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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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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

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


Basics

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.


    Trivalent vaccine

    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


    Sentinel surveillance and test negative controls

    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.


    Sentinel physician contribution strategic clinical epidemiologic laboratory linkage

    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


    Participant profile 2006 07

    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%)


    Danuta m skowronski md mhsc frcpc bc centre for disease control

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


    Danuta m skowronski md mhsc frcpc bc centre for disease control

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


    Danuta m skowronski md mhsc frcpc bc centre for disease control

    60% INFLUENZA A/H3; 40% INFLUENZA B


    Strain characterization 2006 07

    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)


  • Component specific ve estimates 2006 07 canada

    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%)


    Participant profile 2007 08

    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%)


    Strain characterization 2007 08

    STRAIN CHARACTERIZATION, 2007-08


    Sentinel ve results 2006 07 2007 08

    SENTINEL VE RESULTS 2006-07 & 2007-08


    Lessons

    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

    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


    Danuta m skowronski md mhsc frcpc bc centre for disease control

    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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