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