Chronic wasting disease

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Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of mule deer, white-tailed deer, elk (or "wapiti"), and moose ("elk" in Europe). To date, CWD has only been found in members of the deer family. First recognized as a clinical "wasting" syndrome in 1967 in mule deer in a wildlife research facility in northern Colorado, USA, it was identified as a TSE in 1978 and has spread to free-ranging and captive populations in 23 US states and two Canadian provinces.[1] CWD is typified by chronic weight loss leading to death. No relationship is known between CWD and any other TSE of animals or people.

Although reports in the popular press have been made of humans being affected by CWD, a study by the Centers for Disease Control and Prevention suggests, "[m]ore epidemiologic and laboratory studies are needed to monitor the possibility of such transmissions."[2] The epidemiological study further concluded, "[a]s a precaution, hunters should avoid eating deer and elk tissues known to harbor the CWD agent (e.g., brain, spinal cord, eyes, spleen, tonsils, lymph nodes) from areas where CWD has been identified."[2]

Clinical signs[edit]

Most cases of CWD occur in adult animals. The disease is progressive and always fatal. The most obvious and consistent clinical sign of CWD is weight loss over time. Behavioral changes also occur in the majority of cases, including decreased interactions with other animals, listlessness, lowering of the head, lethargy, repetitive walking in set patterns, and a smell like meat starting to rot. In elk, behavioral changes may also include hyperexcitability and nervousness. Affected animals continue to eat grain, but may show decreased interest in hay. Excessive salivation and grinding of the teeth also are observed. Most deer show increased drinking and urination.

Causative agent[edit]

The agent responsible for CWD (and other TSEs, such as scrapie and bovine spongiform encephalopathy) is commonly thought to be a prion, an abnormal form of a normal protein, known as prion protein (PrP), most commonly found in the central nervous system (CNS), and is capable of spreading to the peripheral nervous system (PNS), thus infecting meat, or muscle, of deer and elk. The abnormal PrP infects the host animal by promoting conversion of normal cellular prion protein (PrPC) to the abnormal prion form (PrPCWD). The build-up of PrPCWD in the brain is associated with widespread neurodegeneration. An alternative theory gaining, thus far, limited acceptance is that Spiroplasma, a bacterium devoid of a conventional cell wall, may be the causative agent. This does not eliminate prions from playing some role, but speculation has suggested prions may even be a byproduct of Spiroplasma.[3]


Research is being conducted to develop live-animal diagnostic tests for CWD. Currently, definitive diagnosis is based on post mortem examination (necropsy) and testing. Gross lesions seen at necropsy reflect the clinical signs of CWD, primarily emaciation. Aspiration pneumonia, which may be the actual cause of death, also is a common finding in animals affected with CWD. On microscopic examination, lesions of CWD in the central nervous system resemble those of other TSEs. In addition, scientists use immunohistochemistry to test brain tissue for the presence of the abnormal prion protein to diagnose CWD.

In 2010, a team from New York described detection of PrPSc even when initially present at only one part in a hundred thousand million (10−11) in brain tissue. The method combines amplification with a novel technology called surround optical fiber immunoassay (SOFIA) and some specific antibodies against PrPSc. After amplifying and then concentrating any PrPSc, the samples are labelled with a fluorescent dye using an antibody for specificity and then finally loaded into a microcapillary tube. This tube is placed in a specially constructed apparatus so it is totally surrounded by optical fibres to capture all light emitted once the dye is excited using a laser. The technique allowed detection of PrPSc after many fewer cycles of conversion than others have achieved, substantially reducing the possibility of artefacts, as well as speeding up the assay. The researchers also tested their method on blood samples from apparently healthy sheep that went on to develop scrapie. The animals’ brains were analysed once any symptoms became apparent. The researchers could then compare results from brain tissue and blood taken once the animals exhibited symptoms of the diseases, with blood obtained earlier in the animals’ lives, and from uninfected animals. The results showed very clearly that PrPSc could be detected in the blood of animals long before the symptoms appeared. After further development and testing, this method could be of great value in surveillance as a blood- or urine-based screening test for CWD.[4][5]


The origin and mode of transmission of the prions causing CWD is unknown, but recent research indicates that prions can be excreted by deer and elk, and are transmitted by eating grass growing in contaminated soil.[6][7] Animals born in captivity and those born in the wild have been affected with the disease. Based on epidemiology, transmission of CWD is thought to be lateral (from animal to animal). Maternal transmission may occur, although it appears to be relatively unimportant in maintaining epidemics. An infected deer's saliva is able to spread the CWD prions.[8]

In the mid-1980s, CWD was detected in free-ranging deer and elk in contiguous portions of northeastern Colorado and southeastern Wyoming. Soon after diagnosis of the disease as a TSE, Colorado and Wyoming wildlife management agencies stopped the movement of deer and elk from their research facilities; wild cervids have not been translocated from the endemic area. In May 2001, CWD was also found in free-ranging deer in the southwestern corner of Nebraska (adjacent to Colorado and Wyoming) and later in additional areas in western Nebraska. The limited area of northern Colorado, southern Wyoming, and western Nebraska in which free-ranging deer, moose, and/or elk positive for CWD have been found is referred to as the endemic area. The area in 2006 has expanded to six states, including parts of eastern Utah, southwestern South Dakota, and northwestern Kansas. Also, areas not contiguous (to the endemic area) areas in central Utah and central Nebraska have been found. The limits of the affected areas are not well defined, since the disease is at a low incidence and the amount of sampling may not be adequate to detect it. In 2002, CWD was detected in wild deer in south-central Wisconsin and northern Illinois and in an isolated area of southern New Mexico. In 2005, it was found in wild white-tailed deer in New York and in Hampshire County, West Virginia.[9] In 2008, the first confirmed case of CWD in Michigan was discovered in an infected deer on an enclosed deer-breeding facility. It is also found in the Canadian provinces of Alberta and Saskatchewan.

Chronic wasting disease in North America

In February 2011, the Maryland Department of Natural Resources reported the first confirmed case of the disease in that state. The affected animal was a white-tailed deer killed by a hunter.[10]

CWD has also been diagnosed in farmed elk and deer herds in a number of states and in two Canadian provinces. The first positive farmed elk herd in the United States was detected in 1997 in South Dakota. Since then, additional positive elk herds and farmed white-tailed deer herds have been found in South Dakota (7), Nebraska (4), Colorado (10), Oklahoma (1), Kansas (1), Minnesota (3), Montana (1), Wisconsin (6) and New York (2). As of fall of 2006, four positive elk herds in Colorado and a positive white-tailed deer herd in Wisconsin remain under state quarantine. All of the other herds have been depopulated or have been slaughtered and tested, and the quarantine has been lifted from one herd that underwent rigorous surveillance with no further evidence of disease. CWD also has been found in farmed elk in the Canadian provinces of Saskatchewan and Alberta. A retrospective study also showed mule deer exported from Denver to the Toronto Zoo in the 1980s were affected. In June 2015, the disease was detected in a male white-tailed deer on a breeding ranch in Medina County, Texas. State officials euthanized 34 deer in an effort to contain a possible outbreak.

Species that have been affected with CWD include elk, mule deer, white-tailed deer, black-tailed deer, and moose. Other ruminant species, including wild ruminants and domestic cattle, sheep, and goats, have been housed in wildlife facilities in direct or indirect contact with CWD-affected deer and elk, with no evidence of disease transmission. However, experimental transmission of CWD into other ruminants by intracranial inoculation does result in disease, suggesting only a weak molecular species barrier exists. Research is ongoing to further explore the possibility of transmission of CWD to other species.

CWD transmission pathways[edit]

Direct CWD Transmission[edit]

CWD may be directly transmitted via contact with infected animals, their bodily tissues, and their bodily fluids.[11] Nasal and aerosol transmission of CWD has been demonstrated as a particularly effective direct transmission method.[12] Transmission may result from contact with both clinically affected and infected, but asymptomatic, cervids.[13]

Recent research on Rocky Mountain elk found that with CWD-infected dams, many sub-clinical, there was a high rate (80%) of maternal-to-offspring transmission of CWD prions, regardless of gestational period.[13] While not dispositive relative to disease development in the fetus, this does suggest that maternal transmission may be yet another important route of direct CWD transmission.

Experimental Transmission of CWD[edit]

In addition to the cervid species in which CWD is known to naturally occur, Black-tailed deer and European red deer have been clinically demonstrated to be naturally susceptible to CWD.[14] Other cervid species, including reindeer and caribou, are also suspected to be naturally vulnerable to this disease.[11] Many other non-cervid mammalian species have been experimentally infected with CWD, either orally or via intracerebral inoculation.[11] These species include monkeys, sheep, cattle, prairie voles, mice, and ferrets.[15]

Indirect/Environmental Transmission of CWD[edit]

Environmental transmission has been linked to contact with infected bodily fluids and tissues, as well as contact with contaminated environments.[16][17][18] Once in the environment, CWD prions may remain infectious for many years.[19] Thus, decomposition of diseased carcasses, infected "gut piles" from hunters who field dress their cervid harvests, as well as the urine, saliva, feces, and antler velvet of infected individuals that are deposited in the environment, all have the potential to create infectious environmental reservoirs of CWD.[19]

Diseased carcasses and hunter "gut piles" present potentially significant sources for CWD transmission in several respects. Direct field observation of cervid carcasses and gut piles revealed that as many as 14 species of mammals (including domestic dogs and cats), and 14 species of birds, fed on the carcasses.[20] TSE-susceptible species, including cats, raccoons, and four mustelid species were among the observed scavengers.[20] These carcasses and gut piles were also inspected by other cervids.[20] Thus, as previous studies have demonstrated, cervids may become infected with CWD by direct contact with infected carcasses or indirectly through contact with an environment contaminated by an infected carcass.[19] Cross-species transmission may ultimately result from TSE-susceptible species' oral exposure to infected carcasses and gut piles; some scavenger species, including birds, may also serve as an intermediate disease host or asymptomatic disease spreader.[20]

One avian scavenger, the American crow was recently evaluated as a potential vector for CWD.[21] As CWD prions remain viable after passing through the bird's digestive tract, crows represent a possible mechanism for the creation of environmental reservoirs of CWD.[21][22] Additionally, the crows' extensive geographic range presents ample opportunities for them to come in contact with CWD. This coupled with the population density and longevity of communal roosting sites in both urban and rural locations suggests that the fecal deposits at roosting sites may represent a CWD environmental reservoir.[21] Conservative estimates for crows' fecal deposits at one winter roosting site for one winter season ranged from 391,552 - 599,032 kg.[21]

Similarly, mammalian predators and scavengers, including wolves, mountain lions, coyotes, raccoons, and opossums may play a role in the dispersal of CWD prions through their consumption habits, fecal deposits, and other natural behaviors.[20][21] A study analyzing the infectiousness of CWD prions excreted by coyotes is currently underway.[21]

Another way in which diseased carcasses and gut piles, urine, saliva, and feces from CWD-infected individuals are believed to play a significant role in the environmental transmission of CWD is through the attachment of CWD prions to soil surface particles. Prions bind tightly with most soils, and, as a result, appear to be protected from degradation; these prions are also believed to be conformationally altered such that the prions bound to soil become even more infectious than those not bound to soil.[23] This tight binding also keeps prions near the soil surface, and thus easily accessible to livestock, wildlife, and other species.[24]

CWD in Cervid Tissues[edit]

TSEs were once believed to be limited in scope to brain and central nervous system (CNS) pathology. While this appears true for many TSEs, CWD prions have been identified in other tissues, organs, and bodily fluids, including saliva, feces, urine, antler velvet, blood, muscle, and other tissues, fluids and systems throughout diseased carcasses.[11] Recent research on Rocky Mountain elk dam-fetal calf pairs has also confirmed the presence of CWD prions throughout the bodily tissues of diseased dams, but calls into question prior assumptions that CWD prions concentrate in CNS and lymphoid tissue in all infected individuals, or at all stages of disease progression.[13] In one-third of the diseased maternal carcasses examined, CWD prions were observed in peripheral body tissues and fluids, with no evidence of CWD prions in either CNS or lymphoid tissue.[13]

The potential for human exposure to CWD[edit]

All of these findings have potential implications for human exposure to CWD. Specifically, direct transmission routes have implications for those individuals who farm cervids and to cervid hunters who are in direct contact with live or dead cervids. Indirect or environmental transmission routes have significantly broader potential human health implications, and may impact multiple groups, including, but not limited to, cervid farmers, hunters, venison consumers, meat processors, chefs, taxidermists, anyone who owns, visits, or works in "deer habitat", and anyone who comes into contact with any of these referenced group members.

Even so, while there are several different TSEs affecting humans, both inherited and acquired, to date, there are no confirmed cases of CWD transmission to humans. There is a presumed "species barrier" that purports to prevent the transmission of prion diseases between unrelated species.[25] However, as was demonstrated with a zoonotic variant of the bovine TSE - commonly referred to as "mad cow disease" - the so-called species barrier is not absolute. In fact, some suggest that the "barrier" is more aptly thought of as a "roadblock", making transmission of prion diseases between different species more difficult, but not impossible.[26]

The repeated exposure of avian or mammalian scavengers to CWD prions, along with the existence of multiple strains of the disease in the environment, and the ever-increasing prevalence of this disease, may ultimately result in the transmission of CWD to novel species.[21] This then, may signal an increased risk of natural CWD transmission to humans and other non-cervid species.[11][21][26] Unfortunately, there is currently too much uncertainty relative to routes of exposure, differences in strains, human susceptibility, disease incubation time, and other transmission-related factors to accurately assess the risks to human health posed by CWD.

In the event that CWD is or becomes zoonotic, as with other TSEs, it will undoubtedly provde 100% fatal to those infected. However, CWD's unique status as an environmentally transmissible TSE, with documented long-term viability in the environment, arguably makes the potential public health implications of this disease far graver than that of other known TSEs.

Food safety concern[edit]

Human exposure to CWD-infected cervids in past decades is likely. The highest levels of prion infectivity are present in the central nervous system and lymphatic tissues of CWD-infected cervids; contamination of knives, saws, and muscles with these tissues can easily occur when processing game. Despite the likelihood of exposures, epidemiologic studies of humans living in CWD-endemic areas of Colorado and Wyoming during 1979–2001 have not shown any increases in human TSE cases.[27][28] Ongoing studies by the Colorado Department of Public Health and Environmental Human Prion Disease Surveillance Program, in conjunction with the University of Colorado School of Medicine, have also concluded no convincing cases of CWD transmission to humans have been detected in Colorado.[29] However, if CWD in humans appears like a wasting syndrome similar to that observed in the squirrel monkeys in our study, affected persons might receive a diagnosis of a metabolic disorder and never be tested for TSE. Fortunately, additional laboratory data are consistent with the epidemiologic data, and these results support the conclusion that a species barrier protects humans from CWD infection.[30]


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