----- Original Message -----
From: "Terry S. Singeltary Sr." <[email protected]>
To: <[email protected]>
Sent: Thursday, September 01, 2005 4:31 PM
Subject: Chronic Wasting Disease of Elk: Transmissibility to Humans Examined by Transgenic Mouse Models
From: TSS ()
Subject: Chronic Wasting Disease of Elk: Transmissibility to Humans Examined by Transgenic Mouse Models
Date: September 1, 2005 at 2:20 pm PST
The Journal of Neuroscience, August 31, 2005, 25(35):7944-7949; doi:10.1523/JNEUROSCI.2467-05.2005
Neurobiology of Disease
Chronic Wasting Disease of Elk: Transmissibility to Humans Examined by Transgenic Mouse Models
Qingzhong Kong,1 Shenghai Huang,1 Wenquan Zou,1 Difernando Vanegas,1 Meiling Wang,1 Di Wu,1 Jue Yuan,1 Mengjie Zheng,1 Hua Bai,1 Huayun Deng,2 Ken Chen,3 Allen L. Jenny,4 Katherine O'Rourke,5 Ermias D. Belay,6 Lawrence B. Schonberger,6 Robert B. Petersen,1 Man-Sun Sy,1 Shu G. Chen,1 and Pierluigi Gambetti1
Departments of 1Pathology and 2Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106, 3Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461, 4National Veterinary Services Laboratories, United States Department of Agriculture, Ames, Iowa 50010, 5Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Pullman, Washington 99164, and 6Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333
Chronic wasting disease (CWD), a prion disease affecting free-ranging and captive cervids (deer and elk), is widespread in the United States and parts of Canada. The large cervid population, the popularity of venison consumption, and the apparent spread of the CWD epidemic are likely resulting in increased human exposure to CWD in the United States. Whether CWD is transmissible to humans, as has been shown for bovine spongiform encephalopathy (the prion disease of cattle), is unknown. We generated transgenic mice expressing the elk or human prion protein (PrP) in a PrP-null background. After intracerebral inoculation with elk CWD prion, two lines of "humanized" transgenic mice that are susceptible to human prions failed to develop the hallmarks of prion diseases after >657 and >756 d, respectively, whereas the "cervidized" transgenic mice became infected after 118–142 d. These data indicate that there is a substantial species barrier for transmission of elk CWD to humans.
Key words: chronic wasting disease; CWD; transmissibility to humans; transgenic mice; prion; cervids; deer; elk; species barrier
Chronic Wasting Disease and Potential Transmission to Humans
Ermias D. Belay,* Ryan A. Maddox,* Elizabeth S. Williams,† Michael W. Miller,‡ Pierluigi Gambetti,§ and Lawrence B. Schonberger*
*Centers for Disease Control and Prevention, Atlanta, Georgia, USA; †University of Wyoming, Laramie, Wyoming, USA; ‡Colorado Division of Wildlife, Fort Collins, Colorado, USA; and §Case Western Reserve University, Cleveland, Ohio, USA
Suggested citation for this article: Belay ED, Maddox RA, Williams ES, Miller MW, Gambetti P, Schonberger LB. Chronic wasting disease and potential transmission to humans. Emerg Infect Dis [serial on the Internet]. 2004 Jun [date cited]. Available from: http://www.cdc.gov/ncidod/EID/vol10no6/03-1082.htm
Chronic wasting disease (CWD) of deer and elk is endemic in a tri-corner area of Colorado, Wyoming, and Nebraska, and new foci of CWD have been detected in other parts of the United States. Although detection in some areas may be related to increased surveillance, introduction of CWD due to translocation or natural migration of animals may account for some new foci of infection. Increasing spread of CWD has raised concerns about the potential for increasing human exposure to the CWD agent. The foodborne transmission of bovine spongiform encephalopathy to humans indicates that the species barrier may not completely protect humans from animal prion diseases. Conversion of human prion protein by CWD-associated prions has been demonstrated in an in vitro cell-free experiment, but limited investigations have not identified strong evidence for CWD transmission to humans. More epidemiologic and laboratory studies are needed to monitor the possibility of such transmissions.
The lack of evidence of a link between CWD transmission and unusual cases of CJD, despite several epidemiologic investigations, and the absence of an increase in CJD incidence in Colorado and Wyoming suggest that the risk, if any, of transmission of CWD to humans is low. Although the in vitro studies indicating inefficient conversion of human prion protein by CWD-associated prions raise the possibility of low-level transmission of CWD to humans, no human cases of prion disease with strong evidence of a link with CWD have been identified. However, the transmission of BSE to humans and the resulting vCJD indicate that, provided sufficient exposure, the species barrier may not completely protect humans from animal prion diseases. Because CWD has occurred in a limited geographic area for decades, an adequate number of people may not have been exposed to the CWD agent to result in a clinically recognizable human disease. The level and frequency of human exposure to the CWD agent may increase with the spread of CWD in the United States. Because the number of studies seeking evidence for CWD transmission to humans is limited, more epidemiologic and laboratory studies should be conducted to monitor the possibility of such transmissions. Studies involving transgenic mice expressing human and cervid prion protein are in progress to further assess the potential for the CWD agent to cause human disease. Epidemiologic studies have also been initiated to identify human cases of prion disease among persons with an increased risk for exposure to potentially CWD-infected deer or elk meat (47). If such cases are identified, laboratory data showing similarities of the etiologic agent to that of the CWD agent would strengthen the conclusion for a causal link. Surveillance for human prion diseases, particularly in areas where CWD has been detected, remains important to effectively monitor the possible transmission of CWD to humans. Because of the long incubation period associated with prion diseases, convincing negative results from epidemiologic and experimental laboratory studies would likely require years of follow-up. In the meantime, to minimize the risk for exposure to the CWD agent, hunters should consult with their state wildlife agencies to identify areas where CWD occurs and continue to follow advice provided by public health and wildlife agencies. Hunters should avoid eating meat from deer and elk that look sick or test positive for CWD. They should wear gloves when field-dressing carcasses, bone-out the meat from the animal, and minimize handling of brain and spinal cord tissues. As 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.
Environmental Sources of Prion Transmission in Mule Deer
Michael W. Miller,* Elizabeth S. Williams,† N. Thompson Hobbs,‡ and Lisa L. Wolfe*
*Colorado Division of Wildlife, Fort Collins, Colorado, USA; †University of Wyoming, Laramie, Wyoming, USA; and ‡Colorado State University, Fort Collins, Colorado, USA
Suggested citation for this article: Miller MW, Williams ES, Hobbs NT, Wolfe LL. Environmental sources of prion transmission in mule deer. Emerg Infect Dis [serial on the Internet]. 2004 Jun [date cited]. Available from: http://www.cdc.gov/ncidod/EID/vol10no6/04-0010.htm
Whether transmission of the chronic wasting disease (CWD) prion among cervids requires direct interaction with infected animals has been unclear. We report that CWD can be transmitted to susceptible animals indirectly, from environments contaminated by excreta or decomposed carcasses. Under experimental conditions, mule deer (Odocoileus hemionus) became infected in two of three paddocks containing naturally infected deer, in two of three paddocks where infected deer carcasses had decomposed in situ ≈1.8 years earlier, and in one of three paddocks where infected deer had last resided 2.2 years earlier. Indirect transmission and environmental persistence of infectious prions will complicate efforts to control CWD and perhaps other animal prion diseases.
Prions cannot be directly demonstrated in excreta or soil. However, CWD infection–specific protease-resistant prion protein (PrPCWD) accumulates in gut-associated lymphoid tissues (e.g., tonsils, Peyer patches, and mesenteric lymph nodes) of infected mule deer (11,17,22), which implicates alimentary shedding of the CWD agent in both feces and saliva (10,11,17). Because PrPCWD becomes progressively abundant in nervous system and lymphoid tissues through the disease course (11), carcasses of deer succumbing to CWD also likely harbor considerable infectivity and thus serve as foci of infection. We could not determine the precise mechanism for CWD transmission in excreta-contaminated paddocks, but foraging and soil consumption seemed most plausible. Deer did not actively consume decomposed carcass remains, but they did forage in the immediate vicinity of carcass sites where a likely nutrient flush (23) produced lush vegetation (Figure).
Our findings show that environmental sources of infectivity may contribute to CWD epidemics and illustrate the potential complexity of such epidemics in natural populations. The relative importance of different routes of infection from the environment cannot be discerned from our experiment, but each could play a role in sustaining natural epidemics. Although confinement likely exaggerated transmission probabilities, conditions simulated by this experiment do arise in the wild. Mule deer live in established home ranges and show strong fidelity to historic home ranges (24-26). As a result of such behavior, encounters with contaminated environments will occur more frequently than if deer movements were random. Feces and carcass remains are routinely encountered on native ranges, thus representing natural opportunities for exposure. Social behavior of deer, particularly their tendency to concentrate and become sedentary on their winter range, also may increase the probability of coming into contact with sources of infection in their environment.
The ability of the CWD agent to persist in contaminated environments for >2 years may further increase the probability of transmission and protract epidemic dynamics (8). Because infectivity in contaminated paddocks could not be measured, neither the initial levels nor degradation rate of the CWD agent in the environment was estimable. However, the observed persistence of the CWD agent was comparable to that of the scrapie agent, which persisted in paddocks for ≈1 to 3 years after removal of naturally infected sheep (7). Similarities between the CWD and scrapie agents suggest that environmental persistence may be a common trait of prions. Whether persistence of the BSE prion in contaminated feed production facilities or in environments where cattle reside contributed to BSE cases in the United Kingdom after feed bans were enacted (27) remains uncertain but merits further consideration.
Indirect transmission and environmental persistence of prions will complicate efforts to control CWD and perhaps other animal prion diseases. Historically, control strategies for animal prion diseases have focused on infected live animals as the primary source of infection. Although live deer and elk represent the most plausible mechanism for geographic spread of CWD, our data show that environmental sources could contribute to maintaining and prolonging local epidemics, even when all infected animals are eliminated. Moreover, the efficacy of various culling strategies as control measures depends in part on the rates at which the CWD agent is added to and lost from the environment. Consequently, these dynamics and their implications for disease management need to be more completely understood.
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) first diagnosed in a research facility in Colorado in 1967. It has since been diagnosed in wild mule deer, white-tailed deer and elk. CWD has been discovered in free-ranging cervids in Colorado, New Mexico, New York, Nebraska, South Dakota, Wisconsin, Wyoming and the Canadian province of Saskatchewan. The disease has also been diagnosed in captive cervids in Colorado, Nebraska, New York, South Dakota, Montana, Oklahoma, Kansas and Saskatchewan and Alberta, Canada.
CWD is a neurologic disease of elk and deer characterized by loss of body condition, behavioral abnormalities, and always resulting in death. Currently, there is no reliable live animal testing available for diagnosing CWD, nor is there a treatment available.
Since free-ranging deer and elk in north-central Colorado and southeast Wyoming have been surveyed for CWD, the annual prevalence rates have ranged from 1 to 15%. The overall prevalence rate of CWD in the endemic areas is approximately 5% in mule deer and less than 1% in elk. Prevalence in some mule deer hunt areas is as high as 15%. The prevalence rate is greater in deer 2 ½ years and older and in elk 1 ½ years and older. There does not appear to be a gender prevalence difference. Prevalence rates in other CWD positive states have been extremely low.
Prions are the disease-causing agents associated with CWD and all of the TSE diseases. Prions are mutant versions of proteins that occur normally in the body. The mutant proteins are found on the membranes of nerve cells (neurons) and have the capabilities of transforming other proteins into their own image. Prions are not sensitive to routine sterilization techniques. The only effective techniques are those used to break down proteins such as dilute bleach solution, formic acid (brain tissue preparations for 1 hour), and incineration (at least 1,500 degrees F). They are not destroyed by cooking, formaldehyde, alcohol, or UV light.
CWD in deer and elk is characterized by loss of body condition (emaciation), drooling, behavioral abnormalities, and death.
There is currently no laboratory test available for the disease in a live animal therefore CWD is diagnosed through various techniques on dead animals. The screening test used by the Michigan Department of Natural Resources (MDNR) is Bio-Rad Laboratories- ELISA, a CWD assay (performed by Michigan State University's Diagnostic Center for Population and Animal Health, DCPAH). The ELISA will detect abnormal prion proteins if they are present in a sample. If inconclusive results are received for a sample twice, it is given an immunohistologic examination to confirm a result.
There is no treatment for a deer or elk that has CWD. An animal displaying clinical signs consistent with CWD should be euthanized. Removing the animal may help prevent the spread of the disease.
Transmission: Animal to Animal
Transmission of CWD is possible in species with closely related proteins, thereby being able to exchange prions and cause disease. It is not likely to jump the species barrier. There is no evidence at this time that CWD can be naturally transmitted to livestock or animals other than deer and elk. In deer and elk, the causal agent of CWD is transmissible from infected to uninfected individuals. Both circumstantial and experimental evidence implicates an animal to animal form of transmission. This occurs via horizontal or lateral (contact between adult animal and adult animal, contamination of feed or water sources with saliva, urine, and/or feces, or contact with an infected facility or area), and more rarely as vertical or maternal (mother to offspring via contact).
Once natural transmission occurs, a minimum incubation period (the time from infection to observance of clinical signs) of 18 months is required between exposure to the causal agent and development of the disease. In captive cervid herds a minimal incubation period of 18 to 20 months for mule deer and 18 to 36 months for elk was observed.
Transmission: Animal to Human
To date, there is no evidence that CWD can be naturally transmitted to humans or to animals other than deer and elk. There is no evidence that the agent that causes CWD occurs in the meat. Proteins differ from one species to another therefore prions are unlikely to prosper in a new species. There is a "substantial barrier" to CWD transmission between animals and people.
Providing a supplemental food or water source could increase the likelihood of transmitting this as well as other diseases. It is suspected that if CWD is transmitted horizontally (animal to animal) either by direct contact or environmental contamination then artificial feeding stations for wild cervids could be accelerating the problem on a local level.
Michigan has conducted surveillance for CWD in free-ranging white-tailed deer, elk, moose, and in captive cervids. In 1998, the Michigan Department of Natural Resources (DNR) tested 459 free-ranging white-tailed deer for CWD from the northeast Lower Peninsula. From 2002 to 2004, 16,849 deer, 324 elk, and 20 moose have been tested. In addition, targeted surveillance has been conducted on cervids displaying symptoms consistent with CWD. The majority of samples were obtained through hunter harvested animals. All samples thus far have tested negative for the disease.
Approximately 1,000 deer and 100 elk will be tested for CWD in 2005. The surveillance of free-ranging animals will coordinate with efforts to increase surveillance of privately owned cervids by the Michigan Department of Agriculture (MDA), and must be practical in terms of manpower, money and laboratory capacities.
CWD has not been found in Michigan.
Michigan is taking several steps to prevent the occurrence of CWD in the state. The importation of captive cervids has been banned. A contingency plan to deal with CWD in the event of its discovery in Michigan currently has been developed by state scientists and public health officials. The DNR and MDA are working to increase the level of public education and awareness of the disease through a chronic wasting disease report now available on the Internet, and by educating hunters at public meetings and appearances.
According to public health officials, there is no evidence that CWD can be naturally transmitted to humans, or to animals other than deer and elk. Although there is no evidence that chronic wasting disease affects humans, DNR advises hunters to take simple precautions with the carcass of a deer or elk taken in areas where the disease has been found:
Wear rubber gloves when field dressing carcasses, minimize handling brain or spinal cord tissues and wash hands thoroughly afterwards.
Hunters should bone out carcasses or at least avoid consuming brain, spinal cord, eyes, spleen and lymph nodes of harvested animals.
Hunters should not handle or consume wild animals that appear sick or act abnormally, regardless of the cause.
If a deer or elk is observed exhibiting clinical signs of CWD, particularly poor physical condition, behavioral changes such as loss of fear and incoordination, contact the RAP Line at 1-800-292-7800.
For questions about Chronic Wasting Disease: MDNR Wildlife Disease Laboratory- (517)336-5030
Michigan CWD Surveillance in Free-ranging White-tailed deer and elk.
Michigan has conducted surveillance for CWD on free-ranging white-tailed deer and on captive cervids. In 1998, the Michigan Department of Natural Resources (DNR) tested 459 free-ranging white-tailed deer for CWD from the northeast Lower Peninsula. In addition, targeted surveillance has been conducted on cervids displaying symptoms of CWD. The majority of samples were obtained through hunter harvested animals. All samples thus far have tested negative for the disease.
MI Chronic Wasting Disease Surveillance Map
4,349 Deer, 117 Elk, and 52 target deer (included in total number) were were tested in 2002. All were negative.
The goal for 2003 is 3,720 deer and 125 hunter harvested elk. Targeted Surveillance will continue for deer and elk that exhibit CWD-like symptoms.
----- Original Message -----
From: Lill Juelsen
To: Terry S. Singeltary Sr.
Sent: Friday, September 02, 2005 8:55 AM
Subject: Fw: "Chronic Wasting Disease"
Terry - just got this from a list. Is there a link to more information,
your page again, others I could give them?
anyone ever hear of this? I just got this e-mail from some Michigan group
Forward to a friend:
Please read the following message about chronic wasting disease and take
action by clicking the link below.
Imagine if you will…Chronic Wasting Disease (CWD), the always fatal,
degenerative brain disease of deer and elk (related to mad cow disease),
has been found in Michigan! Now, visualize that deer numbers would be
require to be reduced to near zero in an 11,600 square miles around that
CWD positive case. This picture is not a fairy tale.
Chronic wasting Disease (CWD) is on our doorstep. It has been found in
our neighboring Great Lakes states of Wisconsin and Illinois, and now New
York… we’re nearly surrounded.
Tough policy decisions must be made by Michigan’s lawmakers and natural
resource managers in order to keep this deadly disease from destroying
Michigan’s whitetail deer.
Please click the link below to send a letter to your legislator. Letters
must be received before October 1, 2005. Michigan’s deer need your help!
Deadline for responding:
Please take action by Saturday, October 1, 2005.