Ryan A. Maddox, MPHEpidemiologist

The 60th Annual James Steele Conference on Diseases in Nature Transmissible to Man

June 9-11, 2010

Chronic Wasting Disease:A Zoonotic Disease?

Division of High-Consequence Pathogens and Pathology (proposed)National Center for Emerging and Zoonotic Infectious Diseases

Three Questions

What are transmissible spongiform encephalopathies (TSEs)/ prion diseases?

What is chronic wasting disease (CWD)?

Does CWD transmit to humans?

Transmissible Spongiform Encephalopathies

Sponge-like lesions in the brain tissue of a classic CJD patient

Image courtesy Ermias Belay

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

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

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)

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%)

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.

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.

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.

Transmissible Spongiform Encephalopathies

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

Characteristic Classic CJD Variant CJDMedian age at death 68 years 28 yearsMedian duration of illness 4-5 months 13-14 monthsClinical signs and symptoms

Dementia; early neurologic signs

Prominent psychiatric/behavioral symptoms; painful dyesthesiasis; delayed neurologic signs

Periodic sharp waves on elecroencephalogram

Often present Often absent

“Pulvinar sign” on MRI Not reported Present in >75% of casesPresence of “florid plaques” on neuropathology

Rare or absent Present in large numbers

Immunohistochemical analysis of brain tissue

Variable accumulation

Marked accumulation of protease-resistant prion protein

Presence of agent in lymphoid tissue

Not readily detected

Readily detected

Increased glycoform ratio on immunoblot analysis of protease-resistant prion protein

Not reported Marked accumulation of protease-resistant prion protein

Chronic Wasting Disease (CWD)Captive elk

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.

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.

Chronic Wasting Disease Among Free-Ranging Cervids by County,

United States, June 2010

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

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.

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

Transmission to HumansDoes CWD transmit to humans?

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.

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.

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.

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.

Creutzfeldt-Jakob disease cases investigated for possible causal link

with CWDAdapted 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.

Age Year Codon 129 Western blot

Final diagnosi

s

Ate venison from CWD-

endemic area25 2001 MV Type 1 GSS 102 Yes26 2001 MM Type 2 CJD No28 2002 nd nd GSS 102 No28 1997 MM nd CJD No28 2000 MV Type 1 CJD No30 1999 VV Type 1 CJD No54 2002 VV Type 2 CJD No55 1999 MM Type 1 CJD No61 2000 MM Type 1 CJD Yes63 2002 VV Type 1 CJD No64 2002 MM Type 1 CJD Yes66 2001 MM Type 1 CJD No

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.

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

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.

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

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.

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

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

For more information please contact Centers for Disease Control and Prevention1600 Clifton Road NE, Atlanta, GA 30333Telephone, 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348E-mail: cdcinfo@cdc.gov Web: www.cdc.gov

Questions?

National Center for Emerging and Zoonotic Infectious Diseases

Division of Viral and Rickettsial Diseases

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.