Vaccines Update - Asthma Foundation New Zealand

Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance (SHIVERS)

Comprehensive investigation of influenza epidemiology, aetiology, immunology and vaccine effectiveness

US CDC 5 year funded project Started 2012

9 objectives 1. 2. 3. 4. 5. 6. 7. 8. 9.

Understand severe respiratory diseases caused by influenza & other pathogens Assess influenza vaccine effectiveness Investigate interaction between influenza & other pathogens Understand causes of respiratory mortality Understand non-severe respiratory diseases caused by influenza & other pathogens Estimate influenza infection by conducting serosurvey Identify & quantify risk factors (age, ethnicity, SES etc) for getting influenza Assess immune response among individuals with varying disease spectrum Estimate healthcare, societal economic burden caused by influenza and vaccine cost-effectiveness

Project Team – multi-centre and multi-disciplinary collaboration • ESR—leading organization – – –

Sue Huang—Principle Investigator (PI) Graham Mackereth – Project Manager Ruth Seeds – Project Officer

• Science teams: – Objective 1 Severe illness Sue Huang/Sally Roberts/Colin McArthur/Cameron Grant/Debbie Williamson/Adrian Trenholme/Conroy Wong/Susan Taylor/Graham Mackereth/Don Bandaranayake/Diane Gross/Marc-Alain Widdowson: – Objective 2 Vaccine Effectiveness Nikki Turner/Heath Kelly/Nevil Pierse/Ange Bissielo/Michael Baker/Don Bandaranayake/Sue Huang – Objectives 3 & 7 Interactions between pathogens; risk factors for flu Michael Baker: – Objective 4 causes of respiratory mortality Colin McArthur/Sally Roberts: – Objective 5 Primary Care Surveillance Sue Huang/Nikki Turner – Objective 6 infection risk Sue Huang/Don Bandaranayake: – Objective 8 immune responses Richard Webby, Paul Thomas – Objective 9 economics Des O’Dea:

Study site - Auckland

ADHB and CMDHB Population: 837,696

Two surveillance systems • Hospital-based surveillance: enhanced, active, longitudinal (5 yrs), population based surveillance for hospital SARI cases, ICU admissions and deaths caused by influenza and other respiratory pathogens in Auckland • Community-based surveillance: enhanced, active, longitudinal (4 yrs), population based surveillance for community ILI cases caused by influenza and other respiratory pathogens in Auckland

SHIVERS - Hospital SARI surveillance • all public hospitals in ADHB & CMDHB:

-

Auckland City hospital and Starship Childrens hospital Middlemore hospital and Kidz First Childrens hospital

• SARI case definition: An acute respiratory illness with onset in the last 7 (10) days with a history of fever or measured fever of ≥ 38°C, and cough, requiring hospitalisation • Data captured by case report form

-

Medical records/lab results Interview patients

• Sample: NPS/NPA Q Sue Huang et al Implementing hospital-based surveillance for severe acute respiratory infections caused by influenza and other respiratory pathogens in New Zealand WPSAR Vol 5, No.2 2014

Aims - Hospital-based surveillance (SARI) 1. 5-year surveillance for SARI cases 2. Non-SARI cases: contribution of influenza 3. Incidence, prevalence, demographics, clinical outcomes: SARI, influenza 4. Vaccine effectiveness 5. Etiology of SARI cases caused by influenza and other pathogens 6. Validity of hospital discharge data 6. Risk factors (pregnancy, high BMI etc):

SARI Case ascertainment

SHIVERS SARI and influenza cases, 2013

SARI cases - all others

140

SARI cases - influenza positive 120

2012/2013 SARI cases

80 60 40 20 0

18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 2 4 6 8 10 12 14 16

SARI cases

100

May

Jun

Jul

Aug

Sep

Oct

Nov

Dec

Jan

Week number 2013/2014

Feb

Mar

Apr

SARI definition – Sensitivity of 84% – Specificity 31% – Positive predictive value of 17% – Negative predictive value of 92%.

SHIVERS Influenza cases by type, 2013

Number of viruses

25

A (Not subtyped) A(H3) A(H1N1)pdm09 B (Lineage not determined) B (Yamagata lineage) B (Victoria) Proportion positive for influenza

20

100 90 80 70 60

15

50 40

10

30 20

5

10 0

0 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 Week

Proportion positive

30

SARI related influenza hospitalisations by age groups

SARI influenza incidence (cases per 100 000)

250

200

150

100

50

0

influenza incidence

0 to 1

1 to 4

5 to 19

20 to 34

35 to 49

50 to 64

65 to 79

80 and over

122.0

48.8

7.4

9.7

11.5

31.2

72.3

69.3

SARI related Influenza incidence by ethnic groups SARI influenza incidence (cases per 100 000)

70

60

50

40

30

20

10

0 Influenza incidence

Maori

Pacific

Asian

Others

26.8

50.6

10.5

17.3

SARI related Influenza incidence by socioeconomic status

Known and unknown etiologies for SARI cases

Non-influenza Respiratory Viruses

Number (%)

No. of specimens tested

870

No. of positive specimens

388

Rhinovirus

168 (44)

Respiratory Syncytial Virus

162 (42)

Parainfluenza

55 (14)

- Parainfluenza 3

- 34 % of all PIV

- Parainfluenza 2

- 18 % of all PIV

- Parainfluenza 1

- 3 % of all PIV

Human metapneumovirus

46 (12)

Single virus detection (% of positive)

303 (78)

Multiple virus detection (% of positives)

85 (22)

SHIVERS SARI - other non-influenza respiratory viruses, 2013 45

RSV

100

parainfluenza 1

Number of viruses

35

30

parainfluenza 2 parainfluenza 3

80

rhinovirus

adenovirus hMPV

25

90

70 60

Proportion positive for non-influenza pathogen

50 20 40 15

30

10

20

5

10

0

0 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 Week

Proportion positive

40

SHIVERS - Community ILI surveillance • 18 practices: 103,752 enrolled patients (~14% ADHB & CMDHB popn)

-

ADHB (60,068): ~17% ADHB popn CMDHB (43,684): ~10% of CMDHB popn

• ILI case definition: An acute respiratory illness with onset in the last 10 (7) days with a history of fever or measured fever of ≥ 38°C, and cough, requiring GP consultation • Data requirement:

-

Data from existing PMS Data from an advanced form (includes specimen request form)

• Sample: NPS/throat swab

Advanced form in MedTech

181,603 GP consultations – 2016 (1.1%) met ILI definition • 1802 (89.4%) had lab test – 448 (24.9%) flu positive

ILI case definition – – – –

Sensitivity of 92% Specificity 27% Positive predictive value of 45% Negative predictive value of 85%

SHIVERS ILI and influenza cases, 2013

SHIVERS ILI and influenza 29 April – 3 November 2013

Non-influenza viruses isolated from ILI samples Non-influenza Respiratory Viruses

Number (%)

No. of specimens tested

1686

No. of positive specimens

552

Rhinovirus

221 (40%)

Respiratory Syncytial Virus

154 (28%)

Parainfluenza

97 (17.5%)

- Parainfluenza 2

43 (8 %)

- Parainfluenza 3

43 (8%)

- Parainfluenza 1

11 (2%)

Human metapneumovirus

56 (10%)

Single virus detection (% of positive)

495 (89.7%)

Multiple virus detection (% of positives)

57 (10.3%)

Influenza disease burden by age, ILI vs SARI

Influenza incidence by ethnic groups, ILI vs SARI

Influenza incidence by SES groups, ILI vs SARI

Influenza disease burden, 2013

Vaccine Effectiveness • Case test-negative design – SARI and ILI • Cases = flu positive by PCR • Controls = flu negative by PCR

• Adjusted for timing of influenza season and propensity to be vaccinated = adjOR – Older, chronic diseases more likely to be vaccinated – No difference by ethnicity, gender, income, pregnancy, obesity, self rated health, smoking, assisted living, or timing of admission

Flowchart of all selected, recruited and tested ILI and SARI cases for VE analysis

Meets SARI definition = 2120

SARI no consent = 404

Meets ILI definition = 1891

Recruited sample SARI = 1716 ILI: 1891

Complete records SARI = 1530 ILI = 1809

SARI cases = 1232 ILI cases = 1663

Unique persons SARI = 1042 ILI = 1495

Incomplete records: No vaccination status SARI = 71 ILI = 0 No date of birth SARI = 4 Lab sample not tested SARI = 111 ILI = 82 Exclusions : < 6months of age SARI = 153 ILI = 5 < 9 yrs one dose SARI = 3 ILI = 34 7 days since onset symptoms SARI = 109 ILI = 92 Not in flu season SARI = 167 ILI = 110 Unused repeat admissions SARI = 23 ILI = 58

Influenza positive SARI = 224 (21%) ILI = 482 (32%)

Influenza negative SARI = 818 (79%) ILI = 1013 (68%)

Vaccinated SARI = 82 (36%) ILI = 44 (9%)

Vaccinated SARI = 372 (45%) ILI = 177 (17%)

Estimated vaccine effectiveness (VE), overall by age group and by influenza type and sub-type: crude and propensity adjusted models Hospitalised with Severe Acute Respiratory Illness

Overall

Influenza type or subtype

A(H1N1) A(H3N2) All A All B

Age Group (years)

6m to 17 18 to 64 65 +

General Practice visit for Influenza-like illness

Crude Model*

Propensity Adjusted Model*

Crude Model*

Propensity Adjusted Model*

VE % (95%CI)

VE% (95% CI)

VE % (95% CI)

VE %(95% CI)

32 (7 ,50)

52 (32, 66)

56 (37,70)

56 (34,70)

25 (-132,76)

48 (-74,85)

50 (-68,85)

49 (-90,86)

11 (-33,40)

34 (-2,57)

56 (27,74)

61 (32,77)

15 (-21,40)

39 (10,58)

55 (29,71)

58 (32,74)

65 (36,81)

76 (54,87)

60 (32,77)

54 (19,75)

72 (-22,93)

78 (2,95)

56 (6,79)

56 (6,79)

66 (43,-79)

61 (34,77)

59 (32,75)

55 (24,73)

35 (-25,66)

34 (-28,66)

74 (12,92)

76 (15,93)

*All models were adjusted for the number of weeks from the influenza peak Turner, N. M., Pierse, N., Bissielo, A., Huang, Q. S., Radke, S., Kelly, H. (2014). Effectiveness of seasonal trivalent inactivated influenza vaccine in preventing influenza hospitalisations and primary care visits in Auckland, New Zealand, in 2013. Euro surveillance: bulletin Européen sur les maladies transmissibles= European communicable disease bulletin, 19(34).

Population

Type of outcome

Level of protection (95% CIs)

Infants under 6-months whose mothers received influenza vaccine during pregnancy

Efficacy against laboratory confirmed influenza

41% - 48%15,16

Healthy children under 2 years of age

Efficacy against laboratory confirmed influenza

Insufficient data13,17

Effectiveness against laboratory confirmed influenza

66% (9% - 88%)18

Healthy children aged 6-35 months

Effectiveness against laboratory confirmed influenza

66% (29% - 84%)18

Healthy children under 16 years of age

TIV vaccine efficacy in prevention of laboratory confirmed influenza in Randomised Controlled Trials

59% (41% - 71%)17

Healthy adults (18-65 years)

Effectiveness against influenzalike-illness

30% (17% - 41%)14

Efficacy against influenza symptoms

73% (54% - 84%)14

Elderly aged 65 years and over (Cochrane review 2010)

Effectiveness in preventing influenza, influenza-like-illness, hospitalisations, complications and mortality

Inconclusive due to poor quality of studies19

Elderly aged 65 years and over (Rearranged analysis of Cochrane studies)

Effectiveness against non-fatal and fatal complications

28% (26%-30%)20

Influenza-like illness

39% (35%-43%)20

Laboratory confirmed influenza

49% (33% - 62%)20

NISG 2014, Refs Section 4.9

Conclusions: 2013 •

2013 season low incidence and late peak – – – – –

•

Influenza activity peaked late in week 37 (mid Sept). A (H3N2) and B most commonly detected Very high hospitalisation rates in very young (122,100 000), then 80+ (69/100 000) Pacific hospitalisation rates 4 times higher, Maori 1.5 times higher than other groups Large differences by deprivation with lower quintile 4 times higher rates than upper quintile

2013 the first year of SHIVERS ILI surveillance – Approach was acceptable to working general practice – GP visits for influenza different pattern from hospitalisations • higher rates in mid-ages • less lower socioeconomic presentations

•

Vaccine is ‘moderately’ effective against hospitalisation and general practice influenza

…..2014 • Average flu season • Dominated by A(H1N1), occasional A(H3N2) • 12% B

….2014 • Dominated by A(H1N1) • Few A(H3N2) • 12% B

Ref: ESR 2014

Study participants with influenza-like illness (ILI) and severe acute respiratory infections (SARI) who were influenza positive or negative, by week, New Zealand, 28 April to 31 August 2014

Estimated influenza vaccine effectiveness, by participant age group and by influenza virus type and subtype: crude plus age and time adjusted models, New Zealand, 28 April to 31 August 2014 Influenza-positive

Influenza type/ age group

Influenza-negative

Vaccine Effectiveness Unadjusted Adjusted1 VE % 95% CI VE % 95% CI

Number Vaccinated

Total

%

Number Vaccinated

Total

%

35

148

24

118

371

32

34

N/A

SARI Overall (years)

-42 - 80

-18 - 87

54 N/A 46 74 58

51

19 - 71

65

33 - 81

22

61

43 - 74

48 - 79

N/A

67 N/A 66 57 N/A

73 N/A

50 - 85

-3 - 57

6mo -17

4

42

10

15

193

8

N/A2

18-49

9

58

16

13

52

25

45

-42 - 79

50-64

10

29

34

29

51

57

60

-3 - 84

65+

12

19

63

61

75

81

61

22

119

18

118

371

32

37

384

10

116

535

19 - 74 N/A 23 - 91 -36 - 87

A(H1N1)pdm09

ILI Overall 6mo-17

2

143

1

26

226

12

N/A2

18-49

12

168

7

32

195

16

61

21 - 81

50-64

12

60

20

26

75

35

53

-4 - 79

65+

11

13

85

32

39

82

N/A2

N/A

14

220

6

116

535

22

75

56 - 86

82

N/A2

N/A

N/A 30 - 84 -1 - 82 N/A

A(H1N1)pdm09 65+

1

2

50

32

39

Manuscript in preparation Turner et al 2014

N/A

Gains • SHIVERS data contributed to influenza vaccination policy changes 2013 –