1. Introduction
Seasonal influenza is an acute infectious disease of the respiratory system caused by influenza viruses, and the disease burden of influenza represents one of the major problems for public health worldwide. Usually, most people recover without requiring medical attention. However, influenza can become a severe illness and sometimes lead to hospitalization and death, particularly among high-risk groups such as younger subjects, older adults, pregnant women, and those with underlying conditions [
1].
Worldwide, the annual seasonal influenza affects up to 1 billion people and causes 3–5 million severe cases and up to 650,000 deaths related to respiratory diseases [
2]. In Europe, seasonal influenza virus infects approximately 10–30% of the population and causes hundreds of thousands of hospitalizations [
3].
Influenza is a preventable disease: each year the influenza vaccination is recommended at specific risk groups to reduce the individual risk of disease, hospitalization, and death, to reduce the risk of virus transmission to subjects at high risk of complications or hospitalization, and, lastly, to reduce the social costs associated with influenza morbidity and mortality [
4,
5].
Deep and specific knowledge of the epidemiological circulation of the influenza virus is the basic step to managing the immunization program in order to obtain the highest health value. In this scenario, the aim of the current study was to assess the epidemiology of seasonal influenza in the Italian population through the analysis of data collected and published in the periodic reports of the Italian epidemiological and virological surveillance system for the season 2010/2011 to 2023/2024. The main objective is to identify the key points of influenza epidemiology in order to plan the most appropriate and efficient preventive immunological strategies against influenza.
4. Discussion
The aim of this study was to assess the epidemiological and virological trends of the annual influenza epidemics in Italy from the 2010/2011 season up to now in order to plan the most appropriate preventive strategies in the future.
Time patterns of ILI cases reported in the Italian surveillance system show a relevant variability in the annual epidemic trends, with seasons when the intensity of incidence was very low and others when the intensity was very high, as in the last seasons before the pandemic period and the last seasons. However, some key points are evident from the analysis of the epidemiological surveillance data.
The pediatric and adolescent populations have always reported the highest incidence values of ILI and a longer epidemic period. In particular, in the age group 0–4 years, the epidemic period on average begins at Week 45 of each year (the second week of November), and extends for almost the entire influenza season, with an average duration of 24 weeks. In addition, the average cumulative incidence in this age group (27%) in the pre-pandemic period highlights that more than one-quarter of children (about 558,000 subjects) had ILI each year. This value grew at >60% in the last influenza season. Particularly, considering about 2,000,000 children 0–4 years old in Italy [
7], about >60,000 children have ILI on average in the week with the maximum value of weekly incidence. In the last seasons >100,000 children had ILI in the week of incidence peak. Even if influenza has generally a benign course in these age groups, however, this high number of subjects with ILI has a relevant impact on the health care systems and society. As a matter of fact, influenza may be responsible for hospital admissions (especially in younger children) and for a significant number of lost school days, lost work days by parents, and increased consumption of health resources due to medical examinations, use of antipyretic drugs and use of antibiotics [
8]. In addition, it should be noted that, due to the high incidence rates and the anticipated outset of the epidemic period in this age group compared with the others, the younger population is the main source of infection for the general population and, in particular, can transmit the infection to categories of subjects most at risk of severe morbidity and mortality related to influenza syndrome such as older adults or subjects with chronic disease (diabetics, pulmonary disease, heart disease, etc.) [
9].
Epidemiological surveillance data, however, show a different trend for older adults. The older population is characterized by the lowest rates of ILI incidence (cumulative and maximum week incidence) and a reduced epidemic period (8 weeks on average), with a start towards the beginning of the year (Week 1) and a conclusion at the end of February (Week 8). More than 4% of older adults had ILI each year in the pre-pandemic period but this rate corresponds to >600,000 subjects (considering an older population of 14,000,000 subjects [
7]) and this value has tripled in the last 2 influenza seasons (12% and 15%, respectively). Particularly, about 60,000 subjects had ILI in the week of maximum weekly incidence on average in the pre-pandemic period and this number increased over the years. Therefore, even if the incidence rate is low, the number of cases is consistent. As a matter of fact, it is appropriate to emphasize how the subjects in this age group are at increased risk for influenza complications (which may also evolve into outcomes particularly negative, such as death) due the age and other co-morbidities [
10], leading to a high disease burden with a relevant health and societal impact.
The last weeks of the 2019/2020 influenza season were affected by the circulation of SARS-CoV-2 [
6]. From surveillance data, it seems that the seasonal epidemic stopped abruptly in advance to the 13th week of 2020. Probably, the prevention and protection measures taken in response to the pandemic emergency could have blocked regular and continuous surveillance or slowed the circulation of influenza viruses in the population [
11]. The 2020/2021 influenza season had an abnormal trend compared to previous seasons, with extremely low ILI incidence rates and a total absence of influenza viruses identified in respiratory samples collected and analyzed by the virological surveillance system. Globally, also in the temperate regions of the northern hemisphere, there was an analogous trend, with an influenza season characterized by a viral circulation well below inter-seasonal levels, with sporadic isolations of viruses A and B [
6].
In the 2021/2022 season, a resumption of intensity was observed (although at low values) of the influenza season (in terms of maximum weekly and cumulative ILI incidence) compared to the previous season 2020/2021 at the Italian level. In particular, the 2021/2022 season was characterized by two unusual epidemic peaks: a first epidemic peak between Week 44 and Week 5 and a second peak that extended between Week 10 and 17; the season ended with an ILI incidence level of 2.83 cases per 1000 patients. In the 2019/2020 season, the last season with an epidemic of ILI before the pandemic, the estimated incidence of ILI in the 17th week (last week of surveillance) was much less (0.42‰). In addition, the rate of positivity of the biological samples analyzed by the virological surveillance system was very low (15%), almost half the average calculated value for influenza seasons from 2010/2011 to 2019–2020, indicating the co-circulation of other pathogens, including the SARS-CoV-2 (identified in 29% of samples). Apart from these issues, the key points highlighted in the previous 10-year period before the SARS-CoV-2 pandemic continued to be evident. Therefore, after the significant reduction in the incidence of ILI in the pandemic emergency period 2020/2021 due to control and prevention of infection by SARS-CoV-2, the data of the 2021/2022 season show that influenza viruses continue to circulate, and their spread is increased as the non-pharmacological restrictions applied for the control of the pandemic of COVID-19 have been reduced. This issue is confirmed by the high intensity notified in the last seasons 2022/2023 and 2023/2024, when the epidemiological and virological trends of ILI were confirmed as reported in the last decades but with high intensity.
Another key point is that in the years the start of the epidemic period has been increasingly anticipated. This issue should be taken into account in the planning of the annual vaccination program.
Moreover, the rate of positive samples of the influenza virus, accounting for 31% of the pre-pandemic virus, decreased in the last years despite the fact that the number of samples has significantly increased. It could be related to the great attention to respiratory viruses after the pandemic and the consequent strengthening of the ILI monitoring system. Analysis of virological surveillance data shows that in the analyzed influenza seasons there is a predominant circulation of influenza virus A. Among the viruses A, the H3N2 subtype circulated more than virus H1N1pdm09 in the observed period. In the few pre-pandemic seasons when influenza virus B was the most frequent influenza agent, it co-circulated with influenza virus A and the percentage of influenza virus B did not exceed 60%. Influenza virus B disappeared in the pandemic period (2020/2021 and 2021/2022 seasons) and later it had a limited distribution (21% and 9% in 2022/2023 and 2023/2024 seasons, respectively) due to B/Victoria lineage virus. As a matter of fact, globally, there have been no confirmed detections of circulating B/Yamagata lineage viruses after March 2020 [
12]. In the last few years, the co-circulation of other respiratory pathogens become more evident.
The main limitation of this study is that we assess epidemiological and virological data collected by the surveillance system of ILI and not of laboratory influenza-confirmed cases. However, the ILI can be considered an optimal proxy of influenza case trends, even when there is the circulation of other respiratory agents, as in the last seasons.
This study did not assess any relationship between epidemic season intensity and vaccination coverage in the general population and older adults. The current Italian National Immunization Plan 2023–2025 and the annual Ministerial Circulars for the Prevention and Control of Influenza have set the minimum achievable vaccination coverage goal at 75% and the optimal one at 95% for subjects over sixty-five years of life and high-risk groups [
4,
13]. However, the influenza vaccine coverage in older adults ranged from 62.4% to 48.6% from the 2010/2011 to 2019/2020 seasons. The vaccine coverage increased in 2020/2021 (65.3%) and decreased in the two seasons 2021/2022 and 2022/2023 (58.1% and 56.7%, respectively) in this age group. Instead, the vaccine coverage of the general population was always <24% [
14]. On the other hand, to our knowledge, this is the first study that summarized epidemiological and virological data collected in more than 10 years of surveillance, highlighting some useful key points to consider in future preventive strategies. For example, even if influenza is usually benign in children, the younger population has the highest influenza incidence and the earliest outset of epidemic season. These data confirm the value of vaccinating children and paying attention to beginning the immunization program as soon as possible. This issue could be useful to reduce the number of cases in younger people but also to reduce the virus transmission to older subjects (who usually begin the epidemic season later). Concerning the older adults, they have a lower influenza incidence; however, considering the demographic structure of the Italian population, the number of influenza cases is very relevant in this already fragile population. It has a relevant impact on our healthcare systems each year. In addition, a great number of older adults have other underlying conditions that increase the risk of complications and death.