Key findings - SHIVERS (Southern Hemisphere Influenza and Vaccine

Effectiveness Research and Surveillance)Dr. Sue Huang

Principal investigator of the SHIVERS project

Director, WHO National Influenza Centre

Institute of Environmental Science and Research, Wellington, New Zealand

3rd New Zealand Influenza Symposium, 2 November, 2016

Wellington

Outline

• Background of SHIVERS

• Disease burden and epidemiology

• Vaccine effectiveness

• Risk factors

• Etiology

Acknowledgement• ESR: Don Bandaranayake, Ruth Seeds, Tim Wood, Ange Bissielo, Graham Mackereth, Thomas Metz, Anne

McNicholas, Angela Todd, Namrata Prasad, Laboratory staff, IT staff

• ADHB: Sally Roberts, Colin McArthur, Debbie Williamson, Kathryn Haven, Research nurses, clinical team staff, laboratory staff, IT staff

• CMDHB: Adrian Trenholme, Conroy Wong, Susan Taylor, Shirley Lawrence, Research nurses, clinical team staff, laboratory staff, IT staff

• University of Auckland: Nikki Turner, Cameron Grant, Sarah Redke, Barbara McArdle, Tracey Poole, Anne McLean, Debbie Raroa, Carol Taylor

• University of Otago: Michael Baker, Nevil Pierse, David Murdoch

• Primarycare Advisory Group from PHOs (Procare, East Tamaki, Auckland) and ARPHS: John Cameron, Bruce Adlam, Gary Reynolds, Rosemary Gordon, Leane Els, Marion Howie, Gillian Davies

• ILI sentinel practices

• WHOCC-St Jude: Richard Webby, Paul Thomas

• US-CDC: Mark Thompson, Marc-Alain Widdowson, Jazmin Duque, Diane Gross

• Funding from US-CDC: 1U01IP000480

SHIVERS - 9 objectives 1. Understand severe respiratory diseases

2. Assess influenza vaccine effectiveness

3. Investigate interaction between influenza & other pathogens

4. Understand causes of respiratory mortality

5. Understand non-severe respiratory diseases

6. Estimate influenza infection via serosurvey

7. Identify & quantify risk factors for getting influenza

8. Assess immune response against influenza

9. Estimate influenza related economic burden and vaccine cost-effectiveness

1. Disease burden & epidemiology

• 2012: SARI-Severe influenza

• 2013: ILI-Moderate influenza requiring GP consultation

• 2015: Serosurvey

Mild influenza not requiring GP consultation

Symptomatic/asymptomatic infection

Flu infection (symptomatic/asymptomatic):

?

Flu consultation:

20 818

Flu Hospitalization:

1,600

Flu ICU:

89

Flu

Death:

20

New Zealand Population: 4,470,800

Influenza hospitalisations & vaccination by age, 2012

<1 1-4 5-19 20-34 35-49 50-64 65-79 80+

Hospitalization 411.7 107.8 18.9 28.7 29.3 62.3 130.5 222.7

Vaccination 2.1 12.5 28.2 18.8 39.9 47.9 74.4 74.7

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Huang et al, NZPHSR 2013;11(2):5-6

Impact of SHIVERS on vaccination policy

Free influenza vaccines to children (aged <5 yrs) who have been hospitalized or have a history of significant respiratory illness

Revision in WHO’s final case definition for SARI (Severe Acute Respiratory Illness): from onset within ‘7 days’ to ‘10 days’ – “Global Epidemiological Surveillance Standards for Influenza”

Impact of SHIVERS on improving disease surveillance

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4.2 34.3 33.4 20.9 7.0 0.2

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• World Health Assembly Resolution 64.1

• Aim of PISA: support national, regional and global risk assessment to inform pandemic response decisions

• Virus transmission, seriousness of disease and impact on the healthcare system

• SHIVERS: contributing to WHO-led pilot on Pandemic Influenza Severity assessment

Pandemic Influenza Severity Assessment (PISA)

Extra-ordinary

High

Moderate

Low

No activity

Serosurvey study, 2015

16 ILI GPs

(~100,000)

Enrolled Patient Sample

2,552

Random Patient Sample:- Stratified by age & ethnicity- Oversampled children and

Maori/Pacific

Pre-Season Blood Draw

& Questionnaire

ILI Season Weekly Check

&

ILI: Swab + PCR

Post-Season Blood Draw

& Questionnaire

Symptomatic: - Met ILI based on nurse decision- Swabbed by nurse or went to GP

Flu infection (symptomatic/asymptomatic):

?

Flu consultation:

20 818

Flu Hospitalization:

1,600

Flu ICU:

89

Flu

Death:

20

New Zealand Population: 4,470,800

Full Flu Burden Pyramid

6Deaths

23 in ICU(~1 in 11,000

of flu infected)

471 Hospitalizations

(~1 in 560 of flu infected)

6,791 GP visits

(~1 in 40 of flu infected)

263,000 Flu infected

(~26% of total population)

737,000 Uninfected

74% of total population

(~1 in 44,000 flu infected)

Age and ethnicity adjusted estimates

1,000,000 people over one season

• 26% of population flu infected

• Of infected:

- 80% asymptomatic

- 20% symptomatic

• Of those symptomatic infections:

- 77% did not seek care

- 23% visited a GP

Note: the data on this page was updated by Dr Sue Huang in January 2017. Preliminary data had been presented at the symposium on Nov 2, 2016.

Age distribution among influenza infections

<5yrs 5-19yrs 20-64yrs 65+yrs

uci 41.7 38.3 18.5 17.4

lci 14.5 23.7 11.8 2

mean 26.1 30.6 14.9 7.2

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Influenza severity progression by age

<5yrs 5-19yrs 20-64yrs ≥65yrs

mild ILI SARI ICU Death mild ILI SARI ICU Death mild ILI SARI ICU Death mild ILI SARI ICU Death

uci 64.85 3.0 0.47 0.06 0.00 33.3 4.5 0.049 0.012 0.012 27.9 3.7 0.22 0.018 0.000 34.54 4.7 1.9 0.000 0.160

lci 13.53 1.7 0.28 0.01 0.00 11.2 3.5 0.018 0.000 0.000 11.9 2.9 0.16 0.003 0.000 3.713 2.0 1.3 0.000 0.017

mean 33.0 2.3 0.37 0.03 0.00 20.3 4.0 0.031 0.001 0.001 18.7 3.2 0.19 0.009 0.000 13.6 3.2 1.6 0.000 0.065

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2. Vaccine effectiveness:

• A case test negative control design: estimate VE

• SHIVERS VE data: contributed to WHO/AIVC process for vaccine strain selection for Southern Hemisphere

• Southern Hemisphere countries: VE provided by NZ & Australia

VE BY YEAR

Overall adjusted VE

Turner et al. Vaccine 32.29 (2014): 3687-3693Turner et al. Euro surveillance 19.34 (2014) Pierse et al. Vaccine 34.4 (2016): 503-509Bissielo et al. Euro surveillance 21.1 (2015)

Moderate-High ActivityA(H3N2)B Vic > B Yam after week 35

Low ActivityA(H1N1)Negligible B

Low ActivityA(H3N2)B Yamagata

VE estimate, 2016

Adjusted for age and week time in the season

Influenza type

& age group Number

vaccinated Total %

Number

vaccinated Total % VE % 95%CI VE % 95%CI

SARIOverall 44 152 29 140 490 29 -1 -51 , 32 37 -3 , 61

6 mo-17 yrs 3 42 7 25 270 9 N/A N/A N/A N/A

18-64 yrs 23 81 28 48 126 38 36 -18 , 65 33 -27 , 64

≥65 yrs 18 29 62 67 94 71 34 -58 , 73 43 -43 , 77

A(H3N2) 16 56 29 157 539 29 2 -79 , 47 42 -19 , 72

Influenza B 11 47 23 140 490 29 24 -54 , 62 28 -67 , 69

ILIOverall 74 462 16 117 503 23 37 13 , 55 45 19 , 62

6 mo-17 yrs 10 205 5 20 214 9 50 -9 , 77 56 3 , 80

18-64 yrs 48 235 20 68 258 26 28 -9 , 53 35 -1 , 58

≥65 yrs 16 22 73 29 31 94 82 -2 , 97 82 -2 , 97

A(H3N2) 38 184 21 132 585 23 11 -34 , 41 23 -24 , 52

Influenza B 21 196 11 117 503 23 60 35 , 76 61 32 , 77

Influenza positive Influenza negative Unadjusted Adjusted*

3. Risk factors

• Identify and quantify risk factors for getting influenza:

–Host: socio-demography (Age, ethnicity, Sex, deprivation), underlying conditions (BMI, Diabetes, Asthma, Pregnancy etc)

–Healthcare: Antivirals/vaccinations, oxygen, ICU, healthcare utilization

–Environmental factors: housing conditions, crowding

–Behavioral factors: smoking, contact

Influenza associated risk in pregnant woman, 2012-2014

Pregnancy

Flu +ve,

No./Total

(%)

No. of

pregnant

women

Influenza

incidence

(/100,000)

Flu +ve,

No./Total

(%)

No. of non-

pregnant

women

Influenza

incidence

(/100,000)

RR (95% C.I) p-value

Year 19/25

(36.0)8894 101.2

34/150

(22.7)184302 18.4

5.49

(2.31-11.68)0.0000

Year 25/11

(45.5)9148 54.7

24/127

(18.9)190579 12.6

4.34

(1.29-11.60)0.0060

Year 315/28

(53.6)8842 169.6

67/209

(32.1)190885 35.1

4.83

(2.56-8.55)0.0000

Total 29/64

(45.3)26884 107.9

125/486

(25.7)565766 22.1

4.88

(3.14-7.36)0.0000

Pregnant women (15-45 yrs) Non-pregnant women (15-45 yrs)

4. Etiology

• Integrated respiratory disease surveillance

– Influenza virus: antigenic drift; pandemic influenza

– Non-flu respiratory viruses: under-recognized burden

– Emerging respiratory virus: MERS-CoV

• NZ MoH committed to maintain SARI/ILI surveillance platforms after SHIVERS

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Conclusion • SHIVERS platform– national infrastructure for seasonal influenza control

and pandemic preparedness and other emerging and endemic respiratory pathogens: burden, severity, VE, risk factors, etiology, immunology, clinical outcomes

• Impact of SHIVERS on vaccination policy: Free influenza vaccine is offered to young children with respiratory illness

• Impact of SHIVERS on improving disease surveillance: SHIVERS data contributed to finalize WHO SARI case definition

• SHIVERS results – value in WHO-led severity assessment

• SHIVERS VE study – value in vaccine strain selection

• Disease burden estimate for respiratory viruses– value in guiding vaccine development and vaccination strategies and better prediction