History and evolution of influenza vaccines.

Since the isolation of influenza virus in 1933, a great deal of work was carried out in order to develop influenza vaccines and improve these fundamental tools of prevention in terms of production, quality control, safety and tolerability, and immunogenicity. The paper summarizes the cornerstones of the continuous evolution of influenza vaccines and the most recent and promising developments in this field.

Decline in pneumonia and acute otitis media after the introduction of childhood pneumococcal vaccination in Liguria, Italy.

The effect of the pneumococcal conjugate vaccine immunization programme on pneumococcal-associated or potentially pneumococcal-associated hospital admissions in the Italian region of Liguria was assessed. Hospital admission rates were compared in subjects belonging to birth cohorts before and after the introduction of widespread immunization for 0 - 2-year old children with a seven-valent conjugate vaccine (PCV7). Significant reductions in hospitalization rates for all-cause and pneumococcal pneumonia and for acute otitis media were observed in subjects born after widespread uptake of the vaccine. The preventive fraction (a measure of vaccine effectiveness) ranged from 15.2% for all cause pneumonia to 70.5% for pneumococcal pneumonia. This study contributes to the growing body of information that supports the beneficial effect of PCV7 vaccination.

Silver zeolite antimicrobial activity in aluminium heating, ventilation and air conditioning system ducts.

INTRODUCTION: Air pollution in confined environments is a serious health problem, in that most people spend long periods indoors (in homes, offices, classrooms etc.). Some people (children, the elderly, heart disease patients, asthmatic or allergic subjects) are at greater risk because of their conditions of frailty. The growing use of air-conditioning systems in many public and private buildings aggravates this health risk, especially when these systems are not correctly installed or regularly serviced. The aim of our study was to verify the capacity of Ag+ ions to stop the growth of bacteria and moulds inside the ducts of Heating, Ventilation and Air Conditioning system ducts (HVAC) systems when these ducts were lined with active Ag+ ions zeolite-coated panels. MATERIAL AND METHODS: A Y-shaped HVAC model with two branches was used; one branch was made of traditional galvanized iron, as was the whole system, while the other was lined with active Ag+ zeolite-coated polyurethane panels. During the test, samples of dust present inside both ducts were collected and seeded in liquid and solid media to detect bacteria and moulds. The presence of bacteria was also sought in the air emerging from the outlets of both ducts. RESULTS: Tests made on samples of particulate collected from the two different ducts revealed a lower total bacterial load in the samples collected from the Ag+ zeolite-coated duct than in the samples from the traditional Zn galvanized duct. In addition, the values of bacterial load found in the air emerging from the Ag+ ions zeolite-lined duct were 5 times lower than those found in the air from the traditional galvanized iron duct. CONCLUSIONS: The utilization of Ag+ zeolite-coated panels in air-conditioning systems could improve the quality of the emerging air in comparison with traditional installations in galvanized iron. This innovation could prove particularly advantageous in the event of accidents during the installation of air-conditioning systems or of contaminated aerosols coming from outside.

The epidemiology of mumps in Italy.

In Italy, although vaccination has been recommended for a number of years, vaccination coverage for mumps is still sub-optimal. The objective of the present study was to evaluate the seroprevalence of mumps antibodies in the Italian population, stratified by age, gender and geographical area. The proportion of individuals positive for mumps antibodies remained stable in the age classes 0-11 months and 1 year (25.4% and 30.8%, respectively) and showed a continuous increase after the second year of life. The percentage of susceptible individuals was higher than 20% in persons 2-14 years of age and exceeded 10% in persons 15-39 years of age. No statistically significant differences were observed by gender or geographical area. Comparison between these results and the data obtained from a 1996 survey showed a statistically significant increase in seroprevalence in the age class 2-4 years. No changes were observed in the other age-groups. The results of this study confirm that the efforts made in recent years to improve vaccination coverage within the second year of life should be strengthened.

Assessment of humoral and cell-mediated immunity against Bordetella pertussis in adolescent, adult, and senior subjects in Italy.

Humoral and cell-mediated immunity (CMI) against B. pertussis was assessed in a sample of adolescent, adult and senior subjects distributed in five different geographical areas in Italy. Most (99.1%) subjects had IgG anti-pertussis toxin (PT) antibodies exceeding the minimum detection level [> or = 2 ELISA units (EU)/ml]. There were no significant differences between the genders; 6.2% samples recorded titres > or = 100 EU/ml. CMI was positive [stimulation index (SI) > or = 5] against PT in 39.0% of all samples. This study suggests that B. pertussis continues to circulate in age groups that have been previously considered to be uninvolved in the circulation of this pathogen and that adolescent and adult pertussis boosters may be of value in these populations. Nevertheless, over the last 10 years, large increases in vaccination coverage rates have contributed to reduce the spread of the aetiological agent, especially in the immunized population.

Safety and immunogenicity of two influenza virus subunit vaccines, with or without MF59 adjuvant, administered to human immunodeficiency virus type 1-seropositive and -seronegative adults.

The objective of this study was to evaluate and compare both the safety and tolerability and the humoral and cell-mediated immune responses for two influenza virus subunit vaccines, one with MF59 adjuvant (Fluad) and one without an adjuvant (Agrippal), in healthy and in human immunodeficiency virus type 1 (HIV-1)-infected adult individuals. To achieve this aim, an open, randomized, comparative clinical trial was performed during the 2005-2006 season. A total of 256 subjects were enrolled to receive one dose of vaccine intramuscularly. Blood samples were taken at the time of vaccination and at 1 and 3 months postvaccination. A good humoral antibody response was detected for both vaccines, meeting all the criteria of the Committee for Medical Products for Human Use. After Beyer's correction for prevaccination status, Fluad exhibited better immunogenicity than Agrippal, as shown from the analysis of the geometric mean titers, with significant differences for some virus strains; however, no definitive conclusions on the clinical significance of such results can be drawn, because the method used to estimate antibody response is currently nonstandard for influenza virus vaccines. Significant induction of an antigen-specific CD4+ T-lymphocyte proliferative response was detected at all time points after immunization, for both the vaccines, among HIV-1-seronegative subjects. This was different from what was observed for HIV-1-infected individuals. In this group, significance was not reached at 30 days postvaccination (T30) for those immunized with Agrippal. Also when data were compared between treatment groups, a clear difference in the response at T30 was observed in favor of Fluad (P = 0.0002). The safety profiles of both vaccines were excellent. For HIV-1-infected individuals, no significant changes either in viremia or in the CD4+ cell count were observed at any time point. The results showed good safety and immunogenicity for both vaccines under study for both uninfected and HIV-1-infected adults, confirming current recommendations for immunization of this high-risk category.

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 0-14 years. 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 0-5 years, 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 0-3 years (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 1-3 years. RSVs were more often identified than influenza viruses in infants aged up to 1 year (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.

Rubella seroprofile of the Italian population: an 8-year comparison.

The objective of this study is to evaluate how increasing MMR infant vaccination coverage in recent years has modified the epidemiology of rubella in Italy. A cross-sectional population-based seroprevalence study of rubella antibodies was conducted on 3094 sera, in 2004, and results were compared with data obtained by the same method in 1996. The overall proportion of rubella-seropositive individuals was found to be significantly higher in 2004 with respect to 1996 (84.6% vs. 77.4%). However, an increase in seropositivity was observed only in the 1-19 years age groups. Recent increases in childhood MMR vaccination coverage, therefore, have not had an impact on seroprevalence in women of childbearing age, over 5% of whom remain susceptible to rubella. Preconception screening and postpartum vaccination of susceptible women are fundamental if the WHO target of less than one case of congenital rubella syndrome per 100,000 live births is to be attained.

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

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 34.4 days 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.

Clinical and socio-economic impact of influenza and respiratory syncytial virus infection on healthy children and their households.

This prospective study compared the clinical and socio-economic impact of laboratory-confirmed influenza and respiratory syncytial virus (RSV) infection on healthy children and their families. Among 1,520 otherwise healthy children aged< 15 years attending the Emergency Department for acute conditions other than trauma, influenza viruses and RSV were found in 234 (15.4%) and 116 (7.6%; p<0.0001) patients, respectively. The fact that influenza has a similar global clinical impact on the community to that of RSV infection, but represents a greater socio-economic burden, may contribute to broadening the acceptance of influenza vaccination.

Immunogenicity and Reactogenicity following Primary Immunisation with a Combined DTaP-HBV Vaccine and a Haemophilus influenzae Type B Vaccine Administered by Separate or Mixed Injection.

OBJECTIVES: The aim of this open, randomised, multicentre trial was to evaluate the immunogenicity and reactogenicity of the tetravalent diphtheria-tetanus-acellular pertussis-hepatitis B (DTaP-HBV) vaccine when given either as a mixed or as a separate concomitant injection with the Haemophilus influenzae type b (Hib) vaccine at 3, 5 and 11 months of age. METHODS: Antibody against diphtheria, tetanus, pertussis (ELISA), hepatitis B (radioimmunoassay) and Hib polyribosylribitol phosphate (PRP) [radiolabeled antigen binding assay] was determined. Solicited local and systemic adverse events were evaluated on the day of each vaccination and for three subsequent days. Follow-up of unsolicited and serious adverse events was conducted for 30 days following each vaccination. RESULTS: A total of 360 subjects were enrolled in the study. After completion of the three-dose vaccination course, seroprotective antibody concentrations against diphtheria, tetanus and hepatitis B, together with a pertussis vaccine response, were seen in almost all subjects with immunogenicity results (n = 336). All subjects had post-vaccination Hib anti-PRP antibody concentrations of at least 0.15 mug/mL, and 97.0% and 99.4%, respectively, of the subjects receiving a single or separate injections had Hib anti-PRP antibody concentrations >/=1.0 mug/mL. Addition of the Hib vaccine to the tetravalent DTaP-HBV vaccine did not increase the incidence of local or systemic reactions. CONCLUSIONS: Combination of DTaP-HBV and Hib vaccines in a single injection is safe, immunogenic and well tolerated, and thus has the potential to simplify the childhood immunisation schedule in Italy.

Burden of influenza in healthy children and their households.

OBJECTIVE: A prospective, multicentre study was conducted to evaluate the burden of laboratory confirmed influenza in healthy children and their household contacts. METHODS: The patients were enrolled in four emergency departments (EDs) and by five primary care paediatricians (PCPs) in different Italian municipalities 2 days a week between November 1, 2001 and April 30, 2002. The study involved 3771 children less than 14 years of age with no chronic medical conditions who presented with a respiratory tract infection in EDs or PCP outpatient clinics during the study period. Nasopharyngeal swabs were collected for the isolation of influenza viruses and RNA detection. Information was also collected concerning respiratory illnesses and related morbidities among the study children and their household contacts. RESULTS: Influenza virus was demonstrated in 352 cases (9.3%). In comparison with the influenza negative children, those who were influenza positive had an older mean age, were more often attending day care centres or schools, more frequently experienced fever and croup, received more antipyretics, and had a longer duration of fever and school absence. Furthermore, their parents and siblings had more respiratory illnesses, received more antipyretics and antibiotics, needed more medical visits, missed more work or school days, and needed help at home to care for the ill children for a longer period of time. CONCLUSIONS: Influenza has a significant clinical and socioeconomic impact on healthy children and their families. Prevention strategies should also focus on healthy children regardless of their age because of their role in disease transmission.

Surveillance of influenza in Apulia, Italy, 1999-2000, 2000-2001, 2001-2002, and 2002-2003 seasons.

BACKGROUND: The objective of this study was to evaluate, within the Italian National Influenza Epidemiological and Virological Surveillance, the rate of vaccination coverage, the incidence of Influenza Like-Illness (ILI), the incidence of Acute Respiratory Illness (ARI), and to identify the virus strains circulating in Apulia from 1999 to 2003. METHODS: Vaccination coverage rates were calculated based on the number of doses administered to individuals > 65 years of age. Every week, sentinel physicians reported ILI and ARI cases having occurred among their patients. Voluntary general practitioners (GPs) and paediatricians (Ps) collected oropharyngeal swab samples from patients suspected with ILI. Influenza viruses were isolated and identified by cell culture (MDCK cells) and RT-PCR. Virological surveillance was carried out by the ISS, in collaboration with a network of peripheral laboratories. RESULTS: In Apulia, vaccination coverage progressively increased to 68.6% during the 2002-2003 season. The analysis of ILI cases showed higher incidence rates during the 1999-2000 and 2002-2003 seasons. ARI rates appeared to have a more constant trend. ILI and ARI incidence rates were higher in the 0-14 year age group. CONCLUSION: The increase in vaccination coverage rates and implementation of the network of clinical, and epidemiological and virological surveillance are fundamental for the control and prevention of influenza.

Sero-epidemiology of mumps in western Europe.

Six countries (Denmark, England and Wales, France, Germany, Italy and The Netherlands) conducted large serological surveys for mumps, in the mid-1990s, as part of the European Sero-Epidemiology Network (ESEN). The assay results were standardized and related to the schedules and coverage of the immunization programmes and the reported incidence of mumps. Low incidence of disease and few susceptibles amongst adolescents and young adults was observed in countries with high mumps vaccine coverage (e.g. The Netherlands). High disease incidence and large proportions of mumps virus antibody negative samples in adolescent and young adult age groups was noted in countries with poor vaccine coverage (e.g. Italy). The build-up of susceptibles in older children and adolescents in England and Wales, France, the former West Germany and Italy indicate the possibility of further mumps outbreaks in secondary school environments. To control mumps in western Europe, current MMR immunization programmes will need to be strengthened in a number of countries. Sero-surveillance of mumps is an important component of disease control and its usefulness will be enhanced by the development of an international mumps standard.