Chronic Wasting Disease (CWD) Frequently Asked Questions

Chronic wasting disease (CWD) is a progressive, fatal neurodegenerative disease that comes under the umbrella of transmissible spongiform encephalopathies (TSEs).1 TSEs are caused by prions, or misfolded proteins. Other examples of TSEs include scrapie in sheep, Creutzfeldt-Jakob disease in humans, and bovine spongiform encephalopathy in cattle. CWD is a TSE that affects cervids such as mule deer, black-tailed deer, white-tailed deer, Rocky Mountain elk, sika deer, moose, and wild reindeer.2,3

CWD was first identified in 1967 in a captive mule deer living in a Colorado research facility and detected for the first time in a wild cervid in 1981. Since those detections, CWD has been found in 32 US states, five Canadian provinces, Finland, Norway, South Korea, and Sweden.

CWD is believed to be spread from animal to animal contact through infectious body fluids such as saliva, urine, and feces. Once excreted into the environment, CWD prions can persist for years and withstand extremely high levels of disinfectants such as heat, radiation, and formaldehyde. CWD prions can also bind to certain plants and be transported while remaining infectious.

As more cervids become infected, the frequency of these exposures and subsequent environmental contamination grows. Evidence also suggests that transmission from parents to offspring can occur, although its overall effect on the ecology of CWD is not entirely understood.

Because CWD is now an established wildlife disease in North America, proactive steps should be taken to limit transmission of CWD among animals and reduce the potential for human exposure. Although CWD is not known to infect humans, health agencies have said that people should not consume CWD-positive animals. Since 1997, the World Health Organization has recommended that no agents of any prion disease should enter the human food chain. Likewise, the US Centers for Disease Control and Prevention, Health Canada, and multiple provincial and state health and natural resources agencies recommend that people not consume CWD-positive meat.

Given the typical incubation period of 10 years or longer for prion diseases in humans, improving public health measures now can help prevent human exposure to CWD prions. A better understanding of the risk to humans may reduce the likelihood of a CWD spillover event such as that of bovine spongiform encephalopathy (BSE). With BSE, also known as "mad cow" disease, some British officials in the 1990s declared there was no risk of transmitting BSE prions through the consumption of contaminated beef only to later confirm related human cases of a similar prion disease in the ensuing years.

References

1. Orge L, de Lurdes Pinto M, Cristovão P, et al. Detection of abnormal prion protein by immunohistochemistry. J Vis Exp 2023 May 5;195:e64560. View on JoVE

2. Ness A, Jacob A, Saboraki K, et al. Cellular prion protein distribution in the vomeronasal organ, parotid, and scent glands of white-tailed deer and mule deer. Prion 2022 May 29;16(1):40–57. View on Prion 

3. CDC. Chronic wasting disease (CWD). U.S. Department of Health and Human Services 2021. View on CDC

 

Substantial evidence concludes that CWD is caused by infectious prions.1 Conversion of the hosts’ normal cellular proteins into misfolded versions damages the central nervous system.2 There are no known ways to prevent prion disease progression after infection.

Alternative theories such as the recent suggestion that Spiroplasma bacteria are the causative agent are not supported by scientific evidence. Krysten Schuler, PhD, a wildlife disease ecologist at Cornell University’s Wildlife Health Lab and an expert on CWD, has summarized the evidence that prions cause CWD, and these conclusions are widely accepted in the field.3

References 

1. Davenport KA, Hoover CE, Bian J, et al. PrPC expression and prion seeding activity in the alimentary tract and lymphoid tissue of deer.. PLOS One 2017 Sep 17;12(9). View at PLOS One 

2. Williams ES. Chronic wasting disease. Vet Pathol 2005 Sep;42(5):530–549. View at Sage 

3. Schuler K. Prion hypothesis for CWD: An examination of the evidence. Cornell Wildlife Health Lab 2019 Feb 19. View at Cornell Wildlife Health Lab

Normal, non–disease-causing cellular prion proteins (PrPc) are encoded by the PRNP gene and expressed on the membranes of different cells in many species, including mammals, amphibians, birds, and reptiles.1,2 In contrast, an infectious prion protein (PrPSc) is a misfolded version of its naturally occurring counterpart that ultimately results in prion disease in a susceptible host. PrPSc is unique in that it is highly resistant to degradation by protease, disinfectants such as formalin and alcohol, and environmental factors such as heat and radiation.3 Following introduction sporadically, genetically, or via exposure, PrPSc can interact with PrPc and cause a chain reaction of conversion into misfolded protein.4 The resulting cascade effect generally takes place over long periods of time, as disease-causing prions continue to accumulate and, ultimately, result in clinically evident neurodegeneration.

References

1. Hoover CE, Davenport KA, Henderson DM, et al. Pathways of prion spread during early chronic wasting disease in deer. J Virol 2017 May 15;91(10):e00077-17 . View at ASM

2. Zanusso G, Liu D, Ferrari S, et al. Prion protein expression in different species: Analysis with a panel of new mAbs. PNAS 1998 Jul 21;95(15):8812–8816. View at PNAS

3. Spickler AR. Chronic Wasting Disease. The Center for Food Security and Public Health 2016 Jul. View at CFSPH 

4. Weissmann C, Enari M, Klöhn P, et al. Transmission of prions. J Infect Dis 2002 Dec 1;186(s2). View at Oxford Academic

Infectious CWD-causing prions are most likely transmitted from animal to animal by direct or indirect contact with any of the following infectious body fluids or tissues:

  • Blood 1
  • Urine 2
  • Feces 2
  • Saliva 1,3
  • Brain matter 3
  • Antler velvet 4
  • Reproductive organs 5
  • Semen 5

It remains unclear whether infectious prions can spread via sexual contact between cervids. Excreted substances may contain CWD prions during the preclinical phase of the disease, with the concentration of excreted prions appearing to increase as the disease progresses.6,7 Carcasses of animals infected with CWD have high numbers of prions and can remain infectious for extended periods.8,9,10

References 

1. Mathiason CK, Powers JG, Dahmes SJ, et al. Infectious prions in the saliva and blood of deer with chronic wasting disease. Science 2006 Oct 6;314(5796):133–136. View at Science 

2. Haley NJ, Mathiason CK, Zabel MD, et al. Detection of sub-clinical CWD infection in conventional test-negative deer long after oral exposure to urine and feces from CWD+ deer. PLOS One 2009 Nov 24;4(11). View at PLOS One 

3. Denkers ND, Hoover CE, Davenport KA, et al. Very low oral exposure to prions of brain or saliva origin can transmit chronic wasting disease. PLOS One 2020 Aug 20;15(8). View at PLOS One

4. Angers RC, Seward TS, Napier D, et al. Chronic wasting disease prions in elk antler velvet. Emerg Infect Dis 2009 May;15(5):696–703. View at Emerg Infect Dis 

5. Kramm C, Gomez-Gutierrez R, Soto C, et al. In vitro detection of chronic wasting disease (CWD) prions in semen and reproductive tissues of white tailed deer bucks (Odocoileus virginianus). PLOS One 2019 Dec 30;14(12):e0226560. View at PLOS One

6. Hoover CE, Davenport KA, Henderson DM, et al. Pathways of prion spread during early chronic wasting disease in deer. J Virol 2017 Apr 28;91(10):e00077-17. View at J Virol

7. Henderson DM, Denkers ND, Hoover CE, et al. Longitudinal detection of prion shedding in saliva and urine by chronic wasting disease-infected deer by real-time quaking-induced conversion. J Virol 2015 Sep;89(18):9338–47. View at J Virol 

8. Miller MW, Williams ES, Hobbs NT, et al. Environmental sources of prion transmission in mule deer. Emerg Infect Dis 2004 Jun;10(6):1003–6. View at Emerg Infect Dis 

9. Saunders SE, Bartelt-Hunt SL, Bartz JC. Occurrence, transmission, and zoonotic potential of chronic wasting disease. Emerg Infect Dis 2012 Mar;18(3):369–76. View at Emerg Infect Dis 

10. Zabel M, Ortega A. The ecology of prions. Microbiol Mol Biol Rev 2017 May 31;81(3):e00001-17. View at Microbiol Mol Biol Rev

Clinical Features and Diagnostics

The average time between initial infection to symptom onset is about 18 to 24 months in adult cervids, though there have been cases of up to 5 years.1 Cervids that reach the clinical stage of CWD infection exhibit symptoms such as drastic weight loss, altered gait, confusion, excessive salivation and urination, grinding of teeth, slumped head, drooping ears, and a lack of fear of people.2,3 CWD may also have consequences for reproduction, with some evidence suggesting that some infected cervid species are prone to stillbirths and death soon after birth, although further research is needed.2 Symptoms of CWD are typically evident for several weeks or months before the animal dies, although some infected cervids may live for over a year. 

References

1. Haley NJ, Hoover EA. Chronic wasting disease of cervids: Current knowledge and future perspectives. Annu Rev Anim Biosci 2015 Feb;3(1):305–25. View at Annu Rev Anim Biosci

2. Spickler AR. Chronic Wasting Disease. The Center for Food Security and Public Health 2016 Jul. View at CFSPH 

3. CDC. Chronic wasting disease (CWD). US Department of Health and Human Services 2021. View at CDC

Prion diseases can present in a clinically diverse manner but are always fatal.1 Although research is ongoing, there are currently no vaccines or therapeutics to prevent CWD infection or death in cervids.2,3 These characteristics emphasize the importance of preventing CWD spread whenever possible.

References 

1. Prusiner SB. Prions. Proc Natl Acad USA 1998 Nov 10;95(23):13363-83. View at Proc Natl Acad USA 

2. Napper S, Schatzl HM. Oral vaccination as a potential strategy to manage chronic wasting disease in wild cervid populations. Front Immunol 2023 Apr 14;14:1156451. View at Front Immunol

3. National Institute of Allergy and Infectious Diseases. Therapeutic approaches for prion diseases. US Department of Health and Human Services 2019 Oct 21. View at NIH

Certain polymorphisms in the PRNP gene have been associated with delayed onset of CWD infection in different cervid species, including mule deer, white-tailed deer, and elk.1,2,3 However, no cervids have shown complete genetic resistance to CWD, and the disease is still fatal.4 There are concerns surrounding the consequences of the prolonged incubation periods observed among infected animals with resistant genotypes, as they may shed CWD prions for longer periods.5 Prolonging the time that infected cervids excrete CWD prions would likely further complicate efforts to control transmission. Also, the prevalence of wild cervids with CWD-resistant genotypes is low, indicating that it may be associated with traits less desirable for fitness or long-term survival.6 Continued research on selective breeding and genetic resistance to CWD is warranted, but it does not yet appear to be a viable solution to mitigate the threat of widespread disease. 

References

1. Haley N, Donner R, Merrett K, et al. Selective breeding for disease-resistant PRNP variants to manage chronic wasting disease in farmed whitetail deer. Genes 2021 Sep 10;12(9):1396. View at MDPI

2. Johnson CJ, Herbst A, Duque-Velasquez C, et al. Prion protein polymorphisms affect chronic wasting disease progression. PLOS One 2011 Mar 18;6(3):e17450. View at PLOS One 

3. Robinson SJ, Samuel MD, O’Rourke KI, et al. The role of genetics in chronic wasting disease of North American cervids. Prion 2012 Apr 1;6(2):153–62. View at Prion

4. Moazami-Goudarzi K, Andréoletti O, Vilotte JL, et al. Review on PRNP genetics and susceptibility to chronic wasting disease of Cervidae. Vet Res 2021 Oct 7;52(1):128. View at BMC 

5. Davenport KA, Mosher BA, Brost BM, et al. Assessment of chronic wasting disease prion shedding in deer saliva with occupancy modeling. J Clin Microbiol 2017 Dec 26;56(1):e01243-17. View at J Clin Microbiol

6. Monello RJ, Galloway NL, Powers JG, et al. Pathogen-mediated selection in free-ranging elk populations infected by chronic wasting disease. PNAS 2017 Oct 30;114(46):12208–12. View at PNAS

Currently, there are two validated diagnostic assays, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC), used to determine if a hunter-harvested cervid is infected with CWD prions.1 These are postmortem tests that detect the presence of abnormal prion proteins in the obex area of the brain stem or the retropharyngeal lymph nodes. ELISA testing has not been validated in elk or moose, so samples collected from these animals are confirmed via IHC. Valid ELISA and IHC testing for CWD can be conducted only in federally approved laboratories that are part of the National Animal Health Laboratory Network, so results can take days to weeks. Although ELISA and IHC are not validated food safety tests and therefore cannot guarantee that an animal is free of CWD prions, they are the best available options to reduce human exposure. Continuing to use ELISA and IHC is essential until improved, validated assays are available.

Live-animal (ie, antemortem) testing is challenged by the types of invasive tissue collection typically used to detect CWD. Studies have used IHC to examine tonsillar, medial retropharyngeal lymph node (MRPLN), and rectoanal mucosa-associated lymphoid tissue (RAMALT) with some success.2 However, antemortem tests have considerable limitations that restrict their use. The collection of tissues from live animals is invasive, time-consuming, and expensive.3 The reliability of antemortem IHC testing also depends on factors such as genotypic differences, stage of infection, and the number of diagnostic follicles in the biopsy specimen.4,5,6 The combination of these factors limits the effectiveness of antemortem IHC tests for CWD.

Experimental tests, namely protein misfolding cyclic amplification (PMCA) and real-time quaking-induced conversion (RT-QuIC), are also being evaluated with different tissues and environmental sources.7 Results show that these tests can aide antemortem testing, but their ability to identify true positive cases (test sensitivity) in live cervids may be lower than validated postmortem tests in certain situations.3,8,9 More detailed information on antemortem tests can be found here, courtesy of the Association of Fish & Wildlife Agencies (AFWA) Technical Report on Best Management Practices for Prevention, Surveillance, and Management of Chronic Wasting Disease.10 Further research is needed for the development of a rapid, sensitive, and validated CWD assay.

References

1. US Department of Agriculture. Chronic wasting disease (CWD). USDA APHIS 2020 Jun. View at USDA APHIS 

2. Schneider DA, Lehmkuhl AD, Spraker TR, et al. Tonsil biopsy to detect chronic wasting disease in white-tailed deer (Odocoileus virginianus) by immunohistochemistry. PLOS One 2023 Mar 30;18(3):e0282356. View at PLOS One 

3. Kramm C, Pritzkow S, Lyon A, et al. Detection of prions in blood of cervids at the asymptomatic stage of chronic wasting disease. Sci Rep 2017 Dec 8;7(1):17241. View at Sci Rep

4. Keane D, Barr D, Osborn R, et al. Validation of use of rectoanal mucosa-associated lymphoid tissue for immunohistochemical diagnosis of chronic wasting disease in white-tailed deer (Odocoileus virginianus). J Clin Microbiol 2009 May;47(5):1412–7. View at J Clin Microbiol 

5. Monello RJ, Powers JG, Hobbs NT, et al. Efficacy of antemortem rectal biopsies to diagnose and estimate prevalence of chronic wasting disease in free-ranging cow elk (Cervus elaphus nelsoni). J Wildl Dis 2013 Apr;49(2):270–8. View at J Wildl Dis  

6. Thomsen BV, Schneider DA, O’Rourke KI, et al. Diagnostic accuracy of rectal mucosa biopsy testing for chronic wasting disease within white-tailed deer (Odocoileus virginianus) herds in North America: Effects of age, sex, polymorphism at PRNP codon 96, and disease progression. J Vet Diagn Invest 2012 Sep;24(5):878–87. View at J Vet Diagn Invest 

7. Yuan Q, Rowden G, Wolf TM, et al. Sensitive detection of chronic wasting disease prions recovered from environmentally relevant surfaces. Environ Int 2023 Jun 13;166:107347. View at ScienceDirect 

8. Haley NJ, Siepker C, Walter WD, et al. Antemortem detection of chronic wasting disease prions in nasal brush collections and rectal biopsy specimens from white-tailed deer by real-time quaking-induced conversion. J Clin Microbiol 2016 Mar 25;54(4):1108–16. View at ASM 

9. Haley NJ, Henderson DM, Wycoff S, et al. Chronic wasting disease management in ranched elk using rectal biopsy testing. Prion 2018 Mar 4;12(2):93–108. View at Prion 

10. Gillin C, Mawdsley J. AFWA Technical Report on Best Management Practices for Surveillance, Management and Control of Chronic Wasting Disease. Association of Fish and Wildlife Agencies 2018 . View at AFWA

First, CWD testing regulations vary by state and province, and testing may be voluntary in some areas and required in others.1 Willingness to participate in programs to test for CWD is critical for wildlife agencies to determine the prevalence of CWD in wild cervid populations and for informing hunters if their harvested cervid is infected. Therefore, efforts must be taken to encourage hunter participation in voluntary CWD testing efforts, particularly in areas where cervids are known to be infected. 

Accessibility may be a barrier to testing programs, including issues such as delays in receiving test results, distance to dropoff points, and lab capacity. A survey of hunters in Alberta, Canada, found that two-thirds of who submitted samples for CWD testing in 2018 had to wait at least a month for results.2 This delay is a major deterrent to an effective testing program, because hunters might choose to process or consume the meat in the interim. It is especially concerning for indigenous communities relying on harvested cervids as part of their diet.3 Expanding the availability of sample collection stations or dropoff points, particularly in rural areas, will likely encourage more hunters to participate in CWD testing. Also, establishing more labs approved for CWD testing will reduce bottlenecks caused by an annual wave of samples being collected and analyzed by a limited number of facilities. This effort will generate faster turnaround times for test results, allowing agencies to respond faster to a positive test and hunters to know more quickly if their meat is contaminated.

Last, accurate detection and surveillance are necessary components of a successful CWD testing program. While ELISA and IHC are the accepted tests aimed to reduce human exposure to CWD, more emphasis on developing and validating highly sensitive, rapid, and low-cost alternatives is needed.4 Once optimized, more robust CWD surveillance can be put in place to develop and implement comprehensive CWD management plans. 

References 

1. USDA APHIS. Chronic wasting disease program standards. 2019. View at USDA APHIS

2. Adamowicz W. Perception and public engagement on CWD. Presented to the OFAH CWD Conference. 2019 Mar 16. View at OFAH 

3. Maraud S, Roturier S. Chronic wasting disease (CWD) in Sami reindeer herding: The socio-political dimension of an epizootic in an indigenous context. Animals 2021 Jan 25;11(2):297. View at MDPI 

4. EFSA Panel on Biological Hazards (BIOHAZ). Monitoring of chronic wasting disease (CWD) (IV). EFSA journal 2023 Apr 17;21(4):e07936. View at EFSA

Infected cervids appear healthy for most of their infection, showing clinical symptoms only briefly before death.1 Cervids with clinically evident CWD eventually become emaciated and can die of starvation or pneumonia. Because CWD is a neurodegenerative disease, infected cervids also seem prone to other causes of death, including vehicular collisions and predation. Also, cervids infected with CWD appear more susceptible to hunter harvest because of potential behavioral changes.2 The role of predators, scavengers, and natural decomposition make observations of intact dead cervids relatively rare, regardless of disease status. In combination with the limited number of infected cervids that die of CWD, these factors contribute to the infrequent observation of cervids that die of CWD in the wild. 

References 

1. Williams ES. Chronic wasting disease. Vet Pathol 2005 Sep;42(5):530–49. View at Sage 

2. Edmunds DR, Kauffman MJ, Schumaker BA, et al. Chronic wasting disease drives population decline of white-tailed deer. PLOS One 2016 Aug 30;11(8):e0161127. View at PLOS One

Depending on resource availability and regulations at the state and local levels, organizations such as AFWA and the USDA list incineration, alkaline hydrolysis, landfilling, composting, and onsite burial as potential solutions.1,2 Education and compliance with available disposal methods are necessary to reduce environmental contamination with infectious prions. 

References 

1. Gillin C, Mawdsley J. AFWA Technical Report on Best Management Practices for Surveillance, Management and Control of Chronic Wasting Disease. AFWA 2018 . View at AFWA 

2. USDA APHIS. Chronic wasting disease program standards. 2019. View at USDA APHIS

Current Disease Patterns and Epidemiology

CWD was first documented in 1967 among captive mule deer at a Colorado research facility.1 Since then, CWD has spread across North America, with a notable increase in spread in the past two decades.2 In 2000, CWD was documented in 5 US states and 1 Canadian province, while in 2024, it is present in at least 34 states and 5 provinces.3CWD has also been documented in South Korea, Finland, Norway, and Sweden. Preventive efforts and further scientific research are essential for avoiding further spread of CWD and sustaining healthy cervid populations.

References

1. Williams ES. Chronic wasting disease. Vet Pathol 2005 Sep;42(5):530–49. View at Sage 

2. Richards BJ. Chronic wasting disease distribution in the United States by state and county. US Geological Survey data release 2021 Mar 26. View at USGS 

3. National Wildlife Health Center. Expanding distribution of chronic wasting disease. USGS 2023 Aug 10. View at USGS

Despite speculation, the precise origin of CWD emergence cannot be determined.1 Due to this uncertainty, there is a clear need for additional research, specifically on future disease management and potential pathways of infection. 

References 

1. Cassmann ED, Frese RD, Greenlee JJ. Second passage of chronic wasting disease of mule deer to sheep by intracranial inoculation compared to classical scrapie. J Vet Diagn Invest 2021 May 28;33(4):711–20. View at Sage 

Factors that have contributed to the continued geographic spread of CWD in the United States and globally: 

  • Movement or importation of live, infected animals 1,2,3
  • Fence-line contact between captive and free-ranging animals 4
  • Baiting and feeding practices 3 
  • Transport of CWD-positive carcasses or contaminated materials from high-risk areas 5,6
  • Natural predator and scavenger activities 7,8

It is essential to follow state, provincial, and territorial regulations regarding the movement of live cervids, transportation and disposal of carcasses, and baiting or feeding to help prevent further CWD spread. In addition, implementing uniform policies and regulations based on the best practices for CWD management would help prevent confusion caused by variation in regulations between jurisdictions. 

References

1. Edmunds DR, Kauffman MJ, Schumaker BA, et al. Chronic wasting disease drives population decline of white-tailed deer. PLOS One 2016 Aug 30;11(8):e0161127. View at PLOS One

2. Kim TY, Shon HJ, Joo YS, et al. Additional cases of chronic wasting disease in imported deer in Korea. J Vet Med Sci 2005 Aug;67(8):753–59. View at J Vet Med Sci

3. Gillin C, Mawdsley J. AFWA Technical Report on Best Management Practices for Surveillance, Management and Control of Chronic Wasting Disease. Association of Fish and Wildlife Agencies 2018. View at AFWA 

4. VerCauteren KC, Lavelle MJ, Seward NW, et al. Fence-Line Contact Between Wild and Farmed Cervids in Colorado: Potential for Disease Transmission. USDA Wildlife Services - Staff Publications 2007 Jun 25;722. View at UNL 

5. Pritzkow S, Morales R, Moda F, et al. Grass plants bind, retain, uptake, and transport infectious prions. Cell Rep 2015 May 26;11(8):1168–75. View at Cell Rep 

6. Zabel M, Ortega A. The ecology of prions. Microbiol Mol Biol Rev 2017 May 31;81(3):e00001-17. View at Microbiol Mol Biol Rev 

7. Fischer JW, Phillips GE, Nichols TA, et al. Could avian scavengers translocate infectious prions to disease-free areas initiating new foci of chronic wasting disease? Prion 2013 Jul 1;7(4):263–6. View at Prion 

8. Nichols TA, Fischer JW, Spraker TR, et al. CWD prions remain infectious after passage through the digestive system of coyotes (Canis latrans). Prion 2015 Dec 4;9(5):367–75. View at Prion

The period for which CWD prions can remain viable in the environment is unknown, but they have been shown to do so for at least 2 years.1 However, scrapie, a similar prion that infects goats and sheep, has been shown to remain infectious for at least 16 years.2 Evidence suggests that the period that prions can remain infectious in the environment may be influenced by environmental factors such as soil content. CWD prions that bind to the clay minerals montmorillonite, kaolinite, or quartz appear to be very stable and more infectious than unbound prions.3,4 In contrast, humic acid, commonly found in soil organic matter, has been shown to reduce the infectivity of CWD prions.5 Other factors like weather conditions and prion strain further complicate the ability to determine length of infectivity, and continued research on the topic is warranted.6

References

1. Zabel M, Ortega A. The ecology of prions. Microbiol Mol Biol Rev 2017 May 31;81(3):e00001-17. View at Microbiol Mol Biol Rev 

2. Georgsson G, Sigurdarson S, Brown P. Infectious agent of sheep scrapie may persist in the environment for at least 16 years. J Gen Virol 2006 Dec;87(12):3737–40. View at J Gen Virol

3. Kuznetsova A, McKenzie D, Ytrehus B, et al. Movement of chronic wasting disease prions in prairie, boreal and alpine soils. Pathogens 2023 Feb 7;12(2):269. View at MDPI

4. Johnson CJ, Pedersen JA, Chappell RJ, et al. Oral transmissibility of prion disease Is enhanced by binding to soil particles. PLOS Pathog 2007 Jul;3(7):e93. View at PLOS Pathog 

5. Kuznetsova A, Cullingham C, McKenzie D, et al. Soil humic acids degrade CWD prions and reduce infectivity. PLOS Pathog 2018 Nov 29;14(11):e1007414

View at PLOS Pathog 

6. Yuan Q, Telling G, Bartelt-Hunt SL, et al. Dehydration of prions on environmentally relevant surfaces protects them from inactivation by freezing and thawing. J Virol 2018 Mar 28;92(8):e02191-17 

View at ASM

Public Health and CWD

Thus far, there has not been clear, compelling evidence of direct CWD transmission to humans. A 2006 study assessed the relative risk of Creutzfeldt-Jakob disease (CJD), a prion-associated neurodegenerative disorder in humans, among CWD-endemic areas of Colorado and found no significant increase when compared with nonendemic areas.1 Data on this question are insufficient, and several unknown variables include increasing human exposure, prolonged incubation periods often associated with prion disease transmission, and emerging strain diversity.2 After the bovine spongiform encephalopathy (BSE), colloquially called “mad cow disease,” outbreak, the time between initial consumption of contaminated meat to disease identification in humans was 10 years or longer.3 

Epidemiologic follow-up is challenged by the extended incubation period of prion diseases, and continued research, including observational and in vitro (ie, outside of a living animal) and in vivo (ie, in a living animal) studies, is necessary to assess the risk that CWD might pose to humans. Also, the maintenance of a robust human prion disease surveillance system is essential for identifying and investigating human prion diseases. Meanwhile, the public should use precautions and take steps to avoid exposure to CWD prions whenever possible. 

References

1. Mawhinney S, Pape WJ, Forster JE, et al. Human prion disease and relative risk associated with chronic wasting disease. Emerg Infect Dis 2006 Oct;12(10):1527–35. View at CDC

2. Tranulis MA, Tryland M. The zoonotic potential of chronic wasting disease: A review. Foods 2023 Feb 15;12(4):824. View at MDPI

3. Watson N, Brandel JP, Green A, et al. The importance of ongoing international surveillance for Creutzfeldt-Jakob disease. Nat Rev Neurol 2021 May 10;17(6):362–79. View at Nat Rev

Multiple epidemiologic, in vitro (ie, testing outside of a living animal), and in vivo (ie, testing using an animal model) studies have attempted to assess the integrity of the CWD species barrier between cervids and humans.1 Epidemiologic studies have attempted to determine any occurrence of human prion disease resulting from exposure to CWD prions. No cases of human prion disease have been linked to exposure to CWD prions, but maintaining comprehensive surveillance systems and conducting epidemiologic studies are critical for identifying associations between exposure to CWD prions and the development of human prion-related disease.

In vitro species barrier studies expose the normal human prion protein (PrPc) to CWD prions outside a living organism and measure whether human PrPc is converted. While most in vitro studies have found that conversion was possible, the efficiency is highly variable and may be influenced by different experimental conditions, which obscures the interpretation and assessment of real-world risk.1,2,3 

In vivo studies determine if CWD infection occurs in live animals after exposure to CWD prions. Such studies have often involved using either transgenic mice or nonhuman primates as a model. Studies using humanized transgenic mice as a model of potential CWD infection have so far suggested that a robust CWD species barrier may exist between cervids and humans, but the zoonotic potential of CWD could increase over time as new strains emerge.3,4,5,6 Several studies using nonhuman primates have provided conflicting results between the use of squirrel monkeys and cynomolgus macaques, the latter of which is more genetically similar to humans.7 Squirrel monkeys appear to be highly susceptible to CWD infection following either oral or intracerebral exposure, while no peer-reviewed evidence of infection in cynomolgus macaques has been published.1,8

Major limitations in both in vitro and in vivo studies make the assessment of risk to human health challenging.1 In vitro studies can provide timely insight into the species barrier, but they cannot represent the complexities within a living organism. Also, variations in methodology complicate comparisons of results. In vivo studies of prion diseases are expensive and lengthy owing to the ecology of prion diseases and their prolonged incubation. While in vivo studies can address factors such as the influence of exposure routes, prion interactions taking place in animals might not equate to those in humans. This difference is important in prion studies, in which one polymorphic variation in the host PRNP gene can play a role in susceptibility to infection.6 In vitro and in vivo species barrier studies are important, though they have not provided definitive answers about whether CWD will infect humans or other non-cervid animals.

References

1. Waddell L, Greig J, Mascarenhas M, et al. Current evidence on the transmissibility of chronic wasting disease prions to humans—A systematic review. Transbound Emerg Dis 2018 Feb;65(1):37–49. View at Transbound Emerg Dis 

2. Barria MA, Libori A, Mitchell G, et al. Susceptibility of human prion protein to conversion by chronic wasting disease prions. Emerg Infect Dis 2018 Aug;24(8):1482–9. View at Emerg Infect Dis

3. Morales R. Prion strains in mammals: Different conformations leading to disease. PLOS Pathog 2017 Jul 6;13(7):e1006323. View at PLOS Pathog 

4. Race B, Williams K, Chesebro B. Transmission studies of chronic wasting disease to transgenic mice overexpressing human prion protein using the RT-QuIC assay. Vet Res 2019;50:6. View at Vet Res 

5. Wilson R, Plinston C, Hunter N, et al. Chronic wasting disease and atypical forms of bovine spongiform encephalopathy and scrapie are not transmissible to mice expressing wild-type levels of human prion protein. J Gen Virol 2012 Jul;93(Pt 7):1624–9. View at J Gen Virol 

6. Herbst A, Duque Velasquez C, Triscott E, et al. Chronic wasting disease prion strain emergence and host range expansion. Emerg Infect Dis 2017 Sep;23(9):1598–1600. View at Emerg Infect Dis

7. Hayasaka K, Gojobori T, Horai S. Molecular phylogeny and evolution of primate mitochondrial DNA. Mol Biol Evol 1988 Nov 1;5(6):626–44. View at Oxford 

8. Marsh RF, Kincaid AE, Bessen RA, et al. Interspecies transmission of chronic wasting disease prions to squirrel monkeys (Saimiri sciureus). J Virol 2005 Nov;79(21):13794–6. View at J Virol

Since its discovery in 1967, CWD has spread significantly, both geographically and in prevalence, among free-ranging cervid populations.1 The trend of rising CWD prevalence is paralleled by increasing human exposure (eg, consumption of venison, field-dressing carcasses) to infectious prions.2 Given that human exposure to CWD prions has greatly increased in just the past 10 years, and the incubation in humans may be 10 years or longer (based on BSE and vCJD), it is not possible to determine if CWD-linked prion infections in humans have occurred but have not yet resulted in clinical disease. 

We now understood that as CWD continues spreading in cervids, the prion pathogen is evolving, and novel strains are emerging that may have unique capacities for interspecies transmission.3,4,5,6 Current evidence supports that novel CWD strains are formed when the prion adapts to a new species and/or infects a cervid with genetic variations in its prion protein gene (ie, PRNP) .6,7,8 Therefore, as CWD continues to persist in the environment and more animals are exposed to the prions, the origination of new strains will become more common.6 This scenario is especially concerning for CWD, which may adapt to a host more readily than BSE.10 Also, studies have provided evidence that CWD prions in the neural tissue of an infected cervid can be distinct from CWD prions in the extraneural tissue.10 These same data suggest that prions in extraneural tissue may have a higher zoonotic potential than prions in neural tissue.2

While it is reassuring that no cases of clinical human prion infection have been linked to human exposure to CWD, the apparent CWD species barrier between cervids and humans should be viewed as dynamic. It is not yet known whether CWD will cause human infections, but the growing spread and emergence of unique CWD strains in cervids may indicate that the zoonotic potential of CWD is increasing. Continued research, including observational, in vitro, and in vivo studies, is necessary to assess the risk that CWD might pose to humans. Meanwhile, those who come into contact with infected cervids should use precautions and take steps to avoid exposure to CWD prions whenever possible.

References

1. Rivera NA, Brandt AL, Novakofski JE, et al. Chronic wasting disease in cervids: Prevalence, impact and management strategies. Vet Med 2019 Oct 2;10:123–39. View at DovePress 

2. Osterholm MT, Anderson CJ, Zabel MD, et al. Chronic wasting disease in cervids: Implications for prion transmission to humans and other animal species. MBio 2019 Jul;10(4):e01091-19. View at MBio 

3. Morales R. Prion strains in mammals: Different conformations leading to disease. PLOS Pathog 2017 Jul 6;13(7):e1006323. View at PLOS Pathog  

4. Duque Velasquez C, Kim C, Herbst A, et al. Deer prion proteins modulate the emergence and adaptation of chronic wasting disease strains. J Virol 2015 Dec;89(24):12362–73. View at J Virol

5. Herbst A, Duque Velasquez C, Triscott E, et al. Chronic wasting disease prion strain emergence and host range expansion. Emerg Infect Dis 2017 Sep;23(9):1598–1600. View at Emerg Infect Dis

6. Otero A, Duque Velasquez C, McKenzie D, et al. Emergence of CWD strains. Cell Tissue Res 2023;392(1):135-48. View at Springer 

7. Bian J, Christiansen JR, Moreno JA, et al. Primary structural differences at residue 226 of deer and elk PrP dictate selection of distinct CWD prion strains in gene-targeted mice. PNAS 2019 May 30;201903947. View at PNAS 

8. Hannaoui S, Schatzl HM, Gilch S. Chronic wasting disease: Emerging prions and their potential risk. PLOS Pathog 2017 Nov 2;13(11):e1006619. View at PLOS Pathog

9. Davenport KA, Mosher BA, Brost BM, et al. Assessment of chronic wasting disease prion shedding in deer saliva with occupancy modeling. J Clin Microbiol 2017 Dec 26;56(1):e01243-17. View at J Clin Microbiol

10. Béringue V, Herzog L, Jaumain E, et al. Facilitated cross-species transmission of prions in extraneural tissue. Science 2012 Jan 27;335(6067):472–5. View at Science

The bedrock mission of public health is to prevent disease and promote health. When solid, evidence-based science is available, people's health can be protected through preventive action. In the case of CWD, in which there is inconclusive evidence-based science but some data supporting the potential for increased risk, the underlying premise of public health is to base statements and actions on the precautionary principle. In December 2014, Peter Sandman, PhD, and Jody Lanard, MD, world experts on risk communication, wrote an article on crisis communication lessons from the 2014 Ebola outbreak in West Africa.1 The article focused on four main crisis communication errors that public health officials and government leaders made during the outbreak: (1) over-reassurance; (2) overconfidence and absolutism instead of acknowledgement of uncertainties about Ebola science; (3) mischaracterizing the public as panicking; and (4) ridiculing the public’s Ebola fears instead of accepting and guiding them. These same lessons hold true for CWD risk communication.

Although no human infections from CWD have been documented, current data support that the risk is not zero and may be increasing with time.2 As CWD continues to spread geographically and the prevalence increases among cervid populations in endemic areas, human exposure to CWD prions increases. The current data and unknowns surrounding CWD warrant precautionary measures to limit human exposure to CWD while allowing people to hunt and to support hunting as a critical population-management tool, reducing the risk of cervid-to-cervid CWD transmission. CWD is a complicated public health issue, and it is essential to remain educated and up to date to provide high-quality of risk communication. 

References 

1. Kupferschmidt K. How to talk to the public about ebola: Five tips from risk communication experts. Science 2014 Oct. View at Science 

2. Osterholm MT, Anderson CJ, Zabel MD, et al. Chronic wasting disease in cervids: Implications for prion transmission to humans and other animal species. MBio 2019 Jul;10(4):e01091-19. View at MBio

Given recent studies suggesting a risk of CWD prion transmission to humans, it is prudent to adopt a precautionary approach to human consumption of prion-infected venison. The US Geological Survey (USGS) maintains an updated map showing the distribution of CWD in North America.1 Maps of CWD in Norway and Sweden are also available.2,3 As with other hunting regulations, strategies for CWD management vary among states and provinces. Visiting an appropriate wildlife agency website can provide specific information on CWD, local regulations, and testing procedures if you hunt in an area known to have CWD. 

CDC recommendations when hunting in an area with CWD4:  

  • Do not shoot, handle, or eat meat from cervids that look sick, are acting strangely, or are found dead (roadkill).
  • When field-dressing a cervid:
    • Wear latex or rubber gloves when dressing the animal or handling the meat.
    • Minimize how much you handle the organs of the animal, particularly the brain and spinal cord tissues.
    • Do not use household knives or other kitchen utensils for field dressing.
  • Check state wildlife and public health guidance to see whether testing of animals is recommended or required. Recommendations vary by state, but information about testing is available from many state wildlife agencies.
  • Strongly consider having the cervid tested for CWD before you eat the meat.
  • If you have your cervid commercially processed, consider asking that your animal be processed individually to avoid mixing meat from multiple animals.
  • If your animal tests positive for CWD, do not eat the meat.

Information and resources from the CWD Alliance and the Minnesota Department of Natural Resources provide more specific information for best practices when processing and handling harvested cervids.5,6

References

1. National Wildlife Health Center. Distribution of Chronic Wasting Disease in North America. USGS 2023 Aug 10. View at USGS  

2. Norwegian Institute for Nature Research. Chronic wasting disease (CWD) - information in English. Hjortevilt 2023 Apr 20. View at Hjortevilt 

3. National Veterinary Institute. Map of chronic wasting disease (CWD). SVA 2023 Aug 2. View at SVA 

4. Centers for Disease Control and Prevention. CWD Prevention. US Department of Health and Human Services 2021 Oct 18. View at CDC 

5. CWD Alliance. Recommendations for Hunters. CWD-Info 2023. View at CWD Alliance 

6. MN DNR. Chronic wasting disease management. Minnesota Department of Natural Resources 2023 Aug 1. View at MN DNR

CWD is an important cervid health issue that can harm free-ranging and captive populations over time.1,2,3 While controlling the spread of CWD may be challenging and expensive, current evidence indicates that science-based efforts to limit the transmission of CWD are necessary for the long-term well-being of cervids and the greater wildlife ecology.4

Serious consequences after CWD transmission to other species, including humans or livestock, represent another important aspect of CWD and its continued spread. Some prion diseases, such as BSE and kuru, have severely affected human health and required immediate interventions to prevent further harm.5 It is not yet known whether CWD can infect livestock animals or humans. However, taking steps to limit the transmission of CWD among cervids and reduce human exposure to CWD prions is critical.

CWD also may be cause for concern because of its potential to stifle hunter participation. Hunting practices are important for wildlife conservation and in limiting the prevalence of CWD. However, data indicate that permit demand may be decreasing in areas with confirmed cases of the disease.6,7 To illustrate, a longitudinal study in Colorado found that areas with the largest declines in hunting license sales were associated with the largest increases in CWD-positive adult male deer.8 Gradual decreases in hunter participation would further complicate efforts to control CWD, lead to economic losses, and challenge the model of conservation in North America.9 Moreover, the ongoing spread of CWD could limit state wildlife conservation funding, which is supported largely by deer and elk hunters.

Last, CWD could cause widespread economic loss. Experimental studies have shown that CWD prions can bind to or be taken up into plants, including alfalfa, corn, tomatoes, and wheat, and can remain infectious.10,11 These findings could impinge on trade between countries with and without CWD. For instance, Norway recently placed restrictions on hay and straw exports from North America, requiring a certified veterinarian to confirm that the hay and/or straw is from an area where CWD has not been detected.12 

References

1. Gilbertson MLJ, Brandell EE, Pinkerton ME, et al. Cause of death, pathology, and chronic wasting disease status of white-tailed deer (Odocoileus virginianus) mortalities In Wisconsin, USA. J Wildl Dis 2022 Oct 26;58(4):803–15. View at J Wildl Dis

2. DeVivo MT, Edmunds DR, Kauffman MJ, et al. Endemic chronic wasting disease causes mule deer population decline in Wyoming. PLOS One 2017 Oct 19;12(10):e0186512. View at PLOS One 

3. Miller MW, Wild MA. Epidemiology of chronic wasting disease in captive white-tailed and mule deer. J Wildl Dis 2004 Apr 1;40(2):320–7. View at J Wildl Dis

4. Escobar LE, Pritzkow S, Winter SN, et al. The ecology of chronic wasting disease in wildlife. Biological reviews of the Cambridge Philosophical Society 2019 Nov 21;95(2):393–408. View at Wiley 

5. Osterholm MT, Anderson CJ, Zabel MD, et al. Chronic wasting disease in cervids: Implications for prion transmission to humans and other animal species. MBio 2019 Jul;10(4):e01091-19. View at MBio

6. Conner MM, Wood ME, Hubbs A, et al. The relationship between harvest management and chronic wasting disease prevalence trends in western mule deer (Odocoileus hemionus) herds. J Wildl Dis 2021 Oct 11;57(4):831–43. View at J Wildl Dis

7. Erickson D, Reeling C, Lee JG. The effect of chronic wasting disease on resident deer hunting permit demand in Wisconsin. Animals 2019 Dec 7;9(12):1096. View at MDPI

8. Miller MW, Runge JP, Holland AA, et al. Hunting pressure modulates prion infection risk in mule deer herds. J Wildl Dis 2020 Oct 1;56(4):781–90. View at J Wildl Dis 

9. Durbian F. National Elk Refuge response Strategy for the presence of chronic wasting disease in the Jackson elk herd. US Fish and Wildlife Service 2021. View at US FWS 

10. Pritzkow S, Morales R, Moda F, et al. Grass plants bind, retain, uptake, and transport infectious prions. Cell Rep 2015 May 26;11(8):1168–75. View at Cell Rep 

11. Rasmussen J, Gilroyed BH, Reuter T, et al. Can plants serve as a vector for prions causing chronic wasting disease? Prion 2014 Feb 7;8(1):136–42. View at Prion 

12. World Trade Organization. Regulation concerning additional requirements for imported hay and straw for animal feed. World Trade Organization 2018. View at WTO

The Minnesota Center for Prion Research & Outreach (MNPRO) at the University of Minnesota has published a fact sheet on this topic here.

 

To read more answers to frequently asked questions about CWD, visit the FAQ sections of the CWD Alliance, CFIA, and USGS websites. 

Health professionals with questions about CWD can visit the CWD section of the CDC website for more information. Other helpful resources include the Center for Food Security and Public Health at Iowa State University’s CWD factsheet and the Montana Department of Public Health and Human Services' list of FAQs for healthcare providers. To combat CWD misinformation, the Theodore Roosevelt Conservation Partnership wrote an article that featured three CWD experts responding to skeptics.

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