Assessment of temporally-related acute respiratory illness following influenza vaccination

Abstract

Background: A barrier to influenza vaccination is the misperception that the inactivated vaccine can cause influenza. Previous studies have investigated the risk of acute respiratory illness (ARI) after influenza vaccination with conflicting results. We assessed whether there is an increased rate of laboratory-confirmed ARI in post-influenza vaccination periods.

Methods: We conducted a cohort sub-analysis of children and adults in the MoSAIC community surveillance study from 2013 to 2016. Influenza vaccination was confirmed through city or hospital registries. Cases of ARI were ascertained by twice-weekly text messages to household to identify members with ARI symptoms. Nasal swabs were obtained from ill participants and analyzed for respiratory pathogens using multiplex PCR. The primary outcome measure was the hazard ratio of laboratory-confirmed ARI in individuals post-vaccination compared to other time periods during three influenza seasons.

Results: Of the 999 participants, 68.8% were children, 30.2% were adults. Each study season, approximately half received influenza vaccine and one third experienced ≥1 ARI. The hazard of influenza in individuals during the 14-day post-vaccination period was similar to unvaccinated individuals during the same period (HR 0.96, 95% CI [0.60, 1.52]). The hazard of non-influenza respiratory pathogens was higher during the same period (HR 1.65, 95% CI [1.14, 2.38]); when stratified by age the hazard remained higher for children (HR 1·71, 95% CI [1.16, 2.53]) but not for adults (HR 0.88, 95% CI [0.21, 3.69]).

Conclusion: Among children there was an increase in the hazard of ARI caused by non-influenza respiratory pathogens post-influenza vaccination compared to unvaccinated children during the same period. Potential mechanisms for this association warrant further investigation. Future research could investigate whether medical decision-making surrounding influenza vaccination may be improved by acknowledging patient experiences, counseling regarding different types of ARI, and correcting the misperception that all ARI occurring after vaccination are caused by influenza.

Keywords: Acute respiratory illness; Belief; Influenza; Influenza vaccine; Misperceptions.

Fig. 1

Vaccination exposure comparison groups over time. Hazard of the three outcomes of interest (laboratory-confirmed influenza, laboratory-confirmed non-influenza pathogens, and acute respiratory illness (ARI) symptoms without detectable pathogens) were compared over time between three potential exposure statuses: unvaccinated, post-vaccination risk period, and vaccinated. The arrow denotes a date during which three hypothetical individuals are in different exposure groups. Participants who were not vaccinated only contributed to the unvaccinated interval. Three separate Cox proportional hazards models were conducted, one to assess each of the three ARI outcomes.

Fig. 2

Study flow diagram. Eligible children were 6 months to 17 years, had updated vaccine records in the hospital and/or the New York Citywide Immunization Registry (CIR); children who received two doses of influenza vaccine were excluded from the analysis of the season in which they received two doses. Eligible adults were ≥18 years, were patients at the affiliated hospital, and had ≥1 primary care visit or hospitalization between October 1 and the end of the study season of interest.^a Combined totals do not equal sum of years as participants may have been active in the study for more than one year. Age classification for combined years is based on age on September 1, 2013.

Fig. 3

Frequency distribution of dates of influenza vaccination and onset of acute respiratory illnesses over three influenza seasons.