Transcript 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,

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
National Center for Emerging and Zoonotic Infectious Diseases
Division of High-Consequence Pathogens and Pathology (proposed)
Three Questions
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What are transmissible spongiform encephalopathies
(TSEs)/ prion diseases?
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What is chronic wasting disease (CWD)?
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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
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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?
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Prion theory
 TSEs result from accumulation in the brain cells of an abnormal, ßsheet rich isoform of a host-encoded glycoprotein known as the
prion protein
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Other theories exist
Transmissible Spongiform
Encephalopathies/Prion Diseases
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Human
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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)
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Occurs worldwide
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Annual incidence (U.S.): ~1 case per million population
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Occurs in three different forms:
 Sporadic (~85%)
 Familial (10-15%)
 Iatrogenic (<1%)
Bovine Spongiform Encephalopathy (BSE)
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First recognized among cattle in the UK in 1986
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Outbreak peaked in 1992-1993 (37,280 UK cases
reported in 1992)
 Over 184,000 total cases in UK
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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
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Japan (36), Israel (1), Canada (18), and USA (3) have also
reported cases.
Variant Creutzfeldt-Jakob Disease (vCJD)
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Identified in the 1990s
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172 cases in UK, 25 cases in France
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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)
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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
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Variant CJD outbreak demonstrates that animal prion
diseases can cause disease in humans.
Characteristic
Classic CJD
Variant CJD
Median age at death
68 years
28 years
Median duration of illness
4-5 months
13-14 months
Clinical 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 cases
Presence of “florid plaques” on
neuropathology
Rare or absent
Present in large numbers
Immunohistochemical analysis
of brain tissue
Variable accumulation
Marked accumulation of proteaseresistant prion protein
Presence of agent in lymphoid
tissue
Not readily detected
Readily detected
Increased glycoform ratio on
Not reported
Marked accumulation of proteaseSpongiform Encephalopathies
immunoblotTransmissible
analysis of
resistant prion protein
protease-resistant prion protein
Adapted from Belay E., Schonberger L. Variant Creutzfeldt-Jakob
disease and bovine spongiform encephalopathy. Clin Lab Med
2002;22:849-62.
Chronic Wasting Disease (CWD)
Captive elk
Chronic Wasting Disease (CWD)
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Known natural hosts
 Deer (Odocoileus species)
• White-tailed deer
• Mule deer
 Rocky Mountain elk (Cervus elaphus nelsoni)
 Shira’s moose (Alces alces shirasi)
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Other cervid species may be susceptible.
Chronic Wasting Disease (CWD)
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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)
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Most animals die within several months of onset.
Wide range of ages affected
Clinical symptoms
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Weight loss over weeks or months
Polydipsia and polyuria
Behavioral changes
Excessive salivation
Difficulty swallowing
Ataxia
Chronic Wasting Disease (CWD)
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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
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Eradication is difficult if not impossible.
Transmission to Other Animals
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CWD does not appear to occur naturally outside the
cervid family.
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Transmitted experimentally by intracerebral injection
to mice, ferrets, mink, squirrel monkeys, cattle, sheep,
and goats
Transmission to Humans
Does CWD transmit to humans?
The Problem
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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?
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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
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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.
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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
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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.
Age
Year
Codon 129
Western blot
Final
diagnosis
Ate venison from
CWD-endemic area
25
2001
MV
Type 1
GSS 102
Yes
26
2001
MM
Type 2
CJD
No
28
2002
nd
nd
GSS 102
No
28
1997
MM
nd
CJD
No
28
2000
MV
Type 1
CJD
No
30
1999
VV
Type 1
CJD
No
54
2002
VV
Type 2
CJD
No
55
1999
MM
Type 1
CJD
No
61
2000
MM
Type 1
CJD
Yes
63
2002
VV
Type 1
CJD
No
64
2002
MM
Type 1
CJD
Yes
66
2001
MM
Type 1
CJD
No
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.
The Message
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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)
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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
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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
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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
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Limitations
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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
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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
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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
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Centers for Disease Control and Prevention
 Dr. Larry Schonberger
 Dr. Ermias Belay
 Mr. Joe Abrams
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National Prion Disease Pathology Surveillance Center
 Dr. Pierluigi Gambetti
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State public health and wildlife personnel
 Mrs. Kelly Weidenbach-Vigil
Questions?
For more information please contact Centers for Disease Control and Prevention
1600 Clifton Road NE, Atlanta, GA 30333
Telephone, 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348
E-mail: [email protected]
Web: www.cdc.gov
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