Safety of anti-varicella zoster virus vaccination in patients with multiple sclerosis treated with natalizumab: A case series.

The vaccination with live attenuated vaccines is generally not recommended during natalizumab (NTZ), as it is included among immunosuppressive/immunomodulating therapies. Nevertheless, considering the lack of evidence of a non-Central Nervous System (CNS) immunosuppressive effect of NTZ, after a risk/benefit evaluation, we decided to vaccinate four multiple sclerosis (MS) patients (three with an indication to switch to ocrelizumab for high-risk Progressive Multifocal Leukoencephalopathy (PML) and one for pregnancy planning). No vaccine-related adverse events of any type nor varicella zoster virus (VZV) infections were observed. To the best of our knowledge, these case series represent the first description of the good safety profile of anti-VZV vaccination in MS patients during NTZ treatment.

Cost-Effectiveness of Pneumococcal Vaccination in Adults in Italy: Comparing New Alternatives and Exploring the Role of GMT Ratios in Informing Vaccine Effectiveness.

In Italy, a sequential pneumococcal vaccination with conjugate vaccine (PCV) and polysaccharide vaccine (PPSV23) is recommended for individuals aged ≥ 65 years and those at risk for pneumococcal disease (PD) aged ≥ 6 years. The aim of this study was to assess the cost-effectiveness of the new vaccines, i.e., approved 15-valent and 20-valent PCVs. A published Markov model was adapted to evaluate the lifetime cost-effectiveness of vaccination with PCV15 + PPSV23 versus PCV13 + PPSV23, PCV20 alone, PCV20 + PPSV23, and No Vaccination. Simulated cohorts representing the Italian population, including individuals aged ≥ 65 years, those at risk aged 50-100 years, and those deemed high risk aged 18-100 years were assessed. Outcomes were accrued in terms of incremental PD cases, costs, quality-adjusted life years, life years, and the cost-utility ratio relative to PCV13 + PPSV23. The conservative base case analysis, including vaccine efficacy based on PCV13 data, showed that sequential vaccination with PCV15 or PCV20 in combination with PPSV23 is preferred over sequential vaccination with PCV13 + PPSV23. Especially in the high-risk group, PCV15 + PPSV23 sequential vaccination was dominant over No Vaccination and resulted in an ICUR of €3605 per QALY gained. Including PCV20 + PPSV23 into the comparison resulted in the domination of the PCV15 + PPSV23 and No Vaccination strategies. Additionally, explorative analysis, including the geometric mean titer (GMT) informed vaccine effectiveness (VE) was performed. In the low-risk and high-risk groups, the results of the GMT scenarios showed PCV15 + PPSV23 to be dominant over the other sequential vaccines. These findings suggest that if real-world studies would confirm a difference in vaccine effectiveness of PCV15 and PCV20 versus PCV13 based on GMT ratios, PCV15 + PPSV23 could prove a highly immunogenic and effective vaccination regime for the Italian adult population.

Sero-Epidemiological Study of Bordetella pertussis Infection in the Italian General Population.

A multicenter study was conducted to estimate the prevalence of pertussis IgG antibodies (anti-PTx) in the Italian population. Serum samples (4154) collected in the years 2019−2020 from subjects aged 6 to 90 years were tested. The anti-PTx IgG levels were determined by ELISA test. The limit of detection was 5 IU/mL (International Units per milliliter); values ≥ 40 IU/mL and ≥100 IU/mL indicate an infection that has occurred in recent years and a recent infection (occurred during the last year), respectively. The mean concentration of anti-PTx IgG antibodies in the tested samples was 13 IU/mL; 1.0% of subjects had a titer ≥ 100 IU/mL, 5.3% a titer between 40 and 100 IU/mL, and 38.9% a titer < 5 IU/mL. The mean antibody concentration was significantly higher in males than in females. The age group 25−39 years had the lowest percentage of negative subjects (36.9%) and the highest prevalence of subjects with antibody titers ≥ 100 IU/mL (1.3%). In the age group ≥ 65 years, the prevalence of subjects with titers between 40 and 100 IU/mL (6.7%) and the percentage of negative subjects (44.8%) was higher than in the other age groups. The results highlight the possible role of adolescents and adults in the transmission of B. pertussis.

Monitoring influenza vaccination coverage among healthcare workers during the COVID-19 pandemic: a three-year survey in a large university hospital in North-Western Italy.

Introduction: Healthcare workers (HCWs) are one of the highest priority groups recommended for seasonal influenza vaccination (SIV). Greater awareness of the importance of influenza vaccination was observed among HCWs after the start of the COVID-19 pandemic. The aim of this study was to analyze SIV coverage rates in the 2019-2020, 2020-2021 and 2021-2022 seasons among HCWs employed at the IRCCS Ospedale Policlinico San Martino in Genoa, in order to observe how coverage has changed since the COVID-19 pandemic began. Methods: A retrospective, single-center study was conducted among HCWs working at the IRCCS Ospedale Policlinico San Martino in Genoa. The vaccinated population was stratified by gender, age, qualification and area of activity, and the characteristics of vaccinated HCWs were analyzed. Results: While SIV coverage was below the recommended target in all seasons, a sharp increase was observed in 2020/2021 (12.8%; 40.9% and 23% in 2019/2020, 2020/2021 and 2021/2022, respectively). The mean and median age of vaccinees also increased during the 2020/2021 vaccination campaign (46.7 and 49 years, respectively) in comparison with the 2019/2020 season (43.5 and 45, respectively). In the 2019/2020 and 2021/2022 seasons, a higher proportion of vaccinees were physicians. Vaccinated females outnumbered males, but the coverage rate resulted greater in males than females in all three seasons. While a higher proportion of vaccinated subjects worked in medical areas, the most evident increase over the three years was seen among subjects working in the services area. Conclusions: This survey highlights the importance of studying the determinants that influence vaccination adherence and how the COVID-19 pandemic has affected SIV coverage.

Adverse Reactions after the Third Dose of the BNT162b2 mRNA COVID-19 Vaccine among Medical School Residents in a Regional Reference University Hospital in Italy.

The recent emergence of new variants of concern (VOCs) of SARS-CoV-2 and the uncertain duration of protection provided by the primary immunization cycle have highlighted the need for COVID-19 booster vaccinations. However, only a few studies have assessed the safety and reactogenicity profile of mRNA booster doses. Therefore, we conducted an online survey with the aim of assessing the adverse reaction profile in the 7 days following a third dose of the BNT162b2 vaccine in a population of resident physicians who had already been investigated after the primary vaccination. Among the 512 resident physicians (female = 53.2%, mean age = 29.8 years) invited to participate in the survey, 222 completed the survey (56.5% female, mean age of 29.9 years), with an average time from second to third dose of 8.6 months. The most common adverse reactions were local pain (88.3%), fatigue (58.1%), muscle/joint pain (44.1%), and headache (38.3%), all subsiding in 48-72 h. While the local reaction rate was similar to that following the first two doses, the systemic reactions were considerably less common and milder compared to the second vaccination. Nonetheless, over one third (36.1%) of participants reported interference with their normal activities. These results complement our previous findings and could aid occupational and public health professionals in the counselling of vaccinees.

Incidence of Hospitalisation and Emergency Department Visits for Pneumococcal Disease in Children, Adolescents, and Adults in Liguria, Italy: A Retrospective Analysis from 2012-2018.

Streptococcus pneumoniae infection is responsible for significant morbidity and mortality, particularly in young children and older adults. The aim of this study was to investigate the incidence of hospitalisation and emergency department (ED) visits in relation to episodes of pneumococcal disease (PD) following the introduction of pneumococcal conjugate vaccines (PCVs) into the Liguria region of Italy. Between 2012 and 2018, episodes of all-cause pneumonia (80,152), pneumococcal-specific pneumonia (1254), unspecified pneumonia (66,293), acute otitis media (AOM; 17,040), and invasive PD (IPD; 1788) were identified from in-patient claims, ED and hospital discharge records, and the Liguria Chronic Condition Data Warehouse. In children < 15 years of age, pneumococcal pneumonia-related hospitalisations decreased from 35 to 13 per 100,000 person-years during the study period (p < 0.001); this decrease is potentially related to PCV use in children. All-cause pneumonia hospitalisations remained stable, whereas IPD hospitalisations increased and AOM hospitalisations decreased. In adults, hospitalisations for all-cause pneumonia increased from 5.00 to 7.50 per 1000 person-years (+50%; p < 0.001). Pneumococcal and unspecified pneumonia hospital admissions increased significantly during the study period, considerably affecting those ≥ 65 years of age. IPD hospitalisations varied across all age groups, but a significant change was not observed. Despite pneumococcal vaccination, substantial burden remains for PD in children and adults in Liguria, Italy.

Vaccinations in patients with multiple sclerosis: a real-world, single-center experience.

Vaccines prevent infections in patients with multiple sclerosis (MS). Though recommendations regarding vaccinating patients with MS have been recently published, real-world data regarding vaccines' planning in patients receiving disease-modifying drugs (DMDs) for MS are missing. Our aim was, therefore, to describe vaccination coverage rates, timing-proposal and safety in real-life vaccinating patients with MS undergoing DMDs before the start of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination campaign. Patients followed at our MS-center were referred to individualized immunization-programs customized to Italian recommendations, patients' risks, immunity to exanthematic diseases, ongoing DMDs, or therapy-start urgency. Disease-activity stated the need for an essential immunization-cycle, whose core was composed by four vaccines: meningococcal-B, pneumococcal conjugated, Haemophilus influenzae B, and meningococcal-ACWY vaccines. Vaccines were administered prior to the planned DMD-start when possible, inactivated-vaccines >2 weeks and live-vaccines >4 weeks before treatment-start. Patients received a 6-months clinical-/radiological-follow-up after immunization. One-hundred and ninety-five patients were vaccinated between April 2017 and January 2021. 124/195 (63.6%) started a vaccination-program before therapy-start/-switch and 108/124 (87.1%) effectively completed immunization before new therapy-start without any delay. The time needed for immunization-conclusion reached a median of 27 (confidence interval 22) days in 2020. No increase in clinical-/radiological-activity 3-/6-months after immunization was noted. In conclusion, our study confirmed feasibility and safety of a vaccination-protocol in patients with MS whose duration resulted in a median of 27 days.

Systemic sclerosis and vaccinations: a three-year register-based cohort study about vaccination rate and uptake from Liguria referral center, northwest Italy.

Patients with diffused Systemic Sclerosis (dSSc) are more subject to severe respiratory complications with higher rates of intensive care unit (ICU) admission. Vaccination represents the most effective means of prevention and care for frail patients, such as SSc patients, preventing infections, reducing mortality and morbidity, and granting a better quality of life. Both vaccinations against seasonal influenza and Streptococcus pneumoniae are currently recommended by the European League Against Rheumatism (EULAR) guidelines on vaccination. The aim of this study is to give an updated analysis on S. pneumoniae and seasonal influenza vaccination coverage in a cohort of 91 patients with SSc and to investigate demographic and clinical variables significantly related to vaccine acceptance. The correlation between vaccine administration and other factors was investigated using a binomial logistic regression to evaluate the adjusted odds ratio (aOR). The patients followed up in this study reached higher percentages than the general population, passing the 75% target for both influenza and anti-pneumococcal vaccinations and reaching for influenza vaccine coverage rates of 83.8% for subjects undergoing immunosuppressive therapies and 88.9% for elderly subjects. For the latter group, it is important to emphasize the strong correlation between older age groups and vaccination acceptance.

Effect of the 2020/21 season influenza vaccine on SARS-CoV-2 infection in a cohort of Italian healthcare workers.

OBJECTIVES: Healthcare workers (HCWs) are a priority group for seasonal influenza vaccination (SIV). The 2020/21 SIV campaign was conducted during the second wave of the COVID-19 pandemic. Vaccines, including SIV, may exert non-specific protective effects on other infectious diseases which may be ascribable to the concept of trained immunity. The aim of this study was to explore the association between 2020/21 SIV and SARS-CoV-2 positivity in a cohort of Italian HCWs. METHODS: In this observational study, a cohort of HCWs employed by a large (ca 5000 employees) referral tertiary acute-care university hospital was followed up retrospectively until the start of the COVID-19 vaccination campaign. The independent variable of interest was the 2020/21 SIV uptake. Both egg-based and cell culture-derived quadrivalent SIVs were available. The study outcome was the incidence of new SARS-CoV-2 infections, as determined by RT-PCR. Multivariable Cox regression was applied in order to discern the association of interest. RESULTS: The final cohort consisted of 2561 HCWs who underwent ≥1 RT-PCR test and accounted for a total of 94,445 person-days of observation. SIV uptake was 35.6%. During the study period, a total of 290 new SARS-CoV-2 infections occurred. The incidence of new SARS-CoV-2 was 1.62 (95% CI: 1.22-2.10) and 3.91 (95% CI: 3.43-4.45) per 1000 person-days in vaccinated and non-vaccinated HCWs, respectively, with an adjusted non-proportional hazard ratio of 0.37 (95% CI: 0.22-0.62). E-values suggested that unmeasured confounding was unlikely to explain the association. CONCLUSIONS: A lower risk of SARS-CoV-2 infection was observed among SIV recipients.

Prevalence of Pneumococcal Serotypes in Community-Acquired Pneumonia among Older Adults in Italy: A Multicenter Cohort Study.

Pneumococcal community-acquired pneumonia (CAP) is a leading cause of mortality. Following the introduction of pneumococcal conjugate vaccines (PCVs) in children, a decrease in the burden of the disease was reported. In parallel, an increase in non-vaccine serotypes was also noted. The objective of this study was to assess the current serotype-specific epidemiology of pneumococci among Italian older adults hospitalized for CAP. A prospective study was conducted between 2017 and 2020 in four Italian regions. Subjects aged ≥65 years hospitalized with confirmed CAP were tested for pneumococci using both pneumococcal urinary antigen and serotype-specific urine antigen tests able to identify all 24 serotypes included in the available vaccines. Of the 1155 CAP cases, 13.1% were positive for pneumococci. The most prevalent serotypes were 3 (2.0%), 8 (1.7%), 22F (0.8 %) and 11A (0.7%). These serotypes are all included in the newly licensed PCV20. The serotypes included in PCV13, PCV15 and PCV20 contributed to 3.3%, 4.4% and 7.5% of the CAP cases, respectively. In the context of a low PCV13 coverage among older adults and a high PCV coverage in children, a substantial proportion of CAP is caused by PCV13 serotypes. Higher valency PCV15 and PCV20 may provide additional benefits for the prevention of CAP in vaccinated older adults.

Economic Burden of Pneumococcal Disease in Individuals Aged 15 Years and Older in the Liguria Region of Italy.

Despite the availability of vaccines against Streptococcus pneumoniae, the global incidence and economic cost of pneumococcal disease (PD) among adults is still high. This retrospective cohort analysis estimated the cost of emergency department (ED) visits/hospitalizations associated with non-invasive pneumonia and invasive pneumococcal disease among individuals ≥15 years of age in the Liguria region of Italy during 2012-2018. Data from the Liguria Region Administrative Health Databases and the Ligurian Chronic Condition Data Warehouse were used, including hospital admission date, length of stay, discharge date, outpatient visits, and laboratory/imaging procedures. A ≥30-day gap between two events defined a new episode, and patients with ≥1 ED or inpatient claim for PD were identified. The total mean annual number of hospitalizations for PD was 13,450, costing ~€49 million per year. Pneumonia accounted for the majority of hospitalization costs. The median annual cost of hospitalization for all-cause pneumonia was €38,416,440 (per-capita cost: €26.78) and was €30,353,928 (per-capita cost: €20.88) for pneumococcal and unspecified pneumonia. The total number and associated costs of ED visits/hospitalizations generally increased over the study period. PD still incurs high economic costs in adults in the Liguria region of Italy.

Current Take on Systemic Sclerosis Patients' Vaccination Recommendations.

Systemic sclerosis (SSc) is a rare autoimmune inflammatory rheumatic disease. The prevalence of SSc ranges from 7 to 700 cases per million worldwide. Due to multiple organ involvement and constant inflammatory state, this group of patients presents an increased risk of infectious diseases. This paper aimed to gather the up-to-date evidence on vaccination strategies for patients with SSc and to be a useful tool for the prevention and management of infectious diseases. The authors conducted a scoping review in which each paragraph presents data on a specific vaccine's safety, immunogenicity, and efficacy. The work deals with the following topics: SARS-CoV-2, seasonal influenza, S. pneumoniae, HAV, HBV, HZV, N. meningitidis, H. influenzae, HPV, and diphtheria-tetanus-pertussis.

Reactogenicity of BNT162b2 mRNA COVID-19 Vaccine in a Young Working Age Population: A Survey among Medical School Residents, within a Mass Vaccination Campaign, in a Regional Reference Teaching Hospital in Italy.

Vaccinations are a key prevention measure in fighting the COVID-19 pandemic. The BNT162b2 mRNA vaccine (BioNTech/Pfizer), the first to receive authorization, was widely used in the mass vaccination campaign in Italy. Healthcare workers were identified as a priority group for vaccination, but few studies have assessed its reactogenicity among the young working age population. An online survey was conducted to investigate the adverse reactions occurring in the 7 days following the first and second vaccination doses amongst resident doctors of the University of Genoa, employed at the IRCCS Ospedale Policlinico San Martino of Genoa, between 11 January and 16 March 2021. A total of 512 resident physicians were invited to participate in the study (female = 53.2%; mean age = 28.9 years), of whom 296 (female = 53.4%, mean age = 28.9 years) and 275 (female = 55.3%, mean age = 29.1 years) completed the survey after their first and second vaccination doses, respectively. In the 7 days following the first dose, most common adverse reactions were local pain (96.3%), fatigue (42.6%), headache (33.8%), arthromyalgia (28.0%), and 5.1% reported fever, while following the second dose, participants reported local pain (93.5%), fatigue (74.9%), headache (57.5%), arthromyalgia (58.2%), and fever (30.9%), with a higher prevalence among females. Systemic (but not local) reactions increased following the second vaccination, reaching severe intensity in 9.8% of participants and causing three or more events of moderate intensity in 23.7% of participants. Adverse reactions preventing regular daily activities could cause absenteeism among workers. These results can be useful to inform populations of young individuals, set expectations, and improve adherence to vaccination campaigns.

Recommendations of the Italian society for infectious and tropical diseases (SIMIT) for adult vaccinations.

Vaccination prevents 2-3 million deaths worldwide every year. Nevertheless, vaccine-preventable diseases (VPDs) still cause a considerable number of deaths especially in subjects belonging to "risk groups." These are represented by older adults, immunocompromised individuals and all subjects with underlying chronic medical conditions (cardiovascular, pulmonary, renal and liver chronic diseases, diabetes, immunodeficiency disorders). They have a weaker immune system and, if infected, are more likely to develop severe complications of their condition or of the preventable-infectious disease. This document summarizes the recommendations for vaccination of the main Global Institutional Organizations and analyses the risks of comorbidities associated with infectious disease and the benefits of vaccination for each specific group. The document provides a clear, practical and authoritative guide to adult vaccination.

Health Communication in COVID-19 Era: Experiences from the Italian VaccinarSì Network Websites.

In 2013, in a bid to combat Vaccine Hesitancy (VH) and provide information on vaccines by communicating with the general public and the health community (e.g., healthcare workers and public health operators), the Italian Society of Hygiene and Preventive Medicine (S.It.I.) published the national website "VaccinarSì". The project was subsequently extended to ten Italian Regions. This led to the creation of the VaccinarSì Network, whose websites are publicly owned. The aim of this work was to present the framework of the websites of the VaccinarSì Network and to analyse user behaviour in the pre-COVID-19-era (dating from each website's publication until 31 January 2020) and in the COVID-19-era (from 1 February 2020 to 31 January 2021). Some metrics such as the number of visits to the site (sessions, number of users and average session duration), user behaviour (pages viewed, bounce rate and organic search) and the session acquisition path (direct traffic, referrals and social traffic) were searched, extrapolated and processed with Google Analytics. Qualitative and normally distributed quantitative variables were summarised with their absolute (relative) frequencies and means. Statistical differences between the means of the two periods were evaluated through paired t-test. A two-tailed p-value less than 0.05 was considered to be statistically significant. When the total values recorded over the period were compared, an overall increase in metrics was observed-the number of individual users, visits and individual pageviews rose in a statistically significant way. Our study aimed to highlight how combining disciplines such as health education and digital communication via Information and Communication Technologies (ICT) represents the best strategy to support citizens. This approach gives them the tools to become independent and responsible players that are capable of voluntarily and consciously choosing to adhere to vaccination programs. The VaccinarSì Network's goal for the future is to reach an even wider audience. By building each user's critical knowledge, this network enables users to be active components of a wider, more empowered community.

Will vaccine hesitancy compromise our efforts to face the next SARS-CoV-2 epidemic wave?

We have checked the vaccination history of 389 elderly patients (62.9% males, mean age of 78.5 + 8.4 years) hospitalized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. Information regarding pneumococcal vaccination was available for 354 patients (91.0%): the overall vaccination coverage rate (VCR) was 19.8% (70/354), 11.3% received only 13-valent pneumococcal conjugate vaccine (PCV13), 3.4% were immunized with 23-valent pneumococcal polysaccharide vaccine (PPSV23), 5.1% received both vaccines. VCR among the elderly population in Liguria Region was 26.2% (118,581/453,082), among them 13.7% received PCV13, 12.4% were immunized with at least one dose of PPSV23. Regarding the 2019-2020 influenza season vaccination data were available for 46 patients: 59% of them were immunized. VCR in the elderly population was 51.7% (234,153/453,082).

The seedbeds of Tuberculosis: is it time to target congregate settings and workplaces?

Countries where the incidence of Tuberculosis (TB) is low display a low transmission rate in the general population, and this rate has progressively declined in recent decades; however, TB epidemiology has shown a shift of the disease burden from the general population to specific populations at higher risk, such as vulnerable individuals and hard-to-reach groups. In low-incidence countries, preventive and therapeutic strategies must therefore be geared towards targeted interventions in these populations, with the priority being to promptly identify and treat latent tuberculosis infection (LTBI) rather than manage infectious cases. One of the most complex challenges in this area is to identify population subgroups with increased incidence/prevalence of LTBI/TB. The aim of this study was to provide a concise overview of the main studies and available evidence concerning the epidemiology of TB and LTBI in non-healthcare congregate settings, with specific emphasis on studies conducted in occupational settings and workplaces. Recognizing settings at increased risk might contribute to eliminating TB in low-incidence countries, a challenge which requires tailored responses. Occupational and preventive medicine has a major role to play in directing ad hoc policies and programs of LTBI surveillance. If TB is to be eradicated, it is essential to contain the seedbeds of infection: indeed, as long as a large reservoir of infected subjects exists, new active TB cases may arise at any time.

Systemic Sclerosis and Vaccinations: A Register-Based Cohort Study about Seasonal Influenza and Streptococcus pneumoniae Vaccination Rate and Uptake from Liguria Regional Center, Northwest Italy.

Systemic sclerosis (SSc) is the connective tissue disease with the highest mortality and patients with chronic inflammatory immune-mediated diseases are at high risk of acquiring infections as they are often treated with immunosuppressive or biological drugs. This study, conducted among the patients followed by our clinical immunology, part of the Internal Medicine Department in the Ospedale Policlinico San Martino, Genoa, northwest Italy, has set itself the primary objective of analyzing the vaccine uptake and the vaccination coverage against both seasonal influenza and S. pneumoniae in a cohort of patients with SSc. We evaluated the influenza and pneumococcal vaccination rate among various subgroups of patients and the source of the recommendation for vaccination. We evaluated the vaccination rate changes between the two years considered in our study. We also calculated a binomial logistic regression between vaccination acceptance and clinical and demographics characteristics of the patients to evaluate the adjusted odds ratio (OR) of each factor on vaccination. The vaccination coverage that resulted was significantly higher than in other similar studies. Age over 65 years old, interstitial lung disease, and ongoing immunosuppressive therapy were significantly related with acceptance to both vaccinations using univariate analyses, but the multivariate logistic regression found a significant correlation only with the age and therapy factors.