Chronic Wasting Disease: A Zoonotic Disease?

1. Chronic Wasting Disease:A Zoonotic Disease? Ryan A. Maddox, MPH Epidemiologist The 60th Annual James Steele Conference on Diseases in Nature Transmissible to Man June 9-11, 2010 Division of High-Consequence Pathogens and Pathology (proposed) National Center for Emerging and Zoonotic Infectious Diseases

2. Three Questions • What are transmissible spongiform encephalopathies (TSEs)/ prion diseases? • What is chronic wasting disease (CWD)? • Does CWD transmit to humans?

3. Transmissible Spongiform Encephalopathies Sponge-like lesions in the brain tissue of a classic CJD patient Image courtesy Ermias Belay

4. Transmissible Spongiform Encephalopathies/ Prion Diseases • Neurodegenerative diseases • Rapidly progressive, always fatal • Affect humans and animals • Long incubation periods • Brain, spinal cord, and adjacent tissues are considered infectious* • Prion theory widely accepted

5. What causes TSEs? • Prion theory • TSEs result from accumulation in the brain cells of an abnormal, ß-sheet rich isoform of a host-encoded glycoprotein known as the prion protein • Other theories exist

6. Transmissible Spongiform Encephalopathies/Prion Diseases • Human • Kuru • Creutzfeldt-Jakob disease (CJD) • Variant Creutzfeldt-Jakob disease (vCJD) • GSS, FFI, etc. • Animal • Scrapie • Bovine Spongiform Encephalopathy (BSE, “mad cow disease”) • Chronic Wasting Disease (CWD)

7. Creutzfeldt-Jakob Disease (CJD) • Occurs worldwide • Annual incidence (U.S.): ~1 case per million population • Occurs in three different forms: • Sporadic (~85%) • Familial (10-15%) • Iatrogenic (<1%)

8. Bovine Spongiform Encephalopathy (BSE) • First recognized among cattle in the UK in 1986 • Outbreak peaked in 1992-1993 (37,280 UK cases reported in 1992) • Over 184,000 total cases in UK • Many other European countries have reported cases. • 1069 total cases in Portugal, 1005 in France, 760 in Spain, 464 in Switzerland, and 419 in Germany • Japan (36), Israel (1), Canada (18), and USA (3) have also reported cases.

9. Variant Creutzfeldt-Jakob Disease (vCJD) • Identified in the 1990s • 172 cases in UK, 25 cases in France • Canada, Ireland, Italy, Japan, Netherlands, Portugal, Spain, Saudi Arabia, and USA have also reported cases. • The USA vCJD cases (n=3) are believed to have been exposed outside the United States.

10. Variant Creutzfeldt-Jakob Disease (vCJD) • BSE-vCJD link • Epidemiological evidence • Geographical clustering/ absence of vCJD in BSE-free countries • Laboratory evidence • Experimental studies using macaques and mice • Western blot analysis of infecting prions • Variant CJD outbreak demonstrates that animal prion diseases can cause disease in humans.

11. Transmissible Spongiform Encephalopathies Adapted from Belay E., Schonberger L. Variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. Clin Lab Med 2002;22:849-62.

12. Chronic Wasting Disease (CWD) Captive elk

13. Chronic Wasting Disease (CWD) • Known natural hosts • Deer (Odocoileus species) • White-tailed deer • Mule deer • Rocky Mountain elk (Cervus elaphus nelsoni) • Shira’s moose (Alces alces shirasi) • Other cervid species may be susceptible.

14. Chronic Wasting Disease (CWD) • First identified in the late 1960s in captive mule deer in Colorado • Recognized as a TSE in 1978 • First identified in the wild in 1981 (Colorado elk) • Subsequent surveillance found CWD to be endemic in a contiguous region of Colorado and Wyoming. • In the past decade, CWD diagnosed in free-ranging animals in eleven additional states and two Canadian provinces.

15. Chronic Wasting Disease Among Free-Ranging Cervids by County, United States, June 2010

16. Chronic Wasting Disease (CWD) • Most animals die within several months of onset. • Wide range of ages affected • Clinical symptoms • Weight loss over weeks or months • Polydipsia and polyuria • Behavioral changes • Excessive salivation • Difficulty swallowing • Ataxia

17. Chronic Wasting Disease (CWD) • May be highly transmissible within a population • Multiple potential modes of transmission • Direct (animal-to-animal contact) and indirect (causative agent in environment) • Saliva, urine, feces, placentas, decomposing carcasses, etc. • Soil may serve as a reservoir for CWD prions • Infectious agent remains present for years • Eradication is difficult if not impossible.

18. Transmission to Other Animals • CWD does not appear to occur naturally outside the cervid family. • Transmitted experimentally by intracerebral injection to mice, ferrets, mink, squirrel monkeys, cattle, sheep, and goats

19. Transmission to Humans Does CWD transmit to humans?

20. The Problem • The dramatic increase in CWD identification over a wider geographic area, coupled with the implication of another animal prion disease, BSE, as the cause of vCJD in humans, has raised concerns about whether CWD could be a zoonotic disease. • As a result, studies have been conducted or are underway to determine the possibility of CWD transmission to humans.

21. Who is at risk? • Findings from the Foodborne Diseases Active Surveillance Network (FoodNet) 2006-2007 population survey (n=17,372) • 18.5% of respondents had hunted deer or elk. • 1.3% had hunted in a CWD-endemic area (NE Colorado, SE Wyoming, SW Nebraska). • 67.4% had eaten deer or elk meat.

22. Laboratory Findings • Laboratory investigations with transgenic mice have produced reassuring findings that suggest a significant species barrier exists. • Transgenic mice expressing human prion protein have not been found to be susceptible to CWD by intracerebral injection. • CWD has been transmitted orally to squirrel monkeys; however, transmission to cynomolgus macaques, which are evolutionarily closer to humans, has not yet been demonstrated.

23. Epidemiology • Two epidemiological approaches: • Investigate unusual cases of human prion disease in an effort to detect evidence of CWD transmission. • Attempt to identify prion disease cases among persons with an increased risk of exposure to the CWD agent.

24. Creutzfeldt-Jakob disease cases investigated for possible causal link with CWD Adapted from Belay ED, Maddox RA, Williams ES, Miller MW, Gambetti P, Schonberger LB. Chronic wasting disease and potential transmission to humans. Emerg Inf Dis 2004;10:977-84.

25. The Message • Studies investigating unusual cases of human prion disease have so far not detected evidence of CWD transmission. • Investigated cases lack phenotypic similarity and atypical neuropathologic features. • Only two non-familial CJD cases had a history of exposure to venison from known CWD-endemic areas. • One case had deer tested and they were CWD-negative.

26. The National Prion Disease Pathology Surveillance Center (NPDPSC) • Performs analyses of brain tissue from suspected human TSE cases • So far, no unusual prion subtypes identified among CJD patients with reported venison consumption

27. Colorado and Wyoming • CWD has been endemic in parts of Colorado and Wyoming for decades, so the population of these states could potentially be at increased risk of exposure to the infectious agent. • However, the incidence of CJD and the age distribution of CJD decedents in Colorado and Wyoming are similar to those seen in other parts of the United States.

28. Hunter Studies • Collaborative studies underway in Colorado and Wyoming • Data obtained from hunting licenses • Data are cross-checked with the National Death Index (NDI) to assess hunters’ mortality statuses and causes of death. • So far, no excess number of prion disease cases identified among hunters submitted for NDI search • Limitations • Many years of follow-up necessary due to incubation period • Exact hunt area not always known • Hunting license ≠ hunting success • Hunting success ≠ CWD-positive deer

29. Conclusion • Evidence from laboratory and epidemiological studies is reassuring at this point. However… • Because of the long incubation period typically associated with prion diseases, many years of follow-up are necessary to reliably determine any risk of CWD to humans, and continued surveillance for human prion diseases, particularly in states or regions where CWD has been identified, is essential.

30. Conclusion • Hunters should continue to minimize their exposure risk. • Follow advice from public health and wildlife agencies and consult them to identify areas where CWD has been found • Avoid eating meat from cervids that look sick or test positive for CWD • Wear gloves when field-dressing carcasses, bone-out the meat from the animal, and minimize handling of brain and spinal cord tissues • Avoid eating tissues known to harbor the CWD agent (brain, spinal cord, eyes, spleen, tonsils, lymph nodes) from cervids in areas where CWD has been identified

31. Acknowledgements • Centers for Disease Control and Prevention • Dr. Larry Schonberger • Dr. Ermias Belay • Mr. Joe Abrams • National Prion Disease Pathology Surveillance Center • Dr. Pierluigi Gambetti • State public health and wildlife personnel • Mrs. Kelly Weidenbach-Vigil

32. Questions? The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. National Center for Emerging and Zoonotic Infectious Diseases Division of Viral and Rickettsial Diseases