OS18 - Open Session 2018 Borgo Egnazia (Puglia), Italy 29 - 31 /10/2018 EuFMD Sessions\Open Session\Archive-2018\Open 2018 - Italy\6. Online & Streaming\PPTs

1. FMD Reference Laboratory
Global Status Report for FMD:
Tracking the emergence and spread of new viral lineages
Donald King
Acknowledgements: Valerie Mioulet, Nick Knowles, Anna Ludi, Ginette Wilsden,
Mehreen Azhar, Hannah Baker, Kasia Bachanek-Bankowska, Antonello Di Nardo,
Bob Statham, Lissie Henry, Jemma Wadsworth, Clare Browning, Britta Wood,
Alison Morris, David Paton, Abid Bin-Tarif, Ashley Gray, Beth Johns, Mark Henstock,
Nick Lyons, Dexter Wiseman, Julie Maryan, Sarah Belgrave

2. Seven endemic pools
• Maintain specific FMD virus strains
• Control via (tailored) vaccination and supporting diagnostics
• No reported serotype C outbreaks since 2004 (Kenya and Brazil)
Conjectured global status

3. • Global surveillance and
changing patterns in risk
• Harmonised and improved lab
capacity
• MoU now signed by all “core
members”
• Meeting and annual reports
available:
http://www.foot-and-mouth.org/
Pretoria– November 2017
Core Network Members and affiliates:
1.2 Reporting Period
1st January 2016 - 31st December 2016
1.3 Collated input from
Figure 1-1: Participating laboratories
OIE Reference Laboratory for Foot and
Mouth Disease, Dirección de Laboratorio
Animal
SENASA, Argentina
OIE collaborating centre for validation,
quality assessment and quality control of
diagnostic assays and vaccine testing for
vesicular diseases in Europe, and FAO
Reference Centre for vesicular Diseases
CODA-CERVA, Ukkel, Belgium
OIE Regional Reference Laboratory for
Sub-Saharan Africa (RRLSSA)
BVI, Gabarone, Botswana
Centro Panamericano de Fiebre Aftosa
(PANAFTOSA) and OIE Reference
Laboratory for FMD
Rio de Janeiro, Brazil
FAO FMD Reference Laboratory
National Centre for Foreign Animal Disease National
Centres for Animal Disease, Canadian Food
Inspection Agency, Winnipeg, Manitoba, Canada
OIE and China National FMD Reference
Laboratory
Lanzhou Veterinary Research Institute (LVRI),
CAAS, Gansu, People’s Republic of China
OIE FMD Reference Laboratory
French Agency for Food and, Environmental and
Occupational Health & Safety (ANSES), Maisons-
Alfort, Paris, France
FAO Reference Centre for FMD in South
Asia
Project Directorate on FMD (PDFMD), Indian
Council for Agricultural Research, Mukteswar,
Nainital (Uttarakhand), India
OIE/FAO FMD Reference Laboratory
Istituto Zooprofilattico Sperimentale della Lombardia
e dell'Emilia Romagna (IZSLER), Italy
OIE Reference laboratory for Foot and
Mouth Disease
Animal and Plant Quarantine Agency (QIA), Anyang
city, Gyeonggi-do, Republic of Korea
OIE/FAO FMD Laboratory Network

4. Global surveillance
via the OIE/FAO FMD Laboratory Network
• Since 2014 >2000 virological samples tested per year
• High proportion of samples that are ”no virus detected [NVD]”
• Gaps in surveillance remain in West/Central (and East Africa)
• Review geographical distribution and spread of transboundary
FMDV lineages
• new way to highlight future risks Ind-2001d PanAsia
PanAsia-2 Mya-98
EA-3 Conjectured distribution of important
serotype O FMDV lineages. The extent of
current distribution for each of the viral
lineages is represented within the black
lines, while the location of individual
outbreaks (dots) and affected countries
(shaded in red, according to dates) are
shown. NB: Arrows are drawn to highlight
the regions that are threatened by these
lineages
2017 data:
OA
NVD
FMDV serotypes detected

5. Pool 1
Pool 2
Pool 3
Pool 4
Pool 6
Pool 5
Pool 7
OIE Global status

6. • Two sub-lineages (d and e)
• Since 2013, full genomic sequence data
indicates that there have been multiple
“escapes” from Pool 2
O/ME-SA/Ind-2001: a new pandemic lineage?
Libya
(2013)
Tunisia
Algeria
Morocco
Mauritius
(2016)
Pool 2
Saudi Arabia (2015)
UAE (2015)
Jordan (2017)
Vietnam (2016)
Thailand (2016)
Myanmar (2017)
China (2017)
Russia (2016)
Mongolia (2015/17)
South Korea (2017)
Malaysia (2018)
Saudi Arabia (2016) Myanmar (2015)
Myanmar (2017)
Saudi Arabia (2013)
Sri Lanka
(2014/13)
UAE (2014)
Bahrain (2015x2) Vietnam (2015)
Laos (2015)
d
e
(Bachanek-Bankowska et al., 2018)

7. Spread of A/ASIA/G-VII:
(Bachanek-Bankowska et al., 2018)
Pool 2
Saudi Arabia
Turkey
Iran
Armenia
Israel
• Emerged in 2015 from
Pool 2
• Rapid spread into parts
of West Eurasia (most
recently Israel in 2017)
• Poor in vitro and in vivo
responses for vaccines
that are used in West
Eurasia
• Gap in the coverage of
vaccines have led to the
development of new
tailored vaccine strains
A/SAU/1/2015
A/SAU/2/2015
A/IRN/8/2015
A/IRN/12/2015
A/IRN/25/2015
A-Iran-05 0 0 0 0 0
A-Tur-20-06 0.03 0.06 0.01 0.15 0.01
A-22 0.11 0.11 0.13 nd 0
A-Iran-87 0 0.04 nd nd nd
A-Iran-96 0.04 0.06 nd nd nd
A-Iran-99 0.01 0.01 nd nd nd
A-Sau-95* 0.20 0.19 0.26 0.16 nd
A-May-97 0.14 0.23 0.15 0.23 nd
A-Tur-11 0.01 nd 0.10 0.04 nd
A-Tur-14 0 nd 0 0 nd
A-IND-40-2000* 0.26 nd 0.03 0.24 nd
r-values:
Vaccines

8. Pool 2 Myanmar
IND285(640)/2012*
IND/285/2012*100
IND131(255)/2012*
IND157(336)/2013*
IND403(826)/2012*
BD SI 2 2013*
IND/292/2012*
IND/294/2012*
IND413(852)/2012*
IND400(822)/2012*
86IND120(225)/2012*
IND/120/2012*
IND/121/2012*
IND/16/2012*
IND119(223)/2012*
IND118(222)/2012*
IND15(24)/2012*
IND/118/2012*
IND/283/2012*
IND/305/2012*
IND156(335)/2013*
IND/115/2012*
IND/119/2012*
IND119(224)/2012*
IND114(214)/2012*
IND/114/2012*
IND300(655)/2012*
IND/300/2012*
IND115(217)/2012*
IND/306/2012*
IND288(643)/2012*
88IND411(846)/2012*
IND411(845)/2012*
IND/288/2012*
IND/291/2012*
IND163(334)/2012*
IND163(333)/2012*
IND162(331)/2012*
IND109(208)/2012*
86 IND/303/2012*
IND303(658)/2012*
BAN GA Sr-187 2013*
MYA/14/2017*93
90
• Serotype Asia 1 not reported in
Southeast Asia since 2006/7(?)
• February 2017: FMD outbreaks
in cattle in Myanmar
• Sequence data from RRL-SEA in
Pakchong, Thailand
• New introduction of the virus
from Pool 2
Onward risks?
SEACFMD – 2017:
• ~500,000 head/year move from
Mynamar into Yunnan Province
of PR China
• 5% infected with FMDV
SEA: New outbreaks of Serotype Asia 1

9. Analyses of samples from Nepal
Highlights gaps in regional/National surveillance?
Serotype O:
~94% identity with closest VP1 sequences
Serotype Asia 1:
~91% identity with closest VP1 sequences
How do we interpret
these trees?
1. Rapid evolutionary
change
2. Un-sampled cases

10. Pool 1
Pool 2
Pool 3
Pool 4
Pool 6
Pool 5
Pool 7
FMD outbreaks in North Africa
North Africa
No FMD outbreaks 1999-2013
Near East
Serotype O/SAT 2
Serotype A
Previous SAT 2 outbreaks in Egypt/Libya/Palestine 2012

11. March – April 2017: FMD cases in Algeria and Tunisia
• >100 outbreaks in cattle
• Due to a new FMD virus strain for
the region (A/AFRICA/G-IV)
• Sequences from Algeria (March) and
Tunisia (April) >99% identity
• Most closely related to FMD viruses
from Nigeria
• First cases of Serotype A in the
Maghreb > 30 years
• Algeria 1977
• Tunisia 1984
• in-vitro vaccine matching data for
provides candidates vaccines that
now need testing
VACCINE STRAINS
A/ERI/3/98 A/TUR/20/06 A22/IRQ/64 A/IRN/05
ALG/2/2017 0.41 0.00 0.31 0.00
ALG/3/2017 0.32 0.00 0.32 0.00

12. • Due to the O/EA-3 topotype
• >50 outbreaks
• >99% nt identity to sequences from
Guinea (generated by for
samples collected in July 2018)
• July-September 2018: Reports to OIE of
FMD outbreaks elsewhere in West Africa
(The Gambia, Guinea-Bissau, and Sierra
Leone { + Burkina Faso and Senegal -not
reported to OIE})
• Are these cases linked? – and do they
represent the likely origins of the viruses
that help us understand how FMDV has
recently spread into North Africa?
June 2018: FMD cases in Algeria

13. • Sequences from West
Africa/Algeria are
different to Egypt/
Palestine/Israel
• Western-clade most
similar to sequences
from Nigeria
• Similar picture to
A/AFRICA/G-IV
Different O/EA-3 sub-lineages in Africa
Cameroon 2016
O/CAR/G4258/2013* (KY581680)
O/CAR/G4260/2013* (KY581679)
Nigeria 2014
O/GNA/18Z005582/18* (ANSES)
O/GNA/18Z005587/18* (ANSES)
O/GNA/18Z005583/18* (ANSES)
O/ALG/2/2018
O/ALG/1/2018
O/GNA/18Z005588/18* (ANSES)
Nigeria 2016
O/NIG/1/2007 (KX258020)
O/SUD/1/2005 (GU566056)
O/SUD/3/2005 (GU566058)
Egypt / Palestine / Israel 2017
O/SUD/2/86 (DQ165075)
O/ETH/2/2006 (FJ798127)
O/ETH/3/2004 (FJ798109)
O/ETH/1/2007 (FJ798137)
“East
Africa”
Clade
“West
Africa”
Clade

14. xxxxxxxxxxxxxxxxxxxxxxxx
Uganda
Kenya
Burundi
Rwanda
Tanzania
DRC
Important
Infrequent
Conjectured
regional
connections in
Africa
Sudan
S. Sudan
Ethiopia
Somalia
Eritrea
West Africa
Pool 5
Southern
Africa
Pool 6
Malawi
Maghreb
countries West Eurasia
Pool 3
• Viral sequences highlight most
frequent connections between
countries (reflect trade and
animal movements)
• Trans-Saharan spread of FMD
is infrequent (previously
occurred in 1999)
• New pathways into countries
in North Africa (Maghreb)?
Cattle density map
Egypt
Libya
Samples tested

15. 2017/18 FMD situation – ”headlines”
Colombia
Serotype O
East Asia
Serotype O
Myanmar
Serotype Asia 1
Algeria (Tunisia)
Serotype A
Serotype O
Near East
Serotype O (O/EA-3)
Serotype A (A/ASIA/G-VII)
Serotype SAT 2
Russia
Serotype O
Zambia
Serotype O
South Korea
Serotypes O/A
Pakistan
Serotype O

16. Selecting vaccines to cover risk?
European Perspective
2010-2011
• Outbreaks in Bulgaria
• FMD-free buffer zone
in Turkish Thrace
• Outbreaks in UK in 2001
• Increased FMD circulation
in East Asia
%oftotalrisk
NRL Workshop for FMD – Ascot, UK - May 2016
• New FMD lineages in North
Africa
• Outbreaks in FMD-free
countries

17. Vaccine Antigen Prioritisation: Europe
SELECTING VACCINES
September 2018
NB: Analyses uses best available data, however there are gaps in surveillance and vaccine coverage data
Insufficient Data: C3 Oberbayern [LOW];
SAT2 SAU [HIGH];
SAT3 ZIM 2/83 [LOW]
Risk Profile:
O-TUR/5/2009 [HIGH]
O-3039 [HIGH]
O1-Manisa [HIGH]
O1-Campos [HIGH]
O-BFS/1860 [LOW]
O-SKR/7/2010 [LOW]
O-TAW/98 [↓ LOW]
A-TUR/2006 [HIGH]
A22 Iraq [HIGH]
A-Iran-05 [HIGH]
A-Malaysia 97 [↑ HIGH]
A-Eritrea [MEDIUM]
A-SAU 95 [LOW]
A24 Cruzeiro [↓LOW]
Asia1-Shamir [HIGH]
SAT2 Eritrea 3218 [HIGH]
SAT2-ZIM [MEDIUM]
SAT-1 Rho/78 [MEDIUM]
Vaccine Coverage:
DEFINING RISK
O/ME-SA/Ind2001A/ASIA/G-VII
40%
0%
Regional risks:
Viral
lineages:

18. FMDV vaccines: evidence gaps
Particularly for Africa (from OIE/FAO and EALN-FMD Network Meetings)
[1] in vivo potency tests are rarely done,
particularly those that define cross-
protective responses
[2] Immunogenicity studies for monovalent
(or multivalent vaccines) are rarely
reported
[3] Reference reagents (such as validated
BVS) from vaccines suppliers are not
readily available to the Reference
laboratory community
[4] Not clear that batch serological testing
data is always supplied
[5] Studies that assess vaccine performance
under field conditions are often lacking

19. Production batches
(Batch control)
Formulated product
(Customer requirements)
Licensed vaccine
(Registration)
• Biosecurity and containment
procedures
• GMP and in process controls
• MSV records
• Homologous potency testing in
cattle
• Sterility, adventitious agent and
inocuity testing
• Purity and safety testing
• Stability and duration of immunity
• Confirmation of MSV identity
• Sterility and inocuity tests
• Safety test
• Indirect potency test
• Monitoring of long-term storage
conditions
• Verification of Ag integrity of
batch
• Confirmation of batch identity
• Purity testing
• Defining/validating heterologous
correlates (cattle and other
species)
• Batch testing to generate sera
• Confirmation that batch sera
passes threshold heterologous
responses
• Field studies of post-vaccination
responses
• Vaccination coverage and
outcomes
• Investigation of vaccine failure
• Selection of reference viruses
(to cover regional risks)
• Generation of reference BVS
• Application of in vitro vaccine
matching tests
• Development of harmonised
test formats
• In vivo studies (where required)
• Identification of vaccine gaps
• Tender requirements
• Shelf life
• Antigenic relevance
• Potency
• Purity
• Duration of immunity
• Correlate of immunity
threshold
• Verification /calibration studies
Vx Producers (with audit at registration/purchase)
AU-PANVAC (with assistance from WRLFMD)
Vx producer (with supervision/audit by AU-PANVAC) – or AU-PANVAC
Customer (with support from FMD Reference labs/AU-PANVAC – where needed)
OIE/FAO FMD Lab Network
KEY
VACCINATION PLAN
VaccineQA/QC
Homologousprotection
Vaccineperformance
Heterologous(field)protection
FMDV vaccine QA/QC pipeline for Africa
Defining responsibilities:

20. • Epidemiology of FMD is very dynamic
• New unpredictable patterns in Asia (East and West)
and North Africa
• Threats to FMD-free countries in Europe and
Turkish Thrace
• Sampling of field outbreaks is critical
• Importance of an active FMD Reference
Laboratory Network to facilitate sample
collection from FMD outbreaks in the field– to
feed real-time lab data back to FMD control
programmes
• Impact upon selection and deployment of
vaccines
Talk summary

21. Upcoming events….
• 60th Symposium and celebration on 5th-6th November 2018
• Previous anniversary events……
• OIE/FAO FMD Laboratory Network Meeting @ Pirbright - 7th-8th
November 2018
• E-learning course on FMD Diagnostics – Jan/Feb 2019
• Practical training course on FMD diagnostics for East Africa – Jan 2019
Royal Society, London, 2008John Brooksby (first head of WRLFMD), Pirbright, 1998
40 years 50 years

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

24. New FMD outbreaks in Republic of Korea
A/Iran-05
A/May97
ATUR20/06
A/G-VII
A22
A24(1)
A24(2)SKR/5/2008 0.45 0.12 0 0.47 0.43 0.19 0.35
1PANAFTOSA BVS
2BI BVS
• March 2018: Two FMD outbreaks in pigs due
to A/ASIA/Sea-97
• 2017: One outbreak due to A/ASIA/Sea-97
• 2017: Eight outbreaks due to O/ME-SA/Ind-
2001
• Samples tested at QIA and WRLFMD
• Represent new introductions of FMD into
South Korea from an East/Southeast Asian
country?
• Vaccine matching:
• 2018: 24 FMD outbreaks reported to OIE in
DPR Korea (serotype O - tbc)

25. • 5 FMD outbreaks reported in
Bashkortostan (in the FMD-free zone
without vaccination)
• Reported cases in cattle, sheep and
goats
• New FMDV lineage in ME-SA topotype
(not PanAsia or PanAsia-2)
• Most closely related to FMD viruses in
Pakistan and Iran (2014)
• Reporting of cases in “central Asia”?
O/ME-SA lineage in Russia
October 2017

26. • Two isolates in a new genetic clade
within O/ME-SA/PanAsia-2ANT-10
• Discrete from other ANT-10 viruses
• Collected in Punjab, Pakistan
(2016/17) from cattle and water
buffalo
• No neutralization in VNT with BVS for
O-Manisa, O-3039 or O-TUR-5-09
• New antigenic variant?
• Spread of this lineage needs to be
closely monitored – esp. wrt evidence
of vaccine failure in the field
Poor Ag-match for serotype O viruses from Pakistan

27. 10 20 30 40 50 60 70 80
....|....|....|....|....|....|....|....|....|....|....|....|....|....|....|....|
Ag site 3
O/PAK/14/2017 TTSAGESSDPVTATVENYGGETQVQRRQHTDVSFILDRFVKVTPKDQINVLDLMQTPAHTLVGALLRTATYYFADLEVAV
O/PAK/10/2016 .......A....T...................................................................
O/PAK/4/2017 .......A........................................................................
90 100 110 120 130 140 150 160
....|....|....|....|....|....|....|....|....|....|....|....|....|....|....|....|
Ag site 1
O/PAK/14/2017 KHEGNLTWVPNGAPEAALDNTTNPTAYHKAPLTRLALPYTAPHRVLATVYNGNCKYGESHVPNVRGDLQVLAQKAARALP
O/PAK/10/2016 ....D..........T.............................................T..................
O/PAK/4/2017 ....D..........T........................................S....T...............T..
170 180 190 200 210
....|....|....|....|....|....|....|....|....|....|...
Ag site 1
O/PAK/14/2017 TSFNYGAIKATRVTELLYRMKRAETYCPRPLLAIHPDAARHKQKIVAPVKQLL
O/PAK/10/2016 .................................V..NE...............
O/PAK/4/2017 ....................................NE...............
• VP1
• Complete genome sequences will also be determined using the Illumina MiSeq
Known type O
antigenically important
residues are underlined
Vaccine matching O 3039 O Manisa O TUR/5/2009
O/PAK/14/2017 0.62 0.32 0.48
O/PAK/10/2016 0 0 0
O/PAK/4/2017 0 0.10 0
Residue 198 has been shown to be part of site
1 in type A viruses
↑
Preliminary analyses:

28. FMD Cases in Colombia
• First clinical case reported in South
America since 2013 (Venezuela)
• 7 outbreaks (June and July 2017)
• 5 Outbreaks (October 2018)
• Some close to border with
Venezuela
• Cases in vaccinated cattle
• Sequence data consistent with
indigenous strains from the region
• Lineage 6 described by Malirat
et al., 2011

29. Batch: WRLFMD/2018/00013
COD/13/2006
COD/101/2006
COD/99/2006
COD/57/2006
COD/53/2006
COD/93/2006
COD/92/2006
COD/91/2006
COD/66/2006
COD/100/2006
COD/104/2006
COD/55/2006
COD/58/2006
COD/64/2006
COD/47/2006
COD/11/2006
COD/51/2006
COD/59/2006
COD/60/2006
COD/105/2006
87 COD/95/2006
COD/90/2006
COD/68/2006
COD/77/2006
COD/19/2006
COD/81/2006
COD/83/2006
COD/82/2006
COD/80/2006
COD/15/2006
COD/63/2006
COD/7/2006
94COD/71/2006
COD/36/2006
94 COD/6/2006
73
TAN-CVL-2013-0378*
TAN-CVL-2013-0376*
100
COD/3/2010
COD/1/2010
COD/2/2010
TAN-CVL-2011-0106*
ZAM/4/2010
ZAM/1/2010
76 COD/4/2010
95 ZAM/3/2010
TAN/5/2014
TAN/9/2014
TAN/3/2014
TAN/10/2014
100
TAN-CVL-2012-0318*
UGA/1/2017
TAN/6/2014
TAN/8/2014
TAN/4/2014
TAN/7/2014
TAN-CVL-2013-0364*
TAN-CVL-2012-0321*
TAN-CVL-2013-0362*
100TAN-CVL-2013-0366*
100
93
ZAM/3/2018
ZAM10/2018*
ZAM12/2018*
ZAM/2/2018
ZAM/1/2018
100
96
99
74
• April 2018: FMD outbreaks reported
in cattle - Chisamba and Chibombo
in the Central Province
• Samples received to WRLFMD (and
sequences from BVI) from Chisamba
• Sequenced as O/EA-2
• Represent new south westerly
movement of serotype O into
central Zambia?
• Previous O/EA-2 outbreaks in 2010
close to the border with Tanzania
(Mbala)
FMD outbreaks in Zambia
EA-1
EA-2
EA-3
EA-4
WA
ME-SA (Ind-2001d)
Topotypes
©d-maps.com
1000 km
600 mi

30. OS18