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From: TSS ()
Subject: SCRAPIE USA JULY 2005 UPDATE
Date: September 19, 2005 at 6:42 am PST

SCRAPIE USA JULY 2005 UPDATE

AS of July 31, 2005, there were 120 scrapie infected soure flocks (figure 3). There were 16 new infected and source flocks reorted in July (Figure 4) with a total of 143 flocks reported for FY 2005 (Figure 5). The total infected and source flocks that have been released in FY 2005 are 89 (Figure 6), with 8 flocks released in July. The ratio of infected and source flocks released to newly infected and source flocks for FY = 0.62 : 1. IN addition, as of July 31, 2005, 524 scrapie cases have been confirmed and reported by the National Veterinary Services Laboratories (NVSL), of which 116 were RSSS cases (Figure 7). This includes 76 newly confirmed cases in July 2005 (Figure 8). Fifteen cases of scrapie in goats have been reported since 1990 (Figure 9). The last goat case was reported in May 2005. ...........

snip...

http://www.aphis.usda.gov/vs/nahps/scrapie/monthly_report/monthly-report.html


SCRAPIE USA JUNE 2005 UPDATE


AS of June 30, 2005, there were 114 scrapie infected and source flocks
(Figure 3). There were 14 new infected and source flocks reported in June
(Figure 4) with a total of 123 flocks reported for FY 2005 (Figure 5).


snip...


In addition, as of June 30, 2005, 448 scrapie cases have been confirmed and
reported by the National Veterinary Services Laboratories (NVSL), of which
106 were RSSS cases (Figure 7). This includes 81 newly confirmed cases in
June 2005 (Figure 8). Fifteen cases of scrapie in goats have been reported
since 1990 (Figure 9). The last goat case was reported in May 2005.


snip...end


http://www.aphis.usda.gov/vs/nahps/scrapie/monthly_report/monthly-report.html


From: TSS ()
Subject: SCRAPIE USA UPDATE MARCH - JUNE 2005
Date: August 24, 2005 at 7:03 pm PST

SCRAPIE USA MONTHLY REPORT 2005

AS of March 31, 2005, there were 70 scrapie infected source flocks (Figure
3). There were 11 new infected and source flocks reported in March (Figure
4) with a total of 51 flocks reported for FY 2005 (Figure 5). The total
infected and source flocks that have been released in FY 2005 are 39 (Figure
6), with 1 flock released in March. The ratio of infected and source flocks
released to newly infected and source flocks for FY 2005 = 0.76 : 1. IN
addition, as of March 31, 2005, 225 scrapie cases have been confirmed and
reported by the National Veterinary Services Laboratories (NVSL), of which
53 were RSSS cases (Figure 7). This includes 57 newly confirmed cases in
March 2005 (Figure 8). Fourteen cases of scrapie in goats have been reported
since 1990 (Figure 9). The last goat cases was reported in January 2005. New
infected flocks, source flocks, and flocks released or put on clean-up plans
for FY 2005 are depicted in Figure 10. ...

FULL TEXT ;

http://www.aphis.usda.gov/vs/nahps/scrapie/monthly_report/monthly-report.html

Title: An Epidemiological Review of a Valine-Associated Scrapie Outbreak: Quantification of Genetic Risk and the Impact of Lateral Transmission in the Outbreak


Authors

Evoniuk, J - NORTH DAKOTA STATE UNIV
Stoltenow, C - NORTH DAKOTA STATE UNIV
O'Rourke, Katherine
Moore, B - NORTH DAKOTA STATE UNIV
Redmer, D - NORTH DAKOTA STATE UNIV


Submitted to: American Journal Of Veterinary Research
Publication Acceptance Date: June 8, 2005
Publication Date: August 1, 2005
Citation: Evoniuk, J.M., Stoltenow, C.L., O'Rourke, K.I., Moore, B.L., Redmer, D.A. 2005. Assessment Of The Genetic Risk And Impact Of Lateral Transmission In A Valine-Associated Scrapie Outbreak In Sheep. American Journal Of Veterinary Research. 66(8):1-6.

Interpretive Summary: Scrapie is a fatal neurologic disease of sheep, endemic in the US but the subject of a vigorous eradication program. Scrapie is associated with accumulation of a misfolded form of the sheep prion protein. Control measures in an infected flock include removal of all genetically susceptible sheep. Susceptibility is controlled by naturally occurring differences in the prion protein, designated 171Q (susceptible) or 171R (generally resistant). The resistance of sheep with the 171R form of the gene occurs with one scrapie strain, the most US strain, but these sheep are not protected from the alternative strain, identified as valine associated scrapie. Anecdotal reports have shown that the strain probably occurs in the US but is relatively rare. In this publication, the presence of the valine associated strain was demonstrated through epidemiology and genetic analysis of a large flock of sheep. The study demonstrated that this scrapie strain can infect sheep as adults and is spread efficiently among related and unrelated sheep housed together during lambing seasons. The results suggest that the outbreak was due to the relatively high number of sheep with the susceptible form of the gene, probably introduced through the use of highly prolific rams carrying the gene. Further, transmission of the disease among adults, the prolonged incubation time, the unsuitability of some susceptible sheep to live animal testing, and susceptibility of sheep with the 171R gene suggest that removal of sheep with the genotype AVQR from infected flocks would be prudent.
Technical Abstract: Scrapie is a member of the heterogenous family of transmissible spongiform encephalopathies. Although these disorders appear to be related to misfolding of a host protein rather than an exogenous organism, two distinct disease phenotypes or strains are noted in sheep. Characterization of the scrapie strains in experimental and field settings in the United Kingdom and Europe have included differences in incubation time, survival rates, lateral transmission efficiency and most importantly, genetic susceptibility. Sheep of the prototype strain SSPB/1 are susceptible only if the PRNP (prion protein precursor gene) encodes valine (V) at codon 136; a polymorphism (encoding glutamine to arginine) at codon 171 apparently reduces disease prevalence but increases incubation time and limits tissue distribution to the brain. Sheep with the prototype valine-independent strain CH1641 are susceptible only if homozygous for glutamine (Q) at codon 171. In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q (AAQQ) and the disease phenotype is similar to that seen with experimental strain CH1641. The only genotype useful for strain discrimination is the relatively rare 136AV/171QR. In this study, a flock of sheep with a large number of infected sheep was analyzed. The presence of at least one V136 allele was identified in all but 2 sheep in the study, incubation times were very short in V136 homozygous sheep, probable lateral transmission was demonstrated in 15 sheep, and at least one AVQR sheep was identified. Therefore, this outbreak was probably due to a valine-associated (SSBP/1-like) strain and this report is the first full description of the epidemiology of this strain in US sheep. The high rate of lateral transmission and the susceptibility of 136AV/171QR sheep to scrapie suggest that genotyping for codon 136 may assist management decisions following a scrapie diagnosis and that it may be prudent to remove sheep of the 136AV/171QR genotype from infected flocks.





Project Team

Alverson, Janet
Herrmann, Lynn
Knowles, Donald - Don
O'Rourke, Katherine






Publications

Publications






Related National Programs

Animal Health (103)






Related Projects

Immune Control of Small Ruminant Lentiviruses
Scrapie Control Through Prp Genetics: Production Traits and Economic Implications
Eradication of Ovine Scrapie Tse Through Selective Genetics Using a Two-Flock Model






Page Modified: 09/16/2005


http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=182469


Title: Data Sheet for Scrapie


Author

Alverson, Janet


Submitted to: Animal Health And Production Compendium
Publication Acceptance Date: April 4, 2005
Publication Date: April 20, 2005
Publisher's URL: http://www.cabicompendium.org/ahpc/home.asp
Citation: Alverson, J. 2005. Data Sheet For Scrapie. Animal Health And Production Compendium. Available: HTTP://WWW.CABICOMPENDIUM.ORG/AHPC/HOME.ASP

Interpretive Summary: Scrapie is a fatal disease of sheep and goats characterized by degeneration of the nervous system. It is part of a group of diseases classified as transmissible spongiform encephalopathies (TSEs). These diseases include forms that affect cattle, elk and deer, mink, and humans. The infectious agent is thought to be a prion, an agent smaller than the smallest known virus. Scrapie has a long history with the first descriptions dating back over two hundred and fifty years. Despite this long history, many factors of the disease are still not fully understood including a complete characterization of the infectious agent, how it is transmitted and how it causes disease. Recent evidence linking the human TSE to the cattle TSE (mad cow disease) has increased attention for all TSEs, including scrapie. There are many laboratories in several different countries actively conducting research on scrapie and other TSEs. There is no evidence to date that scrapie is a risk to human health.
Technical Abstract: Scrapie is a fatal neurodegenerative disease of sheep and goats. It is part of a group of diseases classified as transmissible spongiform encephalopathies (TSEs). These diseases include bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in elk and deer, transmissible mink encephalopathy, and Creutzfeldt-Jakob disease (vCJD) in humans. The infectious agent is thought to be a prion, an agent smaller than the smallest known virus. Scrapie has a long history with the first descriptions dating back over two hundred and fifty years. Despite this long history, many factors of the disease are still not fully understood including a complete characterization of the infectious agent, routes of transmission and pathogenesis. Recent evidence linking vCJD in humans to BSE in cattle has increased attention for all TSEs, including scrapie. There are many laboratories in several different countries actively conducting research on scrapie and other TSEs. There is no evidence to date that scrapie is a risk to human health.

http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=178853


Research Project: Development of New Technologies for Detection of Prions in Animal Feed and Environmental Samples
Location: Foodborne Contaminants Research

Title: Scrapie: the Very Model of An Infectious(protein)isoform


Author

Silva, Christopher


Submitted to: Association Official Analytical Chemists Annual Intrl Meeting & Exposition
Publication Acceptance Date: March 14, 2005
Publication Date: May 2, 2005
Citation: Silva, C.J. 2005. Scrapie: The Very Model Of An Infectious (Protein) Isoform [abstract]. 96th Aocs Annual Meeting & Expo. Salt Lake City, Ut, May 2, 2005.

Interpretive Summary: Scrapie is a fatal disease of sheep. It was first described in the 18th century. Since its initial discovery, it has become endemic in most of the world. It is the most intensely studied example of a class of diseases called transmissible spongiform encephalopathies (TSEs). TSEs include scrapie, chronic wasting disease (CWD), bovine spongiform encephalopathy (BSE), Kuru, and Creutzfeld-Jakob Disease (CJD). Research in the 20th century showed scrapie to be caused by a novel infectious agent, the prion. Prions are infectious proteins. They are structural variants of the highly conserved and naturally occurring cellular prion protein called the prion protein. A prion is able to convert the normal cellular prion protein into the infectious form, thus propagating the infection. An infectious dose is estimated at between 100,000 to 1,000,000 molecules. Prions are remarkably stable and survive many forms of sterilization, including autoclaving. It can survive years in the environment. Fields grazed by infected animals will remain infectious for years. Prions possess the worst properties of persistent toxins and virulent pathogens. This presentation will include a historical review of how this obscure sheep pathology leads to the discovery of the prion. It will highlight current research on the structure, detection and pathology of the prion.
Technical Abstract: Scrapie is a fatal neurodegenerative disease of sheep. It was first described in the 18th century. Since its initial discovery, it has become endemic in most of the world. It is the most intensely studied example of a class of diseases called transmissible spongiform encephalopathies (TSEs). TSEs include scrapie, chronic wasting disease (CWD), bovine spongiform encephalopathy (BSE), Kuru, and Creutzfeld-Jakob Disease (CJD). Research in the 20th century showed this disease to be caused by a novel infectious agent, the prion (PrPSc). PrPSc is an infectious isoform of the highly conserved and naturally occurring cellular protein called the prion protein (PrPC). PrPSc is able to convert PrPC into PrPSc, thus propagating the infection. An infectious dose(ID50)is estimated at between 105 to 106 molecules. PrPSc is remarkably stable and survives many forms of sterilization, including autoclaving. It can survive years in the environment. Fields grazed by infected animals will remain infectious for years. Prions possess the worst properties of persistent toxins and virulent pathogens. This presentation will include a historical review of how this obscure sheep pathology lead to the discovery of the prion. It will highlight current research on the structure, detection and pathology of PrPSc.

http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=183678



Research

Title: Experimental Transmission of Sheep Scrapie by Intracerebral and Oral Routes to Genetically Susceptible Suffolk Sheep in the United States

Authors

Hamir, Amirali
Kunkle, Robert - bob
Richt, Juergen
Miller, Janice - ARS RETIRED
Cutlip, Randall - ARS RETIRED
Jenny, Allen - USDA-VS-APHIS-NVSL


Submitted to: Journal Of Veterinary Diagnostic Investigation
Publication Acceptance Date: June 1, 2004
Publication Date: January 1, 2005
Citation: Hamir, A.N., Kunkle, R.A., Richt, J.A., Miller, J.M., Cutlip, R.C., Jenny, A.L. 2005. Experimental Transmission Of Sheep Scrapie By Intracerebral And Oral Routes To Genetically Susceptible Suffolk Sheep In The United States. Journal Of Veterinary Diagnostic Investigation. 17(1):3-9.

Interpretive Summary: Scrapie is a naturally occurring fatal disease of sheep and goats. It affects nervous system of the animal. Susceptibility to the disease is dependent upon genetic makeup of the host and infectious agent. This study documents findings in Suffolk sheep affected with experimental disease. Four-month-old lambs were utilized for the study. They were administered (5 in the brain and 19 orally) scrapie-infected sheep brains. All animals that were administered the infected material directly into the brain revealed signs of scrapie and were euthanized between 13'24 months after administration. In sheep given the material orally, signs of scrapie were seen between 27 and 43 months in 5 of 9 animals. Three of the 4 clinically normal sheep were found to be positive for scrapie by laboratory tests at 15, 20, and 49 months after administration of infected material. There is lack of information on experimental transmission of US scrapie agent in genetically diverse flocks of sheep. This study attempts to partially fill this void by documenting findings of this disease in Suffolks. Since similar investigations are also needed for other breeds of sheep in this country, the present study will serve as a foundation to compare results of other future studies.
Technical Abstract: Scrapie is a naturally occurring fatal neurodegenerative disease of sheep and goats. Susceptibility to the disease is partly dependent upon genetic makeup of the host. This study documents clinicopathological findings and distribution in tissues of abnormal prion proteins (PrPres) by immunohistochemical (IHC) and Western blot (WB) techniques, in tissues of genetically susceptible sheep inoculated with US sheep scrapie agent. Four-month-old Suffolk lambs (QQ or HQ at codon 171) were utilized for the study. They were inoculated (5 intracerebrally and 19 orally) with an inoculum (No. 13-7) consisting of a pool of scrapie-infected sheep brains. Intracerebrally inoculated animals were euthanized when advanced clinical signs of scrapie were observed. Orally inoculated animals were euthanized at pre-determined time-points (4, 9, 12, 15 and 21 months post inoculation, PI) and thereafter when the animals had terminal signs of disease. A detailed postmortem examination was conducted on each carcass and tissues were examined for microscopic lesions and for the presence of PrPres by IHC and WB techniques. All intracerebrally inoculated animals exhibited clinical signs of scrapie and were euthanized between 13 ' 24 months PI. Spongiform lesions in the brains and PrPres deposits in central nervous system (CNS) and lymphoid tissues were seen in these sheep. In orally inoculated sheep, clinical signs of scrapie were seen between 27 and 43 months PI in 5/9 animals. The earliest detectable PrPres was observed in brainstem and lymphoid tissues of a clinically normal sheep at 15 months PI. Three of the 4 clinically normal sheep were found to be positive at 15, 20, and 49 months PI by either histopathology or the PrPres tests. This study was done to partially fill a void in information on experimental studies of US scrapie transmission (by intracerebral and oral routes) in genetically susceptible sheep.


http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=161349


Title: Transmission of Sheep Scrapie to Elk (Cervus Elaphus Nelsoni) by Intracerebral Inoculation: Final Outcome of the Experiment

Authors

Hamir, Amirali
Miller, Janice
Cutlip, Randall
Kunkle, Robert - bob
Jenny, Allen - NVSL/APHIS/USDA, AMES, IA
Stack, Mick - VET LABS, WEYBRIDGE, UK
Chaplin, Melanie - VET LABS, WEYBRIDGE, UK
Richt, Juergen


Submitted to: Journal Of Veterinary Diagnostic Investigation
Publication Acceptance Date: July 7, 2003
Publication Date: July 1, 2004
Citation: Hamir, A.N., Miller, J.M., Cutlip, R.C., Kunkle, R.A., Jenny, A.L., Stack, M.J., Chaplin, M.J., Richt, J.A. 2004. Transmission Of Sheep Scrapie To Elk (Cervus Elaphus Nelsoni) By Intracerebral Inoculation: Final Outcome Of The Experiment. Journal Of Veterinary Diagnostic Investigation. 16(4):316-321.

Interpretive Summary: This is a final report of an experimental transmission of sheep scrapie agent by intracerebral inoculation to Rocky Mountain elk (Cervus elaphus nelsoni). It documents results obtained in experimental and control elk. A preliminary report of this study was published previously. During the first 2 years post inoculation (PI), 3 animals died or were euthanized because of infection or injuries unrelated to scrapie. In years 3 and 4 PI, 3 other elk died after brief terminal neurological episodes. Examination of these animals revealed moderate weight loss but no other lesions. Microscopic examination and laboratory tests of these elk confirmed infection by the scrapie agent. Lesions and tests for the scrapie agent were not detected in the 3 inoculated elk examined during the first 2 years or in the 2 control animals. These findings confirm that intracerebral inoculation of sheep scrapie agent results in positive tests and lesions for the scrapie agent in elk. Based on these findings, this condition cannot be distinguished from chronic wasting disease (CWD) of elk with currently available diagnostic techniques. Results of this study will have most impact on wildlife biologists, veterinarians, and TSE researchers who will become aware that US sheep scrapie is transmissible to elk and that microscopic lesions and laboratory tests used for the diagnosis TSEs cannot differentiate this experimental TSE from CWD of elk and other cervids.
Technical Abstract: This is a final report of an experimental transmission of sheep scrapie agent by intracerebral inoculation to Rocky Mountain elk (Cervus elaphus nelsoni). It documents results obtained in experimental (n = 6) and control (n = 2) elk. A preliminary report of this study was published previously.7 During the first 2 years post inoculation (PI), 3 animals died or were euthanized because of infection or injuries other than spongiform encephalopathy (SE). In years 3 and 4 PI, 3 other elk died after brief terminal neurological episodes. Necropsy of these animals revealed moderate weight loss but no other gross lesions. Microscopically, characteristic lesions of SE were seen throughout the brains and spinal cords, and the tissues were positive for proteinase-K resistant prion protein (PrPres) by immunohistochemistry (IHC) and by Western blot. Also, scrapie-associated fibrils (SAF) were observed by negative stain electron microscopy in the brains of elk with neurologic signs. PrPres and SAF were not detected in the 3 inoculated elk necropsied during the first 2 years or in the 2 control animals. Retrospective analysis of the gene encoding cervid PrP revealed a polymorphism at codon 132. The neurologic elk were either homozygous (MM) or heterozygous (LM). These findings confirm that intracerebral inoculation of sheep scrapie agent results in SE with accumulations of PrPres in the CNS of elk, and based on morphologic and IHC findings, this condition cannot be distinguished from chronic wasting disease (CWD) of elk with currently available diagnostic techniques.


http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=148464


TSS






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