Co-detection of respiratory pathogens among ILI patients: characterization of samples collected during the 2018/19 and 2019/20 pre-pandemic seasons.

Influenza-like illness (ILI) patients co-detected with respiratory pathogens exhibit poorer health outcomes than those with single infections. To address the paucity of knowledge concerning the incidence of concurrent respiratory pathogens, their relationships, and the clinical differences between patients detected with single and multiple pathogens, we performed an in-depth characterization of the oropharyngeal samples of primary care patients collected in Genoa (Northwest Italy), during winter seasons 2018/19-2019/20.The apriori algorithm was employed to evaluate the incidence of viral, bacterial, and viral-bacterial pairs during the study period. The grade of correlation between pathogens was investigated using the Phi coefficient. Factors associated with viral, bacterial or viral-bacterial co-detection were assessed using logistic regression.The most frequently identified pathogens included influenza A, rhinovirus, Haemophilus influenzae and Streptococcus pneumoniae. The highest correlations were found between bacterial-bacterial and viral-bacterial pairs, such as Haemophilus influenzae-Streptococcus pneumoniae, adenovirus-Haemophilus influenzae, adenovirus-Streptococcus pneumoniae, RSV-A-Bordetella pertussis, and influenza B Victoria-Bordetella parapertussis. Viruses were detected together at significantly lower rates. Notably, rhinovirus, influenza, and RSV exhibited significant negative correlations with each other. Co-detection was more prevalent in children aged < 4, and cough was shown to be a reliable indicator of viral co-detection.Given the evolving epidemiological landscape following the COVID-19 pandemic, future research utilizing the methodology described here, while considering the circulation of SARS-CoV-2, could further enrich the understanding of concurrent respiratory pathogens.

Epidemiology and molecular characteristics of respiratory syncytial virus (RSV) among italian community-dwelling adults, 2021/22 season.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infections worldwide. While historically RSV research has been focused on children, data on RSV infection in adults are limited. The goal of this study was to establish the prevalence of RSV in community-dwelling Italian adults and analyze its genetic variability during the 2021/22 winter season. METHODS: In this cross-sectional study, a random sample of naso-/oropharyngeal specimens from symptomatic adults seeking for SARS-CoV-2 molecular testing between December 2021 and March 2022 were tested for RSV and other respiratory pathogens by means of reverse-transcription polymerase chain reaction. RSV-positive samples were further molecularly characterized by sequence analysis. RESULTS: Of 1,213 samples tested, 1.6% (95% CI: 0.9-2.4%) were positive for RSV and subgroups A (44.4%) and B (55.6%) were identified in similar proportions. The epidemic peak occurred in December 2021, when the RSV prevalence was as high as 4.6% (95% CI: 2.2-8.3%). The prevalence of RSV detection was similar (p = 0.64) to that of influenza virus (1.9%). All RSV A and B strains belonged to the ON1 and BA genotypes, respectively. Most (72.2%) RSV-positive samples were also positive for other pathogens being SARS-CoV-2, Streptococcus pneumoniae and rhinovirus the most frequent. RSV load was significantly higher among mono-detections than co-detections. CONCLUSION: During the 2021/22 winter season, characterized by the predominant circulation of SARS-CoV-2 and some non-pharmaceutical containment measures still in place, a substantial proportion of Italian adults tested positive for genetically diversified strains of both RSV subtypes. In view of the upcoming registration of vaccines, establishment of the National RSV surveillance system is urgently needed.

Do the omeprazole family compounds exert a protective effect against influenza-like illness?

BACKGROUND: Infections by influenza viruses place a heavy burden on public health and economies worldwide. Although vaccines are the best weapons against influenza, antiviral drugs could offer an opportunity to alleviate the burden of influenza. Since omeprazole family compounds block the "proton pump", we hypothesized that they could interfere with the mechanism of fusion of the virus envelope and endosomal membrane, thereby hindering the M2 proton pump mechanism of influenza viruses. METHODS: A matched case-control study was performed in 2010-2011 in Italy. Cases were subjects aged over 18 years with a diagnosis of Influenza-like Illness (ILI); 254 case-control pairs were recruited. A multivariable conditional logistic regression analysis was used to assess the association between the prevention of ILI and the administration of omeprazole family compounds. The interaction between omeprazole family compounds and influenza vaccination was also examined. RESULTS: After control for potential confounders, subjects treated with omeprazole family compounds displayed a lower risk of catching ILI (ORadj = 0.29, 95% CI: 0.15-0.52). The risk of ILI in unvaccinated non-OFC users was about six times than that in vaccinated OFC users. CONCLUSIONS: Although confirmation is necessary, these results suggest that omeprazole family compounds could be profitably used in the prevention of ILI.

Prevalence of human papillomavirus in young Italian women with normal cytology: how should we adapt the national vaccination policy?

BACKGROUND: Human Papillomavirus (HPV) is the most common sexually transmitted infection. In Italy, HPV vaccination is now offered free of charge to 12-year-old females. However, some regional health authorities have extended free vaccination to other age-groups, especially to girls under 18 years of age. We conducted a multicentre epidemiological study to ascertain the prevalence of different genotypes of HPV in young Italian women with normal cytology, with the aim of evaluating the possibility of extending vaccination to older females. METHODS: The study was performed in 2010. Women aged 16-26 years with normal cytology were studied. Cervical samples were analyzed to identify the presence of HPV by PCR amplification of a segment of ORF L1 (450 bp). All positive HPV-DNA samples underwent viral genotype analysis by means of a restriction fragment length polymorphism assay. RESULTS: Positivity for at least one HPV genotype was found in 18.2% of the 566 women recruited: 48.1% in the 16-17 age-class, 15.4 in the 18-20 age-class, 21.9% in the 21-23 age-class, and 15.5% in the 24-26 age-class; 10.1% of women were infected by at least one high-risk HPV genotype. HPV-16 was the most prevalent genotype. Only 4 (0.7%), 4 (0.7%) and 3 (0.5%) women were infected by HPV-18, HPV-6 and HPV-11, respectively. Of the HPV-DNA-positive women, 64.1% presented only one viral genotype, while 24.3% had multiple infections. The HPV genotypes most often involved in multiple infections were high-risk. A high prevalence was noted in the first years of sexual activity (48.1% of HPV-DNA-positive women aged 16-17 years); HPV prevalence subsequently declined and stabilized.The estimate of cumulative proportions of young women free from any HPV infection at each age was evaluated; 93.3% and 97.1% of 26 year-old women proved free from HPV-16 and/or HPV-18 and from HPV-6 and/or HPV-11, respectively. CONCLUSIONS: Our findings confirm the crucial importance of conducting studies on women without cytological damage, in order to optimise and up-date preventive interventions against HPV infection, and suggest that vaccinating 26-year-old females at the time of their first pap-test is to be recommend, though this issue should be further explored.

Enhanced passive safety surveillance of the MF59-adjuvanted quadrivalent influenza vaccine in the elderly during the 2021/22 influenza season.

In accordance with European directives, each year the enhanced safety surveillance (ESS) of seasonal influenza vaccines should be conducted in order to detect any potential increase in reactogenicity when the vaccine composition is updated or a new formulation becomes available. The objective of this passive ESS (EPSS) was to assess the frequency of spontaneously reported adverse events (AEs) following vaccination with the 2021/22 formulation of the MF59-adjuvanted quadrivalent influenza vaccine (aQIV) among older adults in Italy through the collection of data within a short time period (start of seasonal influenza vaccination) in order to monitor the reactogenicity of aQIV early in the season. All AEs reported within seven days following vaccination were analyzed by type and seriousness. In all, 1,059 vaccination cards were distributed to individuals aged ≥65 years. Only one, non-serious, spontaneous individual case safety report was submitted, yielding an overall rate of 0.9 per 1,000 doses administered. This report consisted of a reactogenic AE of pyrexia. The EPSS confirmed that the reactogenicity profile of aQIV was consistent with the known safety profile of the previous trivalent formulation. These optimal safety data could bolster public confidence in influenza vaccination and help to improve vaccination coverage.

Three seasons of enhanced safety surveillance of a cell culture-based quadrivalent influenza vaccine.

The objective of this paper is to summarize annual enhanced safety surveillance activity across three seasons (2019/20-2021/22) for cell culture-based quadrivalent influenza vaccine (QIVc; Flucelvax® Tetra) in all age groups. This activity was conducted in primary care setting in Genoa (Italy) during the seasons 2019/20, 2020/21 and 2021/22. All adverse events registered within the first seven days following immunization were analyzed by season, type, age group and seriousness. Over three seasons, 3,603 QIVc exposures were recorded within the enhanced passive safety surveillance activity. No safety signals were identified. The overall reporting rates of individual case safety reports for the seasons 2019/20, 2020/21 and 2021/22 were 1.75%, 0.48% and 0.40%, respectively. The average number of adverse events per individual case safety report was similar (range 3.3-3.8 adverse events per case report) across the three seasons. Most adverse events were reactogenic in nature. The rate of adverse events was similarly low in all age groups. Enhanced passive safety surveillance activity is a feasible approach for the post-marketing monitoring of seasonal influenza vaccines. Within its limitations, results of this study support the favorable safety profile of QIVc. These safety data could further bolster public trust in influenza vaccines with the goal to increase vaccination uptake in all target groups.

Sexual behaviour and risk factors for the acquisition of human papillomavirus infections in young people in Italy: suggestions for future vaccination policies.

BACKGROUND: Human Papillomavirus (HPV) is the most common sexually transmitted infection. The main risk factors correlated with HPV infection are: early sexual debut, the number of partners, frequency and type of sexual contact and partner's sexual histories.We surveyed sexual habits among young people in order to provide information that might orient decision-makers in adopting HPV multi-cohort vaccination policies. METHODS: We administered a questionnaire to students (14-24 years old) in five Italian cities. RESULTS: 7298 questionnaires were analyzed (4962 females and 2336 males); 55.3% of females (95% CI 53.9-56.7) and 52.5% of males (95% CI 50.5-54.5) reported regular sexual activity. The mean age at sexual debut was 15.7 ± 1.6 and 15.6 ± 1.6 for females and males, respectively, and the median age was 16 for both sexes.With regard to contraceptive use during the last year, 63.6% of males and 62.8% of females responded affirmatively; 42.6% of males and 42.8% of females used condoms. CONCLUSION: The results reveal precocious sexual activity among respondents, with the mean age at first intercourse declining as age decreases. Condom use proved to be scant. Considering lifestyle-related risk factors, males appear to have a higher probability of acquiring HPV infection than females.These data support the importance of promoting multi-cohort HPV vaccination strategies for females up to 25 years of age. It is essential to improve vaccination coverage through different broad-spectrum strategies, including campaigns to increase awareness of sexually transmitted diseases and their prevention.

The New Quadrivalent Adjuvanted Influenza Vaccine for the Italian Elderly: A Health Technology Assessment.

BACKGROUND: The elderly, commonly defined as subjects aged ≥65 years, are among the at-risk subjects recommended for annual influenza vaccination in European countries. Currently, two new vaccines are available for this population: the MF59-adjuvanted quadrivalent influenza vaccine (aQIV) and the high-dose quadrivalent influenza vaccine (hdQIV). Their multidimensional assessment might maximize the results in terms of achievable health benefits. Therefore, we carried out a Health Technology Assessment (HTA) of the aQIV by adopting a multidisciplinary policy-oriented approach to evaluate clinical, economic, organizational, and ethical implications for the Italian elderly. METHODS: A HTA was conducted in 2020 to analyze influenza burden; characteristics, efficacy, and safety of aQIV and other available vaccines for the elderly; cost-effectiveness of aQIV; and related organizational and ethical implications. Comprehensive literature reviews/analyses were performed, and a transmission model was developed in order to address the above issues. RESULTS: In Italy, the influenza burden on the elderly is high and from 77.7% to 96.1% of influenza-related deaths occur in the elderly. All available vaccines are effective and safe; however, aQIV, such as the adjuvanted trivalent influenza vaccine (aTIV), has proved more immunogenic and effective in the elderly. From the third payer's perspective, but also from the societal one, the use of aQIV in comparison with egg-based standard QIV (eQIV) in the elderly population is cost-effective. The appropriateness of the use of available vaccines as well as citizens' knowledge and attitudes remain a challenge for a successful vaccination campaign. CONCLUSIONS: The results of this project provide decision-makers with important evidence on the aQIV and support with scientific evidence on the appropriate use of vaccines in the elderly.

Burden of the 1999-2008 seasonal influenza epidemics in Italy: comparison with the H1N1v (A/California/07/09) pandemic.

Despite preventive efforts, seasonal influenza epidemics are responsible for substantial morbidity and mortality every year worldwide, including developed countries. The A/H1N1v pandemic imposed a considerable healthcare and economic burden. In order to obtain an accurate estimate of the economic burden of influenza, and hence to guide policymakers effectively, systematic studies are necessary. To this end, data from epidemiological surveillance are essential. To estimate the impact of the 1999-2008 seasonal influenza epidemics and the H1N1v pandemic, we analyzed data from the Italian Influenza Surveillance System (CIRI NET). In the period 1999-2008, the Italian surveillance network consisted of sentinel general practitioners and pediatricians, who reported cases of Influenza-Like Illness (ILI) and Acute Respiratory Infections (ARI ) observed during their clinical practice from mid-October to late April each year; reports were sent to the Center for Research on Influenza and other Viral Infections (CIRI -IV). CIRI -IV receives data from 9 of the 20 Italian regions: Liguria, Abruzzo, Calabria, Friuli Venezia Giulia, Lombardy, Puglia, Sicily, Tuscany and Umbria. Previous estimates of influenza case costs were used in economic evaluations. Clinical-epidemiological and virological surveillance of the seasonal epidemics from 1999-2008 showed that the highest epidemic period was 2004-2005, when a new variant of the H3N2 influenza virus subtype emerged (A/California/07/04). Indeed, the highest peak of morbidity in the decade occurred in February 2005 (12.6 per 1,000 inhabitants). In 1999-2008, H1N1 subtype strains circulated and co-circulated with strains belonging to the H3N2 subtype and B type. Regarding B viruses in 2001-02, viruses belonged to the B/Victoria/02/07 lineage re-emerged, and in subsequent years co-circulated with viruses belonging to the B/Yamagata/lineage. The estimated costs of seasonal epidemics from 1999-2008 in Italy ranged from €15 to €20 billion, and the costs of the H1N1v pandemic ranged from €1.3 to €2.3 billion. This Italian study yields interesting conclusions: the results of influenza surveillance in several developed countries vary markedly; influenza imposes a considerable social, healthcare and economic burden; most cases that occurred during the pandemic involved subjects under 14 years of age and, although the clinical course of H1N1v influenza was usually mild, the related economic burden was heavy.

An overview on the implementation of HPV vaccination in Europe.

The discovery that the Human PapillomaVirus (HPV) is the necessary cause of cervical cancer has led to the development of prophylactic vaccines. Cervical cancer is the second most common cause of death from cancer among young women in Europe: mortality is still high, despite its important reduction due to screening programs for early detection. Besides cervical cancer, HPV is responsible for a significant proportion of other anogenital cancers and an increasing number of oropharyngeal cancers, representing together an at least equal burden compared to cervical cancer. HPV is also responsible for conditions such as condyloma acuminata (genital warts) and recurrent respiratory papillomatosis. Organized vaccination programs against HPV have the potential to prevent about 70% of cervical cancers and the vast majority of the other HPV-related conditions. Recommendations for HPV vaccination of at least one cohort of females have been issued in nearly all western European countries, and national/regional publicly funded vaccination programs have been introduced in most of them. Different approaches have been chosen for the implementation of HPV vaccination, based on the organization of each country's health care system. A brief outline of these programs in Europe is presented. As for all preventive public health interventions, high coverage of the target population with HPV vaccines pre-exposure is essential to achieve maximum reduction of cases: therefore, in order to obtain the maximum and most equitable coverage and future benefit, programs targeting adolescents before exposure to HPV should be preferred and population-based. Catch-up programs should also be implemented wherever possible, in order to deliver more and even earlier benefits, and effective communication strategies need to be adopted.

Safety and tolerability of bivalent HPV vaccine: an Italian post-licensure study.

One of the most important scientific discoveries of the last century was that persistent infection by some types of HPV is a precondition for the development of cervical cancer. The oncogenic types of HPV are also associated with other tumours (vaginal, vulvar and anal carcinomas, tumours of the head and neck, urethra and penis). Two preventive vaccines are currently available (Cervarix and Gardasil). Both have shown very good efficacy, safety and tolerability profiles. Nonetheless, extensive vaccination requires long-term monitoring of safety and tolerability. The aim of our study was to evaluate the safety and tolerability of the bivalent vaccine Cervarix in Italy. Every participant in the study completed a questionnaire after each dose of vaccine received, with a view to recording adverse events during the first 7 days after vaccination. We registered local (pain, redness, swelling) and systemic symptoms (fever, headache, myalgia, fatigue, arthralgia, itching, gastrointestinal disorders, rash and urticaria). A total of 4,643 subjects were recruited. In all, 7,107 questionnaires were collected: 3,064 after the first dose, 2,367 after the second and 1,676 after the third. No serious adverse events were observed. The most frequent local symptom was pain at the injection site, while fatigue, headache and myalgia were the most common systemic reactions. Pain was reported more frequently after the first dose than after the others, while all the other local and general symptoms were reported most frequently after the third dose. Almost all of the local and general reactions proved to be of negligible intensity and duration and required no medical intervention. Our results show better tolerability of the vaccine in comparison with the data from some controlled clinical studies and from other surveillance programmes conducted internationally. That tolerability proved to be better than in clinical studies could be explained by the absence of the typical apprehension felt by subjects involved in clinical experimentation.

No evidence of SARS-CoV-2 in hospitalized patients with severe acute respiratory syndrome in five Italian hospitals from 1st November 2019 to 29th February 2020.

BACKGROUND: On 9th January 2020, China CDC reported a novel coronavirus (later named SARS-CoV-2) as the causative agent of the coronavirus disease 2019 (COVID-19). Identifying the first appearance of virus is of epidemiological importance to tracking and mapping the spread of SARS-CoV-2 in a country. We therefore conducted a retrospective observational study to detect SARS-CoV-2 in oropharyngeal samples collected from hospitalized patients with a Severe Acute Respiratory Infection (SARI) enrolled in the DRIVE (Development of Robust and Innovative Vaccine Effectiveness) study in five Italian hospitals (CIRI-IT BIVE hospitals network) (1st November 2019 - 29th February 2020). OBJECTIVES: To acquire new information on the real trend in SARS-CoV-2 infection during pandemic phase I and to determine the possible early appearance of the virus in Italy. MATERIALS AND METHODS: Samples were tested for influenza [RT-PCR assay (A/H1N1, A/H3N2, B/Yam, B/Vic)] in accordance with the DRIVE study protocol. Subsequently, swabs underwent molecular testing for SARS-COV-2. [one-step real-time multiplex retro-transcription (RT) PCR]. RESULTS: In the 1683 samples collected, no evidence of SARS-CoV-2 was found. Moreover, 28.3% (477/1683) of swabs were positive for influenza viruses, the majority being type A (358 vs 119 type B). A/H3N2 was predominant among influenza A viruses (55%); among influenza B viruses, B/Victoria was prevalent. The highest influenza incidence rate was reported in patients aged 0-17 years (40.3%) followed by those aged 18-64 years (24.4%) and ≥65 years (14.8%). CONCLUSIONS: In Italy, some studies have shown the early circulation of SARS-CoV-2 in northern regions, those most severely affected during phase I of the pandemic. In central and southern regions, by contrast no early circulation of the virus was registered. These results are in line with ours. These findings highlight the need to continue to carry out retrospective studies, in order to understand the epidemiology of the novel coronavirus, to better identify the clinical characteristics of COVID-19 in comparison with other acute respiratory illnesses (ARI), and to evaluate the real burden of COVID-19 on the healthcare system.

Enhanced Passive Safety Surveillance (EPSS) confirms an optimal safety profile of the use of MF59® -adjuvanted influenza vaccine in older adults: Results from three consecutive seasons.

BACKGROUND: In Europe, the enhanced safety surveillance (ESS) of seasonal influenza vaccines is mandatory, in order to detect any potential increase in reactogenicity when the vaccine composition is updated. The MF59® -adjuvanted influenza vaccine (Fluad™) is the first and the only licensed adjuvanted seasonal influenza vaccine in Europe. OBJECTIVE: Our objective was to summarize the safety data of Fluad™ over three consecutive seasons. METHODS: A passive approach to ESS (EPSS) was adopted, in which reporting of spontaneous adverse events (AEs) by vaccinees and vaccine exposure was estimated, in order to generate a near real-time reporting rate. EPSS was conducted in Italy during the 2015, 2016, and 2017 influenza seasons in the primary care setting. All AEs reported within 7 days following immunization were analyzed by season, type and seriousness. Fisher's exact test was used to compare frequencies between seasons. RESULTS: Total exposure accounted for approximately 1,000 doses of Fluad™ for each season. A total of 0.5% (2015), 0.7% (2016), and 0.5% (2017) individual case safety reports (ICSRs) were received, corresponding to a total of 9 (2015), 18 (2016), and 12 (2017) spontaneous AEs. The frequencies of AEs of interest were below those expected on the basis of the known safety profile of the vaccine. Most AEs were mild-to-moderate in severity. No between-season difference was found. CONCLUSIONS: Our analyses confirmed that the safety data observed were consistent with the known safety profile of Fluad™, which has been amply established over the last 20 years. No significant changes in the safety profile were observed.

In-depth phylogenetic analysis of the hemagglutinin gene of influenza A(H3N2) viruses circulating during the 2016-2017 season revealed egg-adaptive mutations of vaccine strains.

Objectives: The authors conducted an in-depth phylogenetic analysis of the hemagglutinin (HA) gene of A(H3N2) identified during the 2016-2017 season to compare the circulating strains with both the egg-derived and cell-derived 2016-2017 candidate vaccine virus (CVV).Methods: 162 HA1 sequences of H3N2 viruses identified during the 2016-2017 season were phylogenetically analyzed and compared with egg-/cell-derived CVV. The predicted vaccine efficacy (pVE) of egg-/cell-derived CVV against field strains was quantified by Pepitope model.Results: All H3N2 belonged to 3C.2a genetic clade, most (80.2%) to 3C.2a1 sub-clade. Several H3N2 variants circulated in the 2016-2017 season. HA sequences of field H3N2 strains displayed greater identity with cell-derived CVV than with egg-derived CVV. The amino acid substitutions in positions 160 and 194 identified in egg-derived CVV affected the pVE, which was lower for egg-derived CVV than for cell-derived CVV.Conclusions: The results suggested that reduced vaccine effectiveness observed in 2016-2017 season was probably due to changes in the HA of vaccine strains acquired upon adaptation in eggs, which are the basis of most manufacturing systems currently used globally. Egg-free vaccine manufacturing systems would be advisable to improve the effectiveness of influenza vaccines.

Why the Anti-Meningococcal B Vaccination during Adolescence Should Be Implemented in Italy: An Overview of Available Evidence.

Although meningococcal disease has a low incidence in Italy, it is a public health concern owing to its high lethality rate and high frequency of transitory and/or permanent sequelae among survivors. The highest incidence rates are recorded in infants, children and adolescents, and most of the cases are due to Neisseria meningitidis B. In Italy, anti-meningococcal B (anti-MenB) vaccination is free for infants but, despite the considerable disease burden in adolescents, no national recommendation to vaccinate in this age-group is currently available. The aim of this study was to assess the main available scientific evidence to support the Italian health authorities in implementing a program of free anti-MenB vaccination for adolescents. We conducted an overview of the scientific literature on epidemiology, disease burden, immunogenicity and safety of available vaccines, and economic evaluations of vaccination strategies. Each case of invasive meningococcal disease generates a considerable health burden (lethality rate: 9%; up to 60% of patients experience at least one sequela) in terms of impaired quality of life for survivors and high direct and indirect costs (the mean overall cost of acute phase for a single case amounts to about EUR 13,952; the costs for post-acute and the long-term phases may vary widely depending of the type of sequela, reaching an annual cost of about EUR 100,000 in cases of severe neurological damage). Furthermore, vaccination against meningococcus B in adolescence proved cost-effective. The study highlights the need to actively offer the anti-MenB vaccination during adolescence at a national level. This would make it possible to avoid premature deaths and reduce the high costs borne by the National Health Service and by society of supporting survivors who suffer temporary and/or permanent sequelae.

Influenza Vaccination in Italian Healthcare Workers (2018-2019 Season): Strengths and Weaknesses. Results of a Cohort Study in Two Large Italian Hospitals.

BACKGROUND: Annual vaccination is the most effective way to combat influenza. As influenza viruses evolve, seasonal vaccines are updated annually. Within the European project Development of Robust and Innovative Vaccine Effectiveness (DRIVE), a cohort study involving Italian healthcare workers (HCWs) was carried out during the 2018-2019 season. Two aims were defined: to measure influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza cases and to conduct an awareness-raising campaign to increase vaccination coverage. METHODS: Each subject enrolled was followed up from enrollment to the end of the study. Each HCW who developed ILI was swabbed for laboratory confirmation of influenza. Influenza viruses were identified by molecular assays. A Cox regression analysis, crude and adjusted for confounding variables, was performed to estimate the IVE. RESULTS: Among the 4483 HCWs enrolled, vaccination coverage was 32.5%, and 308 ILI cases were collected: 23.4% were positive for influenza (54.2% A(H1N1) pdm09; 45.8% A(H3N2)). No influenza B viruses were detected. No overall IVE was observed. Analyzing the subtypes of influenza A viruses, the IVE was estimated as 45% (95% CI: -59 to 81) for A(H1N1) pdm09. CONCLUSIONS: Vaccination coverage among HCWs increased. Study difficulties and the circulation of drifted variants of A(H3N2) could partly explain the observed IVE.

Appropriateness and preferential use of different seasonal influenza vaccines: A pilot study on the opinion of vaccinating physicians in Italy.

In Italy, several types of influenza vaccine are on the market. Available evidence suggests that no single vaccine type is universally appropriate; rather, different types may be more appropriate for different population strata. However, while the concept of appropriateness/preferential use of single vaccines is usually adopted at the central level, little is known about the attitudes of physicians on the matter. A pilot survey of Italian physicians (N = 372) revealed that most (about 90%) were aware that the available vaccines were different, and that particular vaccines were more appropriate for specific groups. The availability of explicit guidelines on which vaccine to administer to a given population group was deemed desirable by 93.2% of respondents. The results were consistent with the 2018 Italian and UK normative documents, which indicate adjuvanted vaccines as the most appropriate choice for the elderly, and quadrivalent formulations for the younger age-classes. Public health policy implications are discussed.

Burden of rotavirus-associated and non-rotavirus-associated diarrhea among nonhospitalized individuals in central Italy: a 1-year sentinel-based epidemiological and virological surveillance.

A community sentinel pediatrician-based epidemiological and virological surveillance study was conducted to estimate the incidence of gastroenteritis and laboratory-confirmed rotavirus-associated disease. The 1-year cumulative incidence of gastroenteritis in the cohort of children aged 0-5 years was 21%, with the highest rates in the 7-12-month and 13-18-month age groups (41.1% and 41.7%, respectively). Approximately one-third of gastroenteritis cases requiring an office visit or telephone consultation were attributable to rotavirus infection.

Heterogeneous estimates of influenza virus types A and B in the elderly: Results of a meta-regression analysis.

Influenza has many age-dependent characteristics. A previous systematic review of randomized controlled trials showed that the detection rate of influenza B was higher in children than in non-elderly adults. However, no comprehensive reviews have targeted the elderly, who carry the main burden of disease. We aimed to quantify the relative detection rates of virus types A and B among the elderly, to identify factors affecting these proportions, and to compare type distribution among seniors and younger age-classes. A comprehensive literature search was conducted to identify multiseason studies reporting A and B virus type distributions in the elderly. A random-effects meta-analysis was planned to quantify the prevalence of type B among elderly subjects with laboratory-confirmed influenza. Meta-regression was then applied to explain the sources of heterogeneity. Across 27 estimates identified, the type B detection rate among seniors varied from 5% to 37%. Meta-analysis was not feasible owing to high heterogeneity (I2  = 98.5%). Meta-regression analysis showed that study characteristics, such as number of seasons included, hemisphere, and setting, could have contributed to the heterogeneity observed. The final adjusted model showed that studies that included both outpatients and inpatients reported a significantly (P = .024) lower proportion than those involving outpatients only. The detection rate of type B among the elderly was generally lower than in children/adolescents, but not non-elderly adults. Influenza virus type B has a relatively low detection rate in older adults, especially in settings covering both inpatients and outpatients. Public health implications are discussed.

A comprehensive analysis of Italian web pages mentioning squalene-based influenza vaccine adjuvants reveals a high prevalence of misinformation.

Squalene-based adjuvants have been included in influenza vaccines since 1997. Despite several advantages of adjuvanted seasonal and pandemic influenza vaccines, laypeople's perception of such formulations may be hesitant or even negative under certain circumstances. Moreover, in Italian, the term "squalene" has the same root as such common words as "shark" (squalo), "squalid" and "squalidness" that tend to have negative connotations. This study aimed to quantitatively and qualitatively analyze a representative sample of Italian web pages mentioning squalene-based adjuvants used in influenza vaccines. Every effort was made to limit the subjectivity of judgments. Eighty-four unique web pages were assessed. A high prevalence (47.6%) of pages with negative or ambiguous attitudes toward squalene-based adjuvants was established. Compared with web pages reporting balanced information on squalene-based adjuvants, those categorized as negative/ambiguous had significantly lower odds of belonging to a professional institution [adjusted odds ratio (aOR) = 0.12, p = .004], and significantly higher odds of containing pictures (aOR = 1.91, p = .034) and being more readable (aOR = 1.34, p = .006). Some differences in wording between positive/neutral and negative/ambiguous web pages were also observed. The most common scientifically unsound claims concerned safety issues and, in particular, claims linking squalene-based adjuvants to the Gulf War Syndrome and autoimmune disorders. Italian users searching the web for information on vaccine adjuvants have a high likelihood of finding unbalanced and misleading material. Information provided by institutional websites should be not only evidence-based but also carefully targeted towards laypeople. Conversely, authors writing for non-institutional websites should avoid sensationalism and provide their readers with more balanced information.