Public health impact of influenza vaccination in Italy: barriers, benefits and interventions in the field of prevention

Influenza represents one of the infectious diseases with the major clinical and economic burden on health systems and society. Seasonal influenza vaccination (IV) is the most effective defense we have against this infection, despite IV coverage rate is still suboptimal. The main objective of this PhD thesis is to investigate the different benefits and determinant factors of IV, to support public health stakeholders and decision makers in the continuous development of best practices, behaviors and policies in the field of prevention. In order to investigate any potential for improvement in the flu prevention field, two ecological studies were conducted in the seasons 2010/11-2016/17 and 2017/18-2021/22, respectively, to analyze the pneumonia- and influenza (P&I)-related mortality in Italian individuals ≥65 years and to explore if a different IV distribution and administration velocity can affect the incidence of all-cause and respiratory-related hospitalization. Moreover, an economic and fiscal impact model of an influenza immunization programme among Italian healthcare workers (HCWs) has been implemented. In the first ecological study, we investigated spatiotemporal patterns of pneumonia- and influenza-related deaths in Italian adults ≥65 years over the course of 7 years. Fixed- and random-effects panel regression models have than explored possible associations between different factors that play a role in the flu immunization season and local pneumonia- and influenza-related mortality. The spatiotemporal analysis highlighted a North-South gradient whereas regression models correlated a reduction of 1.6–1.9% in P&I-related mortality to each 1% increase in IV coverage rate (P < 0.001). An additional decrease of 0.4% was observed for each 1% increase in the proportion of adjuvanted trivalent IV used. The second ecological study analyzed distributing and administering velocities of adjuvanted trivalent and quadrivalent IVs (aTIV and aQIV, respectively) in a primary care setting and its potential impact on Italian older adults hospitalization risk over 5 epidemic seasons. This study associated a minimization of the time lag between vaccine distribution and administration to a further mitigation of the flu burden. From an economical and fiscal point of view, an incremental 10% increase in IV coverage in Italian HCWs over a five-year period could reduce productivity losses by €4,475,497.16 and increase tax revenues by €327,158.84, promoting a value-based allocation of available healthcare resources. Furthermore, to investigate possible drivers of IV, changes in perception have been monitored through cross-sectional computer assisted web interviews (CAWIs) carried out 2-3 times per year. Each questionnaire involved from 1979 to 2513 adults, representative of the Italian population. The longitudinal survey monitored a general increase in willingness to receive IV from May 2020 to May 2021, partly influenced by the COVID-19 pandemic situation, but even a hesitancy toward COVID-19 and influenza vaccine co-administration. Text/instant messages or email reminders, in particular if sent by the general practitioner, seem to be the most effective resources for increasing IV uptake through active invitation, with greater odds to be vaccinated in the last season in the population group that received a reminder compared to those who did not receive it (adjusted odds ratio (aOR) 6.47, 95% CI: 5.35-7.83). These studies support a higher annual IV coverage in Italy, based on appropriateness criteria and on the adoption of proactive measures and strategies to overcome the observed determinants of hesitancy.