Component specific estimates of influenza vaccine effectiveness based on a sentinel surveillance net

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

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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

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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.
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TRIVALENT VACCINE

• TYPE A B
• A SUBTYPE / H3N2 H1N1 YAMAGATA
  VICTORIA
• B LINEAGE
• STRAIN
• 2004-05 Fujian/411/002
  NewCaledonia/20/99 Shanghai/371/02
  X
• 2005-06 California/7/04
  NewCaledonia/20/99 Shanghai/371/02
  X
• 2006-07 Wisconsin/67/05
  NewCaledonia/20/99 X
  Malaysia/2506/04
• 2007-08 Wisconsin/67/05
  SolomonIslands/3/06 X
  Malaysia/2506/04

OR
AND
VACCINE COMPONENTS
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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
631055-68. Orenstein EW et al. International J
of Epidemiology 200736623-31.
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SENTINEL PHYSICIAN CONTRIBUTIONStrategic
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

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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)

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95 INFLUENZA A (85 H3, 15 H1) 5 INFLUENZA B
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93 INFLUENZA A (40 H3, 60 H1) 7 INFLUENZA B
10
60 INFLUENZA A/H3 40 INFLUENZA B
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STRAIN CHARACTERIZATION, 2006-07

• 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)

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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)

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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)

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STRAIN CHARACTERIZATION, 2007-08
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SENTINEL VE RESULTS 2006-07 2007-08
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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/labora
  tory 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

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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

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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