Quadrivalent influenza vaccine: a new opportunity to reduce the influenza burden.

Influenza illness is caused by influenza A and influenza B strains. Although influenza A viruses are perceived to carry greater risk because they account for the majority of influenza cases in most seasons and have been responsible for influenza pandemics, influenza B viruses also impose a substantial public health burden, particularly among children and at-risk subjects. Furthermore, since the 2001-2002 influenza season, both influenza B lineages, B/Victoria-like viruses and B/Yamagata-like viruses have co-circulated in Europe. The conventional trivalent influenza vaccines have shown a limited ability to induce effective protection when major or minor mismatches between the influenza B vaccine component and circulating strains occur. For this reason, the inclusion of a second B strain in influenza vaccines may help to overcome the well-known difficulties of predicting the circulating B lineage and choosing the influenza B vaccine component. Two quadrivalent influenza vaccines, a live-attenuated quadrivalent influenza vaccine (Q/LAIV) and a split inactivated quadrivalent influenza vaccine (I/QIV), were first licensed in the US in 2012. Since their introduction, models simulating the inclusion of QIV in influenza immunization programs have demonstrated the substantial health benefits, in terms of reducing the number of influenza cases, their complications and mortality. In the near future, evaluations from simulation models should be confirmed by effectiveness studies in the field, and more costeffectiveness analyses should be conducted in order to verify the expected benefits.

Methodological criticisms in the evaluation of Pneumococcal Conjugate Vaccine effectiveness.

Globally, lower respiratory tract infections (LRTIs), including community-acquired pneumonia (CAP), cause considerable of morbidity and mortality in adults, especially in the elderly. In addition to age, underlying medical conditions are associated with an increased risk of CAP. From an aetiological point of view, Streptococcus pneumoniae is the leading cause of adult CAP throughout the world. Two types of vaccine are available for the prevention of pneumococcal diseases: the pneumococcal polysaccharide vaccine (PPV23) and the pneumococcal conjugate vaccine (PCV7, PCV10 and PCV13). An accurate understanding of the LRTIs burden and the types of subjects at risk of CAP, allow to find an appropriately targeted immunization strategy and provide baseline data to evaluate pneumococcal vaccine effectiveness. Given the high variability in available estimates of LRTIs burden and associated risk factors, the objective of the study was to discuss the methodological criticism in its evaluation, in the light of the gradual introduction of PCV13 immunization strategy targeted to elderly and risk groups in middle-high income countries.

Influenza vaccination in the elderly: why are the overall benefits still hotly debated?

The exact magnitude of the benefit of influenza vaccine among elderly individuals is subject of considerable debated. Existing vaccine effectiveness estimates come mostly from observational studies, which may be biased because of difficulties in identifying and adjusting for confounders. In this paper, we examine the potential sources of bias in observational studies of influenza vaccine effectiveness in the elderly and we discuss available evidence regarding the efficacy and effectiveness of licensed influenza vaccines. Although several methodological criticisms among the available analyses on seasonal vaccines for elderly were identified, overall seasonal influenza vaccines showed relevant efficacy/effectiveness in reducing the risk of influenza and its complications in the elderly, considering different measure of outcome.

Silymarin and S-adenosyl-L-methionine (SAMe): two promising pharmacological agents in case of chronic alcoholic hepathopathy. A review and a point of view.

The alcoholic liver disease (ALD) is the leading cause of death from liver failure in Italy and worldwide. Ethanol abstention, a healthy diet, and a significant improvement of life-style are the mainstay of treatment for this disease. Currently, we do not have effective therapeutic options are at our disposal to restore and maintain an improved clinical status. Silymarin is a complementary and alternative medicine often prescribed and self-prescribed; it has anti-oxidant, anti-inflammatory, anti-fibrotic, and metabolic properties. It improves the laboratoristic values and the ultrasonographic grading of liver disease in case of steatosis/steatohepatitis. S-adenosyl-L-methionine (SAMe) is the principal biological methyl donor, and it is also a precursor of glutathione (GSH), essential for the anti-oxidant pathways. SAMe is particularly important for opposing the toxicity of free radicals generated by various toxins, including alcohol. An association between Silymarin and SAMe (labelled as a dietary supplement) has been recently brought to market, and seems to be promising. It could be beneficial in such cases of alcoholic hepathopathies. New therapeutic options are needed by hepatologists to successfully overcome a constantly growing disease.

Influenza vaccination in HIV-positive subjects: latest evidence and future perspective.

Annual influenza vaccination is recommended for persons with human immunodeficiency virus (HIV) infection. Recent reports indicate that immunizations may increase IIeplication in infected individuals. Generally, vaccination against influenza is well tolerated in both children and adult individuals with HNIVand does not induce significant changes in viral load and CD4+ cell counts. The observed increase in viral replication is usually transient and a clear, measurable progression of the underlying HIV disease is hard to be determined. Several studies reported immunogenicity data in HIV+ population, by comparing diferfent influenza vaccines, adjuvanted or not, and different administration routes. Data are encouraging because an adequate immune response is shown, although split/subunit vaccines do not elicite an efficient immune response in these subjects. New strategies have been evaluated to increase the immune response in immunocompromised patients.The aim of this review is to evaluate tolerability, safety, immunogenicity and efficacy of vaccines actually approved for human use and to consider latest evidence and future perspective in HIV positive subjects.

Bacterial carriage and respiratory tract infections in subjects > or = 60 years during an influenza season: implications for the epidemiology of community acquired pneumonia and influenza vaccine effectiveness.

INTRODUCTION: During the 2010/11 influenza season an epidemiological prospective cohort active study was organized, to evaluate etiologic role due to the main bacteria and viruses causing Community Acquired Pneumonia (CAP) and Influenza like-illness (ILl) in elderly and to explore the role of the bacterial nose-pharingeal carriage in subjects with respiratory tract infections. METHODS: An integrated active surveillance of a cohort of adults aged > or = 60 y based on a double prospective and retrospective mechanisms of capture of ILl and CAP cases was organized. Samples were collected from all ILI and CAP prospectively identified. The samples were be tested by multiplex PCR for detection of the main respiratory bacteria and viruses. RESULTS AND DISCUSSION: The study population amounted to 2,551 adults. During the 2010/11 influenza season, the ILl cumulative incidence was 4.2%, that was twice higher than that calculated by regional sentinel-based Influenza surveillance system during the 2010/11 season in the elderly (2.2%). Among 45 patients with ILI of which had been collected the swab, 17 (37.8%) were positive for influenza viruses and 2 (4.4%) for RSV, 6 (13.3%) patients carried Streptococcus pn and 6 (13.3%) Haemophilus in. In the same period, 7 CAP cases were observed; 3 cases were prospectively identified and samples were collected, while 4 cases were retrospectively detected. The CAP cumulative incidence was 0,3%. The influenza vaccine effectiveness in prevention of laboratory-confirmed influenza emerged by our study was 61%, in condition of good antigenic matching between vaccine and circulating strains observed during the 2010/11. These data contribute to better defining the epidemiological picture of upper and lower respiratory tract infections, fundamental information in light of the recent introduction of new vaccines for prevention of pneumonia in the elderly, including 13-valent conjugate pneumococcal vaccine.

Impact of influenza during the post-pandemic season: epidemiological picture from syndromic and virological surveillance.

INTRODUCTION: Following the observation that 1 or 2 pandemic peak due to the circulation ofAHINlv had occurred in most countries and in most World Health Organization (WHO) Regions, WHO declared on August 10"h, 2010 that the world was moving into the post-pandemic period, whose surveillance presents considerable interest both from epidemiological and clinical point of view. We described the epidemiological picture emerged from syndromic and virological surveillance during the post-pandemic season in Liguria, Italy. MATERIALS AND METHODS: An Emergency Department Syndrome surveillance system, based on data collected at "San Martino" and IRCCS "G. Gaslini" Liguria Regional Reference University Hospitals for adults and children is active since July 2007. Monitored syndromes include "Influenza-Like Illness" (ILl) and "Low Respiratory Tract Infections" (LRTI). The Ligurian Regional Reference laboratory for Influenza virological surveillance and diagnosis offers rapid detection of influenza viruses by real-time and block RT-PCR, viral culture and genetic characterization by entire sequence analysis of haemagglutinin- and neuraminidase-coding regions in accordance with the international standards established by the global laboratory network. RESULTS AND DISCUSSION: The integration of syndromic surveillance system and laboratory surveillance for rapid detection and characterization of the disease responsible agent represented a specific and sensitive tool for influenza surveillance. The post-pandemic season was characterized by early onset and by the heaviest impacts for ILI and LRTI among the recent epidemic seasons. In contrast to the picture observed during the pandemic season, the 2010/11 winter was characterized by the intensive circulation of pandemic AH1N1v coupled with sustained activity due to influenza B and Respiratory Syncytial Virus (RSV). Antigenic and molecular characterization of influenza strains confirmed the good matching between circulating and 2010/11 vaccine viruses.

Measles in Italy, July 2009 to September 2010.

Outbreaks of measles continue to occur in Italy, as in other European countries. We present here details of cases reported through the Italian enhanced measles surveillance system from July 2009 to September 2010. In total, 2,151 cases were reported, 42% (n=895) of which were laboratory confirmed. The median age of cases was 18 years and 1,709 of 1,856 cases (92%) were unvaccinated. Many cases with complications were reported (n=305), including three with encephalitis. A total of 652 of 1,822 cases (36%) were hospitalised. Molecular characterisation revealed circulation of a limited number of measles virus genotypes (D4, D8 and B3), which is consistent with the current epidemiology of the disease in Italy. A national measles elimination plan was approved in 2003 with the aim of interrupting endemic measles transmission by 2007. Since elimination was not achieved, the target date was recently moved to 2015. The emphasis of the new elimination plan, approved in March 2011, is on strengthening surveillance, implementing evidence based-interventions to increase measles-mumps-rubella vaccine uptake in children, adolescents and young adults, and implementing communication activities related to the vaccine. The strategies proposed by the plan should be implemented fully and appropriately by all regions in order to meet the elimination goal by 2015.

Sequential outbreaks of multidrug-resistant Acinetobacter baumannii in intensive care units of a tertiary referral hospital in Italy: combined molecular approach for epidemiological investigation.

A laboratory-based surveillance study was conducted from January 2007 to May 2010 in San Martino Tertiary Referral Hospital in Genoa, Italy in which the molecular epidemiology of multidrug-resistant Acinetobacter baumannii was investigated in the five intensive care units (ICUs). A total of 53 A. baumannii strains were isolated from patients admitted to ICUs (69.8%) and to other epidemiologically linked hospital wards (30.2%) and were genotyped by repetitive extragenic palindromic polymerase chain reaction (REP-PCR), multilocus sequence typing (MLST) and adeB sequence typing. REP-PCR fingerprinting analysis, MLST and adeB typing results were well correlated and allowed us to classify strains causing epidemic events into three major epidemic clones: A (REP-I/ST4, adeB-STII genotype) isolated for the first time in May 2007, B (REP-IV/ST95, adeB-STI genotype) from November 2007 to May 2009 and C (REP-VII/ST118, adeB-STII genotype) from July 2008 to May 2010. MLST results demonstrated that epidemic clones A and C were related as they were members of the widespread clonal complex CC92. The genetic determinants of carbapenem resistance were investigated and resistance associated with the presence of the bla(OxA-58-like) gene with ISAba2 and ISAba3 elements flanking it in clone A, and with the bla(OxA-23-like) gene flanked by ISAba1 in clones B and C. A molecular approach allowed the prompt introduction of infection control measures and the evaluation of data in a global epidemiological context.

Case definitions for human poisonings postulated to palytoxins exposure.

A series of case reports and anecdotal references describe the adverse effects on human health ascribed to the marine toxin palytoxin (PLTX) after different exposure routes. They include poisonings after oral intake of contaminated seafood, but also inhalation and cutaneous/systemic exposures after direct contact with aerosolized seawater during Ostreopsis blooms and/or through maintaining aquaria containing cnidarian zoanthids. The symptoms commonly recorded during PLTX intoxication are general malaise and weakness, associated with myalgia, respiratory effects, impairment of the neuromuscular apparatus and abnormalities in cardiac function. Systemic symptoms are often recorded together with local damages whose intensity varies according to the route and length of exposure. Gastrointestinal malaise or respiratory distress is common for oral and inhalational exposure, respectively. In addition, irritant properties of PLTX probably account for the inflammatory reactions typical of cutaneous and inhalational contact. Unfortunately, the toxin identification and/or quantification are often incomplete or missing and cases of poisoning are indirectly ascribed to PLTXs, according only to symptoms, anamnesis and environmental/epidemiological investigations (i.e. zoanthid handling or ingestion of particular seafood). Based on the available literature, we suggest a "case definition of PLTX poisonings" according to the main exposure routes, and, we propose the main symptoms to be checked, as well as, hemato-clinical analysis to be carried out. We also suggest the performance of specific analyses both on biological specimens of patients, as well as, on the contaminated materials responsible for the poisoning. A standardized protocol for data collection could provide a more rapid and reliable diagnosis of palytoxin-poisoning, but also the collection of necessary data for the risk assessment for this family of toxins.

Hospital-acquired infections and leading pathogens detected in a regional university adult acute-care hospital in Genoa, Liguria, Italy: results from a prevalence study.

BACKGROUND: A prevalence study aimed to update the epidemiological scenario of Hospital-Acquired Infections (HAI) was performed at the San Martino University Hospital of Genoa, the Regional Reference Adult-care Center in Liguria, Italy, with more than 1300 beds. MATERIALS AND METHODS: The investigation was performed in all the wards, except the Psychiatric Units, between 19th March and 6Ih April, 2007, using a one-day monitoring system for each ward. International standardized criteria and definitions for the surveillance of HAI were used for the collection of data, which were recorded in specific software for subsequent consolidation, analysis and quality control. RESULTS: The hospital infection control staff actively monitored 912 inpatients: a total of 84 HAI among 72 patients were diagnosed, with an overall prevalence of infections and affected cases of 9.2% (95% CI: 7.3-11.1) and 7.9% (95% CI: 6.1-9.7), respectively. Urinary Tract Infections (UTI) (30.9%), Respiratory Tract Infections (RTI) (28.6%) and Blood Stream Infections (BSI) (21.4%) were found to be the most frequent infections. As expected, both specific prevalence and localization of HAI varied considerably between wards, with the highest values recorded in Intensive Care Units (ICU) and in Functional Rehabilitation wards. RTI (26.3%) and BSI (13.2%) were found primarily represented in ICU, while the highest values of UTI (13.3%) were registered in Functional Rehabilitation Units. Enterococcus spp. (16.8%), Candida spp. (14%), Pseudomonas spp. (12.2), Staphylococcus aureus (10.7%), Escherichia coli (10.3%) and Coagulase-negative staphylococci (CNS) (9.3%) were the most frequent pathogens isolated. The overall rate of administration of antibiotics was 55.3% and penicillin (26.7%), cephalosporins (22.8%) and fluoroquinolones (17.9%) were found to be the leading antibacterial administered. CONCLUSION: Results of the present study have been, and are currently, used for orientating surveillance and control hospital policies, planning activities according to a rational and evidence-based approach.

Evaluation of microbial contamination of air in two haematology departments equipped with ventilation systems with different filtration devices.

BACKGROUND: Nosocomial infections (NI) are above all due to health-care workers practices, but also the contamination of the environment could lead to their rise in health-care facilities. Introduction. In the last years, the incidence of NI has increased due to a substantial rise in the number of immuno-compromised patients. These patients are often gathered in hospital areas declared at "high risk" of infection such as Hematology and Bone Marrow Transplant ward. In this study, we evaluated microbial contamination of the air in two divisions with high risk patients, focusing on the validity of the air system with correlation to the presence or not of the HEPA absolute filters. METHODS: An environmental surveillance study has been carried out in two Divisions of Haematology, in two different Hospitals. Investigations have been performed by sampling air and by analyzing bacterial and fungal growth on microbiology plates after an incubation period. RESULTS: Unit A, without HEPA filters in the ventilation systems, showed a gradual increase in the bacterial load 20 and 60 days after cleaning of the ventilation system. Mycetes and Aspergilli were not present in basal conditions, at 20 or 60 days after decontamination. Unit B, equipped with HEPA filters placed at the inlet vents, showed extremely low values of the bacterial load either in basal conditions or upon inspection 60 days after cleaning. No mycetes were present. DISCUSSION: From the results obtained, it was evident that following the cleaning operation, the quality of the air is excellent in both types of equipment, since no mycetes were present and the bacterial load was < 20 CFU/mc in all the sites tested. However, although in subsequent controls mycetes were absent in both types of equipment, a great difference in the suspended bacterial load was found: Unit B was close to sterility whereas in Unit A a progressive increase was observed.

Prospective evaluation of a prevention protocol for lymphedema following surgery for breast cancer.

Lymphedema is a common complication of axillary dissection and thus emphasis should be placed on prevention. Fifty-five women who had breast-conserving surgery or modified radical mastectomy for breast cancer with axillary dissection were randomly assigned to either the preventive protocol (PG) or control group (CG) and assessments were made preoperatively and at 1, 3, 6, 12 and 24 months postoperatively. Arm volume (VOL) was used as measurement of arm lymphedema. Clinically significant lymphedema was confirmed by an increase of at least 200 ml from the preoperative difference between the two arms. The preventive protocol for the PG women included preoperative upper limb lymphscintigraphy (LS), principles for lymphedema risk minimization, and early management of this condition when it was identified. Assessments at 2 years postoperatively were completed for 89% of the 55 women who were randomly assigned to either PG or CG. Of the 49 women with unilateral breast cancer surgery who were measured at 24 months, 10 (21%) were identified with secondary lymphedema using VOL with an incidence of 8% in PG women and 33% in CG women. These prophylactic strategies appear to reduce the development of secondary lymphedema and alter its progression in comparison to the CG women.

Burden of rotavirus disease and cost-effectiveness of universal vaccination in the Province of Genoa (Northern Italy).

Rotavirus is acknowledged to be a major cause of acute gastroenteritis in infants and young children. As gastroenteritis due to rotavirus is a public health problem and two new vaccines are currently available, we investigated the rotavirus burden and developed a cost-effectiveness analysis, using data collected in the Province of Genoa (Italy), to evaluate the benefits of new borns vaccination. The cost-effectiveness of a rotavirus vaccination programme in the Province of Genoa was performed, in comparison with no vaccination, for both the regional healthcare system (RHS) and society (S). In 2006, admissions to the paediatric emergency department for gastroenteritis numbered 2338 (about 11% of total admissions); of these 33% were hospitalised. In 28% of cases, the children tested positive for rotavirus. During epidemics, paediatricians receive from 3 to 5 calls per day for gastroenteritis, carry out 1 or 2 ambulatory examinations and for children with a severe case history, make house visits. A rotavirus immunisation programme would have a great impact on disease burden, in that 90% coverage would reduce the number of severe cases by more than 85%. From the perspective of both the RHS and S, vaccination proved to be highly cost-effective.

Impact of limited cephalosporin use on prevalence of methicillin-resistant Staphylococcus aureus in the intensive care unit.

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a leading pathogen causing nosocomial infections. Many studies have shown that the restricted use of antibacterials is associated with a decline in resistance. To establish whether an intervention protocol designed to limit the use of cephalosporins can lower mRSA infection rates and impact on Gram-negative bacteria susceptibility in an intensive Care Unit (ICU), we conducted a prospective, non-randomized, before-after intervention study in an 18-bed ICU in Genoa, Italy. The intervention was a hospital antibiotic control policy and the observation was routine monitoring for nosocomial infections and antibiotic use, recording periodically the incidence density and MRSA prevalence. The intervention included a new antibiotic guideline that restricted the use of cephalosporins for all ICU inpatients. The analysis showed that the intervention determined a significant reduction in cephalosporin usage (-70.3%), while fluoroquinolones, mainly ciprofloxacin, increased after introduction of the antibiotic policy (+46.5%). A significant reduction in the percentage of MRSA infections (-30%) and heterogeneous susceptibility patterns in Klebsiella pneumoniae and Pseudomonas aeruginosa were noted.

Human papillomavirus vaccination: what is the best choice? A comparison of 16 strategies by means of a decisional model.

Some European countries decided to include human papillomavirus (HPV) vaccines in national immunization schedules. In order to help decision makers choose the best vaccination policy for females, a decisional model has been developed. The study was performed from the National Health Service perspective. Several hypotheses of multi-cohort vaccination policies were compared. 'Potentially avoidable infections' were chosen as the outcome. The model envisioned a short-term scenario (2008-2011). The best policy was that of vaccinating 12-year-olds and, a year later, those aged 14-16 years; the most expensive strategy was that of vaccinating 12-year-old females and, after 1 year, vaccinating those aged 15, 18 and 25 years. The sensitivity analysis showed that coverage rate has a great effect on the cost of avoidable infections. The study offers stake-holders an important datum-point for the choice of the best HPV policy vaccination in the short term. Indeed, it could generate interesting savings for the National Health Service and a rapid HPV immunization of young girls.

Surveillance of hospital-acquired infections in Liguria, Italy: results from a regional prevalence study in adult and paediatric acute-care hospitals.

A multi-hospital prevalence study of hospital-acquired infections (HAIs) was carried out between 19 March and 6 April 2007 in Liguria, Italy, being the first to be performed in this region. Of the 29 existing public acute hospitals, 25 took part in the investigation (86.2%). In total, 3176 patients were enrolled in the study, representing a regional average bed-occupancy rate of nearly 70%. Three-hundred and ten HAIs were diagnosed from 283 patients, with an overall prevalence of infections and cases of 9.8% and 8.9%, respectively. Prevalence varied considerably between hospitals, ranging from 0 to 24.4% [95% confidence interval (CI): 15.53-33.27]. Urinary tract infections (UTIs) (30.0%) and respiratory tract infections (RTIs) (26.1%) presented the highest relative frequency, followed by bloodstream infections (BSIs) (14.8%), surgical site infections (11.6%) and gastrointestinal infections (6.5%). Intensive care units (ICUs) and haemato-oncological units showed the highest specific prevalence of HAI, respectively 42.5% (95% CI: 34.48-50.52) and 13.3% (6.28-20.32), with RTI and BSI as the predominant infections. Spinal units (33.3%; 13.14-53.46) and functional-rehabilitation units (18.9%; 17.75-24.06) demonstrated a high rate of urinary tract infections. Uni- and multivariate analyses were performed to assess the main risk factors and conditions associated with HAI, both overall and by site. Our study provides an overall picture of the epidemiology of HAI in Liguria, which may be usefully employed as a starting point to plan and organise future surveillance and control programmes.