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 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 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: West EurAsia (Middle East) North Africa ✓ ✓ ✓ ✓ O/ME-SA/Ind-2001 ✓ ✓ ✗ ✓ SAT 2 topotype VII ✓ ✓ SAT 2 topotype IV A/AFRICA/G-IV ✓ ✗ ✗ ✓ A/AFRICA/G-VII ✗ ✓ O/ME-SA/Sharqia-72 ✗ ✓ O/EA-3 ✓ ✓ O/ME-SA/PanAsia-2 A/ASIA/Iran-05 Asia-1 O/ME-SA/PanAsia-2 O/TUR/31/2013 O/TUR/33/2013 O/TUR/38/2013 O/TUR/27/2013 O/TUR/26/2013 O/TUR/12/2013 O/TUR/25/2013 O/TUR/24/2013 Sub-lineage nomenclature used to define different viral genotypes O/TUR/29/2013 O/TUR/36/2013 O/TUR/37/2013 O/ISR/1/2013 O/ISR/2/2013 O/ISR/3/2013 O/ISR/3/2014 O/ISR/4/2014 O/ISR/2/2014 O/ISR/1/2014 2014 2013 2012 2011 • ANT-10 Iran Israel Saudi Arabia Turkey UAE Afghanistan Pakistan Libya O/PAT/13/2013 O/PAT/14/2013 O/ISR/5/2014 O/ISR/6/2014 O/SAU/1/2009 O/SAU/2/2009 O/IRN/41/2009 O/IRN/52/2009 O/IRN/79/2009 O/IRN/42/2009 O/IRN/76/2009 FAR-09 O/IRN/34/2009 O/IRN/64/2009 PanAsia-2 O/IRN/38/2009 O/IRN/35/2009 O/IRN/49/2009 O/IRN/65/2009 ME-SA O/IRN/68/2009 O/IRN/83/2009 O/IRN/89/2009 O/IRN/31/2009 O/IRN/51/2009 O/IRN/60/2009 O/IRN/81/2009 O/IRN/61/2009 O/IRN/80/2009 O/IRN/43/2009 O/IRN/66/2009 O/IRN/75/2009 O/IRN/84/2009 O/IRN/56/2009 O/IRN/21/2012 O/IRN/2/2013 O/IRN/62/2011 O/IRN/71/2011 O/IRN/77/2011 • FAR-09 Iran Israel PAT Turkey O/IRN/57/2009 O/IRN/87/2009 O/IRN/18/2010 O/PAK/16/2010 BAL-09 PUN-10 O/IRN/8/2005 O/IRN/88/2009 O/TUR/257/2008* (FMDI) O/TUR/264/2009* (FMDI) ANT-10 TER-08 SAN-09 PanAsia Irn-2001 Ind-2001 Pak-98 O/IND/53/79 (AF292107) O/IND/R2/75* (AF204276) O1/Manisa/TUR/69 (AY593823) SEA EA-3 EA-2 EA-4 Epidemiology of FMDV in Bulgaria (Burgas): 2011 © Daniel Dalet / d-maps.com 500 km 300 mi • Incursion of FMD into a FMD-free (without vaccination) country in Europe • O/ME-SA/PanAsia-2ANT10 • Use of full genome sequence data generated in real-time to show how sequences are related Bulgaria Kastamonu Bursa Gümüşhane Eskişehir Turkey Antalya Sivas Ağrı Iran • 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) BUL/1/2010 12LPN1 Closest Turkish virus 12LPN3 BUL/11/2011 BUL/30/2011 TCS tree showing linking samples showing putative unsampled intermediates (-O-) Valdazo-Gonzalez et al., PLoS ONE (2012) BUL/26/2011 BUL/20/2011 BUL/32/2011 Vaccine matching data (2013) Serotype O (all O/ME-SA/PanAsia-2 lineages) Matched Vaccine strain Not matched Field isolate O-3039 O/RUSSI O-4625 O/Manisa A/2000 TAW/98 Iran 2012 Iran 2013 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 SIS-10 Iran, Iraq, Turkey and Russia AFG-07 Afghanistan, Pakistan, Iran, Turkey HER-10 Afghanistan, Pakistan, Iran, Kazakhstan, Kyrgyzstan QAZ-11 Iran FAR-11 Pakistan and Iran ESF-10 Iran BAR-08 Egypt and PAT A/AFG/140/2010 A/AFG/163/2010 A/AFG/128/2010 A/AFG/125/2010 A/IRN/125/2010 A/IRN/151/2010 A/PAK/37/2010 A/IRQ/5/2010 A/IRN/24/2011 A/TUR/26/2011 A/TUR/40/2010 A/TUR/1538/2010* (FMDI) A/IRN/4/2011 A/IRN/5/2011 A/IRN/18/2011 A/IRN/30/2011 A/IRN/20/2011 A/IRN/52/2011 A/TUR/14/2011 A/TUR/3/2011 A/TUR/37/2011 A/TUR/63/2011 A/TUR/60/2011 A/TUR/9/2011* (FMDI) A/TUR/6/2011 A/TUR/13/2011 A/TUR/21/2011 A/TUR/24/2011 A/TUR/10/2011 A/TUR/43/2011 A/TUR/5/2011 A/TUR/23/2011 A/TUR/30/2011 A/TUR/35/2011 A/TUR/11/2011 A/TUR/18/2011 A/TUR/47/2011 A/TUR/29/2011 A/TUR/64/2011 A/TUR/16/2011 A/TUR/22/2011 A/TUR/41/2011 A/TUR/7/2011 A/TUR/3/2012 A/TUR/36/2011 A/TUR/5/2012 A/TUR/1/2013 A/TUR/10/2013 A/TUR/7/2013 A/TUR/11/2013 A/IRQ/A218/2012* (FMDI) A/IRQ/A233/2012* (FMDI) A/IRQ/A223/2012* (FMDI) A/IRQ/A222/2012* (FMDI) A/IRN/31/2012 A/IRQ/2012* (JUST) A/TUR/6/2012 A/TUR/4/2013 A/TUR/9/2013 A/TUR/14/2013 A/TUR/30/2013 A/TUR/1233/2012* (FMDI) A/TUR/1204/2012* (FMDI) A/TUR/6/2013 A/TUR/16/2013 A/TUR/18/2013 A/TUR/19/2013 A/TUR/21/2013 A/TUR/35/2013 A/TUR/22/2013 A/TUR/23/2013 A/IRN/78/2009 A/AFG/6/2007 A/BAR/6/2008 A/AFG/10/2010 A/IRN/15/2012 A/IRN/9/2010 A/TUR/1/2008 A/IRN/1/2005 (EF208769) A/TUR/33/2008 A/IRN/9/2011 Iran-99 Irn-96 Iran-87 SIS-10 Iran-05 ASIA FAR-09 AFG-07 BAR-08 HER-10 SIS-12 ESF-10 ARD-07 EZM-07 QAZ-11 A/ASIA/Iran-05 • Replaced the A-Iran-96 and A-Iran-99 strains that were previously circulating in the west Eurasian region • Initially A22/Iraq vaccine provided protection • After 2006, a new vaccines were required (A/Iran2005 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 A22Irq A/TUR/ A/Eri98 17/82 2005 24/64 2006 Egypt 2013 BAR-08 Iran 2012 Iran 2013 SIS-10 Pakistan 2012 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 >6PD50 Shamir vaccine does protect • Lineage has now spread westward into Afghanistan, Iran, Turkey and Bahrain • Spread mirrors recent transboundary movements of O/PanAsia and A/Iran-05 Asia1/AFG/51/2011 Asia1/AFG/55/2011 Asia1/AFG/48/2011 Asia1/PAK/81/2011 Asia1/PAK/67/2011 Asia1/PAK/60/2011 Asia1/PAK/56/2011 Asia1/PAK/53/2011 Asia1/PAK/50/2011 Asia1/PAK/37/2011 Asia1/PAK/33/2011 Asia1/PAK/14/2011 Asia1/PAK/11/2011 Asia1/PAK/111/2010 Asia1/PAK/106/2010 Asia1/PAK/108/2010 Asia1/PAK/7/2011 Asia1/PAK/12/2011 Asia1/PAK/15/2011 Asia1/PAK/35/2011 Asia1/PAK/39/2011 Asia1/PAK/51/2011 Asia1/PAK/54/2011 Asia1/PAK/57/2011 Asia1/PAK/61/2011 Asia1/PAK/68/2011 Asia1/PAK/17/2011 Asia1/PAK/83/2011 Asia1/IRN/49/2011 Asia1/PAK/110/2010 Asia1/PAK/8/2011 Asia1/PAK/13/2011 Asia1/PAK/16/2011 Asia1/PAK/36/2011 Asia1/PAK/49/2011 Asia1/PAK/52/2011 Asia1/PAK/55/2011 Asia1/PAK/58/2011 Asia1/PAK/64/2011 Asia1/PAK/69/2011 Sindh-08 Asia1/PAK/89/2011 Asia1/PAK/90/2011 Asia1/AFG/66/2011 Asia1/AFG/68/2011 Asia1/AFG/73/2011 Asia1/AFG/78/2011 Asia1/IRN/33/2011 Asia1/IRN/38/2011 Asia1/AFG/40/2011 Asia1/PAK/2/2012 Asia1/PAK/3/2012 Asia1/PAK/1/2012 Asia1/PAK/11/2012 Asia1/PAK/36/2012 Asia1/PAK/37/2012 Asia1/IRN/47/2011 Asia1/PAK/10/2013 Asia1/PAK/45/2012 Asia1/PAK/46/2012 Asia1/PAK/18/2012 Asia1/PAK/19/2012 Asia1/PAK/29/2012 Asia1/PAK/9/2013 Asia1/PAK/14/2013 Asia1/PAK/8/2013 Asia1/PAK/7/2013 Asia1/PAK/21/2012 Asia1/PAK/24/2012 Asia1/PAK/25/2012 Asia1/PAK/26/2012 Asia1/PAK/30/2012 Asia1/PAK/10/2012 Asia1/PAK/22/2012 Asia1/PAK/27/2012 Asia1/PAK/35/2012 Asia1/PAK/4/2012 Asia1/PAK/5/2012 Asia1/PAK/42/2012 Asia1/PAK/23/2013 Asia1/PAK/8/2008 Asia1/AFG/1/2001 (DQ121109) Group I Asia1/HKN/19/74 Asia1/Shamir/ISR/89 Asia1/IND/762/2003* (DQ101240) Group III Asia1/IND/14/95* (AF390678) Asia1/IRN/10/2004 (DQ121119) Group VIb Asia1/YNBS/CHA/58 (AY390432) Asia1/IND/63/72* (AY304994) Asia1/IND/18/80 (DQ121116) Group V Asia1/PAK/1/54 (AY593795) 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 100 Cameroon 2005 SAT2/LIB/40/2012 100 79 SAT2/LIB/41/2012 SAT2/LIB/39/2012 SAT2/SUD/1/2007 (GU566071) SAT2/NIG/2/2007 97 93 SAT2/NIG/5/2008 SAT2/NIG/6/2008 89 SAT2/NIG/7/2008 SAT2/NIG/4/2008 100 SAT2/NIG/1/2008 98 SAT2/NIG/2/2008 SAT2/NIG/3/2008 • ~50% particularly in young animals due to myocarditis SAT2/NIG/8/2008 100 SAT2/LIB/1/2003 SAT2/LIB/7/2003 SAT2/NGR/15/2005 86 SAT2/SEN/27/2009 SAT2/EGY/2/2012 SAT2/SAU/6/2000 (AF367135) SAT2/CAR/P12/2000 (VDI 44/1)(HM211082) SAT2/ERI/12/98 (AF367126) • Sequence data supported at least two introductions of SAT 2 FMDV into Egypt SAT2/ERI/1/98 (AY343933) 100 100 SAT2/ERI/4/98 (AY343934) SAT2/EGY/9/2012 SAT2/EGY/11/2012 100 SAT2/EGY/13/2012 SAT2/EGY/6/2012 SAT2/EGY/10/2012 SAT2/EGY/14/2012 SAT2/EGY/15/2012 SAT2/EGY/3/2012 SAT2/EGY/4/2012 SAT2/EGY/5/2012 Within SAT 2 topotype VII 0.01 • 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/PanAsia 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) SAT2/VII/Alx-12 (2012) SAT2/VII/Ghb-12 (2012) Changing global patterns: O/BAN/9/2009 (HQ630681) O/IND/32/2012* (KC506511) O/IND/4/2011* (KC506485) O/IND/5/2011* (KC506486) O/IND/6/2011* (KC506487) O/IND/2/2011* (KC506484) O/IND/38/2011* (KC506492) O/BHU/1/2013 O/SAU/1/2013 O/SAU/4/2013 O/SAU/3/2013 O/SAU/6/2013 O/SAU/7/2013 O/SAU/8/2013 O/LIB/16/2013 O/LIB/1/2013 O/LIB/4/2013 O/LIB/5/2013 O/LIB/7/2013 O/LIB/11/2013 O/LIB/12/2013 O/LIB/22/2013 O/LIB/13/2013 O/LIB/17/2013 O/LIB/2/2013 O/LIB/3/2013 O/LIB/6/2013 O/UAE/4/2008 O/KUW/3/97 (DQ164904) O/OMN/7/2001 (DQ164941) 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/PanAsia-2 and O/EA3 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 PanAsia PanAsia-2 O1/Manisa/TUR/69 (AY593823) SEA K c a b 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 rRT-PCR tests • O/ME-SA/PanAsia-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 SAT1 SAT2 For East African viruses For further information and protocols contact: WRLFMD Simplified summary Transboundary movement patterns of FMDV O/ME-SA/PanAsia-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 Not matched O/ME-SA/Ind-2001: Vaccine strain O/Manis O/TUR O-3039 O-4625 a TAW/98 5/2009 Saudi Arabia 2013 Libya 2013 O/EA-3: Egypt 2012 SAT2 SAT2 Eritrea ZIM/7/83 Egypt 2012