High-dose influenza vaccination

Daniel Dalcin; Jeffrey C. Kwong

doi:10.1503/cmaj.181477

High-dose influenza vaccine contains 4 times the amount of antigen of standard-dose vaccines

High-dose trivalent inactivated influenza vaccine (HD-TIV) contains 60 μg of hemagglutinin per strain, whereas standard-dose vaccines (SD-TIV) contain 15 μg. Given the burden of influenza A subtype H3N2 in older adults and evidence of better efficacy of HD-TIV relative to SD-TIV (Box 1),1^–4 Canada’s National Advisory Committee on Immunization recommends HD-TIV over SD-TIV for adults aged 65 years and older; however, the comparative effectiveness of HD-TIV over other options (MF59-adjuvanted TIV or standard-dose quadrivalent influenza vaccine) is uncertain.5 The HD-TIV is publicly funded for adults aged 65 and older in Ontario and for long-term care residents aged 65 and older in Saskatchewan, Manitoba and Prince Edward Island.

Box 1: Absolute outcome comparisons among adults aged 65 years and older receiving SD-TIV and HD-TIV

Outcome	SD-TIV	HD-TIV
Laboratory-confirmed influenza1	1.9%	1.4%
Hospital admissions for laboratory-confirmed influenza2	1.10 per 10 000 person-weeks	0.86 per 10 000 person-weeks
Post-influenza death3	0.038 per 10 000 person-weeks	0.028 per 10 000 person-weeks
Mild adverse events^*4	29.4%	34.3%

Note: HD-TIV = high-dose trivalent inactivated influenza vaccine,
SD-TIV = standard-dose trivalent inactivated influenza vaccine.
↵* For example, fever, headache, malaise and myalgia.

In older adults, HD-TIV is more efficacious than SD-TIV

A clinical trial involving 31 989 adults 65 years of age and older found that HD-TIV was 24% (95% confidence interval [CI] 10% to 37%) more efficacious than SD-TIV in preventing laboratory-confirmed influenza, with 23% higher efficacy (95% CI 6% to 38%) against influenza A subtype H3N2.1 Influenza A subtype H3N2 accounts for most severe illnesses among older adults. To prevent 1 additional case of influenza, 200 individuals need to receive HD-TIV instead of SD-TIV.1

HD-TIV is associated with reduced hospital admissions and emergency department visits in older adults

A cohort study including adults 65 years and older found that those who had received HD-TIV (n = 929 730) had a 22% (95% CI 16% to 27%) reduction in influenza-coded hospital admissions and emergency department visits compared with those who received SD-TIV (n = 1 615 545).2

HD-TIV is associated with reduced post-influenza deaths among older adults

A cohort study including 2 722 909 adults aged 65 years and older found that HD-TIV was associated with a 36% (95% CI 9% to 56%) reduction in post-influenza deaths compared with SD-TIV during the 2012/13 season, but no reduction during the 2013/14 season.3

Mild adverse events occur more often with HD-TIV than with SD-TIV

Short-term data from clinical trials showed higher rates of mild systemic reactions (e.g., fever) among individuals receiving HD-TIV than among those receiving SD-TIV (relative risk 1.2, 95% CI 1.1 to 1.3), but not serious adverse events (relative risk 0.92; 95% CI 0.85 to 0.99).1^,4

Footnotes

CMAJ Podcasts: author interview at https://soundcloud.com/cmajpodcasts/181477-five
Competing interests: None declared.
This article has been peer reviewed.

References

↵
1. DiazGranados CA,
2. Dunning AJ,
3. Kimmel M,
4. et al
. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med 2014;371:635–45.
OpenUrl CrossRef PubMed
↵
1. Izurieta HS,
2. Thadani N,
3. Shay DK,
4. et al
. Comparative effectiveness of high-dose versus standard-dose influenza vaccines in US residents aged 65 years and older from 2012 to 2013 using Medicare data: a retrospective cohort analysis [published correction appears in Lancet Infect Dis 2015;15: 263]. Lancet Infect Dis 2015;15:293–300.
OpenUrl CrossRef PubMed
↵
1. Shay DK,
2. Chillarige Y,
3. Kelman J,
4. et al
. Comparative effectiveness of high-dose versus standard-dose influenza vaccines among US Medicare beneficiaries in preventing post-influenza deaths during 2012–2013 and 2013–2014. J Infect Dis 2017;215:510–7.
OpenUrl CrossRef
↵
1. Falsey AR,
2. Treanor JJ,
3. Tornieporth N,
4. et al
. Randomized, double-blind controlled phase 3 trial comparing the immunogenicity of high-dose and standard-dose influenza vaccine in adults 65 years of age and older. J Infect Dis 2009;200:172–80.
OpenUrl CrossRef PubMed
↵
Canadian immunization guide chapter on influenza and statement on seasonal influenza vaccine for 2018–2019. An Advisory Committee Statement (ACS). National Advisory Committee on Immunization (NACI). Ottawa: Public Health Agency of Canada; 2018. Available: www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-statement-seasonal-influenza-vaccine-2018-2019.html#2.6 (accessed 2019 Mar. 1).