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Objectives Evidence suggests repeated influenza vaccination may reduce vaccine effectiveness (VE). Using influenza vaccination program maturation (number of years since program inception) [PM] as proxy for population-level repeated vaccination, we assessed the impact on pooled adjusted end-season VE estimates from outpatient test-negative design studies. Methods We systematically searched and selected full-text publications from January 2011 to February 2020 (PROSPERO: CRD42017064595). We obtained influenza vaccination program inception year for each country and calculated PM as the difference between the year of deployment and year of program inception. We categorized PM into halves (cut at the median), tertiles, and quartiles, and calculated pooled VE using an inverse variance, random effects model. The primary outcome was pooled VE against all influenza. Results We included 72 articles from 11,931 unique citations. Across the three categorizations of PM, a lower pooled VE against all influenza for all patients was observed with PM. Substantially higher reductions were observed in older adults (≥65 years). We observed similar results for A(H1N1)pdm09, A(H3N2) and influenza B. Conclusions The evidence suggests influenza VE declines with vaccination PM. This study forms the basis for further discussions and examinations of the potential impact of vaccination PM on seasonal VE.

Background Seasonal influenza vaccination (SIV) rates remain suboptimal in many populations, even in those with universal SIV. Objective To summarize the evidence on interventions on health care providers (physicians/nurses/pharmacists) to increase SIV rates. Methods We systematically searched/selected full-text English publications from January 2000 to July 2019 (PROSPERO-CRD42019147199). Our outcome was the difference in SIV rates between patients in intervention and non-intervention groups. We calculated pooled difference using an inverse variance, random-effects model. Results We included 39 studies from 8370 retrieved citations. Compared with no intervention, team-based training/education of physicians significantly increased SIV rates in adult patients: 20.1% [7.5–32.7%; I2 = 0%; two randomized controlled trials (RCTs)] and 13.4% [8.6–18.1%; I2 = 0%; two non-randomized intervention studies (NRS)]. A smaller increase was observed in paediatric patients: 7% (0.1–14%; I2 = 0%; two NRS), and in adult patients with team-based training/education of physicians and nurses together: 0.9% (0.2–1.5%; I2 = 30.6%; four NRS). One-off provision of guidelines/information to physicians, and to both physicians and nurses, increased SIV rates in adult patients: 23.8% (15.7–31.8%; I2 = 45.8%; three NRS) and paediatric patients: 24% (8.1–39.9%; I2 = 0%; two NRS), respectively. Use of reminders (prompts) by physicians and nurses slightly increased SIV rates in paediatric patients: 2.3% (0.5–4.2%; I2 = 0%; two RCTs). A larger increase was observed in adult patients: 18.5% (14.8–22.1%; I2 = 0%; two NRS). Evidence from both RCTs and NRS showed significant increases in SIV rates with varied combinations of interventions. Conclusions Limited evidence suggests various forms of physicians’ and nurses’ education and use of reminders may be effective for increasing SIV rates among patients.