Cervidae and Camelidae Chronic Wasting Disease Study Guide

Overview and Clinical Importance

Chronic wasting disease (CWD) is a fatal, progressive neurodegenerative prion disease affecting members of the family Cervidae (deer, elk, moose, reindeer, and caribou). First identified in captive mule deer in Colorado in 1967, CWD has since spread to 36 US states, 5 Canadian provinces, South Korea, Norway, Finland, and Sweden. Unlike other transmissible spongiform encephalopathies (TSEs), CWD is unique in affecting free-ranging wildlife and demonstrating efficient horizontal transmission through environmental contamination.

CWD represents a significant topic on the NAVLE and BCSE examinations due to its zoonotic potential concerns, regulatory importance, diagnostic challenges, and wildlife management implications. Understanding the pathophysiology, clinical presentation, diagnostic approach, and management strategies is essential for veterinary practice.

Important Note on Camelidae: While CWD naturally affects cervids, camelids (llamas and alpacas) share grazing environments with cervids in some regions. Current evidence indicates that CWD does NOT naturally affect camelids, and no natural cases have been documented. However, camelids may be exposed to environmental prion contamination in CWD-endemic areas, making this a relevant differential consideration.

Etiology and Pathophysiology

Prion Biology

CWD is caused by prions (proteinaceous infectious particles), which are misfolded isoforms of the normal cellular prion protein (PrPC). The disease-associated misfolded form is designated PrPSc (for scrapie) or PrPCWD. When PrPCWD contacts normal PrPC, it induces conformational change, converting the normal protein to the pathogenic form in a self-propagating chain reaction.

Key Prion Characteristics

Pathogenesis

Following oral exposure (the primary natural route), CWD prions are taken up by gut-associated lymphoid tissue (GALT), particularly Peyer's patches. The agent then spreads to other lymphoid tissues including tonsils, retropharyngeal lymph nodes, and spleen. PrPCWD accumulates in lymphoid tissues early in infection, often months to years before CNS involvement.

Neuroinvasion occurs via retrograde transport along autonomic nerves, primarily the vagus nerve. The dorsal motor nucleus of the vagus at the obex region of the medulla oblongata is typically the first CNS site affected. From there, prions spread throughout the brain, causing progressive neurodegeneration characterized by:

• Spongiform change (vacuolation) in gray matter neuropil
• Intraneuronal vacuolation (perikaryon vacuoles)
• Neuronal degeneration and loss
• Astrocytic hypertrophy and hyperplasia (astrogliosis)
• Amyloid plaque deposition (more common in deer than elk)
• Absence of inflammatory response (no infiltration of inflammatory cells)

Susceptible Species and Genetic Factors

Naturally Susceptible Cervid Species

PRNP Gene Polymorphisms and Susceptibility

The PRNP gene encodes the prion protein and contains polymorphisms that significantly affect CWD susceptibility, incubation time, and disease progression. Understanding these polymorphisms is essential for disease management and selective breeding programs.

Memory Aid - PRNP Polymorphisms: "ELK 132, DEER 95-96" - Elk susceptibility determined at codon 132 (M>L); White-tailed deer at codons 95 and 96. Wild-type genotypes = most susceptible, shortest incubation.

Camelidae and CWD Susceptibility

Important: New World camelids (llamas, alpacas, guanacos, vicunas) are NOT known to be naturally susceptible to CWD. No natural cases have been documented despite habitat overlap with cervids in some regions. Key considerations:

• Camelid PrP differs significantly from cervid PrP at key amino acid positions
• No experimental transmission studies have demonstrated CWD susceptibility in camelids
• Environmental prion contamination in shared grazing areas is a theoretical concern
• Avoid feeding bone meal to camelids as a precautionary measure against TSE exposure

Species NOT Naturally Affected by CWD

• Domestic cattle - Highly resistant via oral route; some susceptibility via intracerebral inoculation
• Sheep and goats - Have their own prion disease (scrapie); CWD transmission requires intracerebral inoculation
• Camelids - No natural cases; appear resistant
• Horses - Not susceptible
• Humans - Strong species barrier; no confirmed cases, but surveillance ongoing

Transmission Routes

CWD is considered the most contagious of all prion diseases due to efficient horizontal transmission and environmental persistence. Understanding transmission is critical for disease management.

Clinical Signs

Clinical signs of CWD are subtle, progressive, and nonspecific, making clinical diagnosis unreliable. The disease course is always fatal, typically over weeks to months after onset of clinical signs. Most affected animals are adults greater than 16 months old.

Classic Clinical Presentation

Memory Aid - CWD Clinical Signs "WASTED": Weight loss progressive, Ataxia and tremors, Salivation excessive, Thirst increased (polydipsia), Ears drooping, Death inevitable

APHIS Clinical Summary: "Behavioral changes, emaciation, weakness, ataxia, salivation, aspiration pneumonia, progressive death."

Diagnosis

Clinical diagnosis of CWD is unreliable due to nonspecific signs. Definitive diagnosis requires laboratory detection of PrPCWD in tissues, primarily postmortem.

Diagnostic Methods

Tissues for Testing

Primary postmortem tissues:

• Obex (brainstem at level of dorsal motor nucleus of vagus) - earliest CNS site affected
• Medial retropharyngeal lymph nodes (MRPLN) - lymphoid tissue; early prion accumulation; BOTH nodes should be tested

Antemortem tissues (research/limited use):

• Rectal mucosa biopsy (RAMALT - recto-anal mucosa-associated lymphoid tissue)
• Tonsil biopsy
• Third eyelid - contains lymphoid follicles; easier to collect than MRPLN
• Saliva, urine, feces, blood - RT-QuIC detection; research applications

Differential Diagnoses

• Malnutrition/starvation - environmental conditions; inadequate feed
• Parasitism - heavy GI parasite burden; meningeal worm (Parelaphostrongylus tenuis)
• Dental disease - prevents adequate feed intake
• Epizootic hemorrhagic disease (EHD)/Bluetongue
• Tuberculosis
• Neoplasia
• Capture myopathy - note: death after chemical immobilization has been observed in CWD-positive animals
• Chronic liver or kidney disease

Treatment, Prevention, and Management

There is NO treatment, vaccine, or cure for CWD. The disease is invariably fatal. Management focuses on surveillance, containment, and prevention of spread.

Prion Decontamination

Prions are extremely resistant to conventional disinfection. Recommended methods for contaminated surfaces/equipment:

• Sodium hypochlorite (household bleach) - 20,000 ppm available chlorine, 1 hour contact time
• Sodium hydroxide - 1-2N NaOH, 1 hour contact time
• Autoclaving - 134°C for 18 minutes (porous load) or 1 hour (gravity displacement)
• Incineration - preferred for carcasses and heavily contaminated materials

Public Health Considerations

No confirmed human cases of CWD have been documented. However, given the zoonotic transmission of BSE to humans (variant CJD), precautions are recommended:

• Do not consume meat from animals that appear sick or test positive
• Have deer tested before consumption in endemic areas
• Avoid consumption of high-risk tissues (brain, spinal cord, eyes, spleen, tonsils, lymph nodes)
• Use proper precautions when field-dressing and processing carcasses
• NIH studies suggest substantial species barrier; human cerebral organoids resistant to CWD transmission

Regulatory Status

• Reportable disease in most US states and Canadian provinces
• USDA-APHIS regulates interstate movement of farmed cervids
• State wildlife agencies manage CWD in free-ranging populations
• Not listed as OIE notifiable disease (no international movement restrictions)