Towards personalized vaccines.

The emergence of vaccinomics and system vaccinology represents a transformative shift in immunization strategies, advocating for personalized vaccines tailored to individual genetic and immunological profiles. Integrating insights from genomics, transcriptomics, proteomics, and immunology, personalized vaccines offer the promise of enhanced efficacy and safety, revolutionizing the field of vaccinology. However, the development of personalized vaccines presents multifaceted challenges, including technical, ethical, economic, and regulatory considerations. Addressing these challenges is essential to ensure equitable access and safety of personalized vaccination strategies. Despite these hurdles, the potential of personalized vaccines to optimize responses and mitigate disease burden underscores the significance of ongoing research and collaboration in advancing precision medicine in immunization.

Overview of adult immunization in Italy: Successes, lessons learned and the way forward.

The exchange of knowledge and best practices in adult immunization are essential to improve vaccination strategies across the European region. Italy has made groundbreaking progress in the field, being one of the first countries to propose a life-course vaccination schedule, broadening the traditional focus on childhood immunization to include adults. All vaccines included in Italy's vaccination schedule are free of charge. Moreover, the country's National Immunization Plan sets clear coverage targets, immunization priorities, and actions to reduce disparities. However, the fragmentation of its National Health System following the constitutional reform of 2001 has led to an increased complexity and regional inequalities regarding immunization. Other challenges the country faces include growing vaccine hesitancy, data gaps and underserved populations. This review describes Italy's adult immunization system, from policy to implementation. The successes, challenges and lessons learned were shared during the first Adult Immunization Board country meeting in Italy, where local experts, healthcare providers, public health representatives, and policymakers engaged in collaborative discussions and shared insights through case studies and presentations (December 2023). These insights are reviewed and discussed in this manuscript.

First real-world data on universal respiratory syncytial virus prophylaxis with Nirsevimab in infants.

Introduction: Respiratory Syncytial Virus (RSV) predominantly affects young children, with a peak incidence in temperate regions of the northern hemisphere from October to May. Children under 24 months of age are particularly vulnerable because of the immaturity of their lungs and immune systems, often leading to severe respiratory infections. The World Health Organization (WHO) recognizes RSV as a global health priority. Recently, Nirsevimab, a long-acting monoclonal antibody (mAb), was authorised to prevent RSV disease in infants. Methods: Our narrative review brings together the effectiveness data of Nirsevimab available in the literature, highlighting the strengths and weaknesses of the published studies and the prevention opportunities represented by the new preparation. Results: All reviewed studies provide evidence for the effectiveness of immunisation with Nirsevimab in real-world settings, beyond the controlled conditions of clinical trials, and highlight its safety and feasibility. Nirsevimab significantly reduces RSV hospitalisations and Intensive Care Unit (ICU) admissions. High coverage and high efficacy of immunisation have been reported, although supply issues and variability in studies present challenges. Conclusions: Continued research and surveillance are critical to understanding the long-term effectiveness of Nirsevimab. Overall, available data provide valuable insights into the efficacy, safety, and impact of immunisation with Nirsevimab in preventing severe RSV infections in infants, highlighting its potential to reduce the burden of RSV-related hospitalisations and improve paediatric health outcomes.

Preventing and Controlling Healthcare-Associated Infections: The First Principle of Every Antimicrobial Stewardship Program in Hospital Settings.

Antimicrobial resistance (AMR) is one of the main public health global burdens of the 21st century, responsible for over a million deaths every year. Hospital programs aimed at improving antibiotic use, referred to as antimicrobial stewardship programs (ASPs), can both optimize the treatment of infections and minimize adverse antibiotics events including the development and spread of AMR. The challenge of AMR is closely linked to the development and spread of healthcare-associated infection (HAIs). In fact, the management of patients with HAIs frequently requires the administration of broader-spectrum antibiotic regimens due to the higher risk of acquiring multidrug-resistant organisms, which, in turn, promotes resistance. For this reason, even before using antibiotics correctly, it is necessary to prevent and control the spread of HAIs in our hospitals. In this narrative review, we present seven measures that healthcare workers, even if not directly involved in the tasks of infection prevention and control, must know, support, and embrace. We hope that this review may raise awareness among all healthcare professionals about the issues with the increasing rate of AMR and the ongoing efforts towards minimizing its rise.

Integrated environmental and clinical surveillance for the prevention of acute respiratory infections (ARIs) in indoor environments and vulnerable communities (Stell-ARI): Protocol.

The epidemiological relevance of viral acute respiratory infections (ARIs) has been dramatically highlighted by COVID-19. However, other viruses cannot be neglected, such as influenza virus, respiratory syncytial virus, human adenovirus. These viruses thrive in closed spaces, influenced by human and environmental factors. High-risk closed communities are the most vulnerable settings, where the real extent of viral ARIs is often difficult to evaluate, due to the natural disease progression and case identification complexities. During the COVID-19 pandemic, wastewater-based epidemiology has demonstrated its great potential for monitoring the circulation and evolution of the virus in the environment. The "Prevention of ARIs in indoor environments and vulnerable communities" study (Stell-ARI) addresses the urgent need for integrated surveillance and early detection of ARIs within enclosed and vulnerable communities such as long-term care facilities, prisons and primary schools. The rapid transmission of ARIs in such environments underscores the importance of comprehensive surveillance strategies to minimise the risk of outbreaks and safeguard community health, enabling proactive prevention and control strategies to protect the health of vulnerable populations. This study consists of designing and validating tools for integrated clinical and environmental-based surveillance for each setting, coupled with analytical methods for environmental matrices. The clinical surveillance involves specialized questionnaires and nasopharyngeal swabs for virus identification, while the environmental surveillance includes air and surface microbiological and chemical monitoring, and virological analysis of wastewater. Integrating this information and the collection of behavioural and environmental risk factors into predictive and risk assessment models will provide a useful tool for early warning, risk assessment and informed decision-making. The study aims to integrate clinical, behavioural, and environmental data to establish and validate a predictive model and risk assessment tool for the early warning and risk management of viral ARIs in closed and vulnerable communities prior to the onset of an outbreak.

Vaccines and allergy: Back to the right places.

Hypersensitivity reactions represent one of the most common causes of hesitancy for adherence to national vaccination programs. The majority of hypersensitivity reactions after vaccination are mild, and anaphylaxis is reported to be rare, although it remains challenging to estimate the frequency attributed to each single vaccine, either because of the lower number of administered doses of less common vaccines, or the administration of simultaneous vaccine in most of the vaccination programs. Although literature remains scattered, international consensus guides clinicians in identifying patients who might need the administration of vaccines in protected environments due to demonstrated hypersensitivity to vaccine components or adjuvants. Here we provide the current guidance on hypersensitivity reactions to vaccines and on vaccination of children with allergy disorders.

Mapping and ranking outcomes for the evaluation of seasonal influenza vaccine efficacy and effectiveness: a delphi study.

BACKGROUND: Protection provided by seasonal influenza vaccination (SIV) may be measured against numerous outcomes, and their heterogeneity may hamper decision-making. The aim of this study was to explore outcomes used for estimation of SIV efficacy/effectiveness (VE) and obtain expert consensus on their importance. RESEARCH DESIGN AND METHODS: An umbrella review was first conducted to collect and map outcomes considered in systematic reviews of SIV VE. A Delphi study was then performed to reach expert convergence on the importance of single outcomes, measured on a 9-point Likert scale, in principal target groups, namely children, working-age adults, older adults, subjects with co-morbidities and pregnant women. RESULTS: The literature review identified 489 outcomes. Following data reduction, 20 outcomes were selected for the Delphi process. After two Delphi rounds and a final consensus meeting, convergence was reached. All 20 outcomes were judged to be important or critically important. More severe outcomes, such as influenza-related hospital encounters and mortality with or without laboratory confirmation, were generally top-ranked across all target groups (median scores ≥8 out of 9). CONCLUSIONS: Rather than focusing on laboratory-confirmed infection per se, experimental and observational VE studies should include more severe influenza-related outcomes because they are expected to exercise a greater impact on decision-making.

Management of intra-abdominal infections: recommendations by the Italian council for the optimization of antimicrobial use.

Intra-abdominal infections (IAIs) are common surgical emergencies and are an important cause of morbidity and mortality in hospital settings, particularly if poorly managed. The cornerstones of effective IAIs management include early diagnosis, adequate source control, appropriate antimicrobial therapy, and early physiologic stabilization using intravenous fluids and vasopressor agents in critically ill patients. Adequate empiric antimicrobial therapy in patients with IAIs is of paramount importance because inappropriate antimicrobial therapy is associated with poor outcomes. Optimizing antimicrobial prescriptions improves treatment effectiveness, increases patients' safety, and minimizes the risk of opportunistic infections (such as Clostridioides difficile) and antimicrobial resistance selection. The growing emergence of multi-drug resistant organisms has caused an impending crisis with alarming implications, especially regarding Gram-negative bacteria. The Multidisciplinary and Intersociety Italian Council for the Optimization of Antimicrobial Use promoted a consensus conference on the antimicrobial management of IAIs, including emergency medicine specialists, radiologists, surgeons, intensivists, infectious disease specialists, clinical pharmacologists, hospital pharmacists, microbiologists and public health specialists. Relevant clinical questions were constructed by the Organizational Committee in order to investigate the topic. The expert panel produced recommendation statements based on the best scientific evidence from PubMed and EMBASE Library and experts' opinions. The statements were planned and graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence. On November 10, 2023, the experts met in Mestre (Italy) to debate the statements. After the approval of the statements, the expert panel met via email and virtual meetings to prepare and revise the definitive document. This document represents the executive summary of the consensus conference and comprises three sections. The first section focuses on the general principles of diagnosis and treatment of IAIs. The second section provides twenty-three evidence-based recommendations for the antimicrobial therapy of IAIs. The third section presents eight clinical diagnostic-therapeutic pathways for the most common IAIs. The document has been endorsed by the Italian Society of Surgery.

The impact of COVID-19 vaccination campaign on pediatric vaccine uptake based on parents' attitudes towards mandatory and recommended vaccination in Southern Italy.

INTRODUCTION: This study investigates the association between parental attitudes towards mandatory and recommended vaccines in the National Immunization Plan (NIP) of Italy and their acceptance of the COVID-19 vaccine in children aged 5-11 years. METHODS: Using data from approximately 42,000 children in Southern Italy, parental attitudes towards previous vaccinations were examined. Mandatory and recommended vaccinations were considered for the analysis, with the first shot of each schedule being considered relevant, regardless of when it was administered or whether the recommended number of doses was administered. A multivariate logistic regression was performed to analyze associations between the covariates of age, sex, adherence to mandatory vaccinations, number of recommended vaccinations, and COVID-19 vaccination. RESULTS: The COVID-19 vaccine acceptance rate was 50.7% in our sample. We revealed a strong association between parental attitudes towards previous vaccinations and the acceptance of the COVID-19 vaccine. Mandatory vaccinations under the NIP showed the highest acceptance rates, and among non-mandatory vaccines, the pneumococcal conjugate vaccine had the highest acceptance rate, potentially due to its co-administration with the hexavalent vaccine. The study identified a trend of lower COVID-19 vaccine coverage in younger children. CONCLUSIONS: The study underscores the importance of co-administration approaches and well-planned vaccination schedules in enhancing vaccine coverage. It suggests that integrating newer vaccines, like the COVID-19 vaccine, into established vaccination schedules could potentially increase acceptance and coverage. The findings highlight the urgency of addressing vaccine hesitancy, particularly in the pediatric population, to ensure high vaccination coverage and effective disease control. Further research is needed to explore the potential strategies to increase vaccine acceptance.

Pre-COVID-19-pandemic RSV epidemiology and clinical burden in pediatric primary care in Italy: a comparative analysis across two regions for the 2019/2020 season.

BACKGROUND: Respiratory syncytial virus (RSV) infection in children under 5 years have a significant clinical burden, also in primary care settings. This study investigates the epidemiology and burden of RSV in Italian children during the 2019/20 pre-pandemic winter season. METHODS: A prospective cohort study was conducted in two Italian regions. Children with Acute Respiratory Infection (ARI) visiting pediatricians were eligible. Nasopharyngeal swabs were collected and analyzed via multiplex PCR for RSV detection. A follow-up questionnaire after 14 days assessed disease burden, encompassing healthcare utilization and illness duration. Statistical analyses, including regression models, explored associations between variables such as RSV subtype and regional variations. RESULTS: Of 293 children with ARI, 41% (119) tested positive for RSV. Median illness duration for RSV-positive cases was 7 days; 6% required hospitalization (median stay: 7 days). Medication was prescribed to 95% (110/116) of RSV cases, with 31% (34/116) receiving antibiotics. RSV subtype B and regional factors predicted increased healthcare utilization. Children with shortness of breath experienced a 36% longer illness duration. CONCLUSIONS: This study highlights a significant clinical burden and healthcare utilization associated with RSV in pre-pandemic Italian primary care settings. Identified predictors, including RSV subtype and symptomatology, indicate the need for targeted interventions and resource allocation strategies. RSV epidemiology can guide public health strategies for the implementation of preventive measures.

RSV Disease Burden in Primary Care in Italy: A Multi-Region Pediatric Study, Winter Season 2022-2023.

INTRODUCTION: Human respiratory syncytial virus (RSV) is one of the most frequent causes of respiratory infections in children under 5 years of age, but its socioeconomic impact and burden in primary care settings is still little studied. METHODS: During the 2022/2023 winter season, 55 pediatricians from five Italian regions participated in our community-based study. They collected a nasal swab for RSV molecular test from 650 patients under the age of 5 with acute respiratory infections (ARIs) and performed a baseline questionnaire. The clinical and socioeconomic burden of RSV disease in primary care was evaluated by two follow-up questionnaires completed by the parents of positive children on Days 14 and 30. RESULTS: RSV laboratory-confirmed cases were 37.8% of the total recruited ARI cases, with RSV subtype B accounting for the majority (65.4%) of RSV-positive swabs. RSV-positive children were younger than RSV-negative ones (median 12.5 vs. 16.5 months). The mean duration of symptoms for all children infected by RSV was 11.47 ± 6.27 days. We did not observe substantial differences in clinical severity between the two RSV subtypes, but RSV-A positive patients required more additional pediatric examinations than RSV-B cases. The socioeconomic impact of RSV infection was considerable, causing 53% of children to be absent from school, 46% of parents to lose working days, and 25% of families to incur extra costs. CONCLUSIONS: Our findings describe a baseline of the RSV disease burden in primary care in Italy before the introduction of upcoming immunization strategies.

Evaluating hepatitis C cascade of care surveillance system in Tuscany, Italy, through a population retrospective data-linkage study, 2015-2021.

This comprehensive retrospective data-linkage study aimed at evaluating the impact of Direct-Acting Antivirals (DAAs) on Hepatitis C Virus (HCV) testing, treatment trends, and access to care in Tuscany over six years following their introduction. Utilizing administrative healthcare records, our work reveals a substantial increase in HCV tests in 2017, attributed to the decision to provide universal access to treatment. However, despite efforts to eradicate chronic HCV through a government-led plan, the target of treating 6,221 patients annually was not met, and services contracted after 2018, exacerbated by the COVID-19 pandemic. Key findings indicate a higher prevalence of HCV screening among females in the 33-53 age group, influenced by pregnancy-related recommendations, while diagnostic tests and treatment uptake were more common among males. Problematic substance users constituted a significant proportion of those tested and treated, emphasizing their priority in HCV screening. Our paper underscores the need for decentralized HCV models and alternative testing strategies, such as point-of-care assays, especially in populations accessing harm reduction services, communities, and prisons. The study acknowledges limitations in relying solely on administrative records, advocating for improved data access and timely linkages to accurately monitor HCV care cascades and inform regional plans. Despite challenges, the paper demonstrates the value of administrative record linkages in understanding the access to care pathway for hard-to-reach populations. The findings emphasize the importance of the national HCV elimination strategy and the need for enhanced data collection to assess progress accurately, providing insights for future regional and national interventions.

Waning intra-season vaccine effectiveness against influenza A(H3N2) underlines the need for more durable protection.

BACKGROUND: The question of whether influenza vaccine effectiveness (VE) wanes over the winter season is still open and some contradictory findings have been reported. This study investigated the possible decline in protection provided by the available influenza vaccines. RESEARCH DESIGN AND METHODS: An individual-level pooled analysis of six test-negative case-control studies conducted in Italy between the 2018/2019 and 2022/2023 seasons was performed. Multivariable logistic regression analyses were performed to estimate weekly change in the odds of testing positive for influenza 14 days after vaccination. RESULTS: Of 6490 patients included, 1633 tested positive for influenza. Each week that had elapsed since vaccination was associated with an increase in the odds of testing positive for any influenza (4.9%; 95% CI: 2.0-8.0%) and for A(H3N2) (6.5%; 95% CI: 2.9-10.3%). This decline in VE was, however, significant only in children and older adults. A similar increase in the odds of testing positive was seen when the dataset was restricted to vaccinees only. Conversely, VE waning was less evident for A(H1N1)pdm09 or B strains. CONCLUSIONS: Significant waning of VE, especially against influenza A(H3N2), may be one of the factors associated with suboptimal end-of-season VE. Next-generation vaccines should provide more durable protection against A(H3N2).

Innovative Techniques for Infection Control and Surveillance in Hospital Settings and Long-Term Care Facilities: A Scoping Review.

Healthcare-associated infections (HAIs) pose significant challenges in healthcare systems, with preventable surveillance playing a crucial role. Traditional surveillance, although effective, is resource-intensive. The development of new technologies, such as artificial intelligence (AI), can support traditional surveillance in analysing an increasing amount of health data or meeting patient needs. We conducted a scoping review, following the PRISMA-ScR guideline, searching for studies of new digital technologies applied to the surveillance, control, and prevention of HAIs in hospitals and LTCFs published from 2018 to 4 November 2023. The literature search yielded 1292 articles. After title/abstract screening and full-text screening, 43 articles were included. The mean study duration was 43.7 months. Surgical site infections (SSIs) were the most-investigated HAI and machine learning was the most-applied technology. Three main themes emerged from the thematic analysis: patient empowerment, workload reduction and cost reduction, and improved sensitivity and personalization. Comparative analysis between new technologies and traditional methods showed different population types, with machine learning methods examining larger populations for AI algorithm training. While digital tools show promise in HAI surveillance, especially for SSIs, challenges persist in resource distribution and interdisciplinary integration in healthcare settings, highlighting the need for ongoing development and implementation strategies.

Exploring the Possible Use of AI Chatbots in Public Health Education: Feasibility Study.

BACKGROUND: Artificial intelligence (AI) is a rapidly developing field with the potential to transform various aspects of health care and public health, including medical training. During the "Hygiene and Public Health" course for fifth-year medical students, a practical training session was conducted on vaccination using AI chatbots as an educational supportive tool. Before receiving specific training on vaccination, the students were given a web-based test extracted from the Italian National Medical Residency Test. After completing the test, a critical correction of each question was performed assisted by AI chatbots. OBJECTIVE: The main aim of this study was to identify whether AI chatbots can be considered educational support tools for training in public health. The secondary objective was to assess the performance of different AI chatbots on complex multiple-choice medical questions in the Italian language. METHODS: A test composed of 15 multiple-choice questions on vaccination was extracted from the Italian National Medical Residency Test using targeted keywords and administered to medical students via Google Forms and to different AI chatbot models (Bing Chat, ChatGPT, Chatsonic, Google Bard, and YouChat). The correction of the test was conducted in the classroom, focusing on the critical evaluation of the explanations provided by the chatbot. A Mann-Whitney U test was conducted to compare the performances of medical students and AI chatbots. Student feedback was collected anonymously at the end of the training experience. RESULTS: In total, 36 medical students and 5 AI chatbot models completed the test. The students achieved an average score of 8.22 (SD 2.65) out of 15, while the AI chatbots scored an average of 12.22 (SD 2.77). The results indicated a statistically significant difference in performance between the 2 groups (U=49.5, P<.001), with a large effect size (r=0.69). When divided by question type (direct, scenario-based, and negative), significant differences were observed in direct (P<.001) and scenario-based (P<.001) questions, but not in negative questions (P=.48). The students reported a high level of satisfaction (7.9/10) with the educational experience, expressing a strong desire to repeat the experience (7.6/10). CONCLUSIONS: This study demonstrated the efficacy of AI chatbots in answering complex medical questions related to vaccination and providing valuable educational support. Their performance significantly surpassed that of medical students in direct and scenario-based questions. The responsible and critical use of AI chatbots can enhance medical education, making it an essential aspect to integrate into the educational system.

Vaccine hesitancy and knowledge regarding maternal immunization among reproductive age women in central Italy: a cross sectional study.

Background: Vaccination in pregnancy offers protection to the mother and the newborn. In Italy, influenza, pertussis, and COVID-19 vaccinations are recommended in pregnancy, but vaccination coverage is still far from the National Immunization Plan goals. We aimed to assess knowledge and attitude on maternal immunization in two groups of Italian women, in pregnancy and in reproductive age (non pregnant). Methods: A cross sectional study on Italian childbearing age women gathering information on their knowledge on maternal immunization and attitudes to receiving influenza and pertussis vaccines in pregnancy was carried out at the University of Rome Tor Vergata, between September 2019 and February 2020. Logistic and multinomial regressions were chosen as statistical tests for our analysis. Results: 1,031 women participated in the survey by answering the questionnaire. Out of these, 553 (53.6%) women were pregnant, and 478 (46.4%) were in the reproductive age. 37% (204/553) of pregnant women and 41% (198/476) of non pregnant women are aware of the existence of an immunization plan for pregnant women in Italy. The group with age between 20 and 30, for both pregnant women and women in the reproductive age, has a better knowledge of vaccination in pregnancy. Working status is a variable associated with more awareness about vaccination during pregnancy only for pregnant women (OR = 2.34, p < 0.00001). Educational status, trimester of pregnancy and knowledge on the topic are associated with vaccine hesitancy in our multivariate analysis for pregnant women. In the reproductive age group women who had a previous pregnancy are more likely to be hesitant towards vaccination in pregnancy, on the other hand the one with a higher knowledge and educational status are more likely to get vaccinated. Conclusions: The study highlights the persistent vaccine hesitancy among Italian women of reproductive age and pregnant women. Despite healthcare providers being identified as a reliable source of information, their recommendations alone are insufficient to overcome vaccine hesitancy. Factors such as employment status, educational level, pregnancy trimester, and knowledge about vaccinations during pregnancy influence vaccine hesitancy. Tailored educational interventions and communication campaigns targeting these areas can help reduce vaccine hesitancy and promote maternal immunization.

Assessing vaccine hesitancy and health literacy using a new Italian vaccine confidence index and a modified Italian medical term recognition test: A cross-sectional survey on Italian parents.

The decline in children's vaccination coverage and the resurgence of preventable infectious diseases draw attention to parents' vaccine hesitancy. Our study introduces two validated tools to independently assess vaccine hesitancy and health literacy among parents with school-age children. We developed a Vaccine Confidence Index (VCI) from 10 Likert items, exploring their relationships through exploratory and confirmatory factor analyses. We modified the IMETER (Italian medical term recognition test) to measure health literacy. We assessed the internal consistency of the modified IMETER and the 10 Likert items using Cronbach's alpha test (α) and McDonald's omega total coefficient (ω) with good results (ω = 0.92, α = 0.90; ω = 0.87, α = 0.82 respectively). We used these tools within a questionnaire conducted on 743 parents recruited from pediatric clinic waiting rooms in Italy, collecting demographic data, information sources on vaccines and vaccine-preventable diseases knowledge. The VCI resulting from factor analyses consisted of six items on a ten-point Likert scale, reflecting the ratio of positive to negative items. The survey revealed significant variations in the VCI according to individual features such as education, use of social networks, or Health institutions as sources of information. Multivariate logistic regression identified an association between vaccine intention and the VCI. Health literacy was functional for 91.2% of participants, but knowledge about vaccine-preventable diseases was generally low. The VCI showed no significant association with health literacy and vaccine-preventable diseases knowledge. The VCI and the modified IMETER effectively assess vaccination attitude and health literacy, offering valuable public health tools for tailoring vaccination campaigns to hesitant population subgroups.