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

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

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 BASICS Jefferson TO et al. Cochrane Database of Systematic Reviews 2007 Issue 2.

TRIVALENT VACCINE TYPE: A B A SUBTYPE / H3N2 H1N1 YAMAGATA VICTORIA B LINEAGE: STRAIN: Fujian/411/0=02 NewCaledonia/20/99 Shanghai/371/02 X California/7/04 NewCaledonia/20/99 Shanghai/371/02 X Wisconsin/67/05 NewCaledonia/20/99 X Malaysia/2506/ Wisconsin/67/05 SolomonIslands/3/06 X Malaysia/2506/04 AND OR VACCINE COMPONENTS

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: Orenstein EW et al. International J of Epidemiology 2007;36:

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: 1)Does this patient meet case definition for ILI? 2)Specify date of: a)Symptom onset b)Specimen collection 3)Was this patient vaccinated during season? 4)Was the last dose received ≥ two weeks prior to ILI onset? 5)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

PARTICIPANT PROFILE, 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%)

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

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

60% INFLUENZA A/H3; 40% INFLUENZA B

STRAIN CHARACTERIZATION, OF 55 INFLUENZA A/H1N1 –29 isolates characterized by HI –All but 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)

COMPONENT SPECIFIC VE ESTIMATES, 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%)

PARTICIPANT PROFILE, Vaccine –Unchanged except for H1N1 A/Solomon Islands/03/ 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%) Poster

STRAIN CHARACTERIZATION, Strainn (%) Influenza A/H1N1 (N=118) A/Brisbane/59/07-like6 (6%) A/Solomon Islands/03/06 (vaccine)101 (94%) Influenza A/H3N2 (N=79) A/Brisbane/10/2007-like62 (98%) A/Wisconsin/67/2005-like (vaccine)1 (2%) Influenza B (N=177) B/Florida/04/2006-like164 (98%) B/Malaysia/2506/2004-like (vaccine)4 (2%)

SENTINEL VE RESULTS & InfluenzaInfluenza AA/H1N1A/H3N2Influenza B Season Subtype Distribution ~90%16%72%~10% Vaccine HI Mismatch NoneHalfAll Age Adjusted VE 47% (18%, 65%) 49% (20%, 68%) 92% (40%, 99%) 41% (6%, 63%) 19% (-112%, 69%) Season Subtype Distribution ~60%28%32%40% Vaccine HI Mismatch 6%98% Age Adjusted VE 58% (43%, 69%) 62% (45%, 74%) 69% (43%, 83%) 54% (27%, 70%) 51% (26%, 68%)

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

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

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 LABORATORY TEAM NML: Yan Li Nathalie Bastien BC: Martin Petric Tracy Chan Annie Mak AB: Kevin Fonseca ON: Steven Drewes QC: Hugues Charest SENTINEL PHYSICIANS IN ALL PARTICIPATING PROVINCES