Our study showed that 10% increase in vaccination coverage corresponded to 11% decrease in nosocomial influenza incidence rate, although statistical significance was not achieved. It was also observed that influenza activity in Singapore predominantly followed the Southern Hemisphere influenza seasonal pattern between 2013 and 2018.
Similar studies, interestingly few, show that HCW vaccination coverage is associated with reduced nosocomial influenza incidence(4,5). Our study observed a similar association, but statistical significance was not reached despite a relatively large number of nosocomial influenza cases. The effect size observed in this study, when measured by proportion of nosocomial influenza (not shown) is similar to that of a study performed in cancer patients(4).
A mismatch in the Northern Hemisphere timing of HCW vaccination and predominantly Southern Hemisphere seasonal peaks in influenza activity in our study may have reduced the effect size observed and contributed to the lack of statistical significance. Furthermore, virulence, vaccine efficacy and the match of vaccine strains vary between influenza seasons and may contribute to significant variation.
Notwithstanding this, the results are encouraging. Firstly, the observed effect size is clinically significant. Secondly, dose-effect relationships were observed in the sensitivity analyses. When non-clinical staff were included in the calculation of vaccine coverage, the association observed was weakened. Decreasing the diagnostic specificity of nosocomial influenza by using less stringent classification thresholds (days from admission to laboratory diagnosis) resulted in a weaker association. This is consistent with a true relationship between HCW influenza vaccination and nosocomial influenza.
Singapore is located 1.3˚N and was deemed to have year-round influenza activity and varying peak periods(6,9). WHO had also recommended Singapore to adopt the Northern Hemisphere influenza vaccine formulation(10). In contrast, our hospital-based data from 2013 to 2018 indicated that influenza activity, both nosocomial and community-acquired, predominantly shows southern hemisphere seasonal peaks. A local study concurs, reporting that “severe epidemics were more commonly observed around middle of the year.(9)"
In view of the findings, Southern Hemisphere vaccination timing and formulation should be adopted in our hospital, if not nationally. Nevertheless, the seasonal profile of influenza activity may not be stable in the tropics and continued influenza surveillance is needed. It also remains important to keep track of significant changes in influenza vaccine formulation to inform whether a northern hemisphere vaccine is required.
The ecological study design has limitations. Potential unmeasured confounders such as improved infection control measures coinciding with improved vaccination uptake may give rise to false associations. Nevertheless, an ecological study is practical and feasible compared to other study designs in assessing the effectiveness of an institutional influenza vaccination program. Particularly, it is challenging to determine an individual patient’s exposure to unvaccinated HCWs.
The study likely underestimates the true incidence of nosocomial incidence. The definition of nosocomial influenza of laboratory diagnosis at seven days or more from admission yields specificity but may underestimate the incidence given that the incubation period is between one to four days. Underestimation may also arise from passive surveillance of laboratory data rather than active sampling of inpatients for influenza.
Nevertheless, our study is well-sized with 256 cases over 2,480,010 patient-days. We also analyze monthly nosocomial influenza incidence rates, while other studies often use the annual proportions of nosocomial influenza amongst all influenza diagnosed which may be difficult to interpret and compare(4,5). This study also presents evidence and a perspective from a tropical country with differing influenza seasonal patterns and less certain vaccination timings to match peak influenza activity.