WHICH VACCINES ARE MOST IMPORTANT? PRAGMATIST: A DECISION SUPPORT TOOL FOR FOOT AND MOUTH DISEASE VACCINE BANK MANAGERS Melissa McLaws 1, Don King 2, Katie Hickey 1, Anna Ludi 2, Keith Sumption 1 European Commission for the Control of Foot and Mouth Disease (EuFMD) 1 WRLFMD The Pirbright Institute 2
Key Messages PRAGMATIST is a tool to assist vaccine bank managers select /maintain the most appropriate antigens Transparent, evidence based Vaccine matching results Other applications: Highlight data gaps and important antigens that do not have a good vaccine available Framework for surveillance to engage international FMD lab/epi networks Next Steps Ongoing efforts to improve data quality User feedback
Context FMD virus: 7 serotypes, multiple strains within serotypes. No cross-protection between serotypes variable between strains within serotypes Multiple vaccine strains available FMD serotypes Viruses in any region are a potential threat to all other regions, no matter how far away, and consequently should be considered for inclusion in antigen banks. (Lombard & Füssel, 2007)
Context FMD virus: 7 serotypes, multiple strains within serotypes. No cross-protection between serotypes variable between strains within serotypes Multiple vaccine strains available Which strains are most important to maintain in my vaccine bank? Viruses in any region are a potential threat to all other regions, no matter how far away, and consequently should be considered for inclusion in antigen banks. (Lombard & Füssel, 2007)
Which strains to maintain in the vaccine bank? Significant financial investment The World Reference Laboratory produces annual recommendations Antigens divided into high, medium and low priority EU perspective: not global in nature Criteria are not clearly defined
PRAGMATIST: PRioritisation of AntiGen MAnagemenT with International Surveillance Tool EuFMD and WRL collaboration Assist risk managers make decisions about the FMD vaccines that they purchase/maintain, based on current risks to countries covered by the bank
Excel spreadsheet 2 distinct considerations: PRAGMATIST: Antigen Priority tool 1. Antigen risk score : which strains pose greatest threat of incursion (left side) and 2. Coverage score : effectiveness of available vaccines to protect against each virus strain (right side) cv cv
Antigen risk score For a given free country/region the strains that pose the greatest threat of incursion will depend on: 1. From what FMD endemic area(s) is the virus most likely to enter the country? (most likely source areas ) 2. Which virus strains are currently circulating in the source areas?
Where is the virus most likely to come from? (Source area score) Virus likely to enter due to illegal/informal activity Legal activities made safe by border and trade restrictions Main routes of incursion: 1. Infected live animals 2. FMDV-contaminated animal product 3. (Fomite, wildlife) Importance of the source area will depend on the user: ie will be different if she is in Australia vs N. America vs. Europe Expert opinion/user input Consider proximity, connectedness, incentive, prevalence
Where is the virus most likely to come from? (Source area score) Expert elicitation at European NRL meeting (May 2016) Source Area Multiplier Divide 100 points according to the risk posed by the source area W. Eurasia 41 E. Asia 11 N. Africa 25 India & S. Asia 9 East Africa 4 West/Central Af 4 Southern Africa 3 S. America 3 100
Relative prevalence of viral strains circulating within the source areas Many virus pools have 3+ serotypes circulating at once, (& multiple strains within serotypes) Relative prevalence of serotypes/strains is dynamic: population immunity (natural or vaccination) ecology of the viruses (eg new strains outcompete older strains) Data: Submissions to WRL and expert opinion
Caution: Data preliminary, For example only! Calculating the Antigen risk score Circulating Strain W. Eurasia aaaaaaaaaaaaaa ssssssssss = E. Asia N. Africa ssssssssssss aaaaaaaa nn ssssssssssss aaaaaaaa 1 India & S. Asia East Africa pppppppppppppppppppp ssssssssss ssssssssssss ssssssssss West/ Central Africa Southern Africa S. America Antigen score source area score 41 11 25 9 4 4 3 3 O/ME-SA/PanAsia-2 30 1230 0 0 5 45 0 0 0 1275 O/ME-SA/PanAsia 10 410 10 110 0 0 0 0 0 0 520 O/SEA/Mya-98 0 32 352 0 0 0 0 0 0 352 O/ME-SA/Ind2001 5 205 3 33 24 600 90 810 0 0 0 0 1648 O/EA-3 0 0 54 1350 0 28 112 20 80 84 0 1434 O/EURO-SA 0 0 0 0 0 0 0 33 99.9 99.9 O/CATHAY 0 8 88 0 0 0 0 0 0 88 A/ASIA/Sea-97 0 36 396 0 0 0 0 0 0 396 A/ASIA/Iran-05 30 1230 0 15 375 0 0 0 0 0 1605 A/ASIA/G-VII 10 410 0 5 45 0 0 0 455 A/AFRICA 0 0 2 50 0 28 112 27 108 84 0 134 A/EURO-SA 0 0 0 0 0 0 0 33 99.9 99.9 Asia-1 0 11 121 0 0 0 0 0 0 121 Asia-1 Sindh-08 13 533 0 0 0 0 0 533 SAT1 0 0 0 0 8 32 26 104 40 24 0 24 SAT 2 2 82 0 5 125 0 28 112 25 100 40 84 0 291 SAT3 0 0 0 0 8 32 2 8 20 24 0 24 C 0 0 0 0 0 0 0 33 99.9 99.9 Cumulative Score 100 100 100 100 100 100 100 99.9 300 Score adjusted for route importance 4100 1100 2500 900 400 400 300 599
Excel spreadsheet 2 distinct considerations: PRAGMATIST: Antigen Priority tool 1. Antigen risk score : which strains pose greatest threat of incursion (left side) and 2. Coverage score : effectiveness of available vaccines to protect against each virus strain (right side) cv cv
Coverage score For each combination of vaccine and field virus strain Percentage of isolates of that particular strain that match the vaccine in question Coverage Vaccine Antigen coverage score no information 0 no matching isolates 0.2 1-20% isolates match 0.4 21-40% isolates match 0.6 41-60% isolates match 0.8 61-80% isolates match 1 81-100% isolates match
SEROTYPE A MSD MSD MSD MSD MSD MSD A22 Iraq A24 Cruzeiro A-Arg/2001 A-Eritrea A-Iran 96 A-Iran-05 A-Malaysai 97 A-SAU 95 A-SAU/23/86 A-TUR/2006 A/ASIA/Sea-97 A/ASIA/Iran-05 A/ASIA/G-VII A/AFRICA A/EURO-SA 0.6 0.4 0.2 0.6 0.4 0.2 0 0.2 0.2 0.6 0.6 0.4 0.4 0.4 Caution: Data preliminary, For example only!
Putting it all together: vaccine score vvvvvvvvvvvvvv ssssssssss = vvvvvvvvvv ssssssssssss nn vvvvvvvvvv ssssssssssss 1 cccccccccccccccc ssssssssss aaaaaaaaaaaaaa ssssssssss SEROTYPE A High scores for vaccines that cover well against : Strains circulating in many areas and/or Strains in most important risky areas and/or Several different strains A/ASIA/Sea-97 A/ASIA/Iran-05 A/ASIA/G-VII A/AFRICA A/EURO-SA A22 Iraq A24 Cruzeiro A-Arg/2001 A-Eritrea A-Iran 96 A-Iran-05 A-Malaysai 97 A-SAU 95 A-SAU/23/86 A-TUR/2006 MSD MSD MSD MSD MSD MSD 0.6 0.4 0.2 0.6 0.4 0.2 0 0.2 0.2 0.6 0.6 0.4 0.4 0.4 960 0 0 375 0 533 400 0 0 1254
Key Messages PRAGMATIST is a tool to assist vaccine bank managers select /maintain the most appropriate antigens Transparent, evidence based Vaccine matching results Other applications: Highlight data gaps and important antigens that do not have a good vaccine available Framework for surveillance to engage international FMD lab/epi networks Next Steps Ongoing efforts to improve data quality User feedback
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