Factors Influencing Frequency of Pediatric Clinically Distinguishable Influenza: A 2 Season Case-Control Study

Background: Little is known about the individual differences in susceptibility to, or lifetime frequency of clinically distinguishable influenza in children. Methods: Rapid enzyme linked immunoassay-confirmed influenza pediatric cases (n = 96) in season 1 (2017-2018) were compared to age-matched (mean 7.7 years) controls (n = 171) with no evidence of influenza in season 1. The 2 cohorts were again studied in season 2 (2018-2019) for influenza outcomes and influences. Medical records, questionnaires, and interviews were used to determine past influenza disease and vaccine histories. Results: After season 2, known lifetime influenza illnesses per year of age averaged 22.6% in cases and 5.6% in controls, with 62% of controls still having never experienced known influenza. Having had prior influenza was marginally significant as a risk for season 1 influenza in cases versus controls (P = .055), yet a significant risk factor in controls for season 2 (P = .018). Influenza vaccine rates were significantly higher in controls than in cases for season 1, with a greater female vaccine benefit. Lack of previous influenza had greater calculated effectiveness (52%) than vaccination (17%-26%) in escaping season 2 influenza. Lifetime rates of vaccination did not correlate with lifetime rates of known influenza in either cohort. Conclusions: Lifetime clinically distinguishable influenza rates varied among children, with many escaping it for years even without being immunized against it. Findings of less than expected clinical influenza, no correlation between vaccination frequency and disease frequency, sex differences, and an association between past clinical influenza and current risk, point to innate differences in individual influenza experiences.