Adjuvanted influenza vaccine for the Italian elderly in the 2018/19 season: an updated health technology assessment.

BACKGROUND: The elderly, defined here as subjects aged ≥ 65 years, are among at-risk subjects for whom annual influenza vaccination is recommended. For the 2018/19 season, three vaccine types are available for the elderly in Italy: trivalent inactivated vaccine (TIV), adjuvanted TIV (aTIV) and quadrivalent inactivated vaccines (QIV). No health technology assessment (HTA) of seasonal influenza vaccination in the elderly has previously been conducted in Italy. METHODS: An HTA was conducted in 2017 to analyze the burden of influenza illness, the characteristics, efficacy, safety and cost-effectiveness of available vaccines and the related organizational and ethical implications. This was then contextualized to the 2018/19 influenza season. Comprehensive literature reviews/analyses were performed and a static mathematical model developed in order to address the above issues. RESULTS: In Italy, influenza is usually less common in the elderly than in other age-classes, but the burden of disease is the highest; >10% of infected elderly subjects develop complications, and about 90% of all influenza-related deaths occur in this age-class. All available vaccines are effective, safe and acceptable from an ethical standpoint. However, aTIV has proved more immunogenic and effective in the elderly. Furthermore, from the third payer's perspective, aTIV is highly cost-effective and cost-saving in comparison with TIV and QIV, respectively. Nevertheless, vaccination coverage needs to be improved. CONCLUSIONS: According to this HTA, aTIV appeared the vaccine of choice in the elderly. HTA should be reapplied whenever new relevant data become available.

[ESCULAPIO: A project to elaborate strategies and actions of multi-purpose health communication on vaccine preventable infectious diseases in order to increase vaccination coverage in the population]. / Progetto ESCULAPIO: Elaborazione di Strategie e di interventi di Comunicazione sanitaria mUlti-obiettivo sulle maLAttie infettive Prevenibili e sulle vaccInazioni come mezzo per aumentare le cOperture vaccinali nella popolazione.

ESCULAPIO Project, funded by the Centre for Disease Prevention and Control (CCM) of the Italian Ministry of Health, for the program 2013, aims at increasing awareness on vaccine preventable infectious diseases (VPID) and vaccination in different targets of population and at spreading the culture of prevention by the development of information/training interventions on VPID. In Tuscany Region (Central Italy), educational courses on VPID in high schools were organized and students were stimulated to prepare informative materials on VPID for lower grade school pupils. Educational games for school pupils were realized in Liguria Region (Northern Italy) with the aim to increase awareness and knowledge of vaccination among primary school children, their families, and teachers. The Sicilian Operative Unit (OU) developed and validated a questionnaire to collect data on the main factors influencing vaccine uptake in a population from Southern Italy and spreading information on vaccines to the general population. Aim of the activities performed in Apulia Region (Southern Italy) was to collect, directly from the public, a set of issues to which people were more "sensitive," in order to perceive the dimension of informative needs and the misinformation in the field of vaccinations. A toll-free telephone line to answer questions on VPID was also the aim of the Apulian activities. The objective of the OU of Sardinia (Southern Italy) was to increase knowledge on VPID and adherence to immunization campaigns in health care workers (HCW) by realizing traditional and e-learning training courses and initiatives of health promotion in healthcare and hospital setting. Interventions to promote vaccinations in maternal and child health services and outreach interventions in case of parental non-compliance with vaccination schedules were performed in the Veneto Region (Northern Italy), with the aim to reach a particular subgroup of the general population: new or future parents. The activities of Veneto Region aimed also at realizing individual interviews with parents and/or home visit, if considered useful, for families not respondents to the active ordinary call.

Clustering of health-related behaviors among early and mid-adolescents in Tuscany: results from a representative cross-sectional study.

Background: A huge amount of literature suggests that adolescents' health-related behaviors tend to occur in clusters, and the understanding of such behavioral clustering may have direct implications for the effective tailoring of health-promotion interventions. Despite the usefulness of analyzing clustering, Italian data on this topic are scant. This study aimed to evaluate the clustering patterns of health-related behaviors. Methods: The present study is based on data from the Health Behaviors in School-aged Children (HBSC) study conducted in Tuscany in 2010, which involved 3291 11-, 13- and 15-year olds. To aggregate students' data on 22 health-related behaviors, factor analysis and subsequent cluster analysis were performed. Results: Factor analysis revealed eight factors, which were dubbed in accordance with their main traits: 'Alcohol drinking', 'Smoking', 'Physical activity', 'Screen time', 'Signs & symptoms', 'Healthy eating', 'Violence' and 'Sweet tooth'. These factors explained 67% of variance and underwent cluster analysis. A six-cluster κ-means solution was established with a 93.8% level of classification validity. The between-cluster differences in both mean age and gender distribution were highly statistically significant. Conclusions: Health-compromising behaviors are common among Tuscan teens and occur in distinct clusters. These results may be used by schools, health-promotion authorities and other stakeholders to design and implement tailored preventive interventions in Tuscany.

[The economic value of vaccinations: a systematic review of Italian economic evaluations and HTA reports]. / Le implicazioni economiche delle vaccinazioni: una revisione sistematica delle valutazioni economiche e di HTA condotte in Italia.

INTRODUCTION: Decision-making in healthcare should rely on evidence-based approaches able to make possible a transparent and robust assessment of all the aspects related to health technologies. One of the assessment elements is represented by the efficiency that is the specific objective of economic evaluations and also of Health Technology Assessment (HTA). The collection and synthesis of evidence is the first indispensable step in order to foster a proper convey of scientific knowledge to the decision-makers. This work, carried out within a broader project on the transfer of evidence from the scientific to the decision making world, is aimed to release an overview of economic evaluations and HTA on vaccines conducted in Italy. The project was carried out within the activities of the ISPOR Italy-Rome Chapter. METHODS: A systematic review of Italian economic evaluations and HTA performed on vaccines and published up to May 2015 was carried out. PubMed, Scopus and the NIHR HTA databases were queried and a hand-search was performed on key journals in the field (Global & Regional Health Technology Assessment; PharmacoEconomics Italian Research Articles; Giornale italiano di HTA; Politiche Sanitarie; HTA Focus - Pills of Clinical Governance; Pillole di Farmacoeconomia; Giornale Italiano di Farmacoeconomia e Farmacoutilizzazione; IJPH; Quaderni dell'IJPH). Studies were considered eligible if showing the results of a full economic evaluations and if performed in Italy. RESULTS: The literature search yielded 10 HTA reports and 33 economic evaluations. Among the latter, 20 (60,6%) were cost-effectiveness analyses. Ten studies (23,3%) assessed the vaccination against S. pneumoniae figuring out that it is cost-effectiveness and even costsaving in cases of newborns and subjects at risk. Nine studies (20,9%) addressed influenza vaccination and demonstrated its dominance on non-vaccination in the elderly. Eight studies (18,6%) evaluated the HPV vaccines concluding that they are cost-effective. Five studies (11,6%) devoted to anti-rotavirus vaccination showing its dominance on non-vaccination, in particular from the society perspective. Vaccination against pertussis, hepatitis B, chicken pox, measles, rubella, mumps were eventually shown cost-saving. The vaccine against Neisseria meningitidis was considered potentially cost-effective. CONCLUSION: The Italian scientific evidence on efficiency of vaccination is broad and allows concluding that vaccinations are value for money interventions.

An eHealth Project on Invasive Pneumococcal Disease: Comprehensive Evaluation of a Promotional Campaign.

BACKGROUND: The recently launched Pneumo Rischio eHealth project, which consists of an app, a website, and social networking activity, is aimed at increasing public awareness of invasive pneumococcal disease (IPD). The launch of this project was prompted by the inadequate awareness of IPD among both laypeople and health care workers, the heavy socioeconomic burden of IPD, and the far from optimal vaccination coverage in Italy, despite the availability of safe and effective vaccines. OBJECTIVE: The objectives of our study were to analyze trends in Pneumo Rischio usage before and after a promotional campaign, to characterize its end users, and to assess its user-rated quality. METHODS: At 7 months after launching Pneumo Rischio, we established a 4-month marketing campaign to promote the project. This intervention used various approaches and channels, including both traditional and digital marketing strategies. To highlight usage trends, we used different techniques of time series analysis and modeling, including a modified Mann-Kendall test, change-point detection, and segmented negative binomial regression of interrupted time series. Users were characterized in terms of demographics and IPD risk categories. Customer-rated quality was evaluated by means of a standardized tool in a sample of app users. RESULTS: Over 1 year, the app was accessed by 9295 users and the website was accessed by 143,993 users, while the project's Facebook page had 1216 fans. The promotional intervention was highly effective in increasing the daily number of users. In particular, the Mann-Kendall trend test revealed a significant (P ≤.01) increasing trend in both app and website users, while change-point detection analysis showed that the first significant change corresponded to the start of the promotional campaign. Regression analysis showed a significant immediate effect of the intervention, with a mean increase in daily numbers of users of 1562% (95% CI 456%-4870%) for the app and 620% (95% CI 176%-1777%) for the website. Similarly, the postintervention daily trend in the number of users was positive, with a relative increase of 0.9% (95% CI 0.0%-1.8%) for the app and 1.4% (95% CI 0.7%-2.1%) for the website. Demographics differed between app and website users and Facebook fans. A total of 69.15% (10,793/15,608) of users could be defined as being at risk of IPD, while 4729 users expressed intentions to ask their doctor for further information on IPD. The mean app quality score assigned by end users was approximately 79.5% (397/500). CONCLUSIONS: Despite its specific topic, Pneumo Rischio was accessed by a considerable number of users, who ranked it as a high-quality project. In order to reach their target populations, however, such projects should be promoted.

Development and validation of the Italian version of the Mobile Application Rating Scale and its generalisability to apps targeting primary prevention.

BACKGROUND: A growing body of literature affirms the usefulness of mobile technologies, including mobile applications (apps), in the primary prevention field. The quality of health apps, which today number in the thousands, is a crucial parameter, as it may affect health-related decision-making and outcomes among app end-users. The mobile application rating scale (MARS) has recently been developed to evaluate the quality of such apps, and has shown good psychometric properties. Since there is no standardised tool for assessing the apps available in Italian app stores, the present study developed and validated an Italian version of MARS in apps targeting primary prevention. METHODS: The original 23-item version of the MARS assesses mobile app quality in four objective quality dimensions (engagement, functionality, aesthetics, information) and one subjective dimension. Validation of this tool involved several steps; the universalist approach to achieving equivalence was adopted. Following two backward translations, a reconciled Italian version of MARS was produced and compared with the original scale. On the basis of sample size estimation, 48 apps from three major app stores were downloaded; the first 5 were used for piloting, while the remaining 43 were used in the main study in order to assess the psychometric properties of the scale. The apps were assessed by two raters, each working independently. The psychometric properties of the final version of the scale was assessed including the inter-rater reliability, internal consistency, convergent, divergent and concurrent validities. RESULTS: The intralingual equivalence of the Italian version of the MARS was confirmed by the authors of the original scale. A total of 43 apps targeting primary prevention were tested. The MARS displayed acceptable psychometric properties. The MARS total score showed an excellent level of both inter-rater agreement (intra-class correlation coefficient of .96) and internal consistency (Cronbach's α of .90 and .91 for the two raters, respectively). Other types of validity, including convergent, divergent, discriminative, known-groups and scalability, were also established. CONCLUSIONS: The Italian version of MARS is a valid and reliable tool for assessing the health-related primary prevention apps available in Italian app stores.

Human papillomavirus detection in paraffin-embedded colorectal cancer tissues.

Human papillomavirus (HPV) has a well-recognized aetiological role in the development of cervical cancer and other anogenital tumours. Recently, an association between colorectal cancer and HPV infection has been suggested, although this is still controversial. This study aimed at detecting and characterizing HPV infection in 57 paired biopsies from colorectal cancers and adjacent intact tissues using a degenerate PCR approach. All amplified fragments were genotyped by means of sequencing. Overall, HPV prevalence was 12.3 %. In particular, 15.8 % of tumour tissues and 8.8 % of non-cancerous tissue samples were HPV DNA-positive. Of these samples, 85.7 % were genotyped successfully, with 41.7 % of sequences identifying four genotypes of the HR (high oncogenic risk) clade Group 1; the remaining 58.3 % of HPV-genotyped specimens had an unclassified ß-HPV. Examining additional cases and analysing whole genomes will help to outline the significance of these findings.

Trends in overweight and obesity prevalence in Tuscan schoolchildren (2002-2012).

OBJECTIVE: The aim of the present study was to examine the prevalence and time trends in childhood overweight including obesity and obesity among Tuscan children from 2002 to 2012. DESIGN: Cross-sectional study at five time points (Tuscan Nutritional Surveillance Surveys conducted in the years of 2002, 2006, 2008, 2010 and 2012). Trained personnel directly measured the height and weight of the subjects. BMI was assessed by means of the International Obesity Task Force (IOTF) and WHO cut-offs. SETTING: Representative sample of children in the Tuscany region (Italy). SUBJECTS: Children (n 7183) aged between 7·5 and 9·5 years (3711 boys and 3472 girls). RESULTS: With respect to the estimation of the absolute prevalence level of childhood overweight, a discrepancy was observed between the two criteria. In all surveys, more boys than girls were overweight (including obesity). Trend analysis showed a significant decrease in the prevalence of overweight including obesity and obesity in Tuscan children from 2002 to 2012 (32·0 % v. 25·8 %, P<0·001 on using IOTF criteria and 37·7 % v. 34·3 %, P<0·001 on using WHO criteria for overweight including obesity; and 10·0 % v. 6·7 %, P<0·001 on using IOTF criteria and 12·5 % v. 11·3 %, P=0·035 on using WHO criteria for obesity). CONCLUSIONS: The present study is the first report from an Italian region showing a significant decrease in childhood obesity and overweight in the last 10 years. This reduction is probably a result of regional and local actions that have taken place in many sectors of society. However, efforts should be made to lower the prevalence of childhood obesity and overweight further.

Uncontrolled Web-based administration of surveys on factual health-related knowledge: a randomized study of untimed versus timed quizzing.

BACKGROUND: Health knowledge and literacy are among the main determinants of health. Assessment of these issues via Web-based surveys is growing continuously. Research has suggested that approximately one-fifth of respondents submit cribbed answers, or cheat, on factual knowledge items, which may lead to measurement error. However, little is known about methods of discouraging cheating in Web-based surveys on health knowledge. OBJECTIVE: This study aimed at exploring the usefulness of imposing a survey time limit to prevent help-seeking and cheating. METHODS: On the basis of sample size estimation, 94 undergraduate students were randomly assigned in a 1:1 ratio to complete a Web-based survey on nutrition knowledge, with or without a time limit of 15 minutes (30 seconds per item); the topic of nutrition was chosen because of its particular relevance to public health. The questionnaire consisted of two parts. The first was the validated consumer-oriented nutrition knowledge scale (CoNKS) consisting of 20 true/false items; the second was an ad hoc questionnaire (AHQ) containing 10 questions that would be very difficult for people without health care qualifications to answer correctly. It therefore aimed at measuring cribbing and not nutrition knowledge. AHQ items were somewhat encyclopedic and amenable to Web searching, while CoNKS items had more complex wording, so that simple copying/pasting of a question in a search string would not produce an immediate correct answer. RESULTS: A total of 72 of the 94 subjects started the survey. Dropout rates were similar in both groups (11%, 4/35 and 14%, 5/37 in the untimed and timed groups, respectively). Most participants completed the survey from portable devices, such as mobile phones and tablets. To complete the survey, participants in the untimed group took a median 2.3 minutes longer than those in the timed group; the effect size was small (Cohen's r=.29). Subjects in the untimed group scored significantly higher on CoNKS (mean difference of 1.2 points, P=.008) and the effect size was medium (Cohen's d=0.67). By contrast, no significant between-group difference in AHQ scores was documented. Unexpectedly high AHQ scores were recorded in 23% (7/31) and 19% (6/32) untimed and timed respondents, respectively, very probably owing to "e-cheating". CONCLUSIONS: Cribbing answers to health knowledge items in researcher-uncontrolled conditions is likely to lead to overestimation of people's knowledge; this should be considered during the design and implementation of Web-based surveys. Setting a time limit alone may not completely prevent cheating, as some cheats may be very fast in Web searching. More complex and contextualized wording of items and checking for the "findability" properties of items before implementing a Web-based health knowledge survey may discourage help-seeking, thus reducing measurement error. Studies with larger sample sizes and diverse populations are needed to confirm our results.

Molecular and serological diversity of Neisseria meningitidis carrier strains isolated from Italian students aged 14 to 22 years.

Neisseria meningitidis is an obligate human commensal that commonly colonizes the oropharyngeal mucosa. Carriage is age dependent and very common in young adults. The relationships between carriage and invasive disease are not completely understood. In this work, we performed a longitudinal carrier study in adolescents and young adults (173 subjects). Overall, 32 subjects (18.5%) had results that were positive for meningococcal carriage in at least one visit (average monthly carriage rate, 12.1%). Only five subjects tested positive at all four visits. All meningococcal isolates were characterized by molecular and serological techniques. Multilocus sequence typing, PorA typing, and sequencing of the 4CMenB vaccine antigens were used to assess strain diversity. The majority of positive subjects were colonized by capsule null (34.4%) and capsular group B strains (28.1%), accounting for 23.5% and 29.4% of the total number of isolates, respectively. The fHbp and nhba genes were present in all isolates, while the nadA gene was present in 5% of the isolates. The genetic variability of the 4CMenB vaccine antigens in this collection was relatively high compared with that of other disease-causing strain panels. Indications about the persistence of the carriage state were limited to the time span of the study. All strains isolated from the same subject were identical or cumulated minor changes over time. The expression levels and antigenicities of the 4CMenB vaccine antigens in each strain were analyzed by the meningococcal antigen typing system (MATS), which revealed that expression can change over time in the same individual. Future analysis of antigen variability and expression in carrier strains after the introduction of the MenB vaccine will allow for a definition of its impact on nasopharyngeal/oropharyngeal carriage.

Do the omeprazole family compounds exert a protective effect against influenza-like illness?

BACKGROUND: Infections by influenza viruses place a heavy burden on public health and economies worldwide. Although vaccines are the best weapons against influenza, antiviral drugs could offer an opportunity to alleviate the burden of influenza. Since omeprazole family compounds block the "proton pump", we hypothesized that they could interfere with the mechanism of fusion of the virus envelope and endosomal membrane, thereby hindering the M2 proton pump mechanism of influenza viruses. METHODS: A matched case-control study was performed in 2010-2011 in Italy. Cases were subjects aged over 18 years with a diagnosis of Influenza-like Illness (ILI); 254 case-control pairs were recruited. A multivariable conditional logistic regression analysis was used to assess the association between the prevention of ILI and the administration of omeprazole family compounds. The interaction between omeprazole family compounds and influenza vaccination was also examined. RESULTS: After control for potential confounders, subjects treated with omeprazole family compounds displayed a lower risk of catching ILI (ORadj = 0.29, 95% CI: 0.15-0.52). The risk of ILI in unvaccinated non-OFC users was about six times than that in vaccinated OFC users. CONCLUSIONS: Although confirmation is necessary, these results suggest that omeprazole family compounds could be profitably used in the prevention of ILI.

Prevalence of human papillomavirus in young Italian women with normal cytology: how should we adapt the national vaccination policy?

BACKGROUND: Human Papillomavirus (HPV) is the most common sexually transmitted infection. In Italy, HPV vaccination is now offered free of charge to 12-year-old females. However, some regional health authorities have extended free vaccination to other age-groups, especially to girls under 18 years of age. We conducted a multicentre epidemiological study to ascertain the prevalence of different genotypes of HPV in young Italian women with normal cytology, with the aim of evaluating the possibility of extending vaccination to older females. METHODS: The study was performed in 2010. Women aged 16-26 years with normal cytology were studied. Cervical samples were analyzed to identify the presence of HPV by PCR amplification of a segment of ORF L1 (450 bp). All positive HPV-DNA samples underwent viral genotype analysis by means of a restriction fragment length polymorphism assay. RESULTS: Positivity for at least one HPV genotype was found in 18.2% of the 566 women recruited: 48.1% in the 16-17 age-class, 15.4 in the 18-20 age-class, 21.9% in the 21-23 age-class, and 15.5% in the 24-26 age-class; 10.1% of women were infected by at least one high-risk HPV genotype. HPV-16 was the most prevalent genotype. Only 4 (0.7%), 4 (0.7%) and 3 (0.5%) women were infected by HPV-18, HPV-6 and HPV-11, respectively. Of the HPV-DNA-positive women, 64.1% presented only one viral genotype, while 24.3% had multiple infections. The HPV genotypes most often involved in multiple infections were high-risk. A high prevalence was noted in the first years of sexual activity (48.1% of HPV-DNA-positive women aged 16-17 years); HPV prevalence subsequently declined and stabilized.The estimate of cumulative proportions of young women free from any HPV infection at each age was evaluated; 93.3% and 97.1% of 26 year-old women proved free from HPV-16 and/or HPV-18 and from HPV-6 and/or HPV-11, respectively. CONCLUSIONS: Our findings confirm the crucial importance of conducting studies on women without cytological damage, in order to optimise and up-date preventive interventions against HPV infection, and suggest that vaccinating 26-year-old females at the time of their first pap-test is to be recommend, though this issue should be further explored.

Use of different subjective health indicators to assess health inequalities in an urban immigrant population in north-western Italy: a cross-sectional study.

BACKGROUND: Despite the steady growth of the immigrant population in Italy, data on the health status of immigrants are scarce. Our main goals were to measure Health-Related Quality of Life (HRQoL), Self-Rated Health (SRH) and morbidity among immigrants in Genoa. We aimed to assess the relative contribution of some social, structural and behavioral determinants to "within-group" health disparities. METHODS: We enrolled 502 subjects by means of snowball sampling. The SF-12 questionnaire, integrated with socio-demographic and health-related items, was used. Multivariate logistic and Poisson regression models were applied in order to identify characteristics associated with poor SRH, lower SF-12 scores and prevalence of self-reported morbidities. RESULTS: Subjects showed relatively moderate levels of HRQoL (median physical and mental scores of 51.6 and 47.3, respectively) and about 15% of them rated their health as fair or poor. Lower scores in the physical dimension of HRQoL were associated with the presence of morbidities and immigration for work and religious reasons, while those who had migrated for religious and family reasons displayed a lower probability of lower scores in the mental dimension of HRQoL. Poor SRH was associated with female gender, overweight/obesity and presence of morbidities. Moreover, compared with immigrants from countries with a low human development index, immigrants from highly developed societies showed significantly lower odds of reporting poor SRH. About one-third of respondents reported at least one medical condition, while the prevalence of multi-morbidity was 10%. Females, over 45-year-olds, overweight and long-term immigrants had a higher prevalence of medical conditions. CONCLUSIONS: Our study confirms the presence of health inequalities within a heterogeneous immigrant population. HRQoL, SRH and morbidity are valid, relatively rapid and cheap tools for measuring health inequalities, though they do so in different ways. These indicators should be used with caution and, if possible, simultaneously, as they could help to identify and to monitor more vulnerable subjects among immigrants.

Sexual behaviour and risk factors for the acquisition of human papillomavirus infections in young people in Italy: suggestions for future vaccination policies.

BACKGROUND: Human Papillomavirus (HPV) is the most common sexually transmitted infection. The main risk factors correlated with HPV infection are: early sexual debut, the number of partners, frequency and type of sexual contact and partner's sexual histories.We surveyed sexual habits among young people in order to provide information that might orient decision-makers in adopting HPV multi-cohort vaccination policies. METHODS: We administered a questionnaire to students (14-24 years old) in five Italian cities. RESULTS: 7298 questionnaires were analyzed (4962 females and 2336 males); 55.3% of females (95% CI 53.9-56.7) and 52.5% of males (95% CI 50.5-54.5) reported regular sexual activity. The mean age at sexual debut was 15.7 ± 1.6 and 15.6 ± 1.6 for females and males, respectively, and the median age was 16 for both sexes.With regard to contraceptive use during the last year, 63.6% of males and 62.8% of females responded affirmatively; 42.6% of males and 42.8% of females used condoms. CONCLUSION: The results reveal precocious sexual activity among respondents, with the mean age at first intercourse declining as age decreases. Condom use proved to be scant. Considering lifestyle-related risk factors, males appear to have a higher probability of acquiring HPV infection than females.These data support the importance of promoting multi-cohort HPV vaccination strategies for females up to 25 years of age. It is essential to improve vaccination coverage through different broad-spectrum strategies, including campaigns to increase awareness of sexually transmitted diseases and their prevention.

Meningococcal glycoconjugate vaccines.

Neisseria meningitidis is a major cause of invasive bacterial infections worldwide. For this reason, efforts to control the disease have been directed at optimizing meningococcal vaccines and implementing appropriate vaccination policies. In the past, plain polysaccharide vaccines containing purified capsular polysaccharides A, C, Y and W135 were developed, but failed to protect infants, who are at greatest risk. Experience with the conjugate Haemophilus vaccine suggested that this approach might well empower meningococcal vaccines. Thus, a very efficacious vaccine against serogroup C Neisseria meningitis was optimized and has been widely used in developed nations since 1999. On the basis of epidemiological changes in the circulation of pathogenic serogroups in the United States, a quadrivalent conjugate vaccine against A, C, Y and W135 serogroups (Menactra™) has been developed and was approved by the U.S. FDA (Food and Drug Administration) in 2005. Recently, another tetravalent conjugate meningococcal vaccine (Menveo™) has been licensed and made available in the United States of America and in the European Union. Finally, in response to large epidemics caused by serogroup A meningococcus in Africa, a new, safe, immunogenic and affordable vaccine has been developed. This review highlights the evolution of conjugate meningococcal vaccines in general and discusses how this kind of vaccine can contribute to preventing meningococcal disease.

An overview on the implementation of HPV vaccination in Europe.

The discovery that the Human PapillomaVirus (HPV) is the necessary cause of cervical cancer has led to the development of prophylactic vaccines. Cervical cancer is the second most common cause of death from cancer among young women in Europe: mortality is still high, despite its important reduction due to screening programs for early detection. Besides cervical cancer, HPV is responsible for a significant proportion of other anogenital cancers and an increasing number of oropharyngeal cancers, representing together an at least equal burden compared to cervical cancer. HPV is also responsible for conditions such as condyloma acuminata (genital warts) and recurrent respiratory papillomatosis. Organized vaccination programs against HPV have the potential to prevent about 70% of cervical cancers and the vast majority of the other HPV-related conditions. Recommendations for HPV vaccination of at least one cohort of females have been issued in nearly all western European countries, and national/regional publicly funded vaccination programs have been introduced in most of them. Different approaches have been chosen for the implementation of HPV vaccination, based on the organization of each country's health care system. A brief outline of these programs in Europe is presented. As for all preventive public health interventions, high coverage of the target population with HPV vaccines pre-exposure is essential to achieve maximum reduction of cases: therefore, in order to obtain the maximum and most equitable coverage and future benefit, programs targeting adolescents before exposure to HPV should be preferred and population-based. Catch-up programs should also be implemented wherever possible, in order to deliver more and even earlier benefits, and effective communication strategies need to be adopted.

Burden of the 1999-2008 seasonal influenza epidemics in Italy: comparison with the H1N1v (A/California/07/09) pandemic.

Despite preventive efforts, seasonal influenza epidemics are responsible for substantial morbidity and mortality every year worldwide, including developed countries. The A/H1N1v pandemic imposed a considerable healthcare and economic burden. In order to obtain an accurate estimate of the economic burden of influenza, and hence to guide policymakers effectively, systematic studies are necessary. To this end, data from epidemiological surveillance are essential. To estimate the impact of the 1999-2008 seasonal influenza epidemics and the H1N1v pandemic, we analyzed data from the Italian Influenza Surveillance System (CIRI NET). In the period 1999-2008, the Italian surveillance network consisted of sentinel general practitioners and pediatricians, who reported cases of Influenza-Like Illness (ILI) and Acute Respiratory Infections (ARI ) observed during their clinical practice from mid-October to late April each year; reports were sent to the Center for Research on Influenza and other Viral Infections (CIRI -IV). CIRI -IV receives data from 9 of the 20 Italian regions: Liguria, Abruzzo, Calabria, Friuli Venezia Giulia, Lombardy, Puglia, Sicily, Tuscany and Umbria. Previous estimates of influenza case costs were used in economic evaluations. Clinical-epidemiological and virological surveillance of the seasonal epidemics from 1999-2008 showed that the highest epidemic period was 2004-2005, when a new variant of the H3N2 influenza virus subtype emerged (A/California/07/04). Indeed, the highest peak of morbidity in the decade occurred in February 2005 (12.6 per 1,000 inhabitants). In 1999-2008, H1N1 subtype strains circulated and co-circulated with strains belonging to the H3N2 subtype and B type. Regarding B viruses in 2001-02, viruses belonged to the B/Victoria/02/07 lineage re-emerged, and in subsequent years co-circulated with viruses belonging to the B/Yamagata/lineage. The estimated costs of seasonal epidemics from 1999-2008 in Italy ranged from €15 to €20 billion, and the costs of the H1N1v pandemic ranged from €1.3 to €2.3 billion. This Italian study yields interesting conclusions: the results of influenza surveillance in several developed countries vary markedly; influenza imposes a considerable social, healthcare and economic burden; most cases that occurred during the pandemic involved subjects under 14 years of age and, although the clinical course of H1N1v influenza was usually mild, the related economic burden was heavy.

Safety and tolerability of bivalent HPV vaccine: an Italian post-licensure study.

One of the most important scientific discoveries of the last century was that persistent infection by some types of HPV is a precondition for the development of cervical cancer. The oncogenic types of HPV are also associated with other tumours (vaginal, vulvar and anal carcinomas, tumours of the head and neck, urethra and penis). Two preventive vaccines are currently available (Cervarix and Gardasil). Both have shown very good efficacy, safety and tolerability profiles. Nonetheless, extensive vaccination requires long-term monitoring of safety and tolerability. The aim of our study was to evaluate the safety and tolerability of the bivalent vaccine Cervarix in Italy. Every participant in the study completed a questionnaire after each dose of vaccine received, with a view to recording adverse events during the first 7 days after vaccination. We registered local (pain, redness, swelling) and systemic symptoms (fever, headache, myalgia, fatigue, arthralgia, itching, gastrointestinal disorders, rash and urticaria). A total of 4,643 subjects were recruited. In all, 7,107 questionnaires were collected: 3,064 after the first dose, 2,367 after the second and 1,676 after the third. No serious adverse events were observed. The most frequent local symptom was pain at the injection site, while fatigue, headache and myalgia were the most common systemic reactions. Pain was reported more frequently after the first dose than after the others, while all the other local and general symptoms were reported most frequently after the third dose. Almost all of the local and general reactions proved to be of negligible intensity and duration and required no medical intervention. Our results show better tolerability of the vaccine in comparison with the data from some controlled clinical studies and from other surveillance programmes conducted internationally. That tolerability proved to be better than in clinical studies could be explained by the absence of the typical apprehension felt by subjects involved in clinical experimentation.

Burden of rotavirus-associated and non-rotavirus-associated diarrhea among nonhospitalized individuals in central Italy: a 1-year sentinel-based epidemiological and virological surveillance.

A community sentinel pediatrician-based epidemiological and virological surveillance study was conducted to estimate the incidence of gastroenteritis and laboratory-confirmed rotavirus-associated disease. The 1-year cumulative incidence of gastroenteritis in the cohort of children aged 0-5 years was 21%, with the highest rates in the 7-12-month and 13-18-month age groups (41.1% and 41.7%, respectively). Approximately one-third of gastroenteritis cases requiring an office visit or telephone consultation were attributable to rotavirus infection.

Heterogeneous estimates of influenza virus types A and B in the elderly: Results of a meta-regression analysis.

Influenza has many age-dependent characteristics. A previous systematic review of randomized controlled trials showed that the detection rate of influenza B was higher in children than in non-elderly adults. However, no comprehensive reviews have targeted the elderly, who carry the main burden of disease. We aimed to quantify the relative detection rates of virus types A and B among the elderly, to identify factors affecting these proportions, and to compare type distribution among seniors and younger age-classes. A comprehensive literature search was conducted to identify multiseason studies reporting A and B virus type distributions in the elderly. A random-effects meta-analysis was planned to quantify the prevalence of type B among elderly subjects with laboratory-confirmed influenza. Meta-regression was then applied to explain the sources of heterogeneity. Across 27 estimates identified, the type B detection rate among seniors varied from 5% to 37%. Meta-analysis was not feasible owing to high heterogeneity (I2  = 98.5%). Meta-regression analysis showed that study characteristics, such as number of seasons included, hemisphere, and setting, could have contributed to the heterogeneity observed. The final adjusted model showed that studies that included both outpatients and inpatients reported a significantly (P = .024) lower proportion than those involving outpatients only. The detection rate of type B among the elderly was generally lower than in children/adolescents, but not non-elderly adults. Influenza virus type B has a relatively low detection rate in older adults, especially in settings covering both inpatients and outpatients. Public health implications are discussed.