Risk factors and attack rates of seasonal influenza ... … · Cameron, Bruce Adlam, Edwin...
Transcript of Risk factors and attack rates of seasonal influenza ... … · Cameron, Bruce Adlam, Edwin...
Risk factors and attack rates of seasonal influenza infection: Results of the SHIVERS sero-epidemiologic
cohort study
Dr. Sue Huang
Principal investigator of SHIVERSDirector, WHO National Influenza Centre
Institute of Environmental Science and ResearchSiena, 1 April, 2019
Influenza - The SHIVERS serosurvey
• Presented by • Edwin Reynolds
• GP (Northland)
• IMAC (University of Auckland)
• ARPHS (Auckland Regional Public Health Service)
Acknowledgement• ESR: Claire Newbern, Ruth Seeds, Don Bandaranayake, Graham Mackereth, Tim Wood, Ange Bissielo,
Thomas Metz, Anne McNicholas, Namrata Prasad, Ben Waite, Jenni Haubrock, Tiffany Walker, Nayyereh
Aminisani, Angela Todd, Lauren Jelly, Judy Bocacao, Jacqui Ralston, Wendy Gunn, IT staff
• ADHB: Sally Roberts, Colin McArthur, Debbie Williamson, Debbie Aley, Kathryn Haven, Bhamita Chand,
Fahimeh Rahnama, 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, William Leung, Trang Khieu
• Primarycare Advisory Group from PHOs (Procare, East Tamaki, Auckland) and ARPHS: John
Cameron, Bruce Adlam, Edwin Reynolds, Rosemary Gordon, Leane Els, Marion Howie, Gillian Davies
• ILI sentinel practices
• WHOCC-St Jude: Richard Webby, Paul Thomas, Sook-san Wong
• US-CDC: Mark Thompson, Marc-Alain Widdowson, Jazmin Duque, Diane Gross
• Funding from US-CDC: 1U01IP000480; Kind support from NZ Ministry of Health
Outline
• Background on SHIVERS & Sero-epidemiologic cohort
• Method
• Results
• Conclusions
SHIVERS (Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance)
• In 2010, US-CDC: Funding opportunity announcement “Influenza and other respiratory diseases in Southern Hemisphere”
• NZ: Southern hemisphere country with temperate climate
• NZ health infrastructure – public funded:
–National Health Index
–>98% of NZers registered with GPs
–NZ population - well-characterised: ethnicity, SES
–NZ labs using PCR as screening assay: great for burden study
• We won a competitive research award from US-CDC (NZ$9m) for 6 years (2012-2017) - SHIVERS
SHIVERS - overarching aims & 9 objectives
Hospital surveillance
disease burden
epidemiology etiologyrisk
factorsimmunology
vaccine effectiveness
prevention strategies
sentinel general practice surveillance
1. Understand severe respiratory diseases
2. Assess influenza vaccine effectiveness
3. Investigate interaction among respiratory pathogens
4. Understand causes of respiratory mortality
5. Understand non-severe respiratory diseases
6. Estimate influenza infection via serosurvey
7. Identify and quantify risk factors for getting influenza
8. Assess immune responses: severe/mild; ethnic groups
9. Estimate Economic burden and vaccine cost-effectiveness
Sero-epidemiologic cohort study, 2015
~90,000 enrolled patient list
(14 ILI GPs)
Enrolled Patient Sample
1,500
Random Patient
Sample:
- Stratified by age &
ethnicity
Pre-Season Blood Draw
& Questionnaire
ILI Season Weekly Check
&
ILI: Swab + PCR
Post-Season Blood Draw
& Questionnaire
- Collect a paired blood and test for HAI
and NAI antibody (seroconversion: 4
fold rise in HAI or NAI titres)
- Monitor ILI weekly and collect ILI
swabs for PCR testing
- Collect risk factor information
Flu infection (symptomatic/asymptomatic):
?
Flu consultation:
20 818
Flu Hospitalization:
1,600
Flu ICU:
89
Flu
Death:
20
New Zealand Population: 4,470,800
Aim: how many people were
actually infected with influenza?
• Mild influenza not requiring GP
visit
• Asymptomatic infections
Predominant strains in 2015
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A(H3N2) ILI-non influenza no-ILI
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May Sep
baseline level
above seasonal level
high seasonal level
moderate seasonal level
low seasonal level
Proportions of HAI and NAI seroconversion
influenza PCR
N = 58
No flu PCR
N = 33
Influenza negative N = 28
Influenza positive N = 30
Unvaccinated cohort N=911
No. person with ILI N =91
No. person with ILI N =13
HAI aloneSeroconverters
N =46
NAI aloneSeroconverters
N =100
No. person with ILI N =52
influenza PCR
N = 9
Influenza negative
N = 8
Influenza positive
N = 1
No flu PCR
N = 4
influenza PCR
N = 42
Influenza negative N = 23
Influenza positive N = 19
No flu PCR
N = 10
HAI & NAI Seroconverters
N =175
No. person with ILI N =131
influenza PCR
N = 100
Influenza negative N = 100
Influenza positive
N = 0
No flu PCR
N = 31
Non-Seroconverters
N =590
• More NAI than HAI seroconversion:
- NAI: 30%, 275/911
- HAI: 24%, 221/911
• Of infected: 31% (100/321) had NAI alone seroconversion
• Of non-seroconverters, no PCR positives: 100% agreement
Huang et al. Journal of Infectious Diseases 2019;219:347-57
Serologically defined infection by age and ethnicity
• The highest attack rates of influenza infection:
- children aged <5 years
- Pacific peoples
NAI alone seroconversion rates - age-specific and strain-specific
Difference (%NAI-%HAI):
• Children < 5yo (14%) vs other ages (4%), p<0.001
• Infected individuals: B (7%) vs A(H3N2) (0.3%), p<0.001
0-4 yo 5-19 yo 20-64 yo ≥65 yo
%HAI 11 11 6 7
%NAI 27 18 11 12
%NAI-%HAI 16 7 4 5
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Influenza B
0-4 yo 5-19 yo 20-64 yo ≥65 yo
%HAI 19 25 11 9
%NAI 22 24 12 7
%NAI-%HAI 3 -1 1 -2
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A(H3N2)
A full influenza burden pyramid
Age and ethnicity adjusted estimates
1,000,000 people over one season
• 32% of population - flu infected
• Of infected:
- 24% developed influenza-like illness
- 76% did not develop ILI
• Of infected with PCR confirmed ILI:
- 26% visited a GP
- 74% did not seek care
Flu infection 319,000 (32% of total population)
Flu GP visits
5,919 (1:62 infected)
Flu Hospitalization
639 (1 in 510 infected)
Flu ICU
26 (1 in 13,000)
Flu
Death
8 (1 in 40,000)
Conclusion
• A third of unvaccinated individuals had either HAI or NAI seroconversion.
• NAI alone seroconversion – 1/3 of all seroconverted individuals: higher in children<5 years and influenza B virus infected individuals
• Importance of NA: measuring NAI and HAI seroconversion - accurate infection rate in sero-epidemiologic cohort studies
• Importance of NA: understand immune correlates of protection, improve vaccine design and vaccine content standardization
Influenza- SHIVERS
• The Southern Hemisphere Influenza and Vaccine Effectiveness, Research and Surveillance (SHIVERS)
• Serosurvey, in 2015
• The results showed that 32% of people were infected with influenza (A or B)
• About 4 out of 5 of these people (76%) were asymptomatic carriers.
• These carriers could have spread the virus among their family, co-workers, classmates and patients without ever realising it.
• Pregnancy and young children at high risk of disease and there are ethnic differences
• Implication for health workers
14
Influenza this winter
• Flu vaccine prevents CV events
• Promotes healthy aging
• As strong a intervention measure as a statin or antihypertensive
• Anti-frailty intervention
16
Efficacy of intervention
Coronary Intervention Prevention Efficacy against AMI
Smoking cessation Secondary 32-43%
Statins Secondary 19-30%
Antihypertensive drugs Secondary 17-25%
Influenza Vaccine Secondary 15-45%