Scrapie Control in EU Goat Population: Has the Last Gap Been Overcome?
Scrapie Control in EU Goat Population: Has the Last Gap Been Overcome?
OPINION ARTICLE
Front. Vet. Sci., 29 September 2020 | https://doi.org/10.3389/fvets.2020.581969
Scrapie Control in EU Goat Population: Has the Last Gap Been Overcome?
Sergio Migliore*, Roberto Puleio and Guido Ruggero Loria
Istituto Zooprofilattico Sperimentale Della Sicilia “A. Mirri”, Palermo, Italy
Introduction
Scrapie is a fatal, neurodegenerative disease that affects sheep and goat worldwide, belonging to the group of transmissible spongiform encephalopathies (TSEs).
Since 2002, Member States (MS) of European Union (EU) have implemented active surveillance to control the risk of scrapie. The EU scrapie eradication policy is mainly aimed to eradicate classical scrapie. The choice of population groups and sample sizes have evolved in the years, as well as the eradication measures and control of disease (selective culling, movement restrictions, reinforced surveillance measures, etc.). In this context, over the past two decades, breeding programs to increase the frequency of the resistance-associated ARR allele in sheep populations have been introduced to minimize TSE risk in MS, but there was not a regulatory effort in adoption of analogous measures for goats. However, scientific knowledge related to scrapie resistance associated with goat PRNP gene polymorphisms has considerably expanded in the last 10 years.
Classical scrapie is considered endemic in many MS. Since its publication, the only measures applicable for TSE control in goat contained in Regulation (EC) No 999/2001 obliged farmers to provide a complete culling of whole flock, with great economic loss and serious concerns for the risk of extinction of endangered breeds. However, over the years, additional measures have been introduced such as monitoring of the infected herd without the obligation of total culling and the possibility of reintroducing goats with unknown genotype after biosafety practices. Nevertheless, these measures could allow the goat population to become the main reservoir of scrapie, affecting the disease eradication program in small ruminant population.
Following a request from the European Commission (EC), the European Food Safety Authority (EFSA) was asked to deliver scientific opinions on the scrapie situation in EU to evaluate the introduction of breeding policies in goats. From 2014, EFSA advised to promote selection and introduction of resistant bucks in EU caprine population (1). More recently, in 2017, based on the latest scientific evidence, EFSA concluded that breeding programs for scrapie resistance in goats should be implemented in MS, taking particular attention to potential negative effects of extinction in rare and endangered breeds (2).
With Regulation (EC) No 2020/772 of June 11, 2020, amending Regulation (EC) No 999/2001, EC laid down new approaches as regards eradication measures for TSEs in goats and in endangered breeds. In this context, the authors discuss advantages and critical points related to the different control measures introduced by EU regulations during the last two decades.
State of the Art
Legislative Basis
Regulation (EC) No 999/2001 establishes rules for the prevention, control, and eradication of certain TSEs, including scrapie in small ruminants. This Regulation dates back to 2001 and, after many subsequent amendments, is still in force today.
In 2003, Regulation (EC) No 260/2003 revised the requirements for eradication measures in case of the detection of TSE in a farm by selective culling of susceptible sheep and by requiring the implementation of measures to increase TSE resistance in the outbreak. Simultaneously, decision 2003/100 (EC) laid down requirements for the establishment of breeding programs for resistance to TSE in sheep, aimed to increase the level of alleles associated with resistance (ARR) and decreasing the frequency of alleles associated with susceptibility (VRQ) in EU sheep population. Commission Regulation (EC) No 1923/20065 and No 727/2007 then integrated the breeding program requirements into Regulation (EC) No 999/2001. In 2006, EFSA confirmed the efficacy of breeding program for TSE resistance in sheep (3).
More recently, on June 11, 2020, Regulation (EC) No 2020/772 amended Annexes I, VII, and VIII to Regulation (EC) No 999/2001 introducing the possibility for the MS to limit slaughtering/culling and destruction to goats which are genetically susceptible to classical scrapie. In addition, the definition of “endangered breed” of Regulation (EU) 2016/1012 replaced the expression of “local breed in danger of being lost to farming” as laid down in Regulation (EU) No 807/2014 (4).
Scrapie in EU Goats
Classical scrapie shows similar epidemiological features in sheep and goats and the involvement of both species in outbreaks is common. Even if the incidence in goats is much lower than in sheep, milk and placenta of infected goats may serve as sources of infection to sheep (5, 6). Scrapie in goat was described for the first time in 1942 (4); since then, clinical cases have been recorded throughout Europe. Animal movements between herds and environmental contamination play relevant roles as risk factors.
In 2019, a total of 325,386 sheep and 138,128 goats were tested in EU. In sheep, 821 cases of classical scrapie were detected in seven MS, whereas 517 cases were reported in goats in seven MS (7). Scrapie in goat is considered endemic in the EU countries with the largest caprine populations with more than 10,500 cases from 2002 to 2017. Between 2002 and 2015, classical scrapie was detected in 10 MS with 2.4 cases out of 10,000 tested heads. In this prevalence study, Cyprus was excluded due to an epidemic over the last 10 years (2).
Genetic Basis
In the last two decades, an extensive review of literature was conducted to identify relevant alleles of goat PRNP to which a breeding program could be based. These studies were conducted within different MS and goat breeds. A considerable dataset has been produced for the following alleles: S127, M142, R143, D145, D146, S146, H154, Q211, and K222. Among them, K222, D146, and S146 alleles confer higher genetic resistance to classical scrapie strains circulating in the EU goat population (2). In 2017, based on a combination of the “weight of evidence” and the “strength of resistance,” EFSA provided a ranking of resistance to classical scrapie, as follows: K222 > D146 = S146 > Q211 = H154 = M142 > S127 = H143 > wild type (2).
Goat Breeding in EU
Goat farming plays an important socioeconomic role in several countries, particularly where there are hills and mountains, and remote, marginal, and even semi-arid areas (8, 9). Europe is the continent with the widest caprine biodiversity with 187 goat breeds, which is 33% of the goat breeds acknowledged worldwide (10). In this context, there are breeds with large population sizes, cosmopolitan and often characterized by a high production, and breeds with small population sizes not yet subjected to conservation programs because of their remoteness or because they are less competitive in terms of production than other selected breeds (9). Such different scenarios obviously have required a different scrapie control strategy.
Discussion
In 2017, EFSA, based on prolonged field experience and experimental studies, concluded that the K222, D146, and S146 variants confer genetic resistance to the classical scrapie strain circulating in the EU goat population (2). EFSA highlighted that the protective effect of K222 is greater than D146 and S146 variants and of ARR allele in sheep, when the 2002 Scientific Steering Committee opinion was published (2). In this regard, a substantial difference between sheep and goats in the new Regulation (EC) No 2020/772 still remains. In sheep, the ARR/ARR homozygous genotype in reproductive males is an essential requirement, whereas in goats, heterozygosity for at least one of K222 and D/S146 alleles is sufficient to avoid the stamping out. It should be remembered that heterozygous variants Q222K and N146S/D in goats do not confer full protection against classical scrapie as reported in natural outbreaks in Greece (11) and in Cyprus (12). In addition, the subsequent restocking of outbreak without genotype consideration after biosafety practices is a considerable risk. These are critical points whose efficacy will be assessed in the future.
The EFSA opinion also highlights that a high selective pressure in some breeds with a low frequency of resistant variants would likely have an adverse effect on genetic diversity and that each MS should be able to design its own genetic selection strategy depending on the breed concerned.
Estimating the frequency of candidate alleles is a preliminary step in understanding the feasibility of a breeding program. Several investigations on goat PRNP were performed in MS in recent years, and some breed-related differences emerged (Table 1). Higher frequency (>24.5%) of 146D or S variants was described in cosmopolitan Boer goat in Great Britain and Netherlands (13–15) and in native Damascus and related breeds in Cyprus (16.5%) (17). A lower frequency (3%) was also described in local and crossbred in Greece (16). To date, this mutation does not seem to be widespread in other MS. In contrast, 222 K variant seems to be more common across the MS. Frequencies between 1.2 and 7.5% were described in cosmopolitan and large population size breeds such as Saanen (1.2–4%) and Alpine (6.4–7.5%) reared in Spain, Netherlands, Italy, France, and Greece (15, 16, 18–20). Very high frequency (29.5%) was described in Dutch Toggenburg in Netherlands (15). Variable frequencies were described in small size of native breeds such as local and crossbred in Greece (0.3–5.6%) (16). In Italy, where a great caprine biodiversity is present, a difference between northern and southern native breeds was described (20), with higher frequencies of 222 K in Southern breed such as Garganica (17.2%), Ionica (7.2%), southern crossbred (22.5%), Girgentana (18.7%), Rossa Mediterranea (12.7%), Argentata dell'Etna (16.3%), Aspromontana (10.3%), and Cilentana (18.2%) (20–23). Many of these breeds are considered in critical or endangered status (24) and for this reason any breeding program should consider the endangered status of each goat population to preserve the genetic variability and the biodiversity together with disease control (21).
TABLE 1
www.frontiersin.org
Table 1. Breeds with S146/D146 and K222 haplotypes reported in literature and their frequencies reported in EU.
Various mutations in the PRNP in different breeds have potentially been positively selected in relation to local circulating scrapie strains originating in specific environmental conditions (25).
A recent study (26) assessed the impact of different breeding strategies in goat using a mathematical model, and it concluded that breeding programs for scrapie resistance could be implemented also in a context of so high biodiversity and also different size of the populations of goats. Nevertheless, the growth rate of resistant goats in some breeds may be slow due to the initial genetic profile not being particularly favorable inside the breed. In cosmopolitan breeds with a large population size, a breeding program in the overall population would be desirable. In contrast, in endangered breeds with a small population, a breeding program should be implemented starting from reproductive nuclei. This scheme is less expansive and protects the endangered breeds even if it takes longer to reach the expected results.
As well as goat breeds, a breeding program for scrapie resistance should consider the particular situation of each MS in terms of the presence of resistant alleles and their relative frequency. For example, in Greece, which has one of the largest goat populations in Europe, a goat-scrapie resistance program targeting the Q211, S146, and K222 alleles was designed (27), whereas in Italy, pilot projects selected positively a singular variant K222.
Although there is a strong interest in disease control among goat farmers in the Northern MS, breeding for resistance is often compromised by the low frequency of resistant alleles. By contrast, in Southern MS where a satisfying frequency of resistant alleles is present, goat farming is mainly related to pastoralism and in several cases there is a lack of interest in starting genetic programs. For this reason, to be successful, new regulations have to consider engaging farmers' cooperation by appropriate risk communication and involving them in the genetic program as well as providing an adequate financial support for goat genotyping.
Regulation (EC) No 2020/772 laid down an alternative tool for scrapie control in EU goat population. It particularly recognized the genetic resistance to classical scrapie in goats carrying at least one of the most recognized alleles (K222, D146, and S146) and preserving them from culling in the case of outbreak. In addition, the new regulation introduces possible derogation measures for endangered breeds according to Regulation (EU) 2016/1012. This new measure will finally strengthen the control of TSEs in small ruminants in the EU and will also have beneficial effects on farming system and for the conservation of goat breed biodiversity.
Author Contributions
SM drafting of the article. RP and GL revised the article. All authors contributed to the article and approved the submitted version.
Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References 1. EFSA BIOHAZ Panel. Scientific Opinion on the scrapie situation in the EU after 10 years of monitoring and control in sheep and goats. EFSA J. (2014) 12:3781. doi: 10.2903/j.efsa.2014.3781
CrossRef Full Text | Google Scholar
2. EFSA BIOHAZ Panel. Genetic resistance to transmissible spongiform encephalopathies. (TSE) in goats. EFSA J. (2017) 15:4962. doi: 10.2903/j.efsa.2017.4962
CrossRef Full Text | Google Scholar
3. EFSA BIOHAZ Panel. Opinion of the Scientific Panel on Biological Hazards on “the breeding programme for TSE resistance in sheep”. EFSA J. (2006) 4:382. doi: 10.2903/j.efsa.2006.382
CrossRef Full Text | Google Scholar
4. Chelle PL. A case of scrapie in goats. Bull de l'Academie Vet de France. (1942) 15:294–5.
5. Schneider DA, Madsen-Bouterse SA, Zhuang D, Truscott TC, Dassanayake RP, O'Rourke KI. The placenta shed from goats with classical scrapie is infectious to goat kids and lambs. J Gen Virol. (2015) 96:2464–9. doi: 10.1099/vir.0.000151
PubMed Abstract | CrossRef Full Text | Google Scholar
6. Konold T, Thorne L, Simmons HA, Hawkins SA, Simmons MM, González L. Evidence of scrapie transmission to sheep via goat milk. BMC Vet Res. (2016) 12:208. doi: 10.1186/s12917-016-0807-4
PubMed Abstract | CrossRef Full Text | Google Scholar
7. EFSA. Annual report of the scientific network on BSE-TSE 2019. EFSA Supp Pub. (2019) 16:1771E. doi: 10.2903/sp.efsa.2019.EN-1771
CrossRef Full Text | Google Scholar
8. Boayzouglu J, Hatziminaoglou I, Morand-Fehr P. The role of the goat in society: past, present and perspectives for the future. Small Rumin Res. (2005) 60:13–23. doi: 10.1016/j.smallrumres.2005.06.003
CrossRef Full Text | Google Scholar
9. Dubeuf JP, Boyazoglu J. An international panorama of goat selection and breeds. Livest Sci. (2009) 120:225–31. doi: 10.1016/j.livsci.2008.07.005
CrossRef Full Text | Google Scholar
10. Gahal S. Biodiversity in goats. Small Rum Res. (2005) 60:75–81. doi: 10.1016/j.smallrumres.2005.06.021
CrossRef Full Text | Google Scholar
11. Fragkiadaki EG, Vaccari G, Ekateriniadou LV, Agrimi U, Giadinis ND, Chiappini B, et al. PRNP genetic variability and molecular typing of natural goat scrapie isolates in a high number of infected flocks. Vet Res. (2011) 42:104. doi: 10.1186/1297-9716-42-104
PubMed Abstract | CrossRef Full Text | Google Scholar
12. Papasavva-Stylianou P, Windl O, Saunders G, Mavrikiou P, Toumazos P, Kakoyiannis C. PrP gene polymorphisms in Cyprus goats and their association with resistance or susceptibility to natural scrapie. Vet J. (2011) 187:245–50. doi: 10.1016/j.tvjl.2009.10.015
CrossRef Full Text | Google Scholar
13. Goldmann W, Ryan K, Stewart P, Parnham D, Xicohtencatl R, Fernandez N, et al. Caprine prion gene polymorphisms are associated with decreased incidence of classical scrapie in goat herds in the United Kingdom. Vet Res. (2011) 42:110. doi: 10.1186/1297-9716-42-110
PubMed Abstract | CrossRef Full Text | Google Scholar
14. Goldmann W, Marier E, Stewart P, Konold T, Street S, Langeveld J, et al. Prion protein genotype survey confirms low frequency of scrapie-resistant K222 allele in British goat herds. Vet Rec. (2016) 178:168. doi: 10.1136/vr.103521
PubMed Abstract | CrossRef Full Text | Google Scholar
15. Windig JJ Hoving RA Priem J Bossers A Keulen LJ and Langeveld JP. Variation in the prion protein sequence in Dutch goat breeds. J Anim Breed Gen. (2016) 133:366–74. doi: 10.1111/jbg.12211
PubMed Abstract | CrossRef Full Text | Google Scholar
16. Bouzalas IG, Dovas CI, Banos G, Papanastasopoulou M, Kritas S, Oevermann A, et al. Caprine PRNP polymorphisms at codons 171, 211, 222 and 240 in a Greek herd and their association with classical scrapie. J Gen Vir. (2010) 91:1629–34. doi: 10.1099/vir.0.017350-0
PubMed Abstract | CrossRef Full Text | Google Scholar
17. EFSA. Scientific and technical assistance on the provisional results of the study on genetic resistance to Classical scrapie in goats in Cyprus. EFSA J. (2012) 10:2972. doi: 10.2903/j.efsa.2012.2972
CrossRef Full Text | Google Scholar
18. Barillet F, Mariat D, Amigues Y, Faugeras R, Caillat H, Moazami-Goudarzi K, et al. Identification of seven haplotypes of the caprine PrP gene at codons 127, 142, 154, 211, 222 and 240 in French Alpine and Saanen breeds and their association with classical scrapie. J Gen Vir. (2009) 90:769–76. doi: 10.1099/vir.0.006114-0
PubMed Abstract | CrossRef Full Text | Google Scholar
19. Acìn C, Martin-Burriel I, Monleon E, Lyahyai J, Pitarch JL, Serrano C, et al. Prion protein gene variability in Spanish goats. Inference through susceptibility to classical scrapie strains and pathogenic distribution of peripheral PrP(sc.). PLoS ONE. (2013) 8:e61118. doi: 10.1371/journal.pone.0061118
PubMed Abstract | CrossRef Full Text | Google Scholar
20. Acutis PL, Colussi S, Santagada G, Laurenza C, Maniaci MG, Riina MV, et al. Genetic variability of the PRNP gene in goat breeds from Northern and Southern Italy. J App Microbiol. (2008) 104:1782–9. doi: 10.1111/j.1365-2672.2007.03703.x
PubMed Abstract | CrossRef Full Text | Google Scholar
21. Migliore S, Agnello S, Chiappini B, Vaccari G, Mignacca SA, Di Marco Lo Presti V, et al. Biodiversity and selection for scrapie resistance in goats: genetic polymorphism in “Girgentana” breed in Sicily, Italy. Small Rum Res. (2015) 125:137–41. doi: 10.1016/j.smallrumres.2015.01.029
CrossRef Full Text | Google Scholar
22. Vitale M, Migliore S, La Giglia M, Alberti P, Di Marco Lo Presti V, Langeveld JP. Scrapie incidence and PRNP polymorphisms: rare small ruminant breeds of Sicily with TSE protecting genetic reservoirs. BMC Vet Res. (2016) 12:141. doi: 10.1186/s12917-016-0766-9
PubMed Abstract | CrossRef Full Text | Google Scholar
23. Fantazi K, Migliore S, Kdidi S, Racinaro L, Tefiel H, Boukhari R, et al. Analysis of differences in prion protein gene (PRNP) polymorphisms between Algerian and southern Italy's goats. Ital J Ani Sci. (2018) 17:578 -85. doi: 10.1016/S1474-4422(18)30205-9
CrossRef Full Text | Google Scholar
24. FAO. Available online at: http://www.fao.org/dad-is/browse-by-country-and-species/en/ (accessed June 30, 2020).
25. Migliore S, Agnello S, D'Avola S, Goldmann W, Di Marco Lo Presti V, et al. A cross-sectional study of PRNP gene in two native Sicilian goat populations in Italy: a relation between prion gene polymorphisms and scrapie incidence. J Genet. (2017) 96:319–25. doi: 10.1007/s12041-017-0776-9
PubMed Abstract | CrossRef Full Text | Google Scholar
26. Sacchi P, Rasero R, Ru G, Aiassa E, Colussi S, Ingravalle F, et al. Predicting the impact of selection for scrapie resistance on PRNP genotype frequencies in goats. Vet Res. (2018) 49:26. doi: 10.1186/s13567-018-0518-x
PubMed Abstract | CrossRef Full Text | Google Scholar
27. Kanata E, Humphreys-Panagiotidis C, Giadinis ND, Papaioannou N, Arsenakis M, Sklaviadis T. Perspectives of a scrapie resistance breeding scheme targeting Q211, S146 and K222 caprine PRNP alleles in Greek goats. Vet Res. (2014) 45:43. doi: 10.1186/1297-9716-45-43
PubMed Abstract | CrossRef Full Text | Google Scholar
Keywords: TSEs: transmissible spongiform encephalopathies, scrapie, PRNP: prion gene name, goat, EU regulation, genetic—disease resistance, biodiversity
Citation: Migliore S, Puleio R and Loria GR (2020) Scrapie Control in EU Goat Population: Has the Last Gap Been Overcome? Front. Vet. Sci. 7:581969. doi: 10.3389/fvets.2020.581969
Received: 10 July 2020; Accepted: 18 August 2020; Published: 29 September 2020.
Edited by:
Satoshi Sekiguchi, University of Miyazaki, Japan Reviewed by:
Timm Konold, Animal and Plant Health Agency, United Kingdom Copyright © 2020 Migliore, Puleio and Loria. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Sergio Migliore, migliore.sergio@gmail.com
"In spite of the poorly defined effects of PRNP genetics, scrapie strain, dose, route and source of infection, the caprine placenta may represent a source of infection to progeny and herd mates as well as a source of persistent environmental contamination."
Could this route of infection be the cause of the many cases of Goat scrapie from the same herd in Michigan USA ?
Has this been investigated ?
(Figure 6) including five goat cases in FY 2008 that originated from the same herd in Michigan. This is highly unusual for goats, and I strenuously urge that there should be an independent investigation into finding the common denominator for these 5 goats in the same herd in Michigan with Scrapie. ...
Kind Regards, Terry
SNIP...
Scrapie Nor-98 like case in California FY 2011 AS of December 31, 2010.
Scrapie cases in goats FY 2002 - 2011 AS of December 31, 2010 Total goat cases = 21 Scrapie cases, 0 Nor-98 like Scrapie cases (21 field cases, 0 RSSS cases)
Last herd with infected goats disignated in FY 2008 Michigan 8 cases
UPDATED RESPONSE ON MY CONCERNS OF GOAT SCRAPIE IN MICHIGAN ;
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Your discussion posting "Scrapie cases Goats from same herd USA Michigan" has been rejected by the moderator as not being appropriate for inclusion on the site.
Dear Mr Singeltary,
Thank you for submitting your comment on BMC Veterinary Research article (2011, 7:7). We have read your comment with interest but we feel that only the authors of the article can answer your question about further investigation of the route of infection of the five goats in Michigan. We advise that you contact the authors directly rather than post a comment on the article.
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SNIP...PLEASE SEE FULL TEXT ;
Tuesday, February 01, 2011
Sparse PrP-Sc accumulation in the placentas of goats with naturally acquired scrapie
Research article
Thursday, March 29, 2012
*** atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012
NIAA Annual Conference April 11-14, 2011San Antonio, Texas
***SCRAPIE GOATS CALIFORNIA 13 CASES TO DATE ! ***
***SCRAPIE GOATS MICHIGAN 8 CASES TO DATE ! ***
(an unusually high amount of scrapie documented in goats for a happenstance of bad luck, or spontaneous event, THAT DOES NOT HAPPEN IN OTHER STATES ??? )
Sunday, June 2, 2013
Characterisation of an Unusual TSE in a Goat by Transmission in Knock-in Transgenic Mice
National Scrapie Eradication Program
August 2020 Monthly Report
Fiscal Year 2020
U.S. Department of Agriculture Animal and Plant Health Inspection Service
Veterinary Services
Strategy and Policy, Ruminant Health Center
Small Ruminant Health
September 15, 2020
Components of Scrapie Surveillance
• Regulatory Scrapie Slaughter Surveillance (RSSS) started April 1, 2003. It is a targeted slaughter surveillance program which is designed to identify infected flocks. Samples have been collected from 664,462 animals since April 1, 2003. As of August 31, 2020, 29,680 samples have been collected in FY 2020, 23,524 from sheep and 6,156 from goats. There have been 488 NVSL confirmed positive animals (473 classical cases – 470 sheep and 3 goats) and 16 Nor98-like cases since the beginning of RSSS. No animals have tested positive for classical scrapie in FY 2020.
Scrapie in Goats –The total number of NVSL confirmed positive cases in goats is 44 since FY 2002. Samples from three of these positive animals were collected through RSSS, one in November 2014, the second in July 2018, and the most recent in June 2019. The remainder of the positive cases have been found through testing of clinical suspects, testing of exposed animals, and trace-out investigations. Figure 1 shows the number of positive cases by State and by fiscal year of last reported case.
P.97: Scrapie transmits to white-tailed deer by the oral route and has a molecular profile similar to chronic wasting disease and distinct from the scrapie inoculum
Justin Greenlee1, S JO Moore1, Jodi Smith1, M Heather WestGreenlee2 and Robert Kunkle1
1National Animal Disease Center; Ames, IA USA
2Iowa State University; Ames, IA USA
The purpose of this work was to determine susceptibility of white-tailed deer (WTD) to the agent of sheep scrapie and to compare the resultant PrPSc to that of the original inoculum and chronic wasting disease (CWD). We inoculated WTD by a natural route of exposure (concurrent oral and intranasal (IN); n = 5) with a US scrapie isolate. All scrapie-inoculated deer had evidence of PrPSc accumulation. PrPSc was detected in lymphoid tissues at preclinical time points, and deer necropsied after 28 months post-inoculation had clinical signs, spongiform encephalopathy, and widespread distribution of PrPSc in neural and lymphoid tissues. Western blotting (WB) revealed PrPSc with 2 distinct molecular profiles. WB on cerebral cortex had a profile similar to the original scrapie inoculum, whereas WB of brainstem, cerebellum, or lymph nodes revealed PrPSc with a higher profile resembling CWD. Homogenates with the 2 distinct profiles from WTD with clinical scrapie were further passaged to mice expressing cervid prion protein and intranasally to sheep and WTD. In cervidized mice, the 2 inocula have distinct incubation times. Sheep inoculated intranasally with WTD derived scrapie developed disease, but only after inoculation with the inoculum that had a scrapie-like profile. The WTD study is ongoing, but deer in both inoculation groups are positive for PrPSc by rectal mucosal biopsy.
***In summary, this work demonstrates that WTD are susceptible to the agent of scrapie, 2 distinct molecular profiles of PrPSc are present in the tissues of affected deer, and inoculum of either profile readily passes to deer.
*** After a natural route of exposure, 100% of WTD were susceptible to scrapie.
PO-039: A comparison of scrapie and chronic wasting disease in white-tailed deer Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture; Agricultural Research Service, National Animal Disease Center; Ames, IA USA
White-tailed deer are susceptible to the agent of sheep scrapie by intracerebral inoculation
snip...
It is unlikely that CWD will be eradicated from free-ranging cervids, and the disease is likely to continue to spread geographically [10]. However, the potential that white-tailed deer may be susceptible to sheep scrapie by a natural route presents an additional confounding factor to halting the spread of CWD. This leads to the additional speculations that
1) infected deer could serve as a reservoir to infect sheep with scrapie offering challenges to scrapie eradication efforts and
2) CWD spread need not remain geographically confined to current endemic areas, but could occur anywhere that sheep with scrapie and susceptible cervids cohabitate.
This work demonstrates for the first time that white-tailed deer are susceptible to sheep scrapie by intracerebral inoculation with a high attack rate and that the disease that results has similarities to CWD. These experiments will be repeated with a more natural route of inoculation to determine the likelihood of the potential transmission of sheep scrapie to white-tailed deer. If scrapie were to occur in white-tailed deer, results of this study indicate that it would be detected as a TSE, but may be difficult to differentiate from CWD without in-depth biochemical analysis.
2012
PO-039: A comparison of scrapie and chronic wasting disease in white-tailed deer
Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture; Agricultural Research Service, National Animal Disease Center; Ames, IA USA
snip...
The results of this study suggest that there are many similarities in the manifestation of CWD and scrapie in WTD after IC inoculation including early and widespread presence of PrPSc in lymphoid tissues, clinical signs of depression and weight loss progressing to wasting, and an incubation time of 21-23 months. Moreover, western blots (WB) done on brain material from the obex region have a molecular profile similar to CWD and distinct from tissues of the cerebrum or the scrapie inoculum. However, results of microscopic and IHC examination indicate that there are differences between the lesions expected in CWD and those that occur in deer with scrapie: amyloid plaques were not noted in any sections of brain examined from these deer and the pattern of immunoreactivity by IHC was diffuse rather than plaque-like.
*** After a natural route of exposure, 100% of WTD were susceptible to scrapie.
Deer developed clinical signs of wasting and mental depression and were necropsied from 28 to 33 months PI. Tissues from these deer were positive for PrPSc by IHC and WB. Similar to IC inoculated deer, samples from these deer exhibited two different molecular profiles: samples from obex resembled CWD whereas those from cerebrum were similar to the original scrapie inoculum. On further examination by WB using a panel of antibodies, the tissues from deer with scrapie exhibit properties differing from tissues either from sheep with scrapie or WTD with CWD. Samples from WTD with CWD or sheep with scrapie are strongly immunoreactive when probed with mAb P4, however, samples from WTD with scrapie are only weakly immunoreactive. In contrast, when probed with mAb’s 6H4 or SAF 84, samples from sheep with scrapie and WTD with CWD are weakly immunoreactive and samples from WTD with scrapie are strongly positive. This work demonstrates that WTD are highly susceptible to sheep scrapie, but on first passage, scrapie in WTD is differentiable from CWD.
2011
*** After a natural route of exposure, 100% of white-tailed deer were susceptible to scrapie.
ZOONOSIS OF SCRAPIE TSE PRION
O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France
Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases).
Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.
*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,
***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),
***is the third potentially zoonotic PD (with BSE and L-type BSE),
***thus questioning the origin of human sporadic cases.
We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.
===============
***thus questioning the origin of human sporadic cases***
===============
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
==============
***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.
***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
PRION 2016 TOKYO
Saturday, April 23, 2016
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France
Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion... Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.
To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.
These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.
Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.
Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
***> why do we not want to do TSE transmission studies on chimpanzees $
5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man.
***> I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough.
***> Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.
snip...
R. BRADLEY
Title: Transmission of scrapie prions to primate after an extended silent incubation period)
*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.
*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.
*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.
***> Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility. <***
Transmission of scrapie prions to primate after an extended silent incubation period
Emmanuel E. Comoy, Jacqueline Mikol, Sophie Luccantoni-Freire, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Valérie Durand, Capucine Dehen, Olivier Andreoletti, Cristina Casalone, Juergen A. Richt, Justin J. Greenlee, Thierry Baron, Sylvie L. Benestad, Paul Brown & Jean-Philippe Deslys Scientific Reports volume 5, Article number: 11573 (2015) | Download Citation
Abstract
Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans and having guided protective measures for animal and human health against animal prion diseases. Recently, partial transmissions to humanized mice showed that the zoonotic potential of scrapie might be similar to c-BSE. We here report the direct transmission of a natural classical scrapie isolate to cynomolgus macaque, a highly relevant model for human prion diseases, after a 10-year silent incubation period, with features similar to those reported for human cases of sporadic CJD. Scrapie is thus actually transmissible to primates with incubation periods compatible with their life expectancy, although fourfold longer than BSE. Long-term experimental transmission studies are necessary to better assess the zoonotic potential of other prion diseases with high prevalence, notably Chronic Wasting Disease of deer and elk and atypical/Nor98 scrapie.
SNIP...
Discussion We describe the transmission of spongiform encephalopathy in a non-human primate inoculated 10 years earlier with a strain of sheep c-scrapie. Because of this extended incubation period in a facility in which other prion diseases are under study, we are obliged to consider two alternative possibilities that might explain its occurrence. We first considered the possibility of a sporadic origin (like CJD in humans). Such an event is extremely improbable because the inoculated animal was 14 years old when the clinical signs appeared, i.e. about 40% through the expected natural lifetime of this species, compared to a peak age incidence of 60–65 years in human sporadic CJD, or about 80% through their expected lifetimes. Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.
The second possibility is a laboratory cross-contamination. Three facts make this possibility equally unlikely. First, handling of specimens in our laboratory is performed with fastidious attention to the avoidance of any such cross-contamination. Second, no laboratory cross-contamination has ever been documented in other primate laboratories, including the NIH, even between infected and uninfected animals housed in the same or adjacent cages with daily intimate contact (P. Brown, personal communication). Third, the cerebral lesion profile is different from all the other prion diseases we have studied in this model19, with a correlation between cerebellar lesions (massive spongiform change of Purkinje cells, intense PrPres staining and reactive gliosis26) and ataxia. The iron deposits present in the globus pallidus are a non specific finding that have been reported previously in neurodegenerative diseases and aging27. Conversely, the thalamic lesion was reminiscent of a metabolic disease due to thiamine deficiency28 but blood thiamine levels were within normal limits (data not shown). The preferential distribution of spongiform change in cortex associated with a limited distribution in the brainstem is reminiscent of the lesion profile in MM2c and VV1 sCJD patients29, but interspecies comparison of lesion profiles should be interpreted with caution. It is of note that the same classical scrapie isolate induced TSE in C57Bl/6 mice with similar incubation periods and lesional profiles as a sample derived from a MM1 sCJD patient30.
We are therefore confident that the illness in this cynomolgus macaque represents a true transmission of a sheep c-scrapie isolate directly to an old-world monkey, which taxonomically resides in the primate subdivision (parvorder of catarrhini) that includes humans. With an homology of its PrP protein with humans of 96.4%31, cynomolgus macaque constitutes a highly relevant model for assessing zoonotic risk of prion diseases. Since our initial aim was to show the absence of transmission of scrapie to macaques in the worst-case scenario, we obtained materials from a flock of naturally-infected sheep, affecting animals with different genotypes32. This c-scrapie isolate exhibited complete transmission in ARQ/ARQ sheep (332 ± 56 days) and Tg338 transgenic mice expressing ovine VRQ/VRQ prion protein (220 ± 5 days) (O. Andreoletti, personal communication). From the standpoint of zoonotic risk, it is important to note that sheep with c-scrapie (including the isolate used in our study) have demonstrable infectivity throughout their lymphoreticular system early in the incubation period of the disease (3 months-old for all the lymphoid organs, and as early as 2 months-old in gut-associated lymph nodes)33. In addition, scrapie infectivity has been identified in blood34, milk35 and skeletal muscle36 from asymptomatic but scrapie infected small ruminants which implies a potential dietary exposure for consumers.
Two earlier studies have reported the occurrence of clinical TSE in cynomolgus macaques after exposures to scrapie isolates. In the first study, the “Compton” scrapie isolate (derived from an English sheep) and serially propagated for 9 passages in goats did not transmit TSE in cynomolgus macaque, rhesus macaque or chimpanzee within 7 years following intracerebral challenge1; conversely, after 8 supplementary passages in conventional mice, this “Compton” isolate induced TSE in a cynomolgus macaque 5 years after intracerebral challenge, but rhesus macaques and chimpanzee remained asymptomatic 8.5 years post-exposure8. However, multiple successive passages that are classically used to select laboratory-adapted prion strains can significantly modify the initial properties of a scrapie isolate, thus questioning the relevance of zoonotic potential for the initial sheep-derived isolate. The same isolate had also induced disease into squirrel monkeys (new-world monkey)9. A second historical observation reported that a cynomolgus macaque developed TSE 6 years post-inoculation with brain homogenate from a scrapie-infected Suffolk ewe (derived from USA), whereas a rhesus macaque and a chimpanzee exposed to the same inoculum remained healthy 9 years post-exposure1. This inoculum also induced TSE in squirrel monkeys after 4 passages in mice. Other scrapie transmission attempts in macaque failed but had more shorter periods of observation in comparison to the current study. Further, it is possible that there are differences in the zoonotic potential of different scrapie strains.
The most striking observation in our study is the extended incubation period of scrapie in the macaque model, which has several implications. Firstly, our observations constitute experimental evidence in favor of the zoonotic potential of c-scrapie, at least for this isolate that has been extensively studied32,33,34,35,36. The cross-species zoonotic ability of this isolate should be confirmed by performing duplicate intracerebral exposures and assessing the transmissibility by the oral route (a successful transmission of prion strains through the intracerebral route may not necessarily indicate the potential for oral transmission37). However, such confirmatory experiments may require more than one decade, which is hardly compatible with current general management and support of scientific projects; thus this study should be rather considered as a case report.
Secondly, transmission of c-BSE to primates occurred within 8 years post exposure for the lowest doses able to transmit the disease (the survival period after inoculation is inversely proportional to the initial amount of infectious inoculum). The occurrence of scrapie 10 years after exposure to a high dose (25 mg) of scrapie-infected sheep brain suggests that the macaque has a higher species barrier for sheep c-scrapie than c-BSE, although it is notable that previous studies based on in vitro conversion of PrP suggested that BSE and scrapie prions would have a similar conversion potential for human PrP38.
Thirdly, prion diseases typically have longer incubation periods after oral exposure than after intracerebral inoculations: since humans can develop Kuru 47 years after oral exposure39, an incubation time of several decades after oral exposure to scrapie would therefore be expected, leading the disease to occur in older adults, i.e. the peak age for cases considered to be sporadic disease, and making a distinction between scrapie-associated and truly sporadic disease extremely difficult to appreciate.
Fourthly, epidemiologic evidence is necessary to confirm the zoonotic potential of an animal disease suggested by experimental studies. A relatively short incubation period and a peculiar epidemiological situation (e.g., all the first vCJD cases occurring in the country with the most important ongoing c-BSE epizootic) led to a high degree of suspicion that c-BSE was the cause of vCJD. Sporadic CJD are considered spontaneous diseases with an almost stable and constant worldwide prevalence (0.5–2 cases per million inhabitants per year), and previous epidemiological studies were unable to draw a link between sCJD and classical scrapie6,7,40,41, even though external causes were hypothesized to explain the occurrence of some sCJD clusters42,43,44. However, extended incubation periods exceeding several decades would impair the predictive values of epidemiological surveillance for prion diseases, already weakened by a limited prevalence of prion diseases and the multiplicity of isolates gathered under the phenotypes of “scrapie” and “sporadic CJD”.
Fifthly, considering this 10 year-long incubation period, together with both laboratory and epidemiological evidence of decade or longer intervals between infection and clinical onset of disease, no premature conclusions should be drawn from negative transmission studies in cynomolgus macaques with less than a decade of observation, as in the aforementioned historical transmission studies of scrapie to primates1,8,9. Our observations and those of others45,46 to date are unable to provide definitive evidence regarding the zoonotic potential of CWD, atypical/Nor98 scrapie or H-type BSE. The extended incubation period of the scrapie-affected macaque in the current study also underscores the limitations of rodent models expressing human PrP for assessing the zoonotic potential of some prion diseases since their lifespan remains limited to approximately two years21,47,48. This point is illustrated by the fact that the recently reported transmission of scrapie to humanized mice was not associated with clinical signs for up to 750 days and occurred in an extreme minority of mice with only a marginal increase in attack rate upon second passage13. The low attack rate in these studies is certainly linked to the limited lifespan of mice compared to the very long periods of observation necessary to demonstrate the development of scrapie. Alternatively, one could estimate that a successful second passage is the result of strain adaptation to the species barrier, thus poorly relevant of the real zoonotic potential of the original scrapie isolate of sheep origin49. The development of scrapie in this primate after an incubation period compatible with its lifespan complements the study conducted in transgenic (humanized) mice; taken together these studies suggest that some isolates of sheep scrapie can promote misfolding of the human prion protein and that scrapie can develop within the lifespan of some primate species.
In addition to previous studies on scrapie transmission to primate1,8,9 and the recently published study on transgenic humanized mice13, our results constitute new evidence for recommending that the potential risk of scrapie for human health should not be dismissed. Indeed, human PrP transgenic mice and primates are the most relevant models for investigating the human transmission barrier. To what extent such models are informative for measuring the zoonotic potential of an animal TSE under field exposure conditions is unknown. During the past decades, many protective measures have been successfully implemented to protect cattle from the spread of c-BSE, and some of these measures have been extended to sheep and goats to protect from scrapie according to the principle of precaution. Since cases of c-BSE have greatly reduced in number, those protective measures are currently being challenged and relaxed in the absence of other known zoonotic animal prion disease. We recommend that risk managers should be aware of the long term potential risk to human health of at least certain scrapie isolates, notably for lymphotropic strains like the classical scrapie strain used in the current study. Relatively high amounts of infectivity in peripheral lymphoid organs in animals infected with these strains could lead to contamination of food products produced for human consumption. Efforts should also be maintained to further assess the zoonotic potential of other animal prion strains in long-term studies, notably lymphotropic strains with high prevalence like CWD, which is spreading across North America, and atypical/Nor98 scrapie (Nor98)50 that was first detected in the past two decades and now represents approximately half of all reported cases of prion diseases in small ruminants worldwide, including territories previously considered as scrapie free... Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.
Like lambs to the slaughter
* 31 March 2001 *
Debora MacKenzie *
Magazine issue 2284
Suspect symptoms
What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?
Exclusive from New Scientist magazine
Four years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious.
The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.
Photo: Murdo McLeod
Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise.
He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals.
Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears.
To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris.
Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.
Brain damage Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health.
But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.
Deslys and colleagues were originally studying vCJD, not sCJD.
They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three.
Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.
As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain.
As expected, they all affected the brain in a different way from BSE and vCJD.
But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology. Multiple strains "The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys.
"You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie," she says.
In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar. But there are more than 20 strains of scrapie, and six of sCJD.
"You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys.
Bruce is cautious about the mouse results, but agrees they require further investigation.
Other trials of scrapie and sCJD in mice, she says, are in progress.
Deformed proteins People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways.
Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD. But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD.
"If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection."
There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere.
Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain.
Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.
Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE.
And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.
More at: Proceedings of the National Academy of Sciences (vol 98, p 4142)
Correspondence about this story should be directed to letters@newscientist.com 1900 GMT, 28 March 2001
* New Scientist
http://www.newscientist.com/dailynews/news.jsp?id=ns9999560
http://www.newscientist.com/article.ns?id=mg16922840.300
http://www.newscientist.com/article.ns?id=mg16922840.300
WEDNESDAY, NOVEMBER 20, 2019
Review: Update on Classical and Atypical Scrapie in Sheep and Goats
THE USA BSE TSE Prion surveillance, testing, feed ban, SRM all failed terribly...to this day!
*>>> ''Assuming that current risk control measures are continuously implemented as mentioned above.''
IN A NUT SHELL ;
(Adopted by the International Committee of the OIE on 23 May 2006)
11. Information published by the OIE is derived from appropriate declarations made by the official Veterinary Services of Member Countries. The OIE is not responsible for inaccurate publication of country disease status based on inaccurate information or changes in epidemiological status or other significant events that were not promptly reported to the Central Bureau,
Friday, December 14, 2012
DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced into Great Britain? A Qualitative Risk Assessment October 2012
snip.....
In the USA, under the Food and Drug Administration's BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system. However, this recommendation is guidance and not a requirement by law. Animals considered at high risk for CWD include:
1) animals from areas declared to be endemic for CWD and/or to be CWD eradication zones and
2) deer and elk that at some time during the 60-month period prior to slaughter were in a captive herd that contained a CWD-positive animal.
Therefore, in the USA, materials from cervids other than CWD positive animals may be used in animal feed and feed ingredients for non-ruminants.
The amount of animal PAP that is of deer and/or elk origin imported from the USA to GB can not be determined, however, as it is not specified in TRACES.
It may constitute a small percentage of the 8412 kilos of non-fish origin processed animal proteins that were imported from US into GB in 2011.
Overall, therefore, it is considered there is a __greater than negligible risk___ that (nonruminant) animal feed and pet food containing deer and/or elk protein is imported into GB.
There is uncertainty associated with this estimate given the lack of data on the amount of deer and/or elk protein possibly being imported in these products.
snip.....
36% in 2007 (Almberg et al., 2011). In such areas, population declines of deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of Colorado, the prevalence can be as high as 30% (EFSA, 2011). The clinical signs of CWD in affected adults are weight loss and behavioural changes that can span weeks or months (Williams, 2005). In addition, signs might include excessive salivation, behavioural alterations including a fixed stare and changes in interaction with other animals in the herd, and an altered stance (Williams, 2005). These signs are indistinguishable from cervids experimentally infected with bovine spongiform encephalopathy (BSE). Given this, if CWD was to be introduced into countries with BSE such as GB, for example, infected deer populations would need to be tested to differentiate if they were infected with CWD or BSE to minimise the risk of BSE entering the human food-chain via affected venison. snip..... The rate of transmission of CWD has been reported to be as high as 30% and can approach 100% among captive animals in endemic areas (Safar et al., 2008).
snip.....
In summary, in endemic areas, there is a medium probability that the soil and surrounding environment is contaminated with CWD prions and in a bioavailable form. In rural areas where CWD has not been reported and deer are present, there is a greater than negligible risk the soil is contaminated with CWD prion. snip..... In summary, given the volume of tourists, hunters and servicemen moving between GB and North America, the probability of at least one person travelling to/from a CWD affected area and, in doing so, contaminating their clothing, footwear and/or equipment prior to arriving in GB is greater than negligible... For deer hunters, specifically, the risk is likely to be greater given the increased contact with deer and their environment. However, there is significant uncertainty associated with these estimates.
snip.....
Therefore, it is considered that farmed and park deer may have a higher probability of exposure to CWD transferred to the environment than wild deer given the restricted habitat range and higher frequency of contact with tourists and returning GB residents.
snip.....
***> READ THIS VERY, VERY, CAREFULLY, AUGUST 1997 MAD COW FEED BAN WAS A SHAM, AS I HAVE STATED SINCE 1997! 3 FAILSAFES THE FDA ET AL PREACHED AS IF IT WERE THE GOSPEL, IN TERMS OF MAD COW BSE DISEASE IN USA, AND WHY IT IS/WAS/NOT A PROBLEM FOR THE USA, and those are;
BSE TESTING (failed terribly and proven to be a sham)
BSE SURVEILLANCE (failed terribly and proven to be a sham)
BSE 589.2001 FEED REGULATIONS (another colossal failure, and proven to be a sham)
these are facts folks. trump et al just admitted it with the feed ban.
see;
FDA Reports on VFD Compliance
John Maday
August 30, 2019 09:46 AM VFD-Form 007 (640x427)
Before and after the current Veterinary Feed Directive rules took full effect in January, 2017, the FDA focused primarily on education and outreach. ( John Maday ) Before and after the current Veterinary Feed Directive (VFD) rules took full effect in January, 2017, the FDA focused primarily on education and outreach to help feed mills, veterinarians and producers understand and comply with the requirements. Since then, FDA has gradually increased the number of VFD inspections and initiated enforcement actions when necessary. On August 29, FDA released its first report on inspection and compliance activities. The report, titled “Summary Assessment of Veterinary Feed Directive Compliance Activities Conducted in Fiscal Years 2016 – 2018,” is available online.
SUNDAY, SEPTEMBER 1, 2019
***> FDA Reports on VFD Compliance
America BSE 589.2001 FEED REGULATIONS, BSE SURVEILLANCE, BSE TESTING, and CJD TSE Prion
***> cattle, pigs, sheep, cwd, tse, prion, oh my!
***> In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006).
Sheep and cattle may be exposed to CWD via common grazing areas with affected deer but so far, appear to be poorly susceptible to mule deer CWD (Sigurdson, 2008). In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006). It is not known how susceptible humans are to CWD but given that the prion can be present in muscle, it is likely that humans have been exposed to the agent via consumption of venison (Sigurdson, 2008). Initial experimental research suggests that human susceptibility to CWD is low and there may be a robust species barrier for CWD transmission to humans (Sigurdson, 2008), however the risk appetite for a public health threat may still find this level unacceptable.
cwd scrapie pigs oral routes
***> However, at 51 months of incubation or greater, 5 animals were positive by one or more diagnostic methods. Furthermore, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study) suggesting that swine are potential hosts for the agent of scrapie. <***
>*** Although the current U.S. feed ban is based on keeping tissues from TSE infected cattle from contaminating animal feed, swine rations in the U.S. could contain animal derived components including materials from scrapie infected sheep and goats. These results indicating the susceptibility of pigs to sheep scrapie, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health. <***
***> Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 month group was positive by EIA. PrPSc was detected by QuIC in at least one of the lymphoid tissues examined in 5/6 pigs in the intracranial <6 months group, 6/7 intracranial >6 months group, 5/6 pigs in the oral <6 months group, and 4/6 oral >6 months group. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%).
***> Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.
MONDAY, AUGUST 24, 2020
Very low oral exposure to prions of brain or saliva origin can transmit chronic wasting disease
WEDNESDAY, APRIL 24, 2019
USDA Announces Atypical Bovine Spongiform Encephalopathy Detection Aug 29, 2018 A Review of Science 2019
WEDNESDAY, JULY 31, 2019
The agent of transmissible mink encephalopathy passaged in sheep is similar to BSE-L
TUESDAY, JUNE 30, 2020
National Scrapie Eradication Program May 2020 Monthly Report Fiscal Year 2020 U.S. Department of Agriculture Animal and Plant Health Inspection Service Veterinary Services Strategy and Policy, Ruminant Health Center Small Ruminant Health June 15, 2020
MONDAY, JULY 27, 2020
APHIS USDA Nor98-like scrapie was confirmed in a sheep sampled at slaughter in May 2020
TUESDAY, SEPTEMBER 22, 2020
APHIS USDA MORE SCRAPIE ATYPICAL Nor-98 Confirmed USA September 15 2020
March 2019
Pennsylvania Scrapie Infected Sheep Goat Flock
WEDNESDAY, NOVEMBER 20, 2019
Sheep Are Susceptible to the Bovine Adapted Transmissible Mink Encephalopathy agent by Intracranial Inoculation and Have Evidence of Infectivity in Lymphoid Tissues
***> ''indicating that sheep inoculated with the bovine TME agent harbor infectivity in their lymph nodes despite a lack of detection with conventional immunoassays.''
TUESDAY, APRIL 24, 2018
ARS Research atypical Nor98 and Michigan Scrapie, CWD, CJD and mad cow feed
MONDAY, FEBRUARY 25, 2019
MAD DOGS AND ENGLISHMEN BSE, SCRAPIE, CWD, CJD, TSE PRION A REVIEW 2019
MONDAY, JULY 27, 2020
BSE Inquiry DFA's a review
FRIDAY, OCTOBER 2, 2020
H.R.925 America's Conservation Enhancement Act 116th Congress 2019-2020 SEC 104 CHRONIC WASTING DISEASE TASK FORCE
https://animalhealthreportpriontse.blogspot.com/2020/10/hr925-americas-conservation-enhancement.html
SUNDAY, OCTOBER 4, 2020
Cattle Meat and Offal Imported from the United States of America, Canada and Ireland to Japan (Prions) Food Safety Commission of Japan
TUESDAY, SEPTEMBER 29, 2020
ISO's Updated 22442 Animal Tissue Standards — What Changed? TSE Prion!
'Why is USDA "only" testing 25,000 samples a year?
TUESDAY, AUGUST 18, 2020
Sheep Scrapie, Bovine BSE, Cervid CWD, ZOONOSIS, TSE Prion Roundup August 18, 2020
MONDAY, OCTOBER 05, 2020
USA, UK, JAPAN, CJD TSE PRION STATISTICS UPDATE OCTOBER 2020
APHIS-2018-0087-0002
PUBLIC SUBMISSION
Comment from Terry Singeltary
Posted by the Animal and Plant Health Inspection Service on Jun 19, 2019
APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087] Singeltary Submission
Greetings APHIS et al,
I would kindly like to comment on APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087], and my comments are as follows, with the latest peer review and transmission studies as references of evidence.
THE OIE/USDA BSE Minimal Risk Region MRR is nothing more than free pass to import and export the Transmissible Spongiform Encephalopathy TSE Prion disease. December 2003, when the USDA et al lost it's supposedly 'GOLD CARD' ie BSE FREE STATUS (that was based on nothing more than not looking and not finding BSE), once the USA lost it's gold card BSE Free status, the USDA OIE et al worked hard and fast to change the BSE Geographical Risk Statuses i.e. the BSE GBR's, and replaced it with the BSE MRR policy, the legal tool to trade mad cow type disease TSE Prion Globally. The USA is doing just what the UK did, when they shipped mad cow disease around the world, except with the BSE MRR policy, it's now legal.
Also, the whole concept of the BSE MRR policy is based on a false pretense, that atypical BSE is not transmissible, and that only typical c-BSE is transmissible via feed. This notion that atypical BSE TSE Prion is an old age cow disease that is not infectious is absolutely false, there is NO science to show this, and on the contrary, we now know that atypical BSE will transmit by ORAL ROUTES, but even much more concerning now, recent science has shown that Chronic Wasting Disease CWD TSE Prion in deer and elk which is rampant with no stopping is sight in the USA, and Scrapie TSE Prion in sheep and goat, will transmit to PIGS by oral routes, this is our worst nightmare, showing even more risk factors for the USA FDA PART 589 TSE PRION FEED ban.
The FDA PART 589 TSE PRION FEED ban has failed terribly bad, and is still failing, since August 1997. there is tonnage and tonnage of banned potential mad cow feed that went into commerce, and still is, with one decade, 10 YEARS, post August 1997 FDA PART 589 TSE PRION FEED ban, 2007, with 10,000,000 POUNDS, with REASON, Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement. you can see all these feed ban warning letters and tonnage of mad cow feed in commerce, year after year, that is not accessible on the internet anymore like it use to be, you can see history of the FDA failure August 1997 FDA PART 589 TSE PRION FEED ban here, but remember this, we have a new outbreak of TSE Prion disease in a new livestock species, the camel, and this too is very worrisome.
WITH the OIE and the USDA et al weakening the global TSE prion surveillance, by not classifying the atypical Scrapie as TSE Prion disease, and the notion that they want to do the same thing with typical scrapie and atypical BSE, it's just not scientific.
WE MUST abolish the BSE MRR policy, go back to the BSE GBR risk assessments by country, and enhance them to include all strains of TSE Prion disease in all species. With Chronic Wasting CWD TSE Prion disease spreading in Europe, now including, Norway, Finland, Sweden, also in Korea, Canada and the USA, and the TSE Prion in Camels, the fact the the USA is feeding potentially CWD, Scrapie, BSE, typical and atypical, to other animals, and shipping both this feed and or live animals or even grains around the globe, potentially exposed or infected with the TSE Prion. this APHIS Concurrence With OIE Risk Designation for Bovine Spongiform Encephalopathy [Docket No. APHIS-2018-0087], under it's present definition, does NOT show the true risk of the TSE Prion in any country. as i said, it's nothing more than a legal tool to trade the TSE Prion around the globe, nothing but ink on paper.
AS long as the BSE MRR policy stays in effect, TSE Prion disease will continued to be bought and sold as food for both humans and animals around the globe, and the future ramifications from friendly fire there from, i.e. iatrogenic exposure and transmission there from from all of the above, should not be underestimated. ...
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. | 11:30 AM
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