Chronic Wasting Disease: new experience in Europe

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Chronic Wasting Disease: new experience in Europe Sylvie L. Benestad, Tran, B. Saure, R. Terland, S. Svendsen, K. Dessen, M. Haugum, M. Opheim, K. Handeland, K. Madslien, Ø. Kolbjørnsen, H. Wisløff, T. Moldal, J. Våge, T. Vikøren,, L. Pirisinu, G. Vaccari, R. Nonno Norwegian Veterinary Institute 6th March 2018, Turin 20 convegno degli istituti zooprofilattici sperimentali sulle EST

239 tests 2008-2015

First European CWD case March 2016 Nordfjella mountain Photo: Norwegian Institute for Nature Research (NINA)

2007 CWD diagnosed in North America (and South Korea) 2018

Mule deer White tail deer Elk / "wapiti Moose Free ranging reindeer

WB TeSeE bio-rad IHC ELISA TeSeE Bio-Rad

CWD clinical signs Behavior changes Terry Spraker, CSU, CO Emaciation Excessive salivation, urination Most of the time no signs, or unspecific signs

Where does it come from? Imported from USA - import life animals - WTD to Finland 1935 - attractants/lures?

Norwegian animals TSE Species Classical type Atypical type Sheep 63 Classical, last 2009 165 Nor98, 13 in 2017 Goat 1 Nor98 in 2005 Cattle 1 H-BSE in 2015 Cat 1 FSE in 1994 Reindeer 18 CWD, first 2016 Moose 3 atypical CWD, first 2016 Red deer 1 atypical CWD, in 2017

Where does it come from? Sheep with classical or atypical/nor98 scrapie??

Where does it come from? Spontaneous case in a cervid??

How does CWD spread within cervids? Directly Via environment

CWD in Norway 200km Cervid species Diagnosed Free ranging reindeer 18 Moose 3 Red deer 1 Totalt 22 1 3 CWD spots Same CWD strain in the 3 species? 1 18 2

Characterization of a prion strain in vitro Different conformations different reactions to Proteinase K treatment:

N-term 12B2 (88-92) 9A2 (98-100) L42 (148-153) F99 (220-225) C-term Reindeer Moose N-term C-term

WB: Norwegian moose prions have different characteristics from other CWD isolates

It is not only host dependent: Norwegian moose was also different from Canadian moose New strain? Need for bio-assay

Bio-assay ongoing Institutions Country Recipient Prion gene from INRA Toulouse France Transgenic mice Sheep (3 lines), cattle and human CEA Jouy-en-Josas France Transgenic mice Macaques ISS Rome Italy Bank voles 2 genotypes UCL London UK Transgenic mice Human PRC Fort Collins USA Transgenic mice Cervids and elk CWRU Cleveland USA Transgenic mice Human ANSES Lyon France Transgenic mice Sheep Roslin Edinburgh/ Alberta University UK/ Canada Conventional mice Mice

Reindeer Age Young, adult Old ELISA Positive Positive Distribution of PrP CWD Lymph nodes and/or brain Moose/red deer In brain but not in lymph nodes Distribution of PrP CWD in the brain Spread, especially in the brain stem Mostly in neurons, in the whole brain Western blot Like CWD in North America Low molecular weigth pattern. Truncated on the N-terminal.

Semi-domesticated 2 populations of reindeer Wild

The sami people and their reindeer no administrative borders

Started 10th August 2017, completed February 2018 Nordfjella, relatively isolated area 2000 reindeer / 25 000 total wild reindeer.

Disease absent Disease absent Entry Small number, localized Small number, cases, eradication localized cases: possible ERADICATION.POSSIBLE Increasing distribution, Increasing eradication unlikely distribution and abondance: eradication unlikely Widespread and abondant distribution; long term management aimed at population suppression and protection

Depopulation of Nordfjella in 2017-2018 2 phases: -Hunters giving heads -State culling 2449 reindeer killed and tested since primary case. 18 positive cases

Primary test: ELISA TeSeE 350mg obex Obex +Ln Opp til total 500mg + 100-150mg LN

Repeated ELISA TeSeE 350mg brainstem 2 1 brain Obex +Ln 3 250mg Ln Ln

Species Dead Sex Age PrPCWD PrP CWD obex LN Rein 1 03.2016 Female 3-4 y POS POS Rein 2 08.2016 Male 7 y POS POS Rein 3 09.2016 Female 4 y POS POS Rein 4 06.2017 Male 4 y not detected POS Rein 5 08.2017 Female 3 y not detected POS Rein 6 08.2017 Male 8 y not detected POS Rein 7 10.2017 Male 2,5 y POS POS Rein 8 11.2017 Male 2,5 y POS POS Rein 9 11.2017 Male Adult POS POS Rein 10 11.2017 Male 5 y POS POS Rein11 12.2017 Female Adult not detected POS Rein12 12.2017 Female Adult POS POS Rein13 01.2018 Male 1,5 y* not detected POS Rein14 01.2018 Male Adult not detected POS Rein15 02.2018 Male Adult not detected POS Rein16 02.2018 Male Adult POS POS Rein17 02.2018 Male Adult POS POS Rein18 02.2018 Female Adult not detected POS Moose 1 05.2016 Female 13 y POS not detected Moose 2 05.2016 Female 14 y POS not available Moose 3 10.2017 Female 13 y POS not detected Red deer 10.2017 Female 16 y POS not detected

Take home messages CWD: new European disease Most contagious of the prion diseases (within cervid population) Wildlife population, management challenges Overlapping cervids populations, both wild and semi domesticated Measures to eradicate/ limit spread completed, unpredictable issue (environment) Need for sensitive test on live animals (RAMALT) /environment (Rt-QuIC) Genetic studies New atypical CWD type in Norwegian moose, Nor16CWD Where is the epicenter? What is the situation in Europe?

Thanks to all the Norwegian colleagues: Veterinary Institute: Pathology technicians Norwegian Institute for Nature Research Ministry of Environment Norwegian Food Safety Authority The hunters And thanks to international colleagues: Olivier Andréoletti, INRA Toulouse, Fr Emmanuel Comoy, CEA Jouy-en-Josas, Fr Romolo Nonno, ISS Rome, It John Collinge, UCL London, UK Glenn Telling, Terry Spraker, PRC Fort Collins, Colorado, USA Qingzhong Kong, CWRU Cleveland, USA Thierry Baron, ANSES, Lyon, Fr Vincent Beringue, INRA, Jouy-en-Josas, Fr Wilfred Goldmann, Roslin Institute, Edinburgh, UK Thank you for your attention!

https://www.vetinst.no/sykdom-ogagens/chronic-wasting-disease http://apps.vetinst.no/skrantesykestatistikk/n O/