The First 30 Years of the Universal Hepatitis-B Vaccination-Program in Italy: A Health Strategy with a Relevant and Favorable Economic-Profile

In 1991, Italy was one of the first countries worldwide to introduce a universal hepatitis-B vaccination for children. Since then, epidemiological data have clearly demonstrated the huge clinical benefits of the vaccination. The aim of this study was to update the favorable economic impact of the hepatitis B virus (HBV) vaccination, 30 years after its implementation. A mathematical model was developed to simulate the clinical/economic impact of the universal HBV-vaccination program versus a hypothetical no-vaccination scenario as a posteriori analysis. We assessed the vaccination benefits over a 30-year-immunization-period (1991–2020), and the following period, 2021–2070. Our data showed a big drop in HBV-related diseases (−82% in infections, chronic disease, and hepatocellular-carcinoma cases), and related costs (−67% in the immunization period and −85% in 2021–2070), attributable to vaccination. The return on investment (ROI) and the benefit-to-cost (BCR) ratios are >1 for the first thirty-year-immunization-period, and are predicted to almost triplicate the economic savings in the period 2021–2070, both for the National Health Service (NHS) and from societal perspectives. Our model confirmed that the implementation of universal HBV-vaccination in Italy during the first 30 years continues to be a cost-saving strategy, and more advantageous effects will be further achieved in the future. The HBV-vaccination strategy greatly expresses a huge impact in both the short- and long-term, and from the clinical and economic point-of-views

Studies of ion channel mechanisms in pancreatic ductal adenocarcinoma (PDAC)

Pancreatic Ductal Adenocarcinoma (PDAC) is the most common type of pancreatic neoplasia, accounting for more than 90% of all pancreatic cancer cases. Despite improvements in early diagnosis and treatment, the 5-year survival rate has remained unvaried for many decades. The aim of this PhD project was to elucidate the roles of two specific ion channels in the pathophysiology of PDAC: voltage-gated sodium channel (VGSC) and the Ca2+- activated K+ channel KCa3.1. Human pancreatic cell lines of different metastatic potential were used: HPDE (human pancreatic ductal epithelial) cells, Panc-1, MiaPaCa-2, BxPC-3 and Capan-1 cells. VGSCs, typically expressed in neuronal, ‘excitable’ cells, were also found earlier to be functional in several different carcinomas, where they are linked to promotion of the metastatic potential. KCa3.1, which serves a diversity of physiological roles such as cell-volume regulation in erythrocytes and migration in macrophages and microglia, may also promote tumour invasiveness as shown for some tumours including gliomas end endometrial cancer. Initially, the expression of different VGSC subtypes (Nav1.1 - Nav1.7) was screened in PDAC cell lines and abundant levels of mRNA and protein were found. However, whole-cell patch clamp recordings detected a small inward current (~ 30 pA/pF) only in the 10% of MiaPaCa-2 cells, one of the most aggressive cell lines available. Based on the PCR, western blot and patch clamp results obtained, we hypothesized that epidermal growth factor receptor (EGFR) might suppress VGSC expression to protect the Na+/H+ exchanger (NHE1), which has been proposed to serve a ’backbone’ function in driving PDAC metastasis by promoting extracellular acidosis. Indeed, when the EGFR pathway was blocked pharmacologically (by AG1478 10 μM) an increased inward Na+ current was detected by whole-cell patch clamp. Further experiments showed that a combination treatment of AG1478 and TTX (tetrodotoxin) and cariporide (an NHE1 inhibitor) and TTX could reduce cell migration further than treatments alone. This suggested that inhibition of the EGF-EGFR signalling cascade increases VGSC activity and this promoted metastatic cell behaviours. We also found that KCa3.1 channel was overexpressed at mRNA, protein and functional levels in PDAC compared to control cells . We demonstrated both pharmacologically and by gene - silencing approach that this channel regulated the migration and proliferation of MiaPaCa-2 cell line, revealing its potential as another target for therapy, as it has been also suggested in other carcinomas (i.e. endometrial cancer). These results are discussed in their respective chapters. The Thesis ends with a General Discussion chapter, where recent findings on the pathophysiology of PDAC are further highlighted in relation to the findings of the thesis.Open Acces

Vaccine Production Process: How Much Does the General Population Know about This Topic? A Web-Based Survey

Background: Vaccine hesitancy has been recognized as a major global health threat by the World Health Organization. Many studies have investigated vaccine safety as a determinant for vaccine hesitancy; however, not much attention has been paid to vaccine production and quality control during the vaccine production process or whether knowledge about this topic may influence vaccine confidence. The aim of this study was to characterize the common knowledge about the vaccine production process. Methods: A freely accessible online questionnaire was developed on Google Modules and disseminated through social networks. A descriptive analysis of the collected answers was performed, and the chi-square test was used to assess significant differences for the sociodemographic characteristics of the study population (age, gender, work or education and training in the healthcare setting, minor offspring). A binary logistic regression model was performed considering these socio-demographic categories as independent variables. Results: The number of collected questionnaire was 135. Most of the participants (127/135, 94.1%) were aware that quality control measures are carried out during manufacturing, although some knowledge gaps emerged in specific aspects of the vaccine production process, without statistically significant differences between age groups. Working in the healthcare setting or being educated in healthcare may be considered predictors for a better understanding that more than 50% of the production time is spent on quality control (AOR = 3.43; 95% CI: 1.84–8.14, p = 0.01) and that considering quality control performed during the vaccine production process is adequate for avoiding contamination (AOR = 7.90; 95% CI: 0.97–64.34; p = 0.05). Conclusions: This study allowed for a characterization of common knowledge about the vaccine production process. It highlighted the need to implement specific strategies to spread correct information about the vaccine production process. This study may contribute to increased confidence and trust in vaccines and vaccination among the general population

Efficacy of HPV Vaccination Regarding Vulvar and Vaginal Recurrences in Previously Treated Women: The Need for Further Evidence

Vulvar and vaginal cancers are relatively rare cancers, but their incidence is increasing worldwide. Overall, 78% of vaginal cancers and 25% of vulvar cancers are associated with Human papillomavirus (HPV) infection. Immunization could be an option for the management of these cases. We researched and assessed the evidence on the efficacy of HPV vaccination administered to women previously treated with surgery, radiotherapy, or chemotherapy with respect to the recurrence of vulvovaginal disease. From 2006 to November 2022, only one study evaluated the efficacy of HPV vaccination with respect to preventing vulvovaginal recurrences in treated women and showed that a quadrivalent HPV vaccine administered after the surgical treatment of vulvar high-grade squamous intraepithelial lesion (HSIL) can reduce vulvar recurrence of the disease. Therefore, the efficacy of HPV vaccination with respect to vulvovaginal recurrence is still an unexplored field. Further studies are needed to produce stronger evidence in order to appropriately support interventions to protect women’s health

A Study of Varicella Seroprevalence in a Pediatric and Adolescent Population in Florence (Italy). Natural Infection and Vaccination-Acquired Immunization

Background: Varicella is a well-known infectious disease that can have severe complications, also in young children. The Universal Varicella Vaccination (UVV) program was introduced in Tuscany (Italy) in 2003, with a two-dose vaccine schedule given to children between their 13th and 15th month, and at 5–6 years old, as a monovalent for varicella (V) or tetravalent (measles, mumps, rubella and varicella (MMRV)) formulation. Although varicella notifications have dramatically fallen in the last two decades, varicella disease underreporting remains a challenge. Methods: A qualitative immunoenzymatic test (ELISA) was used to measure the presence of anti-varicella antibodies in 165 sera of subjects aged 1–18 years residing in the province of Florence (Italy). Information regarding the anamnestic and vaccination status (including disease notification) was also collected. Results: Our study showed an overall varicella seropositivity of 75.8% (reaching the maximum at 96.3% in the 15–18 years age group). We found that varicella disease notification had been recorded for only 7/165 subjects; however, since 42/165 recalled having had the disease, we can hypothesize that some of them must have been underreported. Furthermore, our study showed that the presence of antibodies after the varicella vaccination remained over time, lasting up to 12 years. Conclusions: Although varicella seroprevalence is <95% in almost all our age groups (except for the 15–18 years age group), our data are encouraging and reflect the success of the introduction of the UVV program and the vaccination campaigns promoted in the Tuscany region

Increasing Measles Seroprevalence in a Sample of Pediatric and Adolescent Population of Tuscany (Italy): A Vaccination Campaign Success

Background: Despite the National Plan for the Elimination of Measles and congenital Rubella (NPEMcR), in 2017, a measles outbreak occurred in Italy, due to sub-optimal vaccination coverage (&lt;95%) for many years. Since that year, the anti-measles vaccination became compulsory in minors (0&ndash;16 years) for school attendance. The aim of our study was to assess the immunity/susceptibility against measles in a representative sample of pediatric and adolescent (1&ndash;18 years) residents of the province of Florence (Tuscany, Italy), and to compare these results with two previous surveys (2003 and 2005&ndash;2006). Methods: The enzyme-linked immunosorbent assay (ELISA) was applied for a qualitative measurement of anti-measles antibodies on 165 sera. The anamnestic and vaccination status was also collected. Results: No measles notification was reported. The overall seropositivity was 88.5%; mostly in the 5&ndash;9 years old subjects (97.9%). Among the 152 vaccinated, 92.1% were positive. The seropositivity persisted after many years since the last dose of vaccine and tended to be more long-lasting in those who had received two or three doses. The susceptibility towards measles decreased over time, reaching a lower value in the current survey (8.5%) than in 2003 (30.8%) and in 2005&ndash;2006 (25.5%). Conclusions: This study confirmed the anti-measles vaccination campaign success, which allowed for the increase in vaccination coverage and immunity levels against measles in the Florentine pediatric and adolescent population following the NPEMcR implementation

Rubella Seroprevalence Boost in the Pediatric and Adolescent Population of Florence (Italy) as a Preventive Strategy for Congenital Rubella Syndrome (CRS)

Background: Despite the availability of an effective vaccine since the 1970s, rubella disease and, importantly, congenital rubella syndrome (CRS) remain a public health concern. The aim of this study was to analyze the rubella seroprevalence in the children population of the province of Florence and compare the obtained results to a previous survey conducted in 2005&ndash;2006. Methods: A qualitative measurement of anti-rubella antibodies was performed on 165 sera using the enzyme-linked immunosorbent Assay (ELISA). The anamnestic and vaccination status was also collected. Results: Our study highlighted a very high rubella seroprevalence (85&ndash;100%) in our enrolled population. In the vaccinated group (153/165), 98.7% of them were positive to rubella antibodies. Conclusions: Our study showed the highest seroprevalence rate reached in the province of Florence for rubella in the last 15 years, thanks to the several successful vaccination campaigns promoted in the Tuscany region. Our findings in pediatric and adolescent subjects are a key factor in preventing CRS in adult life, specifically in childbearing women. Thus, the set goal will be to keep the awareness about the vaccination for this preventable disease high

Effectiveness of pneumococcal vaccination on hospitalization and death in the adult and older adult diabetic population: a systematic review

Diabetic patients are at a higher risk of getting pneumococcal disease and are therefore recommended to get vaccinated. The aim of our systematic review is the retrieval and analysis of all available evidence on the effect of pneumococcal vaccination on the risk of hospitalization and death in adult patients with diabetes. MEDLINEand EMBASE were searched from inception until January 2023. We included all studies investigating whether pneumococcal vaccination reduces the risk of dying or being hospitalized in diabetic patients. The Newcastle-Ottawa scale was used to assess risk of bias.  Only two studies, encompassing a total of 68,246 subjects, were considered eligible for inclusion and of high quality. In both studies polysaccharide pneumococcal vaccination was associated with a reduction of the risk of hospitalization or death in adult diabetic patients (aHR: 0.76 in one study, aOR: 0.97 in the other one). However, in neither of the two included studies the lower risk was statistically significant. Further research is needed due to the potentially major clinical implications for diabetic patients. The results of this systematic review can serve as a foundation for future studies, indicating the importance of continuing research in this area to improve patient outcomes.</p

A Study of Hepatitis A Seroprevalence in a Paediatric and Adolescent Population of the Province of Florence (Italy) in the Period 2017–2018 Confirms Tuscany a Low Endemic Area

Background: Italy is considered an area with very low HAV (hepatitis A virus) endemicity. Currently in Italy the anti-HAV vaccine is recommended only for specific risk groups and there is no universal vaccination program. The aim of this study was to assess the level of immunity against hepatitis A in a sample of children and adolescents from the province of Florence. Methods: A total of 165 sera were collected from subjects aged 1 to 18 years, proportionally selected according to the general population size and stratified by age and sex. A qualitative evaluation of anti-HAV antibodies was performed using the enzyme-linked immunosorbent assay (ELISA). Anamnestic and vaccination status data were also collected. Results: Our study showed a hepatitis A seroprevalence of 9.1% in the enrolled population. A statistically significant difference in the prevalence of anti-HAV was found between Italian and non-Italian subjects. About half of the population having anti-HAV antibodies was reported to be vaccinated, and no cases of hepatitis A were found. Conclusions: The data from our study confirmed Tuscany as an area with low HAV endemicity and showed that hepatitis A seroprevalence is significantly higher in foreign children and adolescents. The presence of more seropositive subjects than those vaccinated was probably due to a natural immunization achieved through a subclinical infection and/or to underreporting of the surveillance systems