Five Cases Atypical scrapie in Australia to date

Five Cases Atypical scrapie in Australia to date

Atypical scrapie in Australia

RW Cook, a * J Bingham, b AS Besier, c CL Bayley, d M Hawes, e PL Shearer, f M Yamada, b J Bergfeld, b DT Williams b and DJ Middleton b

Background

Since its initial detection in Norway in 1998, atypical scrapie (‘atypical/Nor98 scrapie’) has been reported in sheep in the majority of European countries (including in regions free of classical scrapie) and in the Falkland Islands, the USA, Canada, New Zealand and Australia.

Case series

The diagnosis in Australia of atypical scrapie in four Merino and one Merino-cross sheep showing clinical signs of neurological disease was based on the detection of grey matter neuropil vacuolation (spongiform change) in the brain (particularly in the molecular layer of the cerebellar cortex) and associated abnormal prion protein (PrP Sc ) deposition in both grey and white matter. Changes were minimal in the caudal brainstem, the predilection site for lesions of classical scrapie.

Conclusion

The distinctive lesion profile of atypical scrapie in these five sheep highlights the diagnostic importance of routine histological evaluation of the cerebellum for evidence of neuropil vacuolation and associated PrP Sc deposition in adult sheep with suspected neurological disease.

Keywords

atypical scrapie; prion disease; sheep; transmissible spongiform encephalopathy

Abbreviations ANZSDP, Australian and New Zealand Standard Diagnostic Procedure; CNS, central nervous system; DMNV, dorsal motor nucleus of the vagus nerve; H&E, haematoxylin and eosin; IHC, immunohistochemistry; NTSESP, National TSE Surveillance Program; PrP Sc , abnormal prion protein isomer; TSE, transmissible spongiform encephalopathy. Aust Vet J 2016 doi: 10.1111/avj.12529

Scrapie is a transmissible spongiform encephalopathy (TSE) or prion disease of small ruminants that occurs in classical and atypical forms. Classical scrapie is characterised histologically by vacuolation and abnormal prion protein (PrP Sc ) immunolabelling of neuronal cytoplasm and grey matter neuropil within the central nervous system (CNS), with a predilection for the caudal brainstem, mainly at the level of the obex and typically involving the dorsal motor nucleus of the vagus nerve (DMNV).1 The Western immuno- blot pattern (‘molecular signature’) of PrP Sc extracted from brains of classical scrapie cases has three bands comprising unglycosylated, monoglycosylated and diglycosylated PrP Sc residues with molecular masses between 18 and 30 kDa.2

In contrast, atypical scrapie (‘atypical/Nor98 scrapie’)is defined by a characteristic neuroanatomical distribution of neuropil vacuolation and PrP Sc immunolabelling in the brain, and a multiband PrP Sc Western immunoblot pattern with a fast-migrating, lower band of molecular mass <15 2="" 5="" also="" and="" at="" basal="" brain.2="" cerebellar="" cerebral="" change="" cortex="" demonstrates="" deposition="" detected="" ganglia.="" grey="" immu-="" immunohistochemistry="" in="" intracytoplasmic="" is="" kda.="" layer="" mainly="" matter="" molecular="" nerve="" neurons.3="" neuropil="" no="" nolabelling="" nucleus="" of="" or="" p="" particularly="" prp="" sc="" sites="" spinal="" spongiform="" the="" there="" these="" throughout="" tract="" trigeminal="" vacuolation="" white="" within="">
Since its initial detection in Norway in 1998,5 atypical scrapie has been reported in sheep in the majority of European countries (including in regions free of classical scrapie)2,6 and in the Falkland Islands,7 the USA,8 Canada,9 New Zealand10 and Australia.11,12 It usually occurs as single cases within sheep flocks, in an older age range than classical scrapie, and is often found in sheep with prion protein genotypes associated with resistance to classical scrapie.2

Worldwide, most cases of atypical scrapie have been detected during surveillance testing of apparently healthy sheep at slaughter or fallen stock (diseased or dead animals) by rapid immunochemical methods introduced for testing of small ruminants for TSE in the European Union from 2002.4,6 Prevalence estimates of atypical scrapie from these two test populations (slaughter and fallen stock) were remarkably uniform across 14 European countries (average 6.1 and 8.2 cases, respectively, per 10,000 tests), in contrast to the more variable and clustered occurrence of classical scrapie.6

The National TSE Surveillance Program (NTSESP) in Australia includes passive surveillance for classical scrapie by histological screening of brains from sheep (at least 18 months of age) with clini- cal signs of progressive neurological disease.13 In this report, we describe the clinical and pathological findings in five NTSESP cases of atypical scrapie detected in New South Wales (in 1999 and 2016), Western Australia (in 2009)11 and Victoria (in 2011 and 2014).12

Case reports

History and clinical findings
Case 1 (euthanased 2 August 1999, New South Wales: archival
NTSESP material). A 2-year-old Merino ewe in mid-gestation devel-
oped hindlimb ataxia, muscle tremors, weakness and depression,
with progression to recumbency in 2 weeks.

*Corresponding author: 2 Evelyn Villa Drive, Alstonville, New South Wales 2477, Australia; cookr@lis.net.au

a Regional Veterinary Laboratory, NSW Department of Primary Industries, Wollongbar, New South Wales 2480, Australia

b CSIRO, Australian Animal Health Laboratory, Geelong, Victoria, Australia

c Animal Health Laboratories, Department of Agriculture and Food, South Perth, Western Australia, Australia

d Gribbles Veterinary Pathology, Clayton, Victoria, Australia

e Department of Economic Development, AgriBio Centre, Bundoora, Victoria,

Australia
f Elizabeth Macarthur Agricultural Institute, NSW Department of Primary Industries,Menangle, New South Wales, Australia

snip...see ;

http://onlinelibrary.wiley.com/wol1/doi/10.1111/avj.12529/full
<15 2="" 5="" also="" and="" at="" basal="" brain.2="" cerebellar="" cerebral="" change="" cortex="" demonstrates="" deposition="" detected="" ganglia.="" grey="" immu-="" immunohistochemistry="" in="" intracytoplasmic="" is="" kda.="" layer="" mainly="" matter="" molecular="" nerve="" neurons.3="" neuropil="" no="" nolabelling="" nucleus="" of="" or="" p="" particularly="" prp="" sc="" sites="" spinal="" spongiform="" the="" there="" these="" throughout="" tract="" trigeminal="" vacuolation="" white="" within="">

http://onlinelibrary.wiley.com/doi/10.1111/avj.12529/epdf?r3_referer=wol&tracking_action=preview_click&show_checkout=1&purchase_referrer=onlinelibrary.wiley.com&purchase_site_license=LICENSE_DENIED_NO_CUSTOMER


Thursday, October 7, 2010

Australia first documented case of atypical scrapie confirmed

http://nor-98.blogspot.com/2010/10/australia-first-documented-case-of.html

Australia Senate BSE TSE Prion Terry S. Singeltary Sr.

http://www.aph.gov.au/~/media/wopapub/senate/senate/commttee/S12742_pdf.ashx

Saturday, April 23, 2016

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.

http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20

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

https://web.archive.org/web/20170126051158/http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf

*** 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.

http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160

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.

==============

https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf

SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online

http://scrapie-usa.blogspot.com/2016/04/scrapie-ws-01-prion-diseases-in-animals.html

1978 SCRAPIE IN CONFIDENCE SCJD

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1978/03/09001001.pdf

<15 2="" 5="" also="" and="" at="" basal="" brain.2="" cerebellar="" cerebral="" change="" cortex="" demonstrates="" deposition="" detected="" ganglia.="" grey="" immu-="" immunohistochemistry="" in="" intracytoplasmic="" is="" kda.="" layer="" mainly="" matter="" molecular="" nerve="" neurons.3="" neuropil="" no="" nolabelling="" nucleus="" of="" or="" p="" particularly="" prp="" sc="" sites="" spinal="" spongiform="" the="" there="" these="" throughout="" tract="" trigeminal="" vacuolation="" white="" within="">
http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1978/06/01001001.pdf


http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1978/06/27001001.pdf


<15 2="" 5="" also="" and="" at="" basal="" brain.2="" cerebellar="" cerebral="" change="" cortex="" demonstrates="" deposition="" detected="" ganglia.="" grey="" immu-="" immunohistochemistry="" in="" intracytoplasmic="" is="" kda.="" layer="" mainly="" matter="" molecular="" nerve="" neurons.3="" neuropil="" no="" nolabelling="" nucleus="" of="" or="" p="" particularly="" prp="" sc="" sites="" spinal="" spongiform="" the="" there="" these="" throughout="" tract="" trigeminal="" vacuolation="" white="" within="">http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1978/06/27002001.pdf


http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1978/06/27003001.pdf


http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1978/06/27004001.pdf


http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1978/08/18001001.pdf
<15 2="" 5="" also="" and="" at="" basal="" brain.2="" cerebellar="" cerebral="" change="" cortex="" demonstrates="" deposition="" detected="" ganglia.="" grey="" immu-="" immunohistochemistry="" in="" intracytoplasmic="" is="" kda.="" layer="" mainly="" matter="" molecular="" nerve="" neurons.3="" neuropil="" no="" nolabelling="" nucleus="" of="" or="" p="" particularly="" prp="" sc="" sites="" spinal="" spongiform="" the="" there="" these="" throughout="" tract="" trigeminal="" vacuolation="" white="" within="">
<15 2="" 5="" also="" and="" at="" basal="" brain.2="" cerebellar="" cerebral="" change="" cortex="" demonstrates="" deposition="" detected="" ganglia.="" grey="" immu-="" immunohistochemistry="" in="" intracytoplasmic="" is="" kda.="" layer="" mainly="" matter="" molecular="" nerve="" neurons.3="" neuropil="" no="" nolabelling="" nucleus="" of="" or="" p="" particularly="" prp="" sc="" sites="" spinal="" spongiform="" the="" there="" these="" throughout="" tract="" trigeminal="" vacuolation="" white="" within="">
http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1978/10/06001001.pdf
<15 2="" 5="" also="" and="" at="" basal="" brain.2="" cerebellar="" cerebral="" change="" cortex="" demonstrates="" deposition="" detected="" ganglia.="" grey="" immu-="" immunohistochemistry="" in="" intracytoplasmic="" is="" kda.="" layer="" mainly="" matter="" molecular="" nerve="" neurons.3="" neuropil="" no="" nolabelling="" nucleus="" of="" or="" p="" particularly="" prp="" sc="" sites="" spinal="" spongiform="" the="" there="" these="" throughout="" tract="" trigeminal="" vacuolation="" white="" within="">


http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1978/10/06002001.pdf
<15 2="" 5="" also="" and="" at="" basal="" brain.2="" cerebellar="" cerebral="" change="" cortex="" demonstrates="" deposition="" detected="" ganglia.="" grey="" immu-="" immunohistochemistry="" in="" intracytoplasmic="" is="" kda.="" layer="" mainly="" matter="" molecular="" nerve="" neurons.3="" neuropil="" no="" nolabelling="" nucleus="" of="" or="" p="" particularly="" prp="" sc="" sites="" spinal="" spongiform="" the="" there="" these="" throughout="" tract="" trigeminal="" vacuolation="" white="" within="">

1979

SILENCE ON CJD AND SCRAPIE

1980

SILENCE ON CJD AND SCRAPIE

*** 1981 NOVEMBER

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1981/11/26001001.pdf
<15 2="" 5="" also="" and="" at="" basal="" brain.2="" cerebellar="" cerebral="" change="" cortex="" demonstrates="" deposition="" detected="" ganglia.="" grey="" immu-="" immunohistochemistry="" in="" intracytoplasmic="" is="" kda.="" layer="" mainly="" matter="" molecular="" nerve="" neurons.3="" neuropil="" no="" nolabelling="" nucleus="" of="" or="" p="" particularly="" prp="" sc="" sites="" spinal="" spongiform="" the="" there="" these="" throughout="" tract="" trigeminal="" vacuolation="" white="" within="">

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1981/11/26001001.pdf
<15 2="" 5="" also="" and="" at="" basal="" brain.2="" cerebellar="" cerebral="" change="" cortex="" demonstrates="" deposition="" detected="" ganglia.="" grey="" immu-="" immunohistochemistry="" in="" intracytoplasmic="" is="" kda.="" layer="" mainly="" matter="" molecular="" nerve="" neurons.3="" neuropil="" no="" nolabelling="" nucleus="" of="" or="" p="" particularly="" prp="" sc="" sites="" spinal="" spongiform="" the="" there="" these="" throughout="" tract="" trigeminal="" vacuolation="" white="" within="">
<15 2="" 5="" also="" and="" at="" basal="" brain.2="" cerebellar="" cerebral="" change="" cortex="" demonstrates="" deposition="" detected="" ganglia.="" grey="" immu-="" immunohistochemistry="" in="" intracytoplasmic="" is="" kda.="" layer="" mainly="" matter="" molecular="" nerve="" neurons.3="" neuropil="" no="" nolabelling="" nucleus="" of="" or="" p="" particularly="" prp="" sc="" sites="" spinal="" spongiform="" the="" there="" these="" throughout="" tract="" trigeminal="" vacuolation="" white="" within="">
Thursday, August 04, 2016

*** MEETING ON THE FEASIBILITY OF CARRYING OUT EPIDEMIOLOGICAL STUDIES ON CREUTZFELDT JAKOB DISEASE 1978 THE SCRAPIE FILES IN CONFIDENCE CONFIDENTIAL SCJD

http://scrapie-usa.blogspot.com/2016/08/meeting-on-feasibility-of-carrying-out.html
<15 2="" 5="" also="" and="" at="" basal="" brain.2="" cerebellar="" cerebral="" change="" cortex="" demonstrates="" deposition="" detected="" ganglia.="" grey="" immu-="" immunohistochemistry="" in="" intracytoplasmic="" is="" kda.="" layer="" mainly="" matter="" molecular="" nerve="" neurons.3="" neuropil="" no="" nolabelling="" nucleus="" of="" or="" p="" particularly="" prp="" sc="" sites="" spinal="" spongiform="" the="" there="" these="" throughout="" tract="" trigeminal="" vacuolation="" white="" within="">

Terry S. Singeltary Sr.