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From: TSS ()
Hamir AN, Kunkle RA, Cutlip RC, Miller JM, O'Rourke KI, Williams ES, Miller MW, Stack MJ, Chaplin MJ, Richt JA. National Animal Disease Center, ARS, USDA, 2300 Dayton Avenue, PO Box 70, Ames, IA 50010, USA. This communication reports final observations on experimental transmission of chronic wasting disease (CWD) from mule deer to cattle by the intracerebral route. Thirteen calves were inoculated intracerebrally with brain suspension from mule deer naturally affected with CWD. Three other calves were kept as uninoculated controls. The experiment was terminated 6 years after inoculation. During that time, abnormal prion protein (PrP(res)) was demonstrated in the central nervous system (CNS) of 5 cattle by both immunohistochemistry and Western blot. However, microscopic lesions suggestive of spongiform encephalopathy (SE) in the brains of these PrP(res)-positive animals were subtle in 3 cases and absent in 2 cases. Analysis of the gene encoding bovine PRNP revealed homozygosity for alleles encoding 6 octapeptide repeats, serine (S) at codon 46, and S at codon 146 in all samples. Findings of this study show that although PrP(res) amplification occurred after direct inoculation into the brain, none of the affected animals had classic histopathologic lesions of SE. Furthermore, only 38% of the inoculated cattle demonstrated amplification of PrP(res). Although intracerebral inoculation is an unnatural route of exposure, this experiment shows that CWD transmission in cattle could have long incubation periods (up to 5 years). This finding suggests that oral exposure of cattle to CWD agent, a more natural potential route of exposure, would require not only a much larger dose of inoculum but also may not result in amplification of PrP(res) within CNS tissues during the normal lifespan of cattle. PMID: 15945388 [PubMed - in process] -------------------------------------------------------------------------------- 1 EUROPEAN COMMISSION HEALTH & CONSUMER PROTECTION DIRECTORATE-GENERAL Scientific Steering Committee Chronic wasting disease AND TISSUES THAT MIGHT CARRY A RISK FOR HUMAN FOOD AND ANIMAL FEED CHAINS REPORT snip... 9 3.3.1 Transmissibility of CWD There are certain key questions with respect to transmissibility: 1. Can CWD be transmitted artificially to other species, e.g. sheep, cattle, humans? 2. What is the natural transmissibility to other species ? 3. Can transmissions inform on possible similarities between the agent and BSE, natural scrapie or another know TSE source, or does the evidence suggest a novel source? Several experimental studies to transmit CWD have been conducted, most by intracerebral (IC) inoculation. Whilst such studies provide information on susceptibility to the most efficient means of interspecies transmission, they do not inform on interspecies susceptibility by natural routes of transmission. For the latter oral or other possible natural exposure route studies are considered the most appropriate. 3.3.1.1 Intracerebral inoculation studies: Mule deer-CWD has been successfully transmitted to ferrets (Mustela putorius furo) by the intracerebral (IC) route (Williams et al., 1982) but failed to transmit to Syrian golden hamsters (Mesocricetus auratus) even after multiple attempts (Williams and Young, 1992). Primary transmission into ferrets resulted in an incubation period of 17-21 months. On subsequent passage this shortened with a 5 months incubation period by the third ferret passage. Unlike mule deer-CWD, ferret-passaged CWD was transmissible to Syrian golden hamsters and increasing the number of transmission passes of CWD in ferrets increased the pathogenicity of the agent for hamsters (Bartz et al, 1998). Transmission of mule deer-CWD to mice is possible, but with a very low efficiency at primary transmission to a panel of mouse strains (RIII, C57BL and VM) and results in incubation periods in excess of 500 days. Serial passage in each mouse strain produced clinical disease in all challenged mouse strain at each passage. The phenotype of disease produced in the mice differed from that of previously strain 10 typed sources, including scrapie and BSE sources, suggesting that the CWD agent is a unique strain of TSE pathogen (Bruce et al., 2000). IC inoculation of mule deer-CWD into squirrel monkeys (Saimiri sciureus) was successful in one animal and mink are also susceptible to IC inoculation of mule deer CWD (Williams and Young, 1992). IC inoculation into one four months old goat with CWD agent resulted in an incubation time of about 6 years. This is longer than what would be expected with scrapie (Williams and Young, 1992). CWD transmission to raccoons (Procyon lotor) remains unsuccessful to date at three years after inoculation (Hamir et al., 2003) but a difference in incubation time was observed after IC infection into raccoons when comparing infection with TME (6 months) and scrapie (2 years) in cattle. Studies in progress at the National Animal Disease Centre (NADC) have shown preliminary evidence of the transmission of mule deer-CWD to sheep. To date, 1 out of 8 sheep inoculated IC with CWD brain suspension has shown clinical signs at 35 months post inoculation. Histopathological changes indistinguishable from those of scrapie were found and IHC examinations of the brain, tonsil and some lymph nodes proved positive. (Janice Miller, Personal Comm.). On-going research on the species barrier is indicating that there is a substantial biological barrier to transmission of CWD from deer to cattle. Preliminary data from experiments in progress in Colorado, Wyoming, and Iowa indicate that only a few calves develop disease after challenge with CWD pathogen from affected mule deer. In 3 calves euthanised between 24 and 27 months post-inoculation (IC), microscopic lesions in the brain were subtle or absent. However, all 3 animals were positive for PrPres by immunohistochemistry (IHC) and Western blot. Three years after challenge, the 10 remaining inoculated cattle were alive and apparently healthy (Hamir et al, 2001; Hamir, 2002). 3.3.1.2 Oral and other natural exposure route studies Homologous CWD has been transmitted by oral inoculation in mule deer, whitetailed deer, and elk in pathogenesis studies that are nearly complete. In addition, homologous CWD has been transmitted in elk at a low dose (0.1 g pooled CWD-elk brain) by oral exposure (Williams, pers. Comm.). Cattle have been inoculated orally with a brain pool from CWD affected mule deer at the University of Wyoming and have not developed any evidence of transmission more than 5 years following exposure. These studies are scheduled to run for 10 years. In addition, bovine calves have been orally inoculated with CWD brain pools from mule deer and from elk; these calves are being sequentially necropsied and results are not yet available (Williams, pers comm). Cattle living in close contact with infected deer and elk have not developed the disease during the first five years of a 10-year study. Twenty-four cattle were housed with resident deer and elk with endemic CWD, in two wildlife research facilities in Wyoming and Colorado. These studies started in 1997 and to date there is no evidence of transmission of CWD to cattle through contact. Control deer have all succumbed to CWD (Williams, 2002). Brains from cattle over 5 years of age and from different ranches within an enzootic area of CWD were examined with H&E and IHC stains and all were found negative (Gould et al, 2003). 3.3.2 Susceptibility of deer and elk to other TSEs Scrapie has been successfully transmitted to 3/5 elk after IC inoculation (Hamir et al., 2003). There is apparently no ongoing work at present to attempt transmission of scrapie to mule deer. snip... 34 6 FOOD AND FEED SAFETY AND HUMAN AND ANIMAL RISK Although CWD is not similar to BSE in terms of epidemiology in that there is no evidence of natural spread of the disease to phylogenetic families other than the cervidae it may theoretically pose a risk for animal and human food safety. 35 6.1 FOOD SAFETY There is no evidence that CWD can be transmitted to humans consuming meat or handling infected cervids or their products, however this possibility cannot be ruled out. The World Health Organisation recommends that people not consume animal products from any animal infected with a TSE disease and public health policies in Canada and the US are consistent with this direction. In Canada, all adult cervids slaughtered under commercial arrangements in the provinces of Saskatchewan, Manitoba and Alberta are tested for CWD and carcasses are only released upon receipt of a negative result. Offals may be disposed off by incineration or deep burial before test results are known. Once a farmed cervid is diagnosed with CWD, the infected animal and all cervids exposed to positive animals are destroyed and the carcasses disposed of by incineration or deep burial. Antler velvet from test negative animals in the herd is released from official control. In NA some health officials advise hunters not to consume meat from animals known to be infected with CWD. In addition, they suggest hunters take simple precautions when field dressing deer or elk taken in areas where the disease is found. Although, in the USA the consumption of meat from CWD affected animals is discouraged, however, there is no ban. So, affected meat probably has been consumed for decades in Colorado and Wyoming (Dr. Williams, Personal communication). When an animal is slaughtered in the United States, some animals are tested for CWD depending on individual State regulations. The carcass is stored until result of the test is returned (test takes one week) and when negative then the carcass is released. In case the carcass is positive, further steps will vary from state to state. Special slaughterhouses for farmed animals do not always exist: sometimes livestock slaughter plants are used for game animals but they have to handle the different species at different times and clean in between but the rules vary from state to state. Fate of road killed deer is not a USDA policy but differs from state to state with considerable variation from location to location. Viscera and other carcass remnants of hunted animals remain in situ (offals etc…). 36 6.2 FEED SAFETY AND ANIMAL HEALTH Although CWD is not similar to BSE in terms of epidemiology in that there is no evidence of natural spread of the disease to phylogenetic families other than the cervidae it may still pose a risk for animal and human food safety. What happens with possible affected carcasses of hunted or slaughtered farmed deer or elk was very much depending on the state, however, the FDA has recently provided new guidance to state public health and agriculture officials throughout the US. FDA does not permit material from CWD positive animals or animals at high risk for CWD to be used as an ingredient in feed for any animal and specifically requiring that renderers do not accept any deer or elk from CWD epizootic areas for any animal feed. This is an extension of the 1997 FDA regulations (feed ban) that put into place the exclusion of ruminant MBM from ruminant feed. This ruling specifically excluded deer and elk from MBM. In Canada there are no mandatory controls on rendering carcasses and offal from cervids other than those tested positive for CWD or animals that have been exposed to test positive animals. However, the Canadian Renderers’ Association has a voluntary ban on the rendering of cervids. Canada prohibits the feeding of ruminant derived proteins to ruminants. 6.3 CJD IN THE USA AND POSSIBLE RELEVANCE TO CWD Recently, the Center for Disease Control (CDC) has issued a new statement concerning CWD and possible human infection: "Although it is generally prudent to avoid consuming food derived from any animal with evidence of a TSE, to date, there is no evidence that CWD has been transmitted or can be transmitted to humans under natural conditions". However, the CDC has renewed surveillance efforts in order to rule out a link between CWD and vCJD. While, to date there has been one case of vCJD reported in US (contracted in the UK), the CDC is working with ongoing investigations in Wyoming and Colorado to track cases of CJD or suspected CJD. 37 CDC reported on the epidemiological investigations carried out on three patients who died of degenerative neurological illness during the period 1993-1999 and who were hunter and/or had a history of consuming venison during wild game feasts. All three patients were aged over 55 and developed neurological symptoms prior to death. Sporadic CJD was confirmed in one case as the cause of death (CDC, 2003). Belay et al., (2001) Recent reports on of 3 unusually young CJD patients (aged 28, 28 and 30 years) who regularly consumed deer or elk meat, which created concern about the zoonotic transmission of CWD. Investigations, however, by CDC found that these were all cases of sporadic CJD of different types. In the USA the occurrence of CJD in persons 30 years or younger is rare (during 1979-1996, only 12 such CJD cases were reported to the CDC and 8 of these resulted from the use of contaminated growth hormone or dura maters grafts). Against the background of the occurrence and recognition of vCJD in 1996 it is difficult to make an epidemiological distinction between an increased incidence of CJD that might represent an indication of a novel exogenous source of infection and an increased ascertainment of CJD cases in young patients due to better surveillance. Belay et al., (2001), from the National Centre for Infectious Diseases have examined the hypothesis that a causal link could be made between the disease in these 3 patients and CWD. They reviewed medical records and interviewed family members and state wildlife and agriculture officials. Brain tissue samples were examined using histopathologic, immunohistochemical, immunoblotting, or prion gene analysis methods. The investigation assessed the presence or absence of CJD risk factors, associations with deer and elk hunting in CWD- enzootic areas and comparison of the evidence from the 3 patients with that of a zoonotic link between vCJD and bovine spongiform encephalopathy. None of the patients had established CJD risk factors or a history of travel to Europe. Two of the patients hunted game animals and one was a daughter of a hunter. Unlike patients with vCJD, the 3 patients did not express a common phenotype of the disease, which did not suggest a causal link between CWD and CJD (there was also heterogeneity among the three patients on the codon 129 : Met/Met, Val/Val and Met/Val respectively). Molecular phenotyping characteristics for the 2 patients studied gave type 1 on Western Blot according to Parchi et al.(1997), which differs from that of vCJD. 38 In conclusion, the CDC report on the CJD in the patients aged over 55 years and the investigation of Belay et al. (2001) related to the young CJD patients found no strong evidence for a causal link between CWD and CJD. Both, however, concluded as well that ongoing national surveillance for CJD and other neurological cases will remain important for continuing to assess the risk, if any, of CWD transmission to humans. Race et al., (2002) described abnormal PrP glycoforms of CWD in comparison to PrP from scrapie and BSE. Analysis of these abnormal PrP glycoform patterns from CWD affected deer and elk, scrapie-affected sheep and cattle and cattle with BSE failed to identify patterns capable of reliably distinguishing these transmissible spongiform encephalopathy diseases. However, PrP-res patterns sometimes differed among individual animals, suggesting the possibility of multiple CWD strains. 7 RISK OF SPREAD TO EUROPE In answering question two, there was a need for a risk assessment to be carried out and to consider the imports of game meat from cervids and or live animal imports from the USA and Canada, if any. Data provided by the US and Canada preliminary indicate that there is no export of live cervids into Europe. If licences for export to EU-countries were granted it could be traced back that these were related to single hunter-related trophies (skin, antlers) by private persons. Data provided by Eurostat confirm the data supplied by USA and Canada that there is no import of live cervids into EU countries originating from Canada or US. Data on game meat provided by Eurostat fall under two different entries related to ‘game meat’: Period 1988-1992 entry is indicated as: ‘Fresh, chilled or frozen meat and edible offal of game (excluding of rabbits, hares and swine)’ Period 1993-2001 entry is indicated as: ‘Meat and edible meat offal of game, fresh, chilled, or frozen (excluding rabbits, hares, pigs and quails)’. A table in Annexe 2 gives the data as provided by Eurostat for the two above-mentioned entries as exported from USA and Canada. 39 In summary over the period 1988-1992 a total of 0,4 ton and 80,1 ton was exported from Canada and USA respectively to the EU. The exports from Canada were to France, UK and the Netherlands and exports from USA were mainly to UK (79,1 ton) and the rest to France. During the period 1993-2001 a total of 0,7 ton and 120,6 ton were exported from Canada and the USA respectively. The main importer from the USA was UK with 103,8 ton and the remaining importing countries were France Netherlands Germany, Spain and Austria. There are no data available on exports of cervid embryo’s and semen from Canada and the USA and also no import data in the EU. The current, planned and proposed surveillance studies in Europe were discussed earlier. Related to the current activities in Europe further surveillance should be encouraged in order to provide more detailed base line data as the current studies are assessed as insufficient to detect a CWD infection in cervids would it be present. 8 SUMMARY AND CONCLUSIONS 8.1 SUMMARY Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of certain species of native North American deer (mule deer and white–tailed deer, and Rocky Mountain elk. A number of States/Provinces in the USA and Canada, (North America, NA) have reported cases in free-ranging and farmed cervids. There are no reports of CWD in areas outside NA with the exception of a single animal imported into Korea from Canada. The natural host range of CWD has so far remained confined to cervids. On-going experimental transmission studies have still not been able to show transmission of CWD from deer to cattle. Additionally, genetic studies show a relatively large phylogenetic 40 difference in PrP sequence between Cervidae, Bovidae and Humans. Those differences suggest an appreciable species barrier for possible transmission of CWD to cattle and humans. However, since the basis of the transmission barrier in relation to the TSE is complex and not solely a function of PrP sequence of donor and recipient it remains theoretically possible that the CWD-agent could infect humans. Infected animals have a widespread tissue distribution of disease-specific PrP and presumably also infectivity in those tissues from an early stage in the incubation period. Epidemiological data have shown that CWD is readily spread by lateral transmission in cervid populations. In experimental studies, oral exposure to only very small doses of infective material resulted in disease in cervid animals. Surveillance data do not as yet provide information on accurate figures of the prevalence of the disease in NA and the risk factors are not well understood. Some control measures for farmed deer are in place. However, movement of free-ranging deer provides a major difficulty for control strategies. The origin of the disease is unknown and the lack of any connection with other animal TSEs provides no clues as to the potential for CWD to be pathogenic for man. Available information indicates that there is only negligible trade in live cervids originating in NA to EU but there are indications of imports of small annual tonnage of edible products from game. It is unclear what, if any, trade exists in antler, embryos or semen from cervids between NA and EU countries. Research and surveillance programs on CWD in farmed or wild Cervidae in Europe did not exist until recently and thus the available data do not allow to draw conclusions about CWD in the Cervidae population in Europe. 8.2 CONCLUSIONS With regard to the initial question of the mandate, a theoretical risk for prion transmission to humans consuming products of CWD affected-cervids of all ages in countries where CWD exists cannot be excluded. Similarly, transmission risk of prions to domestic animals cannot be excluded. There is therefore a scientific basis on which to exclude tissues from animals that carry a CWD risk, from human or animal feed chains. However, the early and widespread involvement of tissues in CWD infected animals does not allow to define a SRM list, neither to define any lower age cut off as has been defined for cattle in relation to BSE. Neither is there sufficient knowledge to define exclusions or amendment of any SRM rule on the basis of relative genetic resistance to infection as has been proposed for sheep and goats in the event that evidence indicates the probable natural occurrence of BSE in these species 5. Although available information indicates imports of live Cervidae from NA to EU and trade in meat products from cervid species as being negligible, it is important to reach certainty that no transfer of risk takes place through trade of live cervids and its derived products. At present, there are no scientific data that CWD is occurring in Cervidae elsewhere than in those countries from which it has been previously reported. However, systematic TSE surveillance of cervid populations has either been absent or has only just started in European countries. Until results of such surveillance become available no conclusion can be drawn with regard to the occurrence of CWD or similar TSE in the cervid population of Europe. http://europa.eu.int/comm/food/fs/sc/ssc/out324_en.pdf Project List Research on BSE "Cousin" Is Top Postdoc Project CDC - Environmental Sources of Prion Transmission in Mule Deer THESE two reports that follow from the OIE about CWD, i take with a grain of salt some of there assessments. FOR one, deer and elk HAVE been fed feed tainted with the TSE agent for decades. ALSO, the TSE agent transmits freely by oral route to deer and elk; Oral transmission and early lymphoid tropism of chronic wasting disease Department of Pathology, College of Veterinary Medicine and Biomedical Author for correspondence: Edward Hoover.Fax +1 970 491 0523. e-mail Mule deer fawns (Odocoileus hemionus) were inoculated orally with a snip... These results indicate that mule deer fawns develop detectable PrP res snip... http://vir.sgmjournals.org/cgi/content/full/80/10/2757 now, just what is in that deer feed? _ANIMAL PROTEIN_ Subject: MAD DEER/ELK DISEASE AND POTENTIAL SOURCES 8420-20.5% Antler Developer snip... _animal protein_ http://www.surefed.com/deer.htm BODE'S GAME FEED SUPPLEMENT #400 snip... _animal protein_ http://www.bodefeed.com/prod7.htm Ingredients Grain Products, Plant Protein Products, Processed Grain By-Products, http://www.bodefeed.com/prod6.htm MORE ANIMAL PROTEIN PRODUCTS FOR DEER Bode's #1 Game Pellets GUARANTEED ANALYSIS Grain Products, Plant Protein Products, Processed Grain By-Products, FEEDING DIRECTIONS http://www.bodefeed.com/prod8.htm INGREDIENTS Grain Products, Roughage Products (not more than 35%), Processed Grain DIRECTIONS FOR USE Deer Builder Pellets is designed to be fed to deer under range http://www.profilenutrition.com/Products/Specialty/deer_builder_pellets.html DEPARTMENT OF HEALTH & HUMAN SERVICES April 9, 2001 WARNING LETTER 01-PHI-12 Brian J. Raymond, Owner Tel: 215-597-4390 Dear Mr. Raymond: Food and Drug Administration Investigator Gregory E. Beichner conducted Our investigation found failure to label your In addition, we note that you are using approximately 140 pounds of The above is not intended to be an all-inclusive list of deviations from http://www.fda.gov/foi/warning_letters/g1115d.pdf snip... full text TSS submission to FDA; -------- Original Message -------- Subject: DOCKET-- 03D-0186 -- FDA Issues Draft Guidance on Use of Material From Deer and Elk in Animal Feed; Availability PDF] Chronic wasting disease in deer and elk in North America [PDF] KELLAR ART. TSS
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