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Danuta M. Skowronski MD, MHSc, FRCPC BC Centre for Disease Control

Component specific estimates of influenza vaccine effectiveness based on a sentinel surveillance network, 2006-07 & 2007-08 Seasons. Danuta M. Skowronski MD, MHSc, FRCPC BC Centre for Disease Control. SPONSORS. BC Centre for Disease Control & BC Ministry of Health

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Danuta M. Skowronski MD, MHSc, FRCPC BC Centre for Disease Control

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  1. Component specific estimates of influenza vaccine effectiveness based on a sentinel surveillance network, 2006-07 & 2007-08 Seasons Danuta M. Skowronski MD, MHSc, FRCPC BC Centre for Disease Control

  2. SPONSORS • BC Centre for Disease Control & BC Ministry of Health • Alberta Health and Wellness • Ontario Ministry of Health & Long-Term Care, Ontario Public Health Laboratory • Institut national de santé publique du Québec • Public Health Agency of Canada and • Canadian Institute of Health Research (CIHR) • Authors acknowledge the important contribution of sentinel physicians

  3. BASICS • Influenza is a moving target • Influenza vaccine is reformulated annually • Periodic RCTs • 80% (95% CI 56-91%) during select seasons of match • 50% (95% CI 27-65%) during select seasons of mismatch • Monitoring the effectiveness of influenza vaccine each year is important • Approach has to be simple, sustainable, reproducible & reliable • Laboratory confirmed outcomes preferred • Since 2004, Canada has used a sentinel surveillance approach to explore influenza vaccine effectiveness (VE) against laboratory-confirmed influenza Jefferson TO et al. Cochrane Database of Systematic Reviews 2007 Issue 2.

  4. TRIVALENT VACCINE TYPE: AB A SUBTYPE / H3N2 H1N1 YAMAGATA VICTORIA B LINEAGE: STRAIN: 2004-05 Fujian/411/0=02 NewCaledonia/20/99 Shanghai/371/02 X 2005-06 California/7/04 NewCaledonia/20/99 Shanghai/371/02 X 2006-07Wisconsin/67/05 NewCaledonia/20/99 X Malaysia/2506/04 2007-08Wisconsin/67/05 SolomonIslands/3/06 X Malaysia/2506/04 OR AND VACCINE COMPONENTS

  5. SENTINEL SURVEILLANCE AND TEST-NEGATIVE CONTROLS • Sentinel networks are an established part of most national/regional influenza surveillance activities • Source population of patients presenting with ILI • Broad platform of participation and specimen contribution • Backbone for test-negative case-control estimation of VE Orenstein WA et al Bull WHO 1985; 63:1055-68. Orenstein EW et al. International J of Epidemiology 2007;36:623-31.

  6. SENTINEL PHYSICIAN CONTRIBUTION:Strategic clinical/epidemiologic/laboratory linkage • Between November and April, collect respiratory specimen from consenting patients presenting with ILI within 7 days of onset • Answer five key questions added to the lab requisition: • Does this patient meet case definition for ILI? • Specify date of: • Symptom onset • Specimen collection • Was this patient vaccinated during 2006-07 season? • Was the last dose received ≥ two weeks prior to ILI onset? • Does this patient have a chronic medical condition? • Submit specimen and requisition to provincial laboratory • PCR (including subtype of influenza A positives) • Virus isolation on cell culture • Gene sequencing and HI strain characterization

  7. PARTICIPANT PROFILE, 2006-07 • Sentinel contribution • BC: 64 MDs in 48 clinic sites • AB: 53 MDs in 43 clinic sites • QC: 30 MDs in 4 clinic sites • 841 participants: • Median age: 36 years • 53% female • 14% with chronic condition • 8% elderly • 20% received vaccination ≥ 2 weeks prior to ILI • Influenza detected in 337/841 (40%) • Ratio of 90A : 10 B • 242 H3N2 (72%); 55 H1N1 (16%); 36 B (12%)

  8. 95% INFLUENZA A (85% H3, 15% H1); 5% INFLUENZA B

  9. 93% INFLUENZA A (40% H3, 60% H1); 7% INFLUENZA B

  10. 60% INFLUENZA A/H3; 40% INFLUENZA B

  11. STRAIN CHARACTERIZATION, 2006-07 • OF 55 INFLUENZA A/H1N1 • 29 isolates characterized by HI • Allbut one WELL-MATCHED to vaccine • One A/SolomonIslands/3/2006-like virus in BC • OF 242 INFLUENZA A/H3N2 • 110 isolates characterized by gene sequence and HI • Equal clustering around A/Brisbane/10/2006 and A/Nepal/921/2006 on gene sequence • Half strain mismatched to vaccine (A/Brisbane/10/2006) by HI • OF 36 INFLUENZA B • 15 isolates characterized by HI • All lineage mismatched to vaccine • B/Shanghai/361/2002-like (YAMAGATA lineage)

  12. COMPONENT SPECIFIC VE ESTIMATES, 2006-07 CANADA • Covariate adjustment • Age, chronic conditions, province, month, interval to ILI visit, swab site • Only age-adjustment influenced VE estimates • Age-adjusted VE • H1N1: 92% (95% CI 40% - 99%) • H3N2: 41% (95% CI 5% - 63%) • B: 19% (95% CI -112% - 67%) • Overall: 47% (95% CI 18% - 65%)

  13. PARTICIPANT PROFILE, 2007-08 Poster 11-007 • Vaccine • Unchanged except for H1N1 • A/Solomon Islands/03/2006 • 1444 participants: • 17% with chronic condition • 8% elderly • 56% female • 22% received vaccination ≥ 2 weeks prior to ILI • Influenza detected in 695/1444 (48%) • Ratio 60 A : 40 B • 215 H3N2 (32%); 189 H1N1 (28%); 265 B (40%)

  14. STRAIN CHARACTERIZATION, 2007-08

  15. SENTINEL VE RESULTS 2006-07 & 2007-08

  16. LESSONS • Regional variation in timing and proportionate mix of circulating viruses • Variation in component-specific match to circulating counterpart • Sentinel networks are part of most national/regional influenza surveillance • Broad based platform for annual surveillance • Strategically linked clinical/epidemiologic/laboratory data • Virus diversity and new variant detection • Efficient and component specific VE estimation • We encourage further development, refinement and expansion • Improved power & precision • Baseline for comparative trend analysis • Immuno-epidemiologic and virologic insights • Evaluation of program changes and comparisons over time • Public health obligation

  17. LIMITS • Surveillance approach, observational design • Assumes vaccinated and unvaccinated have same likelihood of influenza exposure • Present to MD as frequently if either develops ILI of same severity • Sample mostly includes young adults with few elderly • Healthy user bias? • Participation, power, precision • Need to repeat and refine methods • Comparative trend analysis versus literal interpretation of individual point estimates

  18. SENTINEL PHYSICIANS IN ALL PARTICIPATING PROVINCES LABORATORY TEAM NML: Yan Li Nathalie Bastien BC: Martin Petric Tracy Chan Annie Mak AB: Kevin Fonseca ON: Steven Drewes QC: Hugues Charest EPIDEMIOLOGY TEAM BC: Danuta Skowronski Naveed Janjua Marsha Taylor Travis Hottes Lisan Kwindt AB: Jim Dickinson ON: Natasha Crowcroft Erika Bontovics Anne-Luise Winter QC: Gaston De Serres

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