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Vaccinations against Streptococcus pneumoniae are included in infant immunization programs globally. However, a substantial burden due to pneumococcal disease (PD) remains. This study aimed to estimate the cost of emergency department (ED) visits and hospitalizations associated with invasive pneumococcal disease, all-cause pneumonia, and acute otitis media in children <15 years of age in the Liguria region of Italy between 2012 and 2018. The retrospective cohort study used data from the Liguria Region Administrative Health Databases and the Ligurian Chronic Condition Data Warehouse, which contain information on hospital stays, outpatient visits, laboratory/imaging techniques, surgical procedures, and pharmaceutical prescriptions. Patients with one or more ED or inpatient claim for PD (based on International Classification of Diseases, Ninth Revision, Clinical Modification codes) were included. Cost of ED visits and hospitalizations were estimated from the diagnosis-related group system and procedures performed in the ED. In Ligurian children <15 years of age during 2012-2018, the median annual number of hospitalizations plus ED visits due to PD was 4,009, and the median estimated annual cost was €3.6 million. All-cause pneumonia accounted for the majority of hospitalization costs during the study period. Number and costs of ED visits and hospitalizations increased from 2012 to 2018. Despite widespread infant immunization in Liguria, economic costs due to PD-associated ED visits and hospitalizations remained high in children 0-14 years of age.

Objective: we estimated the epidemiological and budget impact of lowering the recommended age for influenza immunization with quadrivalent vaccine actively offered and administered free of charge to persons over 50 years old by public immunization services., Methods: a multi-cohort, deterministic, static Markov model was populated by real-world data on the clinical and economic impact of Influenza-Like Illness and Lower Respiratory Tract Infection over 1 year. Four scenarios featuring different vaccine coverage rates were compared with the base case; coverage rates in subjects with and without risk factors were considered separately., Results: compared with the base case, adopting scenarios 1-4 would reduce the annual number of influenza cases by 6.5%, 10.8%, 13.8% and 3.4%, Emergency Department accesses by 10.7%, 9.1%, 15.4% and 4.6%, complications by 8.9%, 9.9%, 14.7% and 4.1%, and the hospitalization of complicated cases by 11%, 9.1%, 15.4% and 4.5%, respectively. The four scenarios would require an additional investment (vaccine purchase and administration) of €316,996, €529,174, €677,539, and €168,633, respectively, in comparison with the base case. Scenario 1 proved to be cost-saving in the 60-64-year age-group. The incremental costs of implementing the other hypothetical scenarios ranged from 2.7% (scenario 4) to 13.2% (scenario 3)., Conclusions: lowering the recommended age for influenza vaccination to 60 years would allow a high proportion of subjects at risk for severe influenza to be reached and would save money.

Introduction: Influenza occurs worldwide and causes significant disease burden in terms of morbidity, associated complications, hospitalizations, and deaths. Vaccination constitutes the primary approach for controlling influenza. Current influenza vaccines elicit a strain-specific response yet occasionally exhibit suboptimal effectiveness. This review describes the limits of available immunization tools and the future prospects and potentiality of universal influenza vaccines., Areas Covered: New 'universal' vaccines, which are presently under development, are expected to overcome the problems related to the high variability of influenza viruses, such as the need for seasonal vaccine updates and re-vaccination. Here, we explore vaccines based on the highly conserved epitopes of the HA, NA, or extracellular domain of the influenza M2 protein, along with those based on the internal proteins such as NP and M1., Expert Opinion: The development of a universal influenza vaccine that confers protection against homologous, drifted, and shifted influenza virus strains could obviate the need for annual reformulation and mitigate disease burden. The scientific community has long been awaiting the advent of universal influenza vaccines; these are currently under development in laboratories worldwide. If such vaccines are immunogenic, efficacious, and able to confer long-lasting immunity, they might be integrated with or supplant traditional influenza vaccines.

Influenza A and B viruses are responsible for respiratory infections, representing globally seasonal threats to human health. The 2 viral types often co-circulate and influenza B plays an important role in the spread of infection. A 6-year retrospective surveillance study was conducted between 2010 and 2016 in 2 large administrative regions of Italy, located in the north (Liguria) and in the south (Sicily) of the country, to describe the burden and epidemiology of both B/Victoria and B/Yamagata lineages in different healthcare settings. Influenza B viruses were detected in 5 of 6 seasonal outbreaks, exceeding influenza A during the season 2012-2013. Most of influenza B infections were found in children aged ≤ 14 y and significant differences were observed in the age-groups infected by the different lineages. B/Victoria strains prevailed in younger population than B/Yamagata, but also were more frequently found in the community setting. Conversely, B/Yamagata viruses were prevalent among hospitalized cases suggesting their potential role in the development of more severe disease. The relative proportions of viral lineages varied from year to year, resulting in different lineage-level mismatch for the B component of trivalent influenza vaccine. Our findings confirmed the need for continuous virological surveillance of seasonal epidemics and bring attention to the adoption of universal influenza immunization program in the childhood. The use of tetravalent vaccine formulations may be useful to improve the prevention and control of the influenza burden in general population.

In order to estimate the burden of influenza and to describe the genetic evolutionary pattern and antigenic variability of type B viral strains, data deriving from 3 surveillance systems active in Liguria region, Northern Italy, were described. Since the re-emergence of the Victoria lineage in 2001, the clinical-epidemiological and syndromic surveillances demonstrated the heavy burden of influenza like illness (ILI) syndrome. Focusing on type B influenza virus, it predominated or played a relevant epidemic role in the 50% of the evaluated influenza seasons. Furthermore, the virologic surveillance demonstrated the frequent co-circulation of both lineages an heterogeneous circulation of different influenza B strains, determining a partial or complete mismatch in at least 6 influenza seasons. The undemonstrated cross-reactivity between lineages and the unpredictability of predominant lineage arose the scientific debate about the opportunity to include the quadrivalent influenza vaccine among the preventive tools to improve the protection against type B viruses. The integration of different surveillance systems highly contribute to estimate the poorly evaluated burden of type B influenza virus and help to find variants to include in the vaccine formulation.

Influenza is a highly contagious respiratory acute viral disease which imposes a very heavy burden both in terms of epidemiology and costs, in the developed countries as well as in the developing ones. It represents a serious public health concern and vaccination constitutes an important tool to reduce or at least mitigate its burden. Despite the existence of a broad armamentarium against influenza and despite all the efforts and recommendations of international organisms to broaden immunization, influenza vaccination coverage is still far from being optimal. This, taken together with logistic and technical difficulties that can result into vaccine shortage, makes intra-dermal (ID) vaccines, such as Fluzone® ID and Intanza®, particularly attractive. ID vaccines are comparable and, in some cases, superior to intra-muscular/sub-cutaneous vaccines in terms of immunogenicity, safety, reactogenicity, tolerability and cross-protection profiles, as well as in terms of patient preference, acceptance and vaccine selection. Further advances, such as Fluzone® ID with alternative B strains and Quadrivalent Fluzone® ID or the possibility of self-administering the vaccines, make influenza ID vaccines even more valuable.

Rapid population aging has become a major challenge in the industrialized world and progressive aging is a key reason for making improvement in vaccination a cornerstone of public health strategy. An increase in age-related disorders and conditions is likely to be seen in the near future, and these are risk factors for the occurrence of a number of vaccine-preventable diseases. An improvement in infectious diseases prevention specifically aimed at adults and the elderly can therefore also decrease the burden of these chronic conditions by reducing morbidity, disability, hospital admissions, health costs, mortality rates and, perhaps most importantly, by improving the quality of life. Among adults, it is necessary to identify groups at increased risk of vaccine-preventable diseases and highlight the epidemiological impact and benefits of vaccinations using an evidence-based approach. This document provides clinical practice guidance on immunization for adults in order to provide recommendations for decision makers and healthcare workers in Europe. Although immunization is considered one of the most impactful and cost-effective public health measures that can be undertaken, vaccination coverage rates among adults are largely lower than the stated goal of ≥ 95% among adults, and stronger efforts are needed to increase coverage in this population. Active surveillance of adult vaccine-preventable diseases, determining the effectiveness of the vaccines approved for marketing in the last 5 y, the efficacy and safety of vaccines in immunocompromised patients, as well as in pregnant women, represent the priorities for future research.

Systemic Lupus Erythematosus (SLE) is characterized by abnormal autoantibody production and clearance. Infections are among the most important causes of morbidity and mortality in SLE patients; they have an increased frequency of severe bacterial and viral infections possibly due to inherited genetic and immunologic defects and to immunosuppressive therapies. In addition, infectious agents can switch on lupus disease expression and activity. Among the strategies to reduce the risk of infection, vaccination can be considered the most reliable option. Most vaccines are effective and safe in SLE patients, although in certain cases immunogenicity may be sub-optimal and vaccination can trigger a flare. Although these issues are currently unresolved, the risk benefit balance is in favor for vaccination to reduce the risk of infection in SLE patients. In the present review we discuss the preventive strategies currently recommended to reduce bacterial and viral infections in SLE.

Influenza vaccination is a fundamental tool for the prevention of influenza in healthcare settings and its administration to healthcare workers (HCWs) is recommended in more than 40 countries including United States of America and many countries of the European Union. Despite these recommendations, the compliance of HCWs to influenza vaccination is largely inadequate in Italy. Since 2005/06 season, a comprehensive multifaceted intervention project aimed at increasing the seasonal influenza vaccination coverage rates among HCWs was performed at the IRCCS AOU San Martino IST teaching hospital in Genoa, Italy, the regional tertiary adult acute-care reference center with a 1300 bed capacity. Despite almost a decade of efforts, the vaccination coverage rates registered at our hospital steadily remain unsatisfactory and very distant by the minimum objective of 75% defined by the Italian Ministry of Health. During the last influenza season (2013/14), vaccination coverage rates by occupation type resulted 30% among physicians, 11% among nurses and 9% among other clinical personnel.   Further efforts are necessary to prevent the transmission of influenza to patient and novel strategies need to be identified and implemented in order to increase the compliance of HCWs, particularly nurses, with the seasonal influenza vaccination.

Liguria, an administrative region in northern Italy characterized by a decade of high PCV coverage in paediatric age group, has issued new PCV13 recommendations for free active immunization in adults with risk factors and subjects aged ≥ 70 years old. Main aims of this study are: (1) a descriptive epidemiology of the clinical burden of lower respiratory tract infections (LRTI) in adults ≥18 years of age; and (2) a crossover evaluation of the effect of introduction of PCV13 vaccination in adults aged ≥70 years old, in terms of ED accesses for LRTI, obtained by a Syndrome Surveillance System (SSS). The ED access, chief complaint based SSS will allow an active surveillance of a population cohort of >430 000 individuals resident in Genoa metropolitan area, aged ≥18 years old, for a period of 60 months. During pre-PCV period, annual cumulative incidence of ED accesses for LRTI was equal to 7/1000 and 2% in ≥65 and ≥85 year adults, respectively. In ≥65 years adults, more than 70% of subjects identified by the SSS has at least one risk condition, with a peak of 87% in ≥85 year cohort. New Ligurian PCV13 recommendations can potentially reach more than 75% of ED accesses for LRTI. Data highlights the heavy impact of LRTI in terms of ED accesses, especially in the elderly and subjects with chronic conditions and the usefulness of SSS tool for monitoring PCV vaccination effect.

This clinical driven report describes the unexpected detection of a multidrug resistant (MDR) Streptococcus pneumoniae strain. Italy is usually considered a country characterized by a low prevalence of MDR S. pneumoniae. We describe the occurrence of bacterial meningitis sustained by a MDR S. pneumoniae strain in Italy. The first-line treatment was started with ceftriaxone and dexamethasone, but after the identification of such a resistant strain a second-line regimen was needed. The new regimen was chosen on both susceptibility and pharmacokinetic criteria. Linezolid and levofloxacin were started and a dramatic improvement was observed. A more sensitive anamnesis revealed some elements known to be associated to a MDR S. pneumoniae occurrence (immunesuppression, former antibiotic therapy). So this case should pinpoint our attention on risk factors of MDR for a careful choice of antibiotic therapy in serious pneumococcal infections.

In the present study we first compare immunogenicity against vaccine and heterologous circulating A(H1N1)pdm09 strains, tolerability and safety of intradermal Intanza 15 μg and of virosomal adjuvanted, intramuscularly delivered influenza vaccine, Inflexal V, in healthy elderly volunteers. Five-hundred participants were enrolled in the study and randomly assigned to the two vaccine groups to receive either one dose of Intanza 15 μg or Inflexal V vaccine. All subjects reported solicited local and systemic reactions occurred within 7 d after vaccination and unsolicited adverse events up to 21 d post-immunization and any serious adverse event appeared during the study. A subset of 55 participants was randomly selected for immunogenicity and cross-protection evaluations. Serum samples were collected before and 1 and 3 mo after immunization. Antibody responses were measured using hemagglutination inhibition (HI) against all viruses used in the study and neutralization (NT) assays against A(H1N1)pdm09 strains. At least one of the CHMP criteria for influenza vaccine approval in the elderly was met by virosomal vaccine against all the tested viruses; intradermal vaccine met all criteria against all strains. Several parameters of immune response against strains with a different antigenic pattern from that of vaccine A/California/04/09(H1N1)pdm09 were significantly higher in the intradermal vaccine group compared with the virosomal group. Safety and systemic tolerability of both vaccines were excellent, but injection site reactions occurred significantly more frequently in the intradermal vaccination group. Immunogenicity of Intanza 15 μg intradermal vaccine tended to be higher than that of Inflexal V against heterologous strains in healthy elderly.

Antigenic drift, the evolutionary mechanism of influenza viruses, results in an increased susceptibility of vaccinated subjects against circulating viruses. New vaccines able to grant a broader and cross-reactive immune response against drifted influenza variants are needed. Several strategies were explored to enhance the immunogenicity of plain vaccines: adjuvants, carriers and intradermal administration of influenza vaccine emerge as a promising options. To evaluate the ability of a MF59-adjuvanted and intradermal influenza vaccine to elicit an effective antibody response against circulating viruses presenting antigenic patterns different from those of the vaccine strains, we compared antibody responses elicited by "implemented" vaccines and conventional intramuscular trivalent inactivated vaccine against heterologous circulating influenza A viruses. Different studies, simulating different epidemiological pictures produced by the natural antigenic drift of seasonal influenza viruses, highlighted the superior cross-reactivity of the antibodies elicited by MF59 and intradermal vaccines, compared with subunit or split vaccine against heterologous viruses.

A serial cross-sectional study of nasopharyngeal carriage among adults aged 60 y or over was conducted in winter-spring 2012 with the aim to describe circulating Streptococcus pneumoniae in an area, Liguria Administrative Region, where the vaccine was implemented for a decade and coverage in pediatric age group reached a value close to 100% for more than 5 y, determining a picture of very high vaccine immunological pressure. The serotype-specific carriage picture in adults was compared with that observed in children by means of a cross-sectional study performed one year before using the same sampling and laboratory methods.   Cluster sampling enrolled 283 adults, representative of the open population. Detection of multi-serotype carriage was performed using, real-time PCR and primer specific PCRs. Carriage prevalence of participants with at least one positive sample adjusted for age, i.e., period prevalence, was 18.7%, considering the Ligurian population as standard population, showing that the pneumococcal carriage in the elderly is not a rare event as emerged in other surveys. The long-term use of PCV7 has resulted in strong decrease of vaccine types carriage among adults and children. A multivariate analysis showed that age class and contact with children attending day care covariates were strongly associated with Streptococcus pneumoniae carriage. A strong link between the picture observed in < 5-y-old children and ≥ 60-y-old adults emerged: a strong correlation of specific-serotype prevalence between adults and children and risk factor analysis supported the role played by inter-age-group transmission.

This study evaluated safety, tolerability and immunogenicity of intradermal (ID) trivalent inactivated split influenza vaccine, with a lower antigen content (9 mcg HA per strain) than the conventional intramuscular one (15 mcg), in HIV-1-infected adults younger than 60 years. A total of 54 HIV-1-positive participants were enrolled and randomly assigned to receive a single dose of either ID-administered low-antigen-content split inactivated vaccine or intramuscularly-administered (IM) standard-dose inactivated split vaccine. Subjects were provided with a diary to monitor any local and/or systemic reactions to the vaccine for 7 days following vaccination. Serum samples were collected before, 28 days and 90 days after immunization. The plasma HIV-RNA and CD4+ T-lymphocyte count were checked at day 0 and day 90. Serum hemagglutination-inhibition (HI) activity for the three influenza strains included in the vaccine composition was measured to assess the antibody response at one month and 3 months after vaccination. Both vaccines showed optimal safety and tolerability profiles. All the three Committee for Medicinal Products for Human Use immunogenicity criteria for vaccine approval in adults younger than 60 were met by both vaccines against A(H1N1) and A(H3N2) viruses. Both vaccines met mean-fold-increase and seroprotection criteria but failed seroconversion criteria against B virus. No difference in terms of post-vaccination geometric mean titers, mean fold increase, seroprotection and seroconversion rates were found comparing ID and IM vaccines. In conclusion, the recently available low-antigen-content ID vaccine is safe, well-tolerated and as immunogenic as IM standard-dose influenza vaccine.

Among the several strategies explored for (1) the enhancement of the immune response to influenza immunization, (2) the improvement of the vaccine acceptability and (3) the overcoming of the egg-dependency for vaccine production, intradermal administration of influenza vaccine emerges as a promising alternative to conventional intramuscular route, thanks to the recent availability of new delivery devices and the perception of advantages in terms of immunogenicity, safety, reduction of antigen content and acceptability. Data from clinical trials performed in children, adults < 60 y and elderly people and post-marketing surveillance demonstrate that actually, licensed intradermal influenza vaccines, Intanza™ 9 and 15 µg and Fluzone™ Intradermal, administered by the microinjection system Soluvia™, show an excellent acceptability, tolerability and safety profile. Formulations containing 9 and 15 μg per strain demonstrate, respectively, comparable and superior immunogenicity than conventional intramuscular vaccines. Licensed intradermal influenza vaccines can be considered a valid alternative to standard intramuscular vaccination offering significant advantages in low-responder populations and helping to increase influenza vaccination coverage rates especially in people with fear of needles or high apprehension associated with annual vaccination.

On May 9 2011, the US FDA approved Sanofi Pasteur's Fluzone(®) Intradermal influenza vaccine, the first influenza vaccine licensed in the USA that uses a new microinjection system for intradermal delivery of vaccines (Soluvia™, Becton Dickinson). Its antigen content is lower (9 µg hemagglutinin per strain) than the conventional intramuscular vaccine (15 µg) and it is indicated for active immunization of adults aged between 18 and 64 years. Data from the clinical trial assessing immunogenicity and safety of Fluzone Intradermal in adults were consistent with substantial experience accumulated with Intanza(®) 9 µg, the intradermal vaccine licensed on February 26 2009 and launched during the 2010/2011 season in Europe. Fluzone Intradermal is safe and its immunogenicity comparable with that of conventional intramuscular vaccines. Obtaining optimal acceptability of intradermal vaccines may represent an additional asset to help increase the coverage of influenza vaccination in young adults.

Introduction: The main public health strategy for reducing the influenza burden is annual vaccination. However, because the immune response in the elderly and frail subjects is known to be less vigorous than in younger adults, novel strategies have been explored in the last decade to augment immune response after immunization. These have included an increased dosage, multiple dose vaccinations, use of vaccine adjuvants and more efficient routes of vaccine delivery., Areas Covered: This review discusses recent advances in intradermally administered influenza vaccines with particular attention to immunogenicity and safety data from clinical trials performed using appropriate injection systems which, combining consistent injection depth and volume, safety, simplicity and ease-of-use, allowed large scale evaluation., Expert Opinion: Substantial experience has been accumulated with Intanza® 9 and Intanza 15 μg/IDflu® 15 μg, administered using BD's Soluvia™ device, and are the first intradermal trivalent inactivated split-virion influenza vaccines to be licensed for use in 18 - 59 year adults and in elderly people, respectively. Clinical data showed that they are safe and immunogenic and can offer significant advantages in terms of higher acceptability, higher immunogenicity in the elderly and dose-sparing in adults younger than 60 years when compared with intramuscularly administered vaccine.

Importance of the Field: Vaccination is universally considered as the most effective tool for the prevention of influenza, which represents a significant burden, both from a health-care and a socio-economic viewpoint. Conventional non-adjuvanted vaccines have shown suboptimal immunogenicity in the elderly, in patients with serious chronic diseases or the immunocompromised and in young children. The protection offered by non-adjuvanted vaccines may be further reduced by periodic antigenic drifts., Areas Covered in This Review: Between the several strategies proposed to address the need for more immunogenic vaccines than the conventional ones, the most successful strategy is represented by the use of adjuvants. Since 1997, an MF59-adjuvanted subunit influenza vaccine has been licensed in several countries and used in the elderly worldwide. Available data on the safety, immunogenicity and effectiveness of this vaccine have been reported and discussed in details., What the Reader Will Gain: The MF59-adjuvanted vaccine has been shown to enhance immunogenicity and to confer cross-reactivity against heterologous influenza viral strains in the elderly, in adults with serious underlying medical conditions and in healthy infants and young children. Furthermore, its effectiveness has been demonstrated in older adults, reducing hospitalizations for pneumonia, cardiovascular and cerebrovascular diseases., Take Home Message: The vaccine is safe, with an acceptable tolerability profile, thus representing a valid option to optimize the control of seasonal influenza.

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a leading pathogen causing nosocomial infections. Many studies have shown that the restricted use of antibacterials is associated with a decline in resistance. To establish whether an intervention protocol designed to limit the use of cephalosporins can lower mRSA infection rates and impact on Gram-negative bacteria susceptibility in an intensive Care Unit (ICU), we conducted a prospective, non-randomized, before-after intervention study in an 18-bed ICU in Genoa, Italy. The intervention was a hospital antibiotic control policy and the observation was routine monitoring for nosocomial infections and antibiotic use, recording periodically the incidence density and MRSA prevalence. The intervention included a new antibiotic guideline that restricted the use of cephalosporins for all ICU inpatients. The analysis showed that the intervention determined a significant reduction in cephalosporin usage (-70.3%), while fluoroquinolones, mainly ciprofloxacin, increased after introduction of the antibiotic policy (+46.5%). A significant reduction in the percentage of MRSA infections (-30%) and heterogeneous susceptibility patterns in Klebsiella pneumoniae and Pseudomonas aeruginosa were noted.