Foot-and-Mouth Disease Global and regional update Donald King

Foot-and-Mouth Disease Global and regional update Donald King Vesicular Disease Reference Laboratory donald. king@pirbright. ac. uk FMD Ref Lab Team: Valerie Mioulet, Nick Knowles, Anna Ludi, Ginette Wilsden, Bryony Armson, Pip Hamblin, Kasia Bachanek-Bankowska, Kelly Adams, Jemma Wadsworth, Begoña Valdazo-González, Britta Wood, Barsha Thapa, Bob Statham, Ashley Gray, Trish Ryder, Sarah Belgrave, David Paton FMD Reference Laboratory

2010 -2014: Changing patterns and threats SAT 2 and O North Africa and West Eurasia Multiple East Asia 1 Detailed reports can be found at: www. wrlfmd. org

Recent submissions to WRLFMD • Jan – Dec 2013: 401 samples • 259 isolates • Represent 5 FMDV serotypes: O A Asia 1 SAT 2 • No virus isolated 32. 4% of samples • RT-PCR negative in 17. 7% samples • No serotype C since 2004

Field data from West Eurasia and North Africa Sample submissions to WRL (last 10 years) * Sequence data only * Bulgaria Samples sent to WRLFMD (last shipment) * Bahrain 2013 -14 Country Year 2012 Yemen 2009 Somalia 2009 Lebanon 2009 Jordan 2006 2011

Recently circulating FMDV lineages Viral lineage: O/ME-SA/Pan. Asia-2 A/ASIA/Iran-05 Asia-1 O/ME-SA/Ind-2001 SAT 2 topotype VII SAT 2 topotype IV A/AFRICA/G-VII O/ME-SA/Sharqia-72 O/EA-3 West Eur. Asia North Africa (Middle East) ✓ ✓ ✓ ✓ ✗ ✗ ✗ ✓ ✓

O/ME-SA/Pan. Asia-2 Sub-lineage nomenclature used to define different viral genotypes 2014 2013 2012 2011 • ANT-10 Iran Israel Saudi Arabia Turkey UAE Afghanistan Pakistan Libya • FAR-09 Iran Israel PAT Turkey

Epidemiology of FMDV in Bulgaria (Burgas): 2011 • Incursion of FMD into a FMD-free (without vaccination) country in Europe • O/ME-SA/Pan. Asia-2 ANT 10 • Use of full genome sequence data generated in real-time to show sequences are related • Analysis included additional sequences from Turkey and Israel

Complete FMDV sequences recovered from Bulgaria Full genome sequence data: • provides evidence for single introduction into Bulgaria from Turkey • long branches indicative of unsampled infection • either in 4 villages with seropositive domesticated animals • or wildlife (wild boar) TCS tree showing linking samples showing putative unsampled intermediates (-O-) Valdazo-Gonzalez et al. , PLo. S ONE (2012)

Vaccine matching data (2013) Serotype O (all O/ME-SA/Pan. Asia-2 lineages) Matched Vaccine strain Not matched Field isolate O-3039 Iran 2012 Iran 2013 O/RUSSI O-4625 O/Manisa A/2000 TAW/98 * Pakistan 2012 Pakistan 2013 Palestinian AT 2013 UAE 2013 Turkey 2013 * * Single values have yielded borderline matches O/TUR 5/2009

A/ASIA/Iran-05 In the past 3 years: 8 sub-lineages: 2013 2012 2011 SIS-12 Pakistan and Iran Afghanistan, Pakistan, Iran, Turkey SIS-10 Iran, Iraq, Turkey and Russia AFG-07 HER-10 Afghanistan, Pakistan, Iran, Kazakhstan, Kyrgyzstan QAZ-11 Iran FAR-11 Pakistan and Iran ESF-10 Iran BAR-08 Egypt and PAT

A/ASIA/Iran-05 • Replaced the A-Iran-96 and A-Iran-99 strains that were previously circulating in the west Eurasian region • Initially A 22/Iraq vaccine provided protection • After 2006, a new vaccines were required (A/Iran 2005 and A/TUR/2006) • Evidence that these vaccines are now no longer fully matched using in-vitro tests • Full capsid sequences reveal amino acid changes in antigenic sites that may underpin these antigenic changes Upadhyaya et al. , (2013) Vaccine

Vaccine matching data (2013) Serotype A (A/ASIA/Iran-05) Matched Vaccine strain Not matched A/IND A/Iran A 22 Irq A/TUR/ A/Eri 98 17/82 2005 24/64 2006 Egypt 2013 BAR-08 Iran 2012 Iran 2013 SIS-10 Pakistan 2012 Pakistan 2013 HER-10 SIS-12 FAR-11 * Palestinian AT 2013 BAR-08 Turkey 2013 SIS-10 * Single values have yielded borderline matches

Asia 1 • Emergence of a Asia 1 lineage (Sindh-08) with poor match Asia 1 Shamir (ISR/3/89) • First recognised in Pakistan (2008) • However in-vivo potency test using >6 PD 50 Shamir vaccine does protect • Lineage has now spread westward into Afghanistan, Iran, Turkey and Bahrain • Spread mirrors recent transboundary movements of O/Pan. Asia and A/Iran-05

Changing global patterns: SAT 2 in North Africa during 2012 • First FMD cases in Egypt due to serotype SAT 2 since 1950 • Cases associated with high mortality • ~50% particularly in young animals due to myocarditis • Sequence data supported at least two introductions of SAT 2 FMDV into Egypt Within SAT 2 topotype VII • Distinct from other contemporary SAT 2 lineages in the Middle East and North Africa • topotype VII from Libya • topotype IV from Bahrain In partnership with the Animal Health Research Institute, Egypt

North Africa: cross-roads between pools Egypt- Recent FMD Outbreaks Recent FMD outbreaks in Egypt have involved at least 3 serotypes and a number of different topotypes/lineages 1. 2. 3. 4. 5. 6. 7. 8. O/ME-SA/Egy-72 (2006 -2009) O/ME-SA/Pan. Asia 2 (Egy-09) (2009 & 2011) O/EA-3 (2012) A/Africa/G-VII (Ken-05) (2006 & 2009) A/Asia/Iran-05 (Bar-08) (2010 -2011) A/Africa/G-IV (ISM-12) (2012) SAT 2/VII/Alx-12 (2012) SAT 2/VII/Ghb-12 (2012)

Changing global patterns: Serotype O from Indian sub-continent in Libya and Saudi Arabia • Recent report (Nov. 2013) • Samples collected in Libya in Sept/Oct 2013 - submitted via IZSLER (Brescia) • Samples collected in Saudi Arabia in Aug/Nov 2013 • O/ME-SA/Ind-2001 lineage most closely related to viruses from Bhutan and India • O/ME-SA/Pan. Asia-2 and O/EA 3 previously reported in the country • O/ME-SA/Ind-2001 lineage normally restricted to the Indian sub-continent • only previously caused FMD outbreaks in the Middle East (Iran 2009, UAE 20082009, Oman 2001, Bahrain 2001, Kuwait 1997). Dr Ibrahim Eldaghayes

OIE/FAO FMD Lab Network in action: Sharing samples and sequence data - O/ME-SA/Ind-2001 • Involved PD-FMD, IZSLER and Pirbright • Molecular phylogenies of FMD viruses from SAU and LIB • Indicates multiple independent introductions of this lineage from the Indian sub-continent • KAR-13 sub-lineage that is widespread in the region • Reports provided to OIE, FAO and local authorities (can be found at: www. wrlfmd. org)

New tailored diagnostic tools For endemic countries where multiple lineages are circulating • Specific real-time RT-PCR assays • For detection and differentiation of different FMDV lineages • Assays evaluated against circulating strains

Available type-specific r. RT-PCR tests • O/ME-SA/Pan. Asia-2 • A/ASIA/Iran-05 • ASIA For west Eurasian viruses (Middle East) • SAT 2 (topotype VII) – Ahmed et al. , 2012 • O/ME-SA/Ind-2001 – Knowles et al. , in prep • • O A SAT 1 SAT 2 For East African viruses For further information and protocols contact: WRLFMD

Simplified summary Transboundary movement patterns of FMDV O/ME-SA/Pan. Asia-2 A/ASIA/Iran-05 Asia-1 A/ SAT 2 AFRICA ? O/ME-SA/Ind-2001 O/EA-3 • Are these patterns predictable? • Understanding epidemiology of FMD provides a basis to estimate threats of new virus incursions • Phylogeography analysis is underway

Acknowledgements • Support for the WRLFMD and research projects • Collaborating FMD Reference Laboratories and field teams • Partners within the OIE/FAO FMD Network FMD Reference Laboratory

Supplementary in-vitro vaccine matching data Matched Vaccine strain Not matched O/ME-SA/Ind-2001: Saudi Arabia 2013 O/Manis O/TUR O-3039 O-4625 a TAW/98 5/2009 Libya 2013 O/EA-3: Egypt 2012 SAT 2 Eritrea ZIM/7/83 Egypt 2012