Vaccine Hesitancy and Mandatory Immunizations in Emilia-Romagna Region: the case of MMR vaccine.

BACKGROUND AND AIM: An increase of vaccine hesitancy has spread worldwide and lead to reduction in coverage rates. The trivalent Measles-Mumps-Rubella (MMR) vaccine has been one of the most targeted leading due to possible (but never proven) adverse effects. This resulted in an increase of measles cases. The aim of the study is to analyze the 24-months coverage rates for the MMR vaccine in Emilia-Romagna Region (RER) between 2007 and 2018 and to correlate any significant changes to index events. METHODS: Official aggregate data on vaccination coverage at 24-month provided by the RER and the Italian Ministry of health were analyzed and discussed. RESULTS: From 2012 to 2015 a significant reduction in vaccination rates has been registered. In the following years an increase was recorded temporarily related to national and regional laws. CONCLUSION: The mandatory vaccination strategies seem to be in the short period effective in RER to counteract the growing population neegative attitudes towards vaccination and mitigate vaccine hesitancy.

Childhood vaccinations: knowledge, attitudes and practices of paediatricians and factors associated with their confidence in addressing parental concerns, Italy, 2016.

BackgroundPaediatrician recommendations are known to influence parental vaccine decisions.AimOur aim was to examine vaccination knowledge, attitudes and practices among paediatricians in Italy and identify factors associated with their confidence in addressing parental questions.MethodsAn electronic questionnaire survey was conducted from February to March 2016, among a sample of Italian paediatricians.ResultsThe survey was completed by 903 paediatricians (mean age: 56 years). Of 885 who responded to the specific question, 843 (95.3%) were completely favourable to vaccinations. Sixty-six per cent (570/862) felt sufficiently knowledgeable about vaccinations and vaccine-preventable diseases to confidently discuss them with parents. Paediatricians who were male, who were 55 years or older, who had participated in training courses in the last 5 years, who reported that taking courses and reading the scientific literature had contributed to their knowledge, or who had implemented vaccination promotion activities, felt more knowledgeable than other paediatricians. When asked to rate their level of agreement with statements about vaccine safety and effectiveness, only 8.9% (80/903) responded fully as expected. One third (294/878) did not systematically verify that their patients are up to date with the immunisation schedule. Only 5.4% (48/892) correctly identified all true and false contraindications.ConclusionsThe majority of paediatricians in Italy are favourable to vaccination but gaps were identified between their overall positive attitudes and their knowledge, beliefs and practices. Targeted interventions are needed aimed at increasing paediatricians' confidence in addressing parents' concerns, strengthening trust towards health authorities and improving systems barriers.

Active surveillance for safety monitoring of seasonal influenza vaccines in Italy, 2015/2016 season.

BACKGROUND: Surveillance for adverse events following immunization is an important component of any national immunization programme because it is critical to assessing the safety of vaccines and to detecting potentially rare and severe adverse events and responding in a timely manner. We conducted an enhanced active surveillance aimed at assessing the safety of flu vaccines in the 2015-2016 season in Italy. The study was targeted to the population groups for which the seasonal vaccine is recommended in Italy. METHODS: During the study period, a total of 3213 individuals receiving seasonal influenza vaccination were registered on the web-based platform. Any adverse events experienced after 7 days from vaccination by individuals aged six months or more were collected through a telephone interview or by a web-based self-administered questionnaire. All individuals experiencing at least one event during the 7 days of follow-up were contacted for follow-up to 60 days. RESULTS: Overall, 854 events were reported: 845 events (26%) after administration of the first dose and 9 (12%) after the second dose. The majority of adverse events reported after 7 days from the first dose were of little clinical importance, and most involved local symptoms. CONCLUSION: Our data, even though the number of vaccinated individuals was smaller than expected, is consistent with the safety of influenza vaccines in Italy during the 2015-2016 season regarding the most common adverse events. Further efforts are needed to obtain sufficient power to study rarer adverse events. Active monitoring and systematic studies to test generated signals and hypotheses are crucial to intensify awareness among the public and professionals with regard to the safety of vaccines.

Parental vaccine hesitancy in Italy - Results from a national survey.

In Italy, in 2016, we conducted a cross-sectional survey to estimate vaccine hesitancy and investigate its determinants among parents of children aged 16-36 months. Data on parental attitudes and beliefs about vaccinations were collected through a questionnaire administered online or self-administered at pediatricians' offices and nurseries. Parents were classified as pro-vaccine, vaccine-hesitant or anti-vaccine, according to self-reported tetanus and measles vaccination status of their child. Multivariable logistic regression was used to investigate factors associated with hesitancy. A total of 3130 questionnaires were analysed: 83.7% of parents were pro-vaccine, 15.6% vaccine-hesitant and 0.7% anti-vaccine. Safety concerns are the main reported reason for refusing (38.1%) or interrupting (42.4%) vaccination. Anti-vaccine and hesitant parents are significantly more afraid than pro-vaccine parents of short-term (85.7 and 79.7% vs 60.4%) and long-term (95.2 and 72.3% vs 43.7%) vaccine adverse reactions. Most pro-vaccine and hesitant parents agree about the benefits of vaccinations. Family pediatricians are considered a reliable source of information by most pro-vaccine and hesitant parents (96.9 and 83.3% respectively), against 45% of anti-vaccine parents. The main factors associated with hesitancy were found to be: not having received from a paediatrician a recommendation to fully vaccinate their child [adjusted odds ratio (AOR): 3.21, 95% CI: 2.14-4.79], having received discordant opinions on vaccinations (AOR: 1.64, 95% CI: 1.11-2.43), having met parents of children who experienced serious adverse reactions (AOR: 1.49, 95% CI: 1.03-2.15), and mainly using non-traditional medical treatments (AOR: 2.05, 95% CI: 1.31-3.19). Vaccine safety is perceived as a concern by all parents, although more so by hesitant and anti-vaccine parents. Similarly to pro-vaccine parents, hesitant parents consider vaccination an important prevention tool and trust their family pediatricians, suggesting that they could benefit from appropriate communication interventions. Training health professionals and providing homogenous information about vaccinations, in line with national recommendations, are crucial for responding to their concerns.

Association between mothers' screening uptake and daughters' HPV vaccination: a quasi-experimental study on the effect of an active invitation campaign.

OBJECTIVES: In Emilia-Romagna, the Human Papillomavirus (HPV) vaccination campaign started in 2008 offering free vaccines for 1996 and 1997 cohorts. Systematic active invitation was implemented for the 1997 cohort. Our study aimed at measuring the impact of the active invitation campaign on HPV vaccine coverage and on coverage inequalities in 11-year-old girls. Second, we evaluated the effect of the HPV vaccination campaign on participation in cervical cancer screening by mothers of target girls. METHODS: We collected information on vaccination status for girls residing in Reggio Emilia in 2008 and mothers' screening history, before and after the 2008 vaccination campaign. Log-binomial regression models were performed to estimate Relative Risk (RR) and 95% confidence intervals (CIs) of being vaccinated as regarded citizenship, siblings, mothers' education, marital status and screening history, stratified by birth cohort. We also calculated RR of receiving a Pap test after the vaccination campaign as regarded education, daughter's cohort and mothers' decision to have their daughter vaccinated. Interaction between education and cohort in mothers overdue for Pap testing was calculated. RESULTS: Vaccination coverage was 46.3% for the uninvited cohort (1046/2260) and 77.9% for the invited cohort (1798/2307). In the uninvited cohort, daughters' vaccination showed association with mothers' education (8 to 11 years of education vs. graduated mothers, RR 1.61 95% CI 1.14-2.28), citizenship (foreigners vs. Italians, RR 0.45 95% CI 0.37-0.56) and screening history (regular vs. non-participant; RR 1.72 95% CI 1.26-2.36). In the invited cohort, only a slight association with screening history persisted (regular vs. non-participant; RR 1.20 95% CI 1.04-1.40). Highly educated under-screened mothers of the invited cohort showed a higher probability of receiving a Pap test after the vaccination campaign period (RR 1.27 95% CI 1.04-1.56) compared with those not invited, CONCLUSION: Active invitation could increase overall HPV immunisation coverage and reduce socio-demographic inequalities and the association with mothers' screening participation.

Molecular detection and genetic characterization of circulating measles virus in northern Italy.

BACKGROUND: Laboratory diagnosis of measles virus (MV) infection and genetic characterization of circulating MV play an essential role in measles surveillance, allowing proper interventions to interrupt endemic transmission. OBJECTIVES: We describe results obtained using serological and molecular methods to confirm MV infection among suspected cases reported in a large region in the north of Italy during 2010-2014 and the genotyping of the MV strains detected. STUDY DESIGN: Three hundred seventy-two samples (361 urine and 11 oral fluids) were tested for MV-RNA detection. In 281 cases, the serological results for MV-IgM detection were also available. RESULTS: A total of 276 cases were classified as confirmed measles and MV-RNA detection resulted positive for 239/276 cases. Nucleotide sequence analysis revealed sporadic cases of genotypes D9 and different circulations of endemic MV strains (D8, D4 and B3). CONCLUSIONS: This data suggests that there is still an unvaccinated part of the population maintaining the endemic circulation of MV in Italy.

Outbreak of a new measles B3 variant in the Roma/Sinti population with transmission in the nosocomial setting, Italy, November 2015 to April 2016.

A measles outbreak occurred from November 2015 to April 2016 in two northern Italian regions, affecting the Roma/Sinti ethnic population and nosocomial setting. Overall, 67 cases were reported. Median age of 43 cases in three Roma/Sinti camps was four years, nosocomial cases were mainly adults. The outbreak was caused by a new measles virus B3.1 variant. Immunisation resources and strategies should be directed at groups with gaps in vaccine coverage, e.g. Roma/Sinti and healthcare workers.

Matrix-assisted laser desorption ionization-time of flight and comparative genomic analysis of M-18 group a Streptococcus strains associated with an acute rheumatic fever outbreak in northeast Italy in 2012 and 2013.

Acute rheumatic fever (ARF) is a postsuppurative sequela caused by Streptococcus pyogenes infections affecting school-age children. We describe here the occurrence of an ARF outbreak that occurred in Bologna province, northeastern Italy, between November 2012 and May 2013. Molecular analysis revealed that ARF-related group A Streptococcus (GAS) strains belonged to the M-18 serotype, including subtypes emm18.29 and emm18.32. All M-18 GAS strains shared the same antigenic profile, including SpeA, SpeB, SpeC, SpeL, SpeM, and SmeZ. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) analysis revealed that M-18 GAS strains grouped separately from other serotypes, suggesting a different S. pyogenes lineage. Single nucleotide polymorphisms and phylogenetic analysis based on whole-genome sequencing showed that emm18.29 and emm18.32 GAS strains clustered in two distinct groups, highlighting genetic variations between these subtypes. Comparative analysis revealed a similar genome architecture between emm18.29 and emm18.32 strains that differed from noninvasive emm18.0 strains. The major sources of differences between M-18 genomes were attributable to the prophage elements. Prophage regions contained several virulence factors that could have contributed to the pathogenic potential of emm18.29 and emm18.32 strains. Notably, phage ΦSPBO.1 carried erythrogenic toxin A gene (speA1) in six ARF-related M-18 GAS strains but not in emm18.0 strains. In addition, a phage-encoded hyaluronidase gene (hylP.2) presented different variants among M-18 GAS strains by showing internal deletions located in the α-helical and TSßH regions. In conclusion, our study yielded insights into the genome structure of M-18 GAS strains responsible for the ARF outbreak in Italy, thus expanding our knowledge of this serotype.

Neutralizing and cross-neutralizing antibody titres induced by bivalent and quadrivalent human papillomavirus vaccines in the target population of organized vaccination programmes.

Aim of this investigator-initiated study was to evaluate and compare the titres of neutralizing and cross-neutralizing antibodies (NAbs) induced by the bivalent (Cervarix(®)) and quadrivalent (Gardasil(®)) HPV vaccines in a cohort of girls aged 11-13 years from organized vaccination programmes. To this aim, HPV16 and HPV18 NAbs were measured by pseudovirion-based neutralization assays in serum collected at 1-6 months after the third vaccine dose in 107 girls vaccinated with Cervarix(®) and 126 vaccinated with Gardasil(®), while HPV31 and HPV45 cross-NAbs were tested in the first 50 consecutive girls of both vaccine groups. The results of this study demonstrated that all vaccinated girls developed HPV16 and HPV18 NAbs, with the exception of two Gardasil(®) vaccinees with undetectable HPV18 NAbs. Geometric mean titres (GMTs) of both HPV16 and HPV18 NAbs were significantly higher in Cervarix(®) than in Gardasil(®) vaccinees [HPV16 NAb GMT 22,136 (95% CI, 18,811-26,073) vs 5092 (4230-6151), respectively; P<0.0001; HPV18 NAb GMT 11,962 (9536-14,363) vs 1804 (1574-2110), respectively; P<0.0001]. Cross-NAbs to HPV31 and HPV45 were detected more frequently Cervarix(®) (HPV31 NAb positivity rates 92.7% and 36%, respectively; P<0.05) than in Gardasil(®) vaccinees (HPV45 NAb positivity rates 56% and 6%, respectively; P<0.0001). The titres of cross-NAbs against HPV31 and HPV45 were also significantly higher in Cervarix(®) than in Gardasil(®) vaccinees [HPV31 NAb GMT 157.2 (95% CI, 92-269) vs 13.0 (6.5-25.8), respectively; P<0.0001; HPV45 NAb GMT 4.7 (2.1-10.2) vs 1.3 (0.3-3.1), respectively; P<0.01]. In conclusion, in adolescent girls vaccinated within organized vaccination programmes, HPV vaccines drive the generation not only of NAbs to HPV vaccine types, but also of cross-NAbs. The bivalent vaccine induced significantly higher HPV16 and HPV18 NAb titres and more frequently and at higher titre HPV31 and HPV45 cross-NAbs than the quadrivalent vaccine.

Impact of meningococcal C conjugate vaccination campaign in Emilia-Romagna, Italy.

The incidence of reported meningococcal disease in Italy is among the lowest in Europe. The trend of the disease was increasing up to 2005 and then declined after the gradual introduction of a universal Men C vaccination program in 17/21 Italian regions. Since 2006, in Emilia-Romagna region vaccination against Neisseria meningitidis serogroup C was actively offered free of charge in a single dose to the age groups 12-15 months and 14-15 years, in addition to people with defined epidemiological risk. Our aim was to measure the impact of vaccination on the incidence of meningococcal disease caused by different serogroups among the population of Emilia Romagna Region, Northern Italy (approximately 4.5 million inhabitants) subdivided by age. Using surveillance data, we computed the incidence rates of Neisseria meninigitidis related invasive disease per 100.000 inhabitants for the years 2000 to 2012. In addition, the percentage change in incidence and the mortality rates were calculated. Results indicate a 70.1% decrease in the incidence of meningococcus C-related invasive disease after the introduction of MenC universal vaccination. No case of serogroup C related infection was observed since 2006 in children aged 1-4 years. These findings suggest that the single-dose vaccination strategy against serogroup C N.meningitidis targeted to the age groups 12-15 months and 14-15 years was effective in the Emilia-Romagna population. However, the occurrence of two cases of meningiditis in a 5-month child and in a 9-years child suggests caution and careful consideration in surveillance for the next years.

Pneumococcal carriage in young children one year after introduction of the 13-valent conjugate vaccine in Italy.

BACKGROUND: In mid 2010, the 7-valent pneumococcal conjugate vaccine (PCV7) was replaced by the 13-valent conjugate vaccine (PCV13) for childhood immunization in Italy. Our objective in this study was to obtain a snapshot of pneumococcal carriage frequency, colonizing serotypes, and antibiotic resistance in healthy children in two Italian cities one year after PCV13 was introduced. METHODS: Nasopharyngeal swabs were obtained from 571 children aged 0-5 years from November 2011-April 2012. Pneumococcal isolates were serotyped and tested for antimicrobial susceptibility. Penicillin and/or erythromycin non-susceptible isolates were analyzed by Multi Locus Sequence Typing (MLST). RESULTS: Among the children examined, 81.2% had received at least one dose of PCV7 or PCV13 and 74.9% had completed the recommended vaccination schedule for their age. Among the latter, 57.3% of children had received PCV7, 27.1% PCV13, and 15.6% a combination of the two vaccines. The overall carriage rate was 32.9%, with children aged 6-35 months the most prone to pneumococcal colonization (6-23 months OR: 3.75; 95% CI: 2.19-6.43 and 24-35 months OR: 3.15, 95%CI: 2.36-4.22). A total of 184 pneumococcal isolates were serotyped and divided into PCV7 (5.4%), PCV13 (18.0%), and non-PCV13 (82.0%) serotypes. Serotypes 6C, 24F, and 19A were the most prevalent (10.3%, 8.6%, and 8.1%, respectively). The proportion of penicillin non-susceptible (MIC >0.6 mg/L) isolates was 30.9%, while 42.3% were erythromycin resistant. Non-PCV13 serotypes accounted for 75.4% and 70.8% of the penicillin and erythromycin non-susceptible isolates, respectively. CONCLUSIONS: Our results revealed low rates of PCV7 and PCV13 serotypes in Italian children, potentially due to the effects of vaccination. As the use of PCV13 continues, its potential impact on vaccine serotypes such as 19A and cross-reactive serotypes such as 6C will be assessed, with this study providing a baseline for further analysis of surveillance isolates.

Toscana virus infections in northern Italy: laboratory and clinical evaluation.

Toscana virus (TOSv) is a neurotropic arthropod-borne virus that causes meningitis in the Mediterranean basin during the summer months. A total of 120 patients suffering from acute aseptic meningitis between July 1 and October 31, 2010 in northern Italy were evaluated. Eighteen of them (15%) were in the acute stage of TOSv disease.