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.

Seroprotection against tetanus in the Italian general population.

BACKGROUND: Tetanus is a non-communicable disease, preventable with vaccination. Despite the implemented vaccination strategy, a certain number of tetanus cases per year continue to occur. The aim of the study was to evaluate the seroprevalence of anti-tetanus antibodies in the Italian population by age, sex and geographical area. METHODS: To determine the level of tetanus-specific antibodies, an immunoenzymatic assay was used. RESULTS: A total of 3,821 serum samples were collected in the years 2019-20 from healthy subjects aged 6-90 years residing in 13 Italian regions. Overall, 85 % of the tested subjects resulted positive. The rate of subjects protected against tetanus showed a gradual decrease from the younger age groups to the older ones (6-12 years: 93.6 %, 13-24 years: 91.8 %, 25-39 years: 91.0 %, 40-64 years: 78.2 %, ≥ 65 years: 45.3 %); this is particularly evident in the Southern regions and Islands. Moreover, the prevalence of subjects with low protection (<0.1 IU/ml) was significantly higher in the ≥ 65 age group (10.3 %). Males and females' prevalence showed a significant difference only in the oldest age group (M: 60.8 %, F: 30.4 %). In general, a higher prevalence was observed for Northern (90.8 %) and Central regions (87.3 %) than Southern regions and Islands (80.0 %). CONCLUSION: These data, compared with epidemiological ones which showed a high number of cases in the elderly, confirmed that the population with lower protection has a greater risk of contracting the disease, demonstrating the need for adequate immunization through both primary vaccination and boosters for all ages and both sexes, in order to provide lifelong protection.

Seroprevalence of measles antibodies in the Italian general population in 2019-2020.

In Italy, the measles elimination target has not yet been reached despite a significant reduction in cases. A multicenter study was conducted to estimate the prevalence of anti-measles (MV) IgG antibodies in the Italian population by age, sex and geographical area. To determine the level of MV-specific antibodies in sera, the immunoenzymatic assay ELISA was used (Enzygnost Anti-VZV/IgG, Siemens Healthcare Diagnostic Products GmbH, Germany). Overall, 3746 serum samples collected in the years 2019-20 from healthy subjects aged 6-64 years residing in 13 Italian regions. The overall seroprevalence of anti-MV IgG was 91.2 % (90.6 % male, 91.7 % female). Significantly higher seroprevalence values (p < 0.05) were recorded for the extreme age groups of the study population (6-9 years: 94.2 %; 40-64 years: 97.6 %). Subjects 20-39 and 40-64 years old had significantly higher antibody titers suggesting a protection against measles mainly derived from natural infection. Seroprevalence was significantly higher in the South (93.2 %) than in the Northern-Central Italy (88.9 %). The results indicate an increase in the overall seroprevalence data compared to previous investigations. However, further efforts must be made to implement and maintain high measles vaccination coverage to avoid the risk of future epidemic outbreaks.

Diabetes as a risk factor for pneumococcal disease and severe related outcomes and efficacy/effectiveness of vaccination in diabetic population. Results from meta-analysis of observational studies.

AIMS: To collect all available evidence on the effect of diabetes mellitus (DM) as a risk factor for pneumococcal disease incidence and related complications, and on the efficacy/effectiveness of vaccines in patients with DM. METHODS: Two distinct systematic searches on MEDLINE, Cochrane, ClinicalTrials.gov and EMBASE databases were performed, one for each meta-analysis, collecting all observational (cohort and case-control) studies and randomized clinical trials performed on humans up to June 1st, 2023. RESULTS: We retrieved 36 observational studies comparing risk for pneumococcal disease and related complications in people with or without DM, and 11 studies (1 randomized clinical trial and 10 observational studies) assessing conjugated and polysaccaridic vaccines efficacy/effectiveness on preventing such outcomes. People with DM were at higher risk for Invasive Pneumococcal Disease (unadjusted OR 2.42 [2.00; 2.92]); Case-Fatality Rate (unadjusted OR 1.61 [1.25; 2.07], Pneumococcal pneumonia (unadjusted OR 2.98 [2.76; 3.22), and Intensive care unit admission for pneumococcal disease (unadjusted OR 2.09 [1.20; 3.66]). In diabetic individuals vaccinated with conjugated vaccine, incidence of pneumonia specific for vaccine type in a clinical trial (OR 0.237 [0.008; 0.704]), and hospitalization for overall pneumonia during the year following the polysaccharide vaccination in observational studies (unadjusted OR 0.63 [0.45-0.89]) were significantly lower in comparison with unvaccinated DM subjects, with no significant differences for other outcomes. CONCLUSIONS: People with diabetes mellitus are at higher risk for less favourable course of pneumococcal disease and should be therefore targeted in vaccination campaigns; more evidence needs to be collected on vaccination outcomes in people with diabetes.

Available evidence on the co-administration of the four-component meningococcal B vaccine (4CMenB) with three vaccines at the same visit among pediatric individuals.

Vaccine co-administration is a useful strategy for improving vaccine coverage and adherence. In Italy, an update to the national immunization program (NIP) in 2023 included recommendations for co-administration of pediatric vaccines, including the four-component vaccine for meningococcus B (4CMenB), pneumococcal conjugate vaccine (PCV), hexavalent vaccines, and oral rotavirus vaccines. Safety is a major concern when considering vaccine co-administration; therefore, a literature review of the available evidence on 4CMenB co-administration with PCV, hexavalent/pentavalent, and rotavirus vaccines was performed. Of 763 publications screened, two studies were reviewed that reported safety data on 4CMenB co-administration with PCV, hexavalent/pentavalent, and rotavirus vaccines in infants aged 0-24 months. Overall, these studies supported that there were no significant safety signals when co-administering 4CMenB with PCV, hexavalent/pentavalent, and rotavirus vaccines, compared with individual vaccination. This review provides key insights for healthcare professionals on the tolerability of co-administering 4CMenB with routine vaccines.

Artificial Intelligence and Public Health: Evaluating ChatGPT Responses to Vaccination Myths and Misconceptions.

Artificial intelligence (AI) tools, such as ChatGPT, are the subject of intense debate regarding their possible applications in contexts such as health care. This study evaluates the Correctness, Clarity, and Exhaustiveness of the answers provided by ChatGPT on the topic of vaccination. The World Health Organization's 11 "myths and misconceptions" about vaccinations were administered to both the free (GPT-3.5) and paid version (GPT-4.0) of ChatGPT. The AI tool's responses were evaluated qualitatively and quantitatively, in reference to those myth and misconceptions provided by WHO, independently by two expert Raters. The agreement between the Raters was significant for both versions (p of K < 0.05). Overall, ChatGPT responses were easy to understand and 85.4% accurate although one of the questions was misinterpreted. Qualitatively, the GPT-4.0 responses were superior to the GPT-3.5 responses in terms of Correctness, Clarity, and Exhaustiveness (Δ = 5.6%, 17.9%, 9.3%, respectively). The study shows that, if appropriately questioned, AI tools can represent a useful aid in the health care field. However, when consulted by non-expert users, without the support of expert medical advice, these tools are not free from the risk of eliciting misleading responses. Moreover, given the existing social divide in information access, the improved accuracy of answers from the paid version raises further ethical issues.

Efficacy and effectiveness of Herpes zoster vaccination in adults with diabetes mellitus: a systematic review and meta-analysis of clinical trials and observational studies.

AIM: The risk for Herpes zoster (HZ) and its complications is higher in people with diabetes mellitus (DM). Our aim is to assess efficacy and effectiveness of the currently available live-attenuated zoster vaccine (LZV) and recombinant zoster vaccine (RZV) in adults with DM. METHODS: A Systematic Review and Meta-analysis of clinical trials and observational studies comparing incidence of HZ and its complications in vaccinated and unvaccinated people with DM was performed, on PubMed, Cochrane, Clinical Trials.gov and Embase databases, up to January 15th, 2023. Risk of bias was assessed through the Cochrane Collaboration tool and the Newcastle-Ottawa Scale. The protocol was registered on the PROSPERO website (CRD42022370705). RESULTS: Only three observational studies reported LZV efficacy and effectiveness in people with DM. A lower risk for HZ infection (MH-OH Ratio 95% CI = 0.52 [0.49, 0.56] was observed, for unadjusted analysis, and 0.51 [0.46, 0.56] for adjusted analysis, both with P < 0.00001 and no heterogeneity). No data on LZV safety were reported. A pooled analysis of two trials comparing RZV and placebo, showed a reduced risk for HZ incidence: (95% CI Odds Ratio: 0.09 [0.04-0.19]), with no difference in severe adverse events and mortality. CONCLUSIONS: In our meta-analysis of three observational studies LZV showed a 48% effectiveness in reducing HZ incidence in adults with diabetes whereas in a pooled analysis of two RCTs, RZV showed a 91% efficacy. No data are available on the effects of vaccination on the incidence and severity of HZ-related complications among subjects with diabetes.

Influenza: Diabetes as a risk factor for severe related-outcomes and the effectiveness of vaccination in diabetic population. A meta-analysis of observational studies.

AIMS: In order to better define the need for influenza vaccination in people with diabetes (DM), we collected all available evidence on the effect of DM as a risk factor for complications of both seasonal and pandemic influenza, and on the specific effectiveness of vaccines in patients with DM. DATA SYNTHESIS: Two distinct systematic searches on MEDLINE, Cochrane, ClinicalTrials.gov and Embase databases were performed, one for each metanalysis, collecting all observational studies and randomized clinical trials performed on humans up to May 31st, 2022. We retrieved 34 observational studies comparing risk for influenza complications in people with or without diabetes, and 13 observational studies assessing vaccine effectiveness on preventing such complications. Mortality for influenza and hospitalization for influenza and pneumonia resulted significantly higher in individuals with versus without DM, both when unadjusted and adjusted data are analyzed. In diabetic individuals vaccinated for influenza overall hospitalization, hospitalization for influenza or pneumonia and overall mortality are significantly lower in comparison with not vaccinated DM subjects, both when unadjusted and adjusted data were analyzed. CONCLUSION: This systematic review and meta-analysis shows that: 1) influenza is associated with more severe complications in diabetic versus not diabetic individuals and 2) influenza vaccination is effective in preventing clinically relevant outcomes in adults with DM with a NNT (number needed to treat) of 60, 319, and 250 for all-cause hospitalization, specific hospitalization, and all-cause mortality, respectively. The identification of diabetic patients as the target of vaccination campaigns for influenza appears to be justified by available clinical evidence.

Assessment of Pertussis Underreporting in Italy.

A study was conducted to assess the degree of pertussis underreporting in Italy. An analysis was performed to compare the frequency of pertussis infections estimated using seroprevalence data with the pertussis incidence based on reported cases among the Italian population. For this purpose, the proportion of subjects who had an anti-PT ≥ 100 IU/mL (indicative of B. pertussis infection within the last 12 months) was compared with the reported incidence rate among the Italian population ≥5 years old, divided into two age groups (6-14 and ≥15 years old), obtained from the European Centre for Disease Prevention and Control (ECDC) database. The pertussis incidence rate in the Italian population ≥5 years old reported by the ECDC in 2018 was 6.75/100,000 in the 5-14 age group and 0.28/100,000 in the ≥15 age group. The proportion of subjects recruited in the present study with an anti-PT ≥ 100 IU/mL was 0.95% in the 6-14 age group and 0.97% in the ≥15 age group. The estimated rate of pertussis infections based on seroprevalence was approximately 141-fold and 3452-fold higher than the reported incidence in the 6-14 age group and in the ≥15 age group, respectively. Quantification of underreporting can allow for the burden of pertussis, as well as the impact of ongoing vaccination, to be better evaluated.

Sero-Epidemiological Study of Varicella in the Italian General Population.

The aim of this study was to analyze the seroprevalence of varicella in Italy and to evaluate the impact of varicella vaccination, which has been mandatory for newborns since 2017. The levels of VZV-specific IgG antibodies were determined by the ELISA method in residual serum samples obtained from subjects aged between 6 and 64 years and residing in 13 Italian regions. Overall, 3746 serum samples were collected in the years 2019 and 2020. The overall seroprevalence was 91.6% (89.9% in males and 93.3% in females; p = 0.0002). Seroprevalence showed an increasing trend (p < 0.0001) starting in the younger age groups: 6-9 years: 84.1%; 10-14 years: 88.7%; 15-19 years: 89.3%; 20-39 years: 93.1% and >40 years: 97.0%. The seroprevalence data obtained in the present study were compared with those relating to previous sero-epidemiological surveys conducted, respectively, in the years 1996-1997, 2003-2004 and 2013-2014, taking into consideration only data from regions monitored in all surveillance campaigns. The comparison highlighted for the period 2019-2020 showed significantly higher values in the age groups 6-9 (p < 0.001), 10-14 (p = 0.018) and 15-19 years (p = 0.035), while in adults, the trend did not change over time (ns). These results highlight the positive impact of varicella vaccination in Italy.

Available evidence and potential for vaccines for reduction in antibiotic prescriptions.

Bacterial antibiotic resistance is a public health issue. It means that drugs become ineffective, infections persist and have a huge impact on the health of patients and their spreading increases. To address a complex threat such as bacterial antibiotic resistance different and integrated approaches are needed including discovery of new antibiotics, improvement of diagnostics tools and improvement of antibiotic stewardship. Absolutely relevant are prevention of infections as well as decrease in the use of antibiotics. Vaccines are an important tool in the fight against bacterial antibiotic resistance and can help prevent it in several ways. Indeed, vaccines are highly effective in preventing diseases that might otherwise require the use of antibiotics to treat symptoms and associated complications. Preventing infections through vaccination helps reduce the need for and widespread and inappropriate use of antibiotics, including for secondary bacterial infections.

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.

Active surveillance of adverse events after immunization (AEFI) from the Local Health Unitof Ferrara, Italy.

Introduction: Vaccine vigilance implies the collection, evaluation, analysis and communication of adverse events following immunization (AEFI) and is a useful tool for vaccine monitoring allowing, even after approval and marketing, to check its safety/tolerability. The multiregional project "Active surveillance of adverse vaccine reactions", joined by the AUSL of Ferrara, is aimed at making parents of children, who have undergone at least one vaccination provided by the regional vaccination calendar in the first 24 months of life, aware of the reporting of any AEFI via mobile phone-SMS. Methods: An analysis of the project data, collected in the period March 2018 - May 2019, was carried out, to evaluate the effectiveness of the reporting tool and the type and frequency of AEFI. Anonymized data were analyzed by number, gender, distribution by age, type of vaccine, adverse event, severity and outcome. Results: A total of 1,494 consents and 983 SMS messages were obtained from parents. The vaccine doses carried out were 1,984 (28.3% hexavalent, 28% PCV13, 17% anti-rotavirus, 14.3% Men-B). Almost all (99.5%) AEFI were classified as "not serious". Based on the Organ System Class (SOC), most reports are related to "General Disorders and Administration Site Conditions" (52.3%), followed by "Psychiatric Disorders" (26.5%) and "Metabolic and nutrition disorders" (12.5%). Conclusions: The reported AEFI are in line with the ones reported in the literature. Reporting via SMS is a valid vaccine surveillance tool contributing to the qualitative and quantitative improvement of the information transmitted.

COVID-19: opinions and behavior of Italian general population during the first epidemic phase.

BACKGROUND AND AIM: On January 9, 2020, the World Health Organization (WHO) declared that Chinese health authorities had identified a new coronavirus strain never before isolated in humans, the 2019-nCoV later redefined SARS-CoV-2, that still today represent a public health problem. The present survey started on 10 February 2020 with the aim of a) assessing the risk perception in healthcare workers and young students, following the evolution of attitudes, perception and knowledge over time, b) provide useful information to the general population during survey. RESULTS: A study sample consisting of 4116 Italian individuals of both sexes was enrolled. High levels of risk perception, low perception of self-efficacy and low levels of knowledge scores (24.55 ± 5.76 SD) were obtained indicating the need for continuous population monitoring as well as further communication strategies carried out at institution levels. CONCLUSION: The results of the present study could help public health authorities in carrying out informative campaigns for general population and could be an important tool in evaluating public knowledge and misperceptions during the management of the COVID-19. (www.actabiomedica.it).

Experts' Opinion for Improving Pertussis Vaccination Rates in Adolescents and Adults: A Call to Action.

This article highlights the importance of diphtheria-tetanus-acellular pertussis (with reduced antigen content, dTap) vaccination in preventing pertussis, a respiratory infection that is still widespread and easily transmitted. In particular, it highlights the need to receive a booster vaccination throughout life to maintain high antibody levels, which decrease through time. This document collects the opinions that emerged from the comparison between major Italian experts in the field of vaccination. This working group was created to promote a "call to action", aimed at raising awareness among all institutions, public health authorities, and health workers involved in the vaccination process, about the importance of dTap vaccine administration and with the mindset of implementing the strategic vaccination plan provided by the National Vaccine Plan (NVP). In fact, despite this vaccine being included in the NVP, there are some issues attributable to the practice of vaccination (local health authorities, vaccination centers, occupational health services, gynecology centers, societies of work). Therefore, it is necessary that the Ministry defines the vaccination coverage objectives, identifies the groups of subjects who should receive the booster vaccine (subjects exposed to greater risk of infection, subjects over 60, pregnant women), and applies all the necessary measures to encourage the implementation of this practice.

Improving vaccination rates in older adults and at-risk groups: focus on pertussis.

Despite the implementation of effective paediatric vaccination programmes, pertussis remains a global health problem. Disease epidemiology has changed over time, shifting towards the adolescent and adult populations. In adults, the true burden of pertussis is greatly underestimated and pertussis vaccine coverage rates are suboptimal, including individuals with chronic conditions. Here, we report the outcomes of a virtual international scientific workshop to assess the evidence on the burden of pertussis in older adults and identify potential solutions to improve uptake of pertussis vaccines. In adults, pertussis is underdiagnosed in part due to atypical or milder clinical presentation and the lack of testing and case confirmation. However, contemporary epidemiological data denoted an increase in the burden of pertussis among adolescents and adults. This might be related to a variety of reasons including the waning of immunity over time, the lack of booster vaccination, and the improved diagnostic methods that led to increased recognition of the disease in adults. Pertussis sequelae can be severe in older adults, particularly those with existing chronic medical conditions, and the vulnerability of these groups is further enhanced by low pertussis vaccine coverage. Possible measures to increase vaccine uptake include strengthening and harmonisation of immunisation guidelines, healthcare professionals taking a more active role in recommending pertussis vaccination, involvement of vaccination centres and pharmacies in the vaccination process, and improving knowledge of pertussis burden and vaccine efficacy among the general population.

How has COVID-19 pandemic changed flu vaccination attitudes among an Italian cancer center healthcare workers?

A retrospective study was conducted among Italian cancer healthcare workers (HCWs) to describe how influenza vaccination attitudes have changed during the COVID-19 pandemic. The analysis was conducted on the last three influenza seasons (2018/19, 2019/20 and 2020/21). To account for different relationships and proximity with patients, the study population was grouped into three main professional categories: health personnel, administrative staff and technicians. Moreover, to explore the factors affecting the coverage of influenza vaccine, a multinomial regression analysis was performed.Over the years, the influenza vaccination uptake showed a gradual increase across the overall staff, the highest coverage (53.8%) was observed in the season 2020/21, in particular, for health personnel (57.7%). In general, males resulted in more adherent to vaccination campaigns; nevertheless, this gap decreased in the last season. A total of 28.6% workers were always vaccinated throughout the past three seasons, a remarkable 25.2% (mainly young and females) received for the first time the influenza vaccination in 2020/21.In this dramatic health crisis, the attitudes of HCWs toward flu vaccination have changed. The COVID-19 outbreak increased adherence to flu vaccination, reaching the highest coverage in the campaign 2020/21. However, further efforts should be made to achieve greater vaccination coverage.

The future for COVID-19 vaccines: public health assessment and perspectives based on scientific evidence.

The development and use of messenger RNA-based (mRNA) vaccines against the SARS-CoV-2 spike protein have proven to be highly effective against symptomatic COVID-19, especially for severe forms. Since the declaration of a public health emergency in early 2020, however, the SARS-CoV-2 virus has continuously evolved, giving rise to several variants that have caused and continue to cause concern in the scientific community. Currently, viruses circulating worldwide belong to the Omicron lineage, with several identified sub-variants. In response to virus mutation, mRNA vaccines have been adapted into bivalent vaccines containing two mRNAs: one encoding the original Wuhan SARS-CoV-2 spike protein and one encoding the BA.1 or BA.4-5 spike protein of the Omicron sub-variant. This strategy is based on the hypothesis that the immune system's response improves when variants are included in the vaccine, leading to an increase in the magnitude and diversity of both the humoral and cellular immune response. The evidence gathered to date confirms the use of bivalent vaccines as the optimal strategy. In the light of current knowledge, and in the awareness of the impossibility of making precise predictions on the evolution of the COVID-19 pandemic, as a group of experts we propose some considerations for the progressive evolution of vaccination against SARS-CoV-2 from pandemic to endemic vaccination.

Trends in influenza coverage rates in five consecutive immunisation seasons in the Local Health Unit of Ferrara (North Italy).

Seasonal influenza epidemics yearly affects 5-15% of the world's population, resulting in 3-5 million serious cases and up to 650,000 deaths. Elderly, pregnant women and individuals with underlying conditions are at increased risk of complications. According to the Italian National Immunisation Prevention Plan 2017-2019, these categories benefit from free vaccination but coverage rate in Italy are below desirable levels. The study considered the coverage rate in five consecutive influenza seasons (2010/2011-2014/2015) in Local Health Unit (LHU) of Ferrara (Italy). The amount of delivered vaccinations was not constant, with a decreasing trend. Coverage rose with increasing age, but the 75% target of over-65 years old individuals immunised was never achieved. In addition to age, coverage rates varied also according to District (the area of residence within the LHU). The District with the lowest vaccination coverage was the Western District. Higher levels of immunisation were observed in South-Eastern District in the pediatric age and in North-Central District in adult age group with a statistically significant difference. In the considered timespan, the percentage of immunisations delivered by the General Practitioners (GPs) increased. The trend in the LHU of Ferrara was similar to regional and national data, conditioned in the 2014/2015 season by the spreading of worrying news, although unfounded, on the safety of the vaccine. The GPs were essential in ensuring vaccine uptake, growing the percentage of delivered doses and achieving as much as possible effective elderly immunisation.