Semiannual Versus Annual Influenza Vaccination in Older Adults in the Tropics: An Observer-blind, Active-comparator–controlled, Randomized Superiority Trial

Abstract

Background: Antibody titres and vaccine effectiveness decline within six months after influenza vaccination in older adults. Biannual vaccination may be necessary to provide year-round protection in the tropics where influenza is present throughout the year. Methods: Tropical Influenza Control Strategies (TROPICS1) was a single-centre, 1:1 randomised, observer-blinded, active-comparator controlled, superiority study in 200 community-resident adults aged ≥65 years. Participants received standard-dose trivalent inactivated influenza vaccination (IIV3) at enrolment, and either tetanus-diphtheria-pertussis vaccination or IIV3 six months later. Primary outcome was the proportion of participants with haemagglutination-inhibition (HI) geometric mean titre (GMT) ≥1:40 one month after the second vaccination (Month 7). Secondary outcomes included GMTs to Month 12, the incidence of influenza-like illness (ILI), and adverse reactions after vaccination. This study is registered with ClinicalTrials.gov: NCT02655874. Findings: At Month 7, the proportion of participants with a HI tire ≥1:40 against A/H1N1 increased by 21•4% (95% CI 8•6-33•4) in the six-monthly vaccination group. This proportion was not significantly higher for A/H3N2 (4•3, 95% CI-1•1-10•8) or B (2•1, 95% CI-2•0-7•3). Six-monthly vaccination significantly increased GMTs against A/H1N1 and A/H3N2 at Month 7, but not B. Participants receiving repeat IIV3 reported a significantly lower incidence of ILI in the six months after the second vaccination (relative vaccine efficacy of 57•1%, 95% CI 0•6-81•5). The frequency of adverse events was similar after first or second influenza vaccination. Interpretation: Six-monthly influenza vaccination in older residents of tropical countries is a simple intervention with the potential for improving protection against infection.

Influenza in temperate and tropical Asia: a review of epidemiology and vaccinology

“…A clinical trial in Singapore randomized 200 older adults to annual versus six-monthly standard-dose influenza vaccination with follow up for 1 year. 65 Participants who received repeat vaccination had significantly HI titers to A/H3N2 and A/H1N1 midway through the year, though titers waned and were not significantly different between groups six months later. Immune response to the vaccine after 6 months were significantly lower than the first dose for all three strains in the vaccine.…”

Epidemiological trends in notified influenza cases in Australia’s Northern Territory, 2007‐2016

“…Categories marked ND indicate that there were no notifications for Indigenous or non-Indigenous Australians that year to a significant increase in the proportion of participants with antibody titres ≥1:40 for H1N1 virus only. 26 Despite there not being an increase seen in the proportion of participants with antibody titres ≥1:40 for the H3N2 or B viruses, there may still be some clinical benefits for biannual vaccination. 26 A lower proportion of participants that received biannual vaccination reported influenza-like illnesses,…”

“…26 Despite there not being an increase seen in the proportion of participants with antibody titres ≥1:40 for the H3N2 or B viruses, there may still be some clinical benefits for biannual vaccination. 26 A lower proportion of participants that received biannual vaccination reported influenza-like illnesses,…”

“…although it was noted that the sample used in this study was too small to detect whether there was a reduction in laboratory-confirmed influenza. 26 Given that influenza outbreaks in the February-March period are occurring in the Top End, a vaccination campaign against these outbreaks would be best focused on this region. However, it appears (Table S1).…”

Vaccines for International Travel

“…Recent evidence suggests that travelers immunized with the current vaccine formulation more than 6 months earlier may consider revaccination because immunity clearly declines to close to zero by this time. 100 Data supporting revaccination is limited but enticing.…”