The Emergence of Exotic Bluetongue the importance of vaccination and future threats

Uwe Mueller-Doblies, Narender Maan, Kyriaki Nomikou, Sushila Maan, and Peter Mertens

Biosecurity Group and Vector Borne Diseases Programme, Institute for Animal Health , Pirbright UK.

USDA ARS 1st International Biosafety & Biocontainment Symposium The reference labs at IAH-Pirbright

Reference labs in VtVector-bDiborne Diseases Programme

• Bluetongue • • Lumpy Skin Disease • and Pox • African Swine Fever Overview

• Bluetongue Disease • Blue Tongue Disease • Dynamic of recent emergence in Europe • Aspects of Emergence – climatic changes – vector competency – live attenuated – recombination • Biosafety Issues

• Overview

• Bluetongue Disease • Blue Tongue Disease Viruses • DiftDynamic of recent emergence i iEn Europe • Aspects of Emergence • Biosafety Issues Bluetongue: Clinical signs and disease in Europe

“On a global basis, the second most economically important disease of livestock after Foot and Mouth” Coronitis Conjunctivitis

Ca ttle Pos t Mor tem: FLI Haemorrhage of the aorta

FLI Coronitis Conjunctivitis

Ca ttle Pos t Mor tem: FLI Haemorrhage of the aorta

FLI : Dummy calf at pasture 1b - Williamson, et al Vet Record 20 4-week old calf with behavioural & locomotory problems. Brain with cerebral hemispppyheres replaced by a fluid filled sac. (Wouda et al 2008) Bluetongue : Classification and distribution Classification of species (serogroups)

1-Afr ican horse s ic kness v irus (AHSV) 2-Bluetongue virus (BTV) 3-Changuinola virus (CGLV) 4-Chenuda virus (CNUV) Tentative species / 5-Chobar Gorge virus (CGV) unassigned viruses 6-Corriparta virus (CORV) 7-Epizootic hemorrhagic disease virus (EHDV) Andasibe virus (ANDV) 8-Equine encephalosis virus (EEV) Ife virus (IFEV) 9- Eubenangee virus (()EUBV) Itupiranga virus (ITUV ) 10-Ieri virus (IERIV) Japanaut virus (JAPV) 11- Great Island virus (GIV) Kammavanpettai virus (KMPV) 12- Lebombo virus (LEBV) Lake Clarendon virus (LCV) 13-Orungo virus (ORUV) Matucare virus (MATV) 14-Palyam virus (PALV) Tembe virus (TMEV) 15- St Croix River Virus (SCRV) Codajas virus (COV) 16-Umatilla virus (UMAV) Tracambe virus (TRV) 17-Wad Medani virus (WMV) 18-WlllWallal v irus (WALV) TlTotal : 12 unassignedid viruses 19-Warrego virus (WARV) 20-Wongorr virus (WGRV) 21- Peruvian horse sickness virus (PHSV) 22- Yunnan Orbivirus (YUOV)

Total: 22 virus species, 161 serotypes

Global distribution of the 25 Bluetongue virus serotypes Bluetongue virus serotype Regio n (I = virus serotype isolated: S = serological evidence for each serotype (detection of neutralising antibodies) - 1234567891011121314151617181920212223242526 AfricaIIIIIIIIIIIIIIIII-II-I-I-‐

Middle East-I-I-I--SI-SSSIIS-SS---I-I

India + I I I ISISSISSSSSSI I I -SS- I - - ‐ Pakistan I I Australia I I--- -I--S--II---II-I--‐ [ 6 ] [4]

South East Asia and IIII--I-IISIS--SISSSI -I--‐ Indonesia

China I I I I ------I --I I ------I USA I [1,2 I - I I ---I I - I I --I - I --I - I - ‐ ]

Central and South I - I I - I - I --II II-SI ------‐ America

I* Europe I* I* I I* - I* - I* I R ---I* ------I* ‐ [5] The global distribution of Bluet ongue vi rus ( pre 2006) vector species from Europe, Africa and the USA C. obsoletus C. sonorensis

CiiC. imicol a C. impunctatus (pulicaris complex) Adult female Culicoides nubeculosus (from the insect colony at IAH Pirbright)

~1mm Bluetongue virus: Structure and serological properties BTV-1 BTV-1 Virus particle Core particle Assembly of the major bluetongue virus capsid protiteins The outer surface of the BTV virus particle VP and VP5 - Encoded by segments 2 and 6 (Cryo-EM and x-ray crystallography reconstruction)

60 VP2 trimers encoded by Seg-2

120 VP5 trimers encoded by Seg-6 The Genome segments of the 24 BTV serotypes analysed by SDS-PAGE

B

1 2 3

4 6 5

7 8 9

10 Primers for identification of BTVEuropean serotypesBTV by serotypes Rt-PCR by Rt-PCR since1998 Type FWD Primer RVS Primer Product BP) 1 BTV-1/2/p406F GAGAACARGAARAATATATGAGAACARGAARAATATAT BTV-1/2/p968R TYATACGTTGAGAAGTTTTGTTYATACGTTGAGAAGTTTTGT 1686 1686 (1A) 2 BTV-2/2/p198F TATCAGTTAATAGTGCATTTATCAGTTAATAGTGCATT BBTV-2/2/p416RTV-2/2/p416R TACTAAAKATTACTAAAKATATACTTCTCCGTATACTTCTCCGT 653 (2A) 3C BTV-3/2/p340F GAACTAATGAGGACAGAT BTV-3/2/p840R TGAGATCGTCGTCTGAAGAT 1500 4 BT4/67/F GCTTAACTATAAACCAACGAGG GCTTAACTATAAACCAACGAGG BT4/775/R GTATCAACCTGACCGCGTCG 2124 5 5NIG/123/F TACGGATCATAAATGGATGG 5NIG/791/R TATATGCTCACAGATATCT 2004 6 BT6/301/F GGTGGTATGTATAGAGGAGGTGGTATGTATAGAGGAAGAG BT6/853/R CAAAGGGAACCTCGCGCGTAATCCAAAGGGAACCTCGCGCGTAATC 1656 7 BT7/83/F GATGTATCCATAGCGGCAT BT7/853/R GATAGATAAGCGAATCGAG 2310 8 BT8/101/F GAATGATGGTCATAGCGAG BT8/500/R CGATGTGCGCATTCCTCTC 1197 9 BTV-9/2/p491F GGSAATATATTTCTRATGGGGSAATATATTTCTRATGG BTV-9/2/p867R GGAAAACGGAAAACTGATTGGCAATTGATTGGCAAT 1128 (9C) 10 BT10/183/F GATGTTCCACATCTTACAG BT10/803/R GTGAAACCTAATGAAATTG 1860 11 BT11/147/F TGTATTGTTAAGGCTAGG BT11/770/R GTCATCGTATAGTATCAT 1569 1569 12 BT12/111/F GGATCACAATATAGATGTG BT12/776/R CTACGATCATATGATAACTC 1995 13A BT13/157/F CGAGGAAAGCGGATACCAC BTV-13/2/p631R TGCTTAATGCTCAAACTCG 1422 14 BT14/121/F GAAGGTTAGCTTAGGTTTG BT14/805/R CTCCGCTTCATCCAGCTC 2052 15 BT15/343/F GTGGCAGAACGCAGAGGCAG BT15/806/R G TGAGACATATAATGTTCAAG 1389 16B BTV-16/2/p266F GCGATAAGAGATAMTTGGATGCGATAAGAGATAMTTGGAT BTV-16/2/p924R GCCGAAGGTGCGATCTGGCCG GCCGAAGGTGCGATCTGGCCG 1974 (-Nig) 17 BTV-17/2/p146F GCGAATGCTGCCAACGCTG BTV-17/2/p653R GCGCGACTTTCCTAAACG 1521 18 BT18/160/F GTCTTATCATATAGAGCCAG BT18/828/R GTACTCAGATAATAGTCGAG 2004 19 BT19/190/F TGTGCTCAAGCAAGCGCGTAT BT19/841/R GTCATCGTCGAGTGCGTG 1953 20 BT20/135/F CATTACTCGATAGATTACC BT20/812/R GTACGTCGTCAGCAATCTG 2031 21 BT21/116/F GAGGAATGGCTGAACTGG BT21/754/R GCCTCCACACAGCGAAGACAG 1914 22 BTV-22/311F GACGCGTTGGATAGGATAT BTV-22/682R GCTTATACCTCGCATCATCG 1113 23 BT23/459/F GCTTAGACCTGGCGATAAG BT23/653/R GTTTAACATGCATACTCAG 582 24 BT24/313/F TGGATTTATCTACACGATT BT24/783/R CATAAGCTCCAACTTCAAC 1410 16 RSArrrr-16-AJ585137

2 RSArrrr-13-AJ585134 RSArrrr-03-AJ585124 BTV-2-Taiwan-AY493687 RSArrrr-21-AJ585142 RSArrrr-02-AJ585123 RSArrrr- 06-AJ585127 1 E RSArrrr-14-AJ585135 RSArrrr-01-AJ585122 W RSArrrr- 05-AJ585126 9 RSArrrr- 09-AJ585130

RSArrrr- 07-AJ585128

RSArrrr- 19-AJ585140 RSArrrr-23-AJ585144

RSArrrr-10-AJ585131

RSArrrr-18-AJ585139 RSArrrr-24-AJ585145 8 RSArrrr-17-AJ585138 RSArrrr/08-AJ585129 RSArrrr-11-AJ585132 RSArrrr-20-AJ585141 RSArrrr-04-AJ585125 4 RSArrrr-22-AJ585143 RSArrrr-15-AJ585136 0.05 RSArrrr-12-AJ585133

www.iah.bbsrc.ac.uk/dsRNA virus proteins/btv-seg-2.htm BT in Europe 1998 to 2006: Transmission and spread London Kyiv North GERMANY POLAND Brussels Leipzig Atlantic Bonn BELGIUM Frankfurt Krakow UKRAINE Ocean Prague Lviv NorthernmostLe Havre LUX. Distribution of BTV to 1997 Paris CZECHOSLOV AKIA

Strasbourg MOLDOV A Vienna Bratislava Nantes Munich AUSTRIA Budapest Kra FRANCE Bern Graz HUNGAR Y Cluj-Napoca SWITZERLAND Geneva Pecs SLOVENIA Zagreb ROMANIA Bordeaux Milan Venice CROA TIA Lyon Constanta Bucharest Black BOSNIA ITALY Belgrade Sarajevo SERBIA Varna Sea Bilbao Marseille MONACO Florence BULGARIA Samsun Porto MONTENEGRO ANDORRA Adraidic Sofiya Sea Titograd Skopje Barcelona Rome Istanbul PORTUGAL MACEDONIA Madrid Tirane Thessaloniki Bursa Ankara Naples ALBANIA Lisbon SPAIN Kayseri Valencia TURKEY Aegean GREECE Giziantep Tyrrhenian Sea Izmir Konya Sevilla Sea Athens Antalya Malaga Patrai La Palermo Gibraltar Nicosia Tangier Algiers Tunis Oran Constantine CRETE B Rabat LEBANON Casablanca TUNISIA Haifa MOROCCO Tel Aviv J Marrakech Ghardaia ISRAE Tripoli Benghazi Alexandria Misra th Gulf of Sidra Cairo

Beni Suef El Minya

Asyut

Luxor ALGERIA LIBYA EGYPT BTV-10 in Spain & Portugal 1956 - 60, BTV-4 in Turkey and Cyprus during 1980’s . Aswan BTV-3 in Lesbos and Rhodes 1979.

250 Km Al Jawf North GERMANY POLAND Brussels Leipzig Atlantic Bonn BELGIUM Frankfurt Krakow UKRAINE Ocean Prague Lviv NorthernmostLe Havre DistributionLUX. ofCulicoides imicola, to 1997 RUS Paris Northern most distribution ofCZECHOSLOV Culicoides AKIA imicola (to 1997)

Strasbourg MOLDOVA Vienna Bratislava Nantes Munich AUSTRIA Budapest Krasnodar FRANCE Bern Graz HUNGARY Cluj-Napoca SWITZERLAND Geneva Pecs SLOVENIA Zagreb ROMANIA Bordeaux Milan Venice CROATIA Lyon Constanta Bucharest Black BOSNIA ITALY Belgrade Sarajevo SERBIA Varna Sea Bilbao Marseille MONACO Florence BULGARIA Trab Samsun Porto MONTENEGRO ANDORRA Adraidic Sofiya Sea Titograd Skopje Barcelona Rome Istanbul PORTUGAL MACEDONIA Madrid Tirane Thessaloniki Bursa Ankara Naples ALBANIA Lisbon Diyarba SPAIN Kayseri Valencia TURKEY Aegeaegean GREECE Giz iantep Tyrrhenian Sea Izmir Konya Sevilla Sea Halab Athens Antalya Malaga Patrai Latakia Palermo SY Gibraltar Nicosia Tangier Hims Algiers Tunis CYPRUS Oran Constantine CRETE Beirut Rabat LEBANON Damascu Casablanca TUNISIA Haifa MOROCCO Amman Mediterranean Sea Tel Aviv Jerusalem Marrakech Ghardaia JORDAN ISRAEL Tripoli Benghazi Alexandria Misrath Gulf of Sidra Al Aqab Cairo

Beni Suef T El Minya

Asyut

Luxor EGYPT ALGERIA LIBYA Aswan

250 Km Al Jawf Areas of BTV transmission by novel BTV 1 & 8 BTV-9 vectors of the ( 2007) obsoletus &/or pulicaris complexes.

C. imicola has moved northwards into Europe, accompanied by outbreaks of BTV, 1, 2, 4, 9 & 16 15 distinct strains of nine different BTV serotypes have invaded Europe, with new introductions every year Since 1998

This evidence supports that a fundamental ‘step-change’ in the epidemiology of BTV that has bldlihbeen related to climate change BTV -1 polymerase activity

RNA 2500

2000 trates into ss 1500 belled sub

aa 1000

500 of radio l nn 0 0 1020304050 corporatio nn I

Temperature Recent climate warming in Europe.

1.5

1 1961- oo

0.5 ge (oC) ge compared t ,, aa 0 1850 1860 1870 1880 1890 1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 -0.5 1990 aver re deviation uu

-1 Temperat -151.5 Year Recent warming trend in Europe. observed annual temperature deviations in Europe over the last 140 yy(ears (1850 to 2000 ) com pared to the 1961 to 1990 avera g()gpge (ºC) as light pink bars. Su ppperimposed as a continuous dark pink line is the 10-year smoothed trend of these annual temperature deviations (reproduced with permission from EEA, 2004). (Purse et al 2005 Nature Reviews) Wind blowing dust from the Sahara across Italy and the Mediterranean Islands The 10 introductions of different BTV strains into Europe and north Africa 1998 to end of 2006

BTV-8

2006 BTV- type 8? 2003 BTV-9

1999 2004 BTV-1 BTV-4 1978 BTV-15 20061999 1998 BTV-1 BTV-2 BTV-16 BTV-4 & 2001 BTV-4 2006200220002002 2006 BTV-8 in Europe: 2006 onwar ds Initial identification of NET2006/01 as BTV-8

Serotyping. Confirmed Confirmed by by typing typing primers primers against against S2 S2 as being type 8. There is a faint band for BTV1 but it is completely of the wrong size.

Serotype 1 2 2 3 4 4 5 5 6 7 8 8 8 9

10 10 11 11 12 13 14 15 15 16 17 18 19 20

RNA controls – Seg7 21 22 22 23 24 The Spread of BTV outbreaks from 21st of August to 8th October 2006 European BTV situation 2007 BTV-8i8 in G ermany Outbreaks 2006/2007

3500 GoatZiege 10659 Sheep 7582 3000 SheepSchaf Goat 109

2007 Boviden 22 Fallow 18 CattleRind 2500 Moufflon 11

ss Deer 3 GoatZiege Total 18404 2000 SheepSchaf 2006 ahl Fälle ahl ber case zz CattleRind

mm 1500 An Nu

1000

500

0 23 28 33 38 43 48 Thanks to FLI-Wusterhausen, Germany KW Status: 16.11.2007 Bluetongue in Germany 2033 cases reported 1st June 2007 to 18th July 2008 Bluetongue in Germany 2033 cases reported 1st May to 17th Oct 2008 BTV-8inFrance8 in France Outbreaks caused up to start of August 2008 by: BTV-8 ● and BTV-1 ● Outbreaks caused up to Late October 2008 by : BTV-8 ● BTV-8 outbreak Northern Europe • year 1:, low level initial spread (mainly in cattle), low mortality.

• 2nddyea year: high le v el spr ead in ca ttle an d s h eep v er y severe. Vaccination • 3rd year: Recovered animals but few susceptible animals remain, so fewer cases.

• 4th year (projected) Few sources of remain and most animals immune. Potential for eradication BTV vaccines

• 3 Options – Live attenuated strains • (unsafe in Northern European sheep – transmitted in the field)

– Inactivated virus vaccines • (used in the UK/France/Spain 2008/2009)

– NtNext generati on vacc ines • (not yet commercially available) The effect of Vaccination with live attenuated BTV stitrains i iUKhn UK sheep

Pyrexia and viraemia duration recorded in Dorset Poll sheep after vaccination

No. of sheep Pyrexia Max viraemia titre Max viraemia Min viraemia Serotype showing duration recorded* duration (days) duration (days) pyrexia range (days)

BTV2 2/4 1 4.75 17 17

BTV4 2/4 2 4254.25 16 11

BTV9 4/4 1-5 5.25 15 7

BTV16 4/4 6 6836.83 19 17

BTV16 3/3 1 6.0 23 10

*(log10TCID/50)

Veronesi E. et al., Live attenuated bluetongue vaccine viruses in Dorset Poll sheep before and after the passage in vector midges (Diptera: ). Vaccine 2005; 23: 5509-5516 Sheep inoculated with BTV-4 vaccine virus

Acute respiratory dysfunction

Swelling and discolouring of the lips and tongue and copious salivation

Cyanosis of the whole oral cavity including the tongue (acute oxygen deficiency) After compulsory vaccination, in France with inactivated vaccines, only three isolates of BTV-8 and no isolates of BTV-1 wer e m ade du ring 2009 BTV in the UK during 2007 -9 First Incursion of BTV-8 to the UK (2007)

Air concentration plume and particle trajectories overnight on 4/5 Aug 2007 are believed to have caused the first outbreaks of BTV-8 in Suffolk

© Crown copyright Met Office BTV-8 Protection and Surveillance zones (()1st Jan 2008) Peterborough BTV-8NET(2006)

C1507T T-2126-A

Debbie, Ashford, No change G-571-A Denmark Colchester G1374A A-987-C C2346T G1500A

A2430G G843T Purleigh T-40450-C

C1809T Sevenoaks

Cambridge A-423-G

G-222-A

No change Lowestoft, Lorraine BTV-8NET(2007)

A1518G

C2545T Synonymous substitution

Chelmsford Non-synonymous substitution October 2008: Modelling post vaccination

no vaccination 50% vaccine cover Sales of BTV-8 vaccines in the UK (to A ugus t 2008) • Protection zone: – Total required = 11,914,834 – Total sold = 9, 853, 140 (= 82. 7% cover)

• OtidthPZOutside the PZ – Total Required = >>10,000.000 – Total sold (so far) = 1,230,000 Zones as of Monday 20th October 2008: No insect transmission but importation of 196 viraemic animals No further cases of Insect transmitted BTV were observed after the intensive vaccintion camppgaign ag ainst BTV-8 in the Summer of 2008 • The UK has now been reclassified a low risk zone. • However, Vaccination in the UK has dropped to below 10%. • It is al so d roppi ng very rapidl y i n th e rest of north ern Europe. • As the seropositive animals are replaced, the risk of further outbreaks will inevitably return New BTV serotypes 2008-2010

BTV-255S Swi tz erl an d BTV-26 Kuwait BTV -25 2008 Toggenburg orbivirus, Cases in in Switzerland

No ✖ clinical ✖ signs of infection Phylogenetic analysis of full length Seg-2 of BTV serotypes BTV-9/IND2005/01 BTV RSArrrr/19 BTV-19-USA2003/04 BTV RSArrrr/09 BTV-9-Caribbean BTV RSArrrr/07 BTV RSArrrr/02 BTV-5/USA2003/05 BTV-2 Caribbean BTV-2/M21946 BTV RSArrrr/05 AY493687-BTV-2-Taiwan BTV-2IND1982/01 TOV S2 ORF 25 BTV-1/X06464 BTV RSArrrr/04 4 BTV RSArrrr/01 BTV-23/U04200 BTV RSArrrr/20 20 BTV-11/M17437 BTV RSArrrr/23 BTV RSArrrr /11 BTV RSArrrr/18 BTV-11/ZIM2003/02 11 BTV RSArrrr/08 BTV RSArrrr/17 17 BTV-6-USA2006-01 BTV-17/S72158 BTV RSArrrr/06 BTV-17 Caribbean BTV-14-USA2003/03 BTV RSArrrr/14 BTV-24 Caribbean BTV RSArrrr/21 24 BTV RSArrrr/24 BTV-3/X55801 BTV RSArrrr/03 BTV RSArrrr/10 BTV-3-USA2006-10 BTV-10/L29027 BTV-13/D00153 BTV-10-IND2005/04 BTV RSArrrr/13 10 BTV-10-USA2002/03 BTV-16ISA1991/01 BTV-10-caribbean BTV-16-ISR2003/01 BTV RSArrrr/16 0.05 BTV-15/ZIM2003/08 BVT-22-USA2002/02 BTV RSArrrr/15 Nucleotype A BVT-22-Caribbean BTV RSArrrr/12 BTV RSArrrr/22 BTV-12/NIG1982/09 BTV -26 2010 From sheep in Kuwait 2010   582 bp 394 bp 657 bp 1113 bp 1113 11 3 Kb

2 Kb

1 Kb

M 1 2 3 4 5 6 M

Electrophoretic analysis of cDNA products from Seg-2 of KUW2010/02 usiBTVing BTV-26 specifi c Seg-primer-pairs.

Maan et al ., Identification of a novel bluetongue virus serotype (BTV-26) from Kuwait (Emerging Infectious Diseases – submitted 2010) E RSArrrr/09-AJ585130 D RSArrrr/05-AJ585126 RSArrrr/23-AJ585144 RSArrrr/08-AJ585129 RSArrrr/19-AJ585140 F RSArrrr/18-AJ585139 RSArrrr/07-AJ585128 100

I RSArrrr/02-AJ585123 100 BTV-25/TOV-EU839840 K 100 RSArrrr/01-AJ585122 BTV-26/KUW2010/02- H L 100 HM590642 100 RSArrrr/16-AJ585137 100 RSArrrr/10-AJ585131 B RSArrrr/03-AJ585124 100 RSArrrr/24-AJ585145 RSArrrr/13-AJ585134 100 100 RSArrrr/11-AJ585132 RSArrrr/21-AJ585142 RSArrrr/17-AJ585138 RSArrrr/14-AJ585135 RSArrrr/04 -AJ585125 A RSArrrr/06-AJ585127 100 RSArrrr/20-AJ585141 C

RSArrrr/15-AJ585136 J RSArrrr/22-AJ585143 0.05 G RSArrrr/12-AJ585133

Neighbour-joining tree showing relationships between VP2 of KUW2010/02 with BTV 1-25. BTV-7/RSArrrr/07 BTV-19RSArrrr/19 EHDV-4/NIG1968/01 BTV-15RSArrrr/15 EHDV-1/USA1955/01 EHDV-6/BAR1983/01 BTV-25/TOV BTV-15AUS EHDV-1/NIG1967/01 EHDV-2/CAN1962/01 BTV-26/KUW2010/02 EHDV-8/AUS1982/06 EHDV-2/AUS1979/05 EHDV-7/AUS1981/06 EHDV-5/AUS1977/01 EHDV-2/JAP1959/01 BTV-16/China BTV-1RSA EHDV-6/AUS1981/07 BTV-12/Jamaica BTV-2/USA-OnaB BTV-2 /USA-Ona-A BTV-12/China 100 BTV-1/China BTV-6/RSArrrr/06 BTV-2/China BTV-6/USA2006/01 100 BTV-23 India BTV-4/Greece 1999 BTV-1/Australia BTV-1/France BTV-3/laReunion EEV BTV-2/Tai wan BTV- 8/NET2006/04 CHUV

AHSV-1 AHSV-2 AHSV-9 AHSV-3

0.1

Neighbour-joining tree showing relationships BRDV between VP7[[]T13] of PHSV CMPV YUOV KUW2010/02 with other . SCRV New Virus strains and from “natural gggyene technology” BTV-4 in Morocco and Spain (2010) BTV-4 in Spain and Morocco (2010)

Fig 1: Locations of BTV-4 outbreaks in Spain (green dots) and Morocco (pink and yellow dots). The release location for the forward NAME runs is identified by the yellow dot. Wind-borne spread of BTV-4toSpain4 to Spain

From Climate modelling (NAME) BTV-4 could have spread from Morocco into Spain on the following dates: 20-21st, 29-30th, 15-16th, or 16-17th August 2010

© Crown copyright Met Office Similarity between BTV-4 2009 (MOR 2009/09) and previous strains of BTV 1 and 4 from Morocco

BTV-4 MOR 2004/02 BTV-4 Morocco 2009 BTV-1 MOR 2006/06 ( MOR 2009-09 ) % similarity with % similarity with MOR 2009-09 Genome segment Number MOR 2009-09

98.8% 1 99.8% 49.9% 99.6% 2

99.4% 3 94.90%

95.9% 4 99.8%

96.8% 5 100%

99.8% 6 69.2%

94.1% 7 100% (4MOR2009/10) - 8 - - 9 - - 10 - Summary

• New European BTV strains every year since 1998 . What will arrive next? • Multiple serotypes (e.g. BTV-1, 4, 6, 8 and 11) make detection and control (vaccination) more difficult . • The whole of Europe is now ‘at risk’ from further incursions of BTV, (new serotypes) • Genetic exchange (reassortment) can lead to novel virus strains (which may be more dangerous) • New viruses will emerge, even within well characterised genera and species (BTV-25 and 26). • New cross-reactive vaccines are needed •Europe is under threat from other orbiviruses (e.g. AHSV and EHDV), and other Recent outbreaks of West Nile, Chicungunya, Biosafety Considerations

• What containment level is appropriate for work on BTV – transfer of reagents from foreign animal disease labs to lregionaldiagnostic labs – transfer of exotic virus strains to low containment labs • Vector-borne transmission is most relevant in the field but not exclusive – -oral transmission has been observed in the field Acknowledgements I would like to thank • Members of the Arbovirology Programme, at IAH Pirbright

• Many many International Colleagues who have provided virus samples and data.

• Funding support from DEFRA, BBSRC, OIE and the European Commission (OrbiVac - Grant no .: 245266; WildTech - Grant no.: 222633-2) EMIDA grant OrbiNet - K1303206.