Elizabeth S. Williams

Chronic wasting disease of captive mule deer: a spongiform encephalopathy.

In the past 12 years (1967–79) a syndrome we identify as chronic wasting disease has been observed in 53 mule deer (Odocoileus hemionus hemionus) and one black-tailed deer (Odocoileus hemionus columbianus) held in captivity in several wildlife facilities in Colorado and more recently in Wyoming. Clinical signs were seen in adult deer and included behavioral alterations, progressive weight loss and death in 2 weeks to 8 months. Gross necropsy findings included emaciation and excess rumen fluid admixed with sand and gravel. Consistent histopathologic change was limited to the central nervous system and characterized by widespread spongiform transformation of the neuropil, single or multiple intracytoplasmic vacuoles in neuronal perikaryons and intense astrocytic hypertrophy and hyperplasia. Presented is a clinical characterization of chronic wasting disease and pathologic evidence supporting the conclusion that the disease is a specific spontaneously occurring form of spongiform encephalopathy.

Infectious diseases of wild mammals

Viral and prion diseases: Rabies Morbilliviral diseases Bluetongue, epizootic haemorrhagic diseases, and other orbivirus realted diseases Arbovirus infections Picornaviruses Parvoviruses Herpesvirus infections Poxviruses Adenoviruses Papillomavirus infections Pestivirus infections Coronaviral infections Rodent-borne haemorrhagic fever viruses Orthomyxoviruses and paramyxoviruses Calicivirus infections transmissible spongiform encephalopathy Bacterial and mycotic diseases: Tularemia Plague and yersiniosis Pasteurellosis Mycobacterial diseases Anthrax Disease due to mycoplasmas Chlamydiosis of koalas Lyme borreliosis Order rickettsiales Miscellaneous bacterial infections Mycotic diseases.

Environmental Sources of Prion Transmission in Mule Deer

Whether transmission of the chronic wasting disease (CWD) prion among cervids requires direct interaction with infected animals has been unclear. We report that CWD can be transmitted to susceptible animals indirectly, from environments contaminated by excreta or decomposed carcasses. Under experimental conditions, mule deer (Odocoileus hemionus) became infected in two of three paddocks containing naturally infected deer, in two of three paddocks where infected deer carcasses had decomposed in situ ≈1.8 years earlier, and in one of three paddocks where infected deer had last resided 2.2 years earlier. Indirect transmission and environmental persistence of infectious prions will complicate efforts to control CWD and perhaps other animal prion diseases.

Chronic Wasting Disease

Chronic wasting disease (CWD) is a unique transmissible spongiform encephalopathy (TSE) of mule deer (Odocoileus hemionus), white-tailed deer (O. virginianus), and Rocky Mountain elk (Cervus elaphus nelsoni). The natural history of CWD is incompletely understood, but it differs from scrapie and bovine spongiform encephalopathy (BSE) by virtue of its occurrence in nondomestic and free-ranging species. CWD has many features in common with scrapie, including early widespread distribution of disease-associated prion protein (PrPd) in lymphoid tissues, with later involvement of central nervous system (CNS) and peripheral tissues. This distribution likely contributes to apparent efficiency of horizontal transmission and, in this, is similar to scrapie and differs from BSE. Clinical features and lesions of CWD are qualitatively similar to the other animal TSEs. Microscopically, marked spongiform lesions occur in the central nervous system (CNS) after a prolonged incubation period and variable course of clinical disease. During incubation, PrPd can be identified in tissues by antibody-based detection systems. Although CWD can be transmitted by intracerebral inoculation to cattle, sheep, and goats, ongoing studies have not demonstrated that domestic livestock are susceptible via oral exposure, the presumed natural route of exposure to TSEs. Surveillance efforts for CWD in captive and free-ranging cervids will continue in concert with similar activities for scrapie and BSE. Eradication of CWD in farmed cervids is the goal of state, federal, and industry programs, but eradication of CWD from free-ranging populations of cervids is unlikely with currently available management techniques.

Oral transmission and early lymphoid tropism of chronic wasting disease PrPres in mule deer fawns (Odocoileus hemionus )

Mule deer fawns (Odocoileus hemionus) were inoculated orally with a brain homogenate prepared from mule deer with naturally occurring chronic wasting disease (CWD), a prion-induced transmissible spongiform encephalopathy. Fawns were necropsied and examined for PrPres, the abnormal prion protein isoform, at 10, 42, 53, 77, 78 and 80 days post-inoculation (p.i.) using an immunohistochemistry assay modified to enhance sensitivity. PrPres was detected in alimentary-tract-associated lymphoid tissues (one or more of the following: retropharyngeal lymph node, tonsil, Peyers patch and ileocaecal lymph node) as early as 42 days p.i. and in all fawns examined thereafter (53 to 80 days p.i.). No PrPres staining was detected in lymphoid tissue of three control fawns receiving a control brain inoculum, nor was PrPres detectable in neural tissue of any fawn. PrPres-specific staining was markedly enhanced by sequential tissue treatment with formic acid, proteinase K and hydrated autoclaving prior to immunohistochemical staining with monoclonal antibody F89/160.1.5. These results indicate that CWD PrPres can be detected in lymphoid tissues draining the alimentary tract within a few weeks after oral exposure to infectious prions and may reflect the initial pathway of CWD infection in deer. The rapid infection of deer fawns following exposure by the most plausible natural route is consistent with the efficient horizontal transmission of CWD in nature and enables accelerated studies of transmission and pathogenesis in the native species.

Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease.

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of deer and elk, and little is known about its transmissibility to other species. An important factor controlling interspecies TSE susceptibility is prion protein (PrP) homology between the source and recipient species/genotypes. Furthermore, the efficiency with which the protease‐resistant PrP (PrP‐res) of one species induces the in vitro conversion of the normal PrP (PrP‐sen) of another species to the protease‐resistant state correlates with the cross‐species transmissibility of TSE agents. Here we show that the CWD‐associated PrP‐res (PrPCWD) of cervids readily induces the conversion of recombinant cervid PrP‐sen molecules to the protease‐resistant state in accordance with the known transmissibility of CWD between cervids. In contrast, PrPCWD‐induced conversions of human and bovine PrP‐sen were much less efficient, and conversion of ovine PrP‐sen was intermediate. These results demonstrate a barrier at the molecular level that should limit the susceptibility of these non‐cervid species to CWD.

Prion disease: Horizontal prion transmission in mule deer

Epidemics of contagious prion diseases can be perpetuated by horizontal (animal to animal) and maternal (dam to offspring, before or after birth) transmission, but the relative importance of each mechanism is unclear. Here we compare the incidence of chronic wasting disease (CWD) in captive mule deer (Odocoileus hemionus) that is attributable to horizontal or maternal transmission. We find that horizontal transmission is remarkably efficient, producing a high incidence of disease (89%) in a cohort of deer in which maternal transmission was improbable. Our results indicate that horizontal transmission is likely to be important in sustaining CWD epidemics.

Chronic wasting disease of deer and elk: A review with recommendations for management

Chronic wasting disease (CWD) has emerged as an important disease of wild and farmed cervids in North America. Of the transmissible spongiform encephalopathies (TSEs), or prion diseases, CWD is the only 1 found in free-ranging species. Because the TSEs include infamous diseases like bovine spongiform encephalopathy (BSE) of cattle and variant Creutzfeldt-Jakob disease of humans, CWD by association has become a disease of interest beyond the parochial concerns where it is found. Consequently, wildlife managers are faced with developing programs for addressing CWD. Mule deer (Odocoileus hemionus), white-tailed deer (O. virginianus), and Rocky Mountain elk (Cervus elaphus nelsoni) are the only species known to be naturally susceptible to CWD. Although implications of CWD are not entirely clear at this time, we know that CWD is a fatal, contagious disease of mature reproductive segments of deer and elk populations. It has been endemic in free-ranging cervids in a core area of contiguous portions of southeastern Wyoming and northeastern Colorado, USA, for a minimum of 20 years and probably longer. The known geographic distribution of endemic CWD is relatively limited at this time, although as results of intensified surveillance become available, this may change. Foci of CWD in free-ranging deer have been identified distant from the core endemic area as far east as Wisconsin. Distribution has greatly expanded in the last decade or more via commerce in infected farmed elk; as a result, CWD recently has been found in multiple jurisdictions of the plains, foothills, and Rocky Mountains of western North America, and in South Korea. Studies of the biology and natural history of CWD over the last few years have resulted in a better understanding of its pathogenesis and epidemiology. Chronic wasting disease is transmitted horizontally from infected to susceptible cervids. Early involvement of alimentary tract-associated lymphoid tissues during incubation suggests plausible routes for transmission via feces or saliva. Residual environmental contamination also appears to be important in sustaining epidemics. Studies of CWD epidemiology led to development of models to help explain the history of CWD as well as forecast its impacts on deer and elk populations. Improved tests allow CWD to be diagnosed early in incubation, long before clinical signs appear. Where CWD is not known to occur, managers should be, and in some cases are, developing surveillance programs and regulations that prevent or reduce the likelihood that CWD will be introduced into their jurisdictions. Where CWD is already endemic, responsible agencies are conducting surveillance to assess status and trends in prevalence and geographic distribution, managing deer and elk populations to limit spread, and developing and evaluating techniques for further controlling and perhaps eradicating CWD. Programs for addressing the challenges of CWD management will require interagency cooperation, commitment of funds and personnel, and applied research.

SPONGIFORM ENCEPHALOPATHY IN FREE-RANGING MULE DEER (ODOCOILEUS HEMIONUS), WHITE-TAILED DEER (ODOCOILEUS VIRGINIANUS) AND ROCKY MOUNTAIN ELK (CERVUS ELAPHUS NELSONI) IN NORTHCENTRAL COLORADO

Between March 1981 and June 1995, a neurological disease characterized histologically by spongiform encephalopathy was diagnosed in 49 free-ranging cervids from northcentral Colorado (USA). Mule deer (Odocoileus hemionus) were the primary species affected and accounted for 41 (84%) of the 49 cases, but six Rocky Mountain elk (Cervus elaphus nelsoni) and two white-tailed deer (Odocoileus virginianus) were also affected. Clinical signs included emaciation, excessive salivation, behavioral changes, ataxia, and weakness. Emaciation with total loss of subcutaneous and abdominal adipose tissue and serous atrophy of remaining fat depots were the only consistent gross findings. Spongiform encephalopathy characterized by microcavitation of gray matter, intraneuronal vacuolation and neuronal degeneration was observed microscopically in all cases. Scrapie-associated prion protein or an antigenically indistinguishable protein was demonstrated in brains from 26 affected animals, 10 using an immunohistochemical staining procedure, nine using electron microscopy, and seven using Western blot. Clinical signs, gross and microscopic lesions and ancillary test findings in affected deer and elk were indistinguishable from those reported in chronic wasting disease of captive cervids. Prevalence estimates, transmissibility, host range, distribution, origins, and management implications of spongiform encephalopathy in free-ranging deer and elk remain undetermined.

EPIZOOTIOLOGY OF CHRONIC WASTING DISEASE IN FREE-RANGING CERVIDS IN COLORADO AND WYOMING

Surveillance and epidemic modeling were used to study chronic wasting disease (CWD), a transmissible spongiform encephalopathy that occurs naturally among sympatric, free-ranging deer (Odocoileus spp.) and Rocky Mountain elk (Cervus elaphus nelsoni) populations in contiguous portions of northeastern Colorado and southeastern Wyoming (USA). We used clinical case submissions to identify endemic areas, then used immunohistochemistry to detect CWD-infected individuals among 5,513 deer and elk sampled via geographically-focused random surveys. Estimated overall prevalence (prevalence, 95% confidence interval) in mule deer (4.9%, 4.1 to 5.7%) was higher than in white-tailed deer (2.1%, 0.5 to 3.4%) or elk (0.5%, 0.001 to 1%) in endemic areas; CWD was not detected in outlying portions of either state. Within species, CWD prevalence varied widely among biologically- or geographically-segregated subpopulations within the 38,137 km2 endemic area but appeared stable over a 3-yr period. The number of clinical CWD cases submitted from an area was a poor predictor of local CWD prevalence, and prevalence was typically ≥1% before clinical cases were first detected in most areas. Under plausible transmission assumptions that mimicked field data, prevalence in epidemic models reached about 1% in 15 to 20 yr and about 15% in 37 to 50 yr. Models forecast population declines once prevalence exceeded about 5%. Both field and model data supported the importance of lateral transmission in CWD dynamics. Based on prevalence, spatial distribution, and modeling, we suggest CWD has been occurring in northeastern Colorado and southeastern Wyoming for >30 yr, and may be best represented as an epizootic with a protracted time-scale.