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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
• 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:
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
2006-07 Wisconsin/67/05 NewCaledonia/20/99 X Malaysia/2506/04
2007-08 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; 63:1055-68.Orenstein EW et al.
International J of Epidemiology 2007;36:623-31.
%100/1 XunvaccvaccORefficacyVaccine
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 2006-07 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, 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%)
British Columbia: influenza detection by subtype by week
0
10
20
30
40
50
60
70
47 49 50 51 52 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Week number
Res
pira
tory
spe
cim
en c
ount
Negative
H3N2
H1N1
B
95% INFLUENZA A (85% H3, 15% H1); 5% INFLUENZA B
Alberta: influenza detection by subtype by week
0
5
10
15
20
25
47 48 49 50 51 52 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Week number
Resp
irato
ry s
peci
men
cou
nt Negative
Unknown
H3N2
H1N1
B
93% INFLUENZA A (40% H3, 60% H1); 7% INFLUENZA B
Quebec: influenza detection by subtype by week
0
2
4
6
8
10
12
14
16
18
20
47 48 49 50 51 52 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Week number
Res
pira
tory
spe
cim
en c
ount
Negative
H3N2
B
60% INFLUENZA A/H3; 40% INFLUENZA B
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)
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
• 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%)
Poster 11-007
STRAIN CHARACTERIZATION, 2007-08
Strain n (%)
Influenza A/H1N1 (N=118)
A/Brisbane/59/07-like 6 (6%)
A/Solomon Islands/03/06 (vaccine) 101 (94%)
Influenza A/H3N2 (N=79)
A/Brisbane/10/2007-like 62 (98%)
A/Wisconsin/67/2005-like (vaccine) 1 (2%)
Influenza B (N=177)
B/Florida/04/2006-like 164 (98%)
B/Malaysia/2506/2004-like (vaccine) 4 (2%)
SENTINEL VE RESULTS 2006-07 & 2007-08
Influenza Influenza A A/H1N1 A/H3N2 Influenza B
2006-07 Season
Subtype Distribution
~90% 16% 72% ~10%
Vaccine HI Mismatch
None Half All
Age Adjusted VE
47%
(18%, 65%)
49%
(20%, 68%)
92%
(40%, 99%)
41%
(6%, 63%)
19%
(-112%, 69%)
2007-08 Season
Subtype Distribution
~60% 28% 32% 40%
Vaccine HI
Mismatch6% 98% 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 TEAMBC: Danuta Skowronski
Naveed JanjuaMarsha TaylorTravis HottesLisan Kwindt
AB: Jim Dickinson
ON: Natasha CrowcroftErika Bontovics
Anne-Luise Winter
QC: Gaston De Serres
LABORATORY TEAM
NML: Yan Li Nathalie Bastien
BC: Martin PetricTracy ChanAnnie Mak
AB: Kevin Fonseca
ON: Steven Drewes
QC: Hugues Charest
SENTINEL PHYSICIANS IN ALL PARTICIPATING PROVINCES