss and nervous signs. Therefore any disease which causes weight loss or nervous signs must be considered as a differential of CWD, and CWD must be considered as a differential diagnosis in other diseases causing weight loss or nervous signs.
• Seasonal changes in weight are normal in these species, which may mask early weight loss.
• Poor nutrition, which may occur in wild deer during winter or drought conditions, is probably the commonest cause of weight loss.
• Aspiration pneumonia may occur as a result of CWD, therefore CWD must be considered if necropsy findings indicate aspiration pneumonia.
• "Sudden death", for example following handling, or unusual losses due to trauma, may also occur in animals with CWD.
• Enzootic haemorrhagic disease (EHD) may cause sudden death to chronic disease, with signs including anorexia, lethargy, excess salivation, weakness and incoordination, all of which may be seen in cervids with CWD. Also, as with individuals affected with CWD, affected animals may often be found near water. However other signs seen in EHD are not typical of CWD.

(For listings of other diseases (particularly those causing weight loss and/or neurological signs) see: CWD Literature Reports: Literature Reports for Similar Diseases (Disease Reports))

• CWD Literature Reports: Literature Reports for Similar Diseases (Disease Reports)

Specific Medical Treatment (Antiserum, Antidote, Anti-(viral/bacterial/fungal) etc.)

• At present no medical treatment is available against CWD.
• Some limited in vitro work has suggested the possibility that in the future it may be possible to develop antibodies which would be effective in prevention and treatment of prion diseases.

• CWD Literature Reports: Specific Medical Treatment (Disease Reports)

General Nursing and Surgical Techniques

• There is no effective nursing care.
• Improved food provision is not effective in reversing weight loss in affected individuals.
• Antibiotics may treat pneumonia associated with the disease but will not affect the course of the CWD and its eventual fatal outcome.

• CWD Literature Reports: General Nursing and Supportive Care Techniques (Disease Reports)

Not applicable for this disease.

• CWD Literature Reports: Surgical Techniques (Disease Reports)- not applicable for this disease

Vaccination & Prophylactic Treatment

• At present no vaccines are available against CWD; there are therefore no applicable vaccine regimes.
• The recent finding of an antibody specific for the pathological form of PrP may lead to the development of vaccines in the future.

• CWD Literature Reports: Vaccination Regimes (Disease Reports)

• CWD Literature Reports: Vaccine Developments (Disease Reports)

• At present no prophylactic treatment is available against CWD.
• Several compounds have been shown to inhibit PrP^res production in cell-free systems and/or in scrapie-infected neuroblastoma cells and some of these compounds have been shown to prolong the incubation period in hamsters if given starting prior to, or at the same time as, peripheral inoculation of scrapie agent. However at this time no compounds are considered effective for treatment of the TSE diseases.

• CWD Literature Reports: Prophylactic Treatment (other than vaccines) (Disease Reports) (other than vaccines)

Environmental and Population Control Measures

• There is the potential for CWD to be transmitted via a contaminated environment; disinfection of the environment is an important consideration for this disease.
• To date efforts at disinfection of sites which have been heavily contaminated have been unsuccessful. It is unclear what factors may have been responsible for these failures.
• For disinfection of implements that may have been contaminated, such as knives used in butchering deer, sodium hypochlorite (household bleach at greater than 2% free chlorine, diluted one part bleach to four parts water, at room temperature for one hour) or sodium hydroxide (caustic soda, soda lye, at 38 g per litre of water at room temperature for one hour) are recommended as disinfectants.
• It should be noted that there are considerable concerns regarding the complete assurance of decontamination of objects which may have become contaminated with TSE agents (for this reason it has been suggested that surgical instruments used in operations involving the brain, spinal cord or eyes of persons known or suspected to have CJD should be discarded).

• CWD Literature Reports: General Environment Changes, Cleaning and Disinfection (Disease Reports)

• Prion Protein Literature Reports: Chemical Toxicities / Disinfectants (Chemical Reports)
• Prion Protein Literature Reports: Physical Susceptibility (Inactivation) (Chemical Reports)

• In captive cervids all individuals on affected premises may be killed as part of CWD control.
• In free-ranging cervids a variety of population control strategies may be used although the efficacy of any one or combination of these strategies has not been established:
  • Culling of clinical suspects may be used to remove potential sources of infection.
  • Targeted removal of yearling males in infected areas may be used to reduce the risk of such animals moving the disease into a new area when they naturally disperse.
  • Aggressive depopulation may be used to decrease the risk of animals transporting the disease out of the affected area during seasonal migration or in areas in which the disease has been detected only recently, and in which the prevalence of disease within the population is relatively low, as a strategy to reduce the population, limit disease transmission and eliminate the disease from the area.
  • Population reduction may be undertaken in an area not yet affected by the disease, with the aim of reducing the risk that it will be introduced into the area. 
• Restrictions on baiting and feeding of free-ranging cervids may be used to reduce unnatural close contact between individuals. Such contact is likely to increase the risk of transmission of CWD and other diseases.

• CWD Literature Reports: Population Control Measures (Disease Reports)

• Quarantine of affected herds or premises, together with testing for further cases, may be useful following detection of CWD within a captive herd.
• It is recommended that live cervids should not be transported out of areas in which CWD is known to occur.
• It is recommended also that whole carcasses and those parts of the carcass most likely to contain CWD infectivity should not be removed from areas in which CWD is known to occur.

• Literature Reports: Isolation and Quarantine