R. Gasparini

Socioeconomic impact of influenza on healthy children and their families

Background. Recent studies indicate that influenza can be clinically important in otherwise healthy children. However, the interpretation of many studies is limited because of lack of laboratory confirmation of influenza-like illnesses. Therefore it is difficult to conclude whether the socioeconomic impact of influenza justifies vaccinating all children regardless of age or underlying chronic disorders. Methods. We prospectively collected data from 3771 children younger than 14 years of age presenting to emergency departments or primary care pediatricians with symptoms of respiratory tract infection during the influenza season of 2001 to 2002. Influenza infections were verified by virus culture or polymerase chain reaction. We additionally randomized 303 children age 6 months to 5 years to receive either influenza vaccine (n = 202) or no vaccination (n = 101) before the influenza season. The socioeconomic impact of influenza was assessed for both the participating children and their household contacts. Results. Influenza was documented in 352 (9.3%) of the 3771 children. Compared with influenza-negative children, children with influenza had longer durations of fever and absenteeism from day care or school (P < 0.0001). Further the numbers of medical visits, missed work or school days and the need for help at home to care for the sick children were higher among the household contacts of influenza-positive children (P < 0.0001). Influenza vaccination reduced significantly the direct and indirect influenza-related costs in healthy children and their unvaccinated family members. Conclusions. The findings of this study support a wider use of influenza vaccine in healthy children of all ages to reduce the socioeconomic burden of influenza on the community.

Combination hepatitis C virus antigen and antibody immunoassay as a new tool for early diagnosis of infection.

Summary.u2002 Reduction of the window period of hepatitis C virus (HCV) infection represents an important goal in the transfusional and diagnostic setting. A prototype assay designed to simultaneously detect circulating HCV antigen and anti‐HCV, has been developed. Aim of this study was to evaluate the performance of this new assay in terms of specificity and sensitivity and to compare its efficacy with commercial assays. To evaluate the specificity of the assay, 400 samples from the general population and 100 ‘difficult’ sera, negative for anti‐HCV, were tested. To assess sensitivity, the new test was used on 76 PCR‐positive and anti‐HCV negative sera, seven natural or commercial seroconversion panels that included 17 RNA‐positive and anti‐HCV negative sera and 31 anti‐HCV positive sera, 20 weak anti‐HCV positive sera, 80 viraemic and anti‐HCV‐positive sera from patients infected with different subtypes and 10 sera from patients with HBV–HCV or HIV–HCV co‐infections. Of 500 anti‐HCV negative samples, 499 (99.8%) were negative with a cut‐off index <0.5, while one sample was within the grey zone. Of the 93 HCV‐RNA positive and anti‐HCV negative sera from patients and panels, 85 (91.4%) resulted positive, and one had the cut‐off index in the grey zone. The reduction in the diagnostic window period observed with the new test and HCV‐RNA assays were equal, on average, to 24 and 34.4u2003days respectively. All anti‐HCV positive sera were positive. The new assay shows high sensitivity and specificity and could be a useful tool not only in the diagnostic setting, where procedures to reduce the window period, such as antigen or HCV‐RNA detection, are not currently recommended, but also in the screening of blood donations, when nucleic acid technologies is not feasible because of costs, organization, emergency and/or logistic difficulties.

Cost-effectiveness of new adult pneumococcal vaccination strategies in Italy.

Community-acquired pneumonia (CAP) and invasive pneumococcal disease (IPD) are very relevant pathologies among elderly people (≥ 65 y old), with a consequent high disease burden. Immunization with the 23-valent pneumococcal polysaccharide vaccine (PPV23) has been differently implemented in the Italian regions in the past years, reaching overall low coverage rates even in those with medical indications. In 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) became available and recommended in the universal Italian infant immunization program. Since October 2012, indications for use of PCV13 were extended to subjects ≥ 50 y to prevent invasive pneumococcal diseases. The Italian decision makers should now revise regional indications for the prevention of pneumococcal diseases in the elderly. Pharmaco-economic analyses represent a useful tool to value the feasibility of new immunization programs and their sustainability. Therefore, an ad hoc population model was developed in order to value the clinical and economic impact of an adult pneumococcal vaccination program in Italy. Particularly, different immunization scenarios were modeled: vaccination of 65 y-olds (1 cohort strategy), simultaneous vaccination of people aged 65 and 70 y (double cohort strategy) and, lastly, immunization of people aged 65, 70 and 75 y (triple cohort strategy), thus leading to the vaccination of 5, 10 and 15 cohorts during the 5 y of the program. In addition, the administration of a PPV23 dose one year after PCV13 was evaluated, in order to verify the economic impact of the supplemental serotype coverage in elderly people. The mathematical model valued the clinical impact of PCV13 vaccination on the number of bacteraemic pneumococcal pneumonia (BPP) and pneumococcal meningitis (PM) cases, and related hospitalizations and deaths. Although PCV13 is not yet formally indicated for the prevention of pneumococcal CAP by the European Medicine Agency (differently from FDA, whose indications include all pneumococcal diseases in subjects ≥ 50 y), the model calculated also the possible impact of vaccination on CAP cases (non-bacteraemic), considering the rate of this disease due to S. pneumoniae. The results of the analysis show that, in Italy, an age-based PCV13 vaccination program in elderly people is cost-effective from the payer perspective, with costs per QALY ranging from 17,000 to 22,000 Euro, according to the adopted vaccination strategy. The subsequent PPV23 offer results in an increment of costs per QALY (from 21,000 to 28,000 Euro, according to the vaccination strategy adopted). Pneumococcal vaccination using the conjugate vaccine turned out to be already favorable in the second year of implementation, with incremental costs per QALY comparable to those of other already adopted prevention activities in Italy (for instance, universal HPV vaccination of 12 y-old girls), with further benefits obtained when extending the study period beyond the 5-y horizon of our analysis.

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

BackgroundHuman 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.MethodsWe administered a questionnaire to students (14–24u2009years old) in five Italian cities.Results7298 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 15.7u2009±u20091.6 and 15.6u2009±u20091.6 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.ConclusionThe 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 25u2009years 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.

Detection and genotyping of human papillomavirus in urine samples from unvaccinated male and female adolescents in Italy.

The introduction of vaccination against Human Papillomavirus (HPV) in adolescent girls in 2006 has focused virological surveillance on this age group. As few studies have evaluated HPV infections in young populations, further data are needed in order to improve and extend prophylactic policy and to monitor epidemiological changes. The present study aimed at evaluating overall and type-specific HPV prevalence in both female and male adolescents in Italy. HPV DNA detection and genotyping was performed on urine samples collected from 870 unvaccinated adolescents (369 females, 501 males, 11-18 years of age) in five cities in Italy. Following DNA extraction by means of a commercial kit (NucliSENS®-miniMAG®, bioMérieux), the L1 gene fragment was PCR amplified and genotyped by restriction fragment length polymorphism analysis. HPV DNA was detected in 1.5% of all samples, and in 3% and 0.4% of samples from females and males, respectively. In approximately 70% of HPV DNA positive adolescents, the infection was due to a single genotype, with 88.9% of genotypes belonging to the HR-clade. The only two HPV-positive boys (14 and 18 years old) had HPV-70 genotype. Only one of the 11 HPV-infected girls was in the 11-14 age-group. HPV prevalence was 4.2% in girls aged 15-18 years and 60% of infections were due to vaccine types HPV-16 or HPV-6/-11. This is one of the few studies, the first conducted in Italy, on HPV infection in adolescents. Urine testing is the easier way of detecting HPV infection in younger populations. Our data revealed a very low HPV prevalence, and no infections were observed in the 12-year-old vaccine target population. The majority of infections were seen in females aged 15-18 years. Overall, more than 50% and 30% of the potentially persistent HPV infections detected in this group could have been prevented by the quadrivalent and the bivalent vaccines, respectively.

Influenza and respiratory syncytial virus in infants and children: relationship with attendance at a paediatric emergency unit and characteristics of the circulating strains

A study was carried out on 2,696 Italian children, aged 0–14xa0years. The goals were: (1) to define the age-related impact of acute respiratory infections (ARI), measured as the risk of attendance at the Paediatric Emergency Room, (2) to better define the importance and proportion of influenza and respiratory syncytial virus (RSV) infections and (3) to acquire deeper knowledge of the influenza strains circulating in infants and children. A standardised emergency unit attendance risk (EUAR) was calculated, by age group for ARI. Specific EUARs were also calculated for the two pathogens. Pharyngeal swabs were tested by polymerase chain reaction (PCR) for influenza and RSVs. Isolation in Madine-Darby canine kidney cells (MDCK) and Hep cells, haemagglutination inhibition (HI) testing and HA1 gene sequence analysis were performed for influenza viruses. Most of the patients enrolled were aged 0–5xa0years, 1,139 (84.6%) and 1,061 (78.5%) in the two seasons, respectively. The most represented age class was that of 1 year olds (331 cases in 2001–2002 and 301 in 2002–2003). The highest EUAR for ARI was in patients aged 0–3xa0years (16.8 and 12.9 during the two seasons). The same was observed on calculating this risk by specific pathogens: 17.4 and 5.5 for influenza and 13.0 and 12.7 for RSV. Virological analysis was performed on 2,696 samples, 595 of which proved positive (22%). The highest number of isolates (326) came from patients aged 1–3xa0years. RSVs were more often identified than influenza viruses in infants aged up to 1xa0year (32 vs. 20 isolates). Of 265 strains isolated in 2001–2002, 103 were RSVs (87 type A, 16 B) and 162 were influenza (90 type A, 72 B). HI showed that influenza B viruses were related to two lineages, B/Victoria/2/87 (32%) and B/Yamagata/16/88 (68%). Of 330 strains isolated in 2002–2003, 102 were RSVs (91 type A, 11 B) and 228 were influenza viruses (220 type A, 8 B). A/H3N2 strains belonged to two clusters, A/Panama/2007/99-like and A/Fujian/411/02-like, a new variant. This paper discusses the possible role of the identified flu strains in determining EUARs among the population by age class.

Morpho-structural variations of bacterial spores after treatment in steam vacuum assisted autoclave.

We describe the activities of the Croatian Committee for Antibiotic Resistance Surveillance and report surveillance results for 1999. Twenty-two Croatian microbiology laboratories participated in the study. Resistance rates for the organisms isolated in different centers varied widely, but certain trends were apparent. Penicillin resistance in pneumococci (38%), methicillin resistance in Staphylococcus aureus (22%), the production of extended spectrum beta-lactamases by Klebsiella pneumoniae (21%), and imipenem resistance in Pseudomonas aeruginosa (11%) represent major resistance problems, especially in large hospitals. A comprehensive system of antimicrobial resistance surveillance, combined with training and external quality control programs, has identified high rates of resistance in key pathogens in some regions of Croatia. The program has heightened awareness of the problems of antimicrobial resistance and contributed to ongoing improvements in laboratory practice.

Evaluation of the economic burden of Herpes Zoster (HZ) infection

The main objective of this systematic review was to evaluate the economic burden of Herpes Zoster (HZ) infection. The review was conducted in accordance with the standards of the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” guidelines. The following databases were accessed: ISI/Web of Knowledge (WoS), MEDLINE/PubMed, Scopus, ProQuest, the Cochrane Library and EconLit. Specific literature on health economics was also manually inspected. Thirty-three studies were included. The quality of the studies assessed in accordance with the Consolidated Health Economic Evaluation Reporting Standards checklist was good. All studies evaluated direct costs, apart from one which dealt only with indirect costs. Indirect costs were evaluated by 12 studies. The economic burden of HZ has increased over time. HZ management and drug prescriptions generate the highest direct costs. While increasing age, co-morbidities and drug treatment were found to predict higher direct costs, being employed was correlated with higher indirect costs, and thus with the onset age of the disease. Despite some differences among the selected studies, particularly with regard to indirect costs, all concur that HZ is a widespread disease which has a heavy social and economic burden.

Influenza epidemiology in Italy two years after the 2009–2010 pandemic: Need to improve vaccination coverage

Since 2000, a sentinel surveillance of influenza, INFLUNET, exists in Italy. It is coordinated by the Ministry of Health and is divided into two parts; one of these is coordinated by the National Institute of Health (NIH), the other by the Inter-University Centre for Research on Influenza and other Transmissible Infections (CIRI-IT). The influenza surveillance system performs its activity from the 42nd week of each year (mid-October) to the 17th week of the following year (late April). Only during the pandemic season (2009/2010) did surveillance continue uninterruptedly. Sentinel physicians – about 1,200 general practitioners and independent pediatricians – send in weekly reports of cases of influenza-like illness (ILI) among their patients (over 2% of the population of Italy) to these centers. In order to estimate the burden of pandemic and seasonal influenza, we examined the epidemiological data collected over the last 3 seasons (2009–2012). On the basis of the incidences of ILIs at different ages, we estimated that: 4,882,415; 5,519,917; and 4,660,601 cases occurred in Italy in 2009–2010, 2010–2011 and 2011–2012, respectively. Considering the ILIs, the most part of cases occurred in < 14 y old subjects and especially in 5–14 y old individuals, about 30% and 21% of cases respectively during 2009–2010 and 2010–2011 influenza seasons. In 2011–2012, our evaluation was of about 4.7 million of cases, and as in the previous season, the peak of cases regarded subjects < 14 y (about 29%). A/California/07/09 predominated in 2009–2010 and continued to circulate in 2010–2011. During 2010–2011 B/Brisbane/60/08 like viruses circulated and A/H3N2 influenza type was sporadically present. H3N2 (A/Perth/16/2009 and A/Victoria/361/2011) was the predominant influenza type-A virus that caused illness in the 2011–2012 season. Many strains of influenza viruses were present in the epidemiological scenario in 2009–2012. In the period 2009–2012, overall vaccination coverage was low, never exceeding 20% of the Italian population. Among the elderly, coverage rates grew from 40% in 1999 to almost 70% in 2005–2006, but subsequently decreased, in spite of the pandemic; this trend reveals a slight, though constant, decline in compliance with vaccination. Our data confirm that 2009 pandemics had had a spread particularly important in infants and schoolchildren, and this fact supports the strategy to vaccinate schoolchildren at least until 14 y of age. Furthermore, the low levels of vaccination coverage in Italy reveal the need to improve the catch-up of at-risk subjects during annual influenza vaccination campaigns, and, if possible, to extend free vaccination to at least all 50–64-y-old subjects. Virologic and epidemiological surveillance remains critical for detection of evolving influenza viruses and to monitor the health and economic burden in all age class annually.

Human Papillomavirus Vaccine

Human Papillomavirus (HPV) is a widely distributed and common virus, that causes benign lesions (such as warts and papillomas) but, if not cleared, can lead to malignant lesions as well, such as intraepithelial lesions and neoplasia. An extensive body of researches has demonstrated that E1 and E2 are involved in viral transcription and replication, E5, E6, and E7 act as oncoproteins, whilst L1 and L2 contribute to the formation of the capsid. However, this view has been recently challenged, since also E2 could play a role in HPV-induced carcinogenesis. Therefore, a complex picture is emerging, opening new ways and perspectives. The present article provides an overview of the biology of HPV, paying particular attention to its structural details and molecular mechanisms. The article also shows how this knowledge has been exploited for developing effective vaccines, both prophilactic/preventive and therapeutic ones. L1-based prophylactic vaccines, like Gardasil, Cervarix, and Gardasil 9, have been already licensed, whilst L2-based second generation preventive vaccines are still under clinical trials. New, highly immunogenic and effective vaccines can be further developed thanks to computer-aided design and bioinformatics/computational biology. The optimization of combinational therapies is another promising opportunity.