Neural correlates of response to joint attention in 2-to-5-year-olds in relation to ASD and social-communicative abilities: An fNIRS and behavioral study.

Autism spectrum disorder (ASD) is associated with life-long challenges with social cognition, and one of its earliest and most common manifestations is atypical joint attention, which is a pivotal skill in social-cognitive and linguistic development. Early interventions for ASD children often focus on training initiation of joint attention (IJA) and response to joint attention bids (RJA), which are important for social communication and cognition. Here, we used functional near-infrared spectroscopy and behavioral measures to test typically developing (TD, n = 17) and ASD children (n = 18), to address the relationship between the neural correlates of RJA and social-communicative behavior. Group-level differences were present for RJA-specific activation over right temporal sites, where TD children showed higher levels of activation during RJA than ASD children, whereas the two groups did not differ in the control condition. Correlations between neural activation and behavioral traits suggest that, in ASD children, neural activation during RJA is related to the frequency of RJA behavior when the former is measured over left temporal sites, and to social affect symptoms when considered for right temporal sites. Possible implications of the evidenced correlations are discussed.

Setting up and managing the largest COVID-19 mass vaccination center in Lombardy, Italy.

Background: The rapid global spread of severe acute respiratory syndrome coronavirus (SARS-CoV-2) was met with the rollout of vaccination campaigns at mass vaccination centers. The Palazzo delle Scintille, Milan, was designated by the Lombardy regional administration as a vaccination site with the target of processing about 9,000 users daily. Methods: For this observational study, we compared data on vaccinations delivered at the Palazzo delle Scintille with coronavirus disease (COVID-19)-related regional data. Results: Between 25 April 2021 and 28 February 2023, a total of 1,885,822 COVID-19 doses were administered; the mean hourly rate was 289 (247.2), the mean daily rate was 3185.5 (3104.5), the mean user age was 49.5 years (10.7). The Comirnaty vaccine (Pfizer-BioNTech) was most often given (1,072,030/1,885,822; 56.8%). Between 4 December 2021 and 15 January 2022, the daily dose rate was above the maximum daily capacity set by the regional administration. Conclusion: The trend for daily dose rates administered at the Palazzo delle Scintille center was in line with COVID-19-related regional data. The center played a major role in the regional mass vaccination campaign.

Genomic Characterization of Carbapenem-Resistant Acinetobacter baumannii (CRAB) in Mechanically Ventilated COVID-19 Patients and Impact of Infection Control Measures on Reducing CRAB Circulation during the Second Wave of the SARS-CoV-2 Pandemic in Milan, Italy.

COVID-19 has significantly affected hospital infection prevention and control (IPC) practices, especially in intensive care units (ICUs). This frequently caused dissemination of multidrug-resistant organisms (MDROs), including carbapenem-resistant Acinetobacter baumannii (CRAB). Here, we report the management of a CRAB outbreak in a large ICU COVID-19 hub Hospital in Italy, together with retrospective genotypic analysis by whole-genome sequencing (WGS). Bacterial strains obtained from severe COVID-19 mechanically ventilated patients diagnosed with CRAB infection or colonization between October 2020 and May 2021 were analyzed by WGS to assess antimicrobial resistance and virulence genes, along with mobile genetic elements. Phylogenetic analysis in combination with epidemiological data was used to identify putative transmission chains. CRAB infections and colonization were diagnosed in 14/40 (35%) and 26/40 (65%) cases, respectively, with isolation within 48 h from admission in 7 cases (17.5%). All CRAB strains belonged to Pasteur sequence type 2 (ST2) and 5 different Oxford STs and presented blaOXA-23 gene-carrying Tn2006 transposons. Phylogenetic analysis revealed the existence of four transmission chains inside and among ICUs, circulating mainly between November and January 2021. A tailored IPC strategy was composed of a 5-point bundle, including ICU modules' temporary conversion to CRAB-ICUs and dynamic reopening, with limited impact on ICU admission rate. After its implementation, no CRAB transmission chains were detected. Our study underlies the potentiality of integrating classical epidemiological studies with genomic investigation to identify transmission routes during outbreaks, which could represent a valuable tool to ensure IPC strategies and prevent the spread of MDROs. IMPORTANCE Infection prevention and control (IPC) practices are of paramount importance for preventing the spread of multidrug-resistant organisms (MDROs) in hospitals, especially in the intensive care unit (ICU). Whole-genome sequencing (WGS) is seen as a promising tool for IPC, but its employment is currently still limited. COVID-19 pandemics have posed dramatic challenges in IPC practices, causing worldwide several outbreaks of MDROs, including carbapenem-resistant Acinetobacter baumannii (CRAB). We present the management of a CRAB outbreak in a large ICU COVID-19 hub hospital in Italy using a tailored IPC strategy that allowed us to contain CRAB transmission while preventing ICU closure during a critical pandemic period. The analysis of clinical and epidemiological data coupled with retrospective genotypic analysis by WGS identified different putative transmission chains and confirmed the effectiveness of the IPC strategy implemented. This could be a promising approach for future IPC strategies.

Anti-Sars-CoV-2 vaccination campaign in children aged 5-11 years: the experience of a mass vaccination center in the city of Milan.

BACKGROUND AND AIM: After the approval of the anti-Sars-CoV-2 vaccines for the pediatric population, it is necessary to encourage the immunization of children aged 5-11 years, as this can reduce intergenerational transmission. Therefore, this goal has become a priority for the COVID 19 vaccination campaign in Italy. In the city of Milan, the mass vaccination center (MVC) Fiera Milano City, previously settled for general population, became the main site to host pediatric vaccinations. The center was consequently remodeled to ensure a suitable space for children. This paper provides an overview on the organization strategy implemented by Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico. The modular structure and the wide surface available in the center allowed the administration of hundreds of vaccines per day, especially in the first opening phase. METHODS: All the data for the entire period of activity of Fiera MCV, from December 16th 2021 to February 20th 2022, were analyzed using descriptive statistics. RESULTS: During the entire period of activity, from 16 December 2021 to 20 February 2022, 23% of the population in the province of Milan aged 5-11 years has been reached and vaccinated with at least one shot of vaccine in this center. CONCLUSIONS: Despite an enthusiastic response in the first weeks of the campaign, a progressive reduction in vaccination adherence was observed, maybe due to the absence of restrictive measures for unvaccinated children in Italy.

Diagnostic accuracy of rapid antigen test for COVID-19 in an emergency department.

Use of antigen tests for the diagnosis of COVID-19 has become widespread. The aim of this study was to evaluate the diagnostic accuracy of the nasopharyngeal rapid antigen diagnostic (RAD) immunoassay LumiraDx UK in an Emergency Department (ED). All patients admitted to our ED between November 11 and December 8, 2020, and had both a RAD test and a real-time-reverse-transcription-polymerase-chain-reaction (RT-PCR) test were enrolled. RAD was considered as the index test and RT-PCR test was used as the reference standard. Sensitivity, specificity, negative and positive predictive values, and likelihood ratios were calculated with the 95% confidence interval. The sensitivity and specificity of RAD were 34.2% and 92.3%. Positive and negative likelihood ratios were 4.4 and 0.71. Our results demonstrate that the diagnostic accuracy of the LumiraDx RAD test is too low for routine use as a diagnostic method in the ED.

Italy's rollout of COVID-19 vaccinations: The crucial contribution of the first experimental mass vaccination site in Lombardy.

BACKGROUND: In occurrence of the coronavirusdisease 19 (COVID-19) pandemic, carrying out an efficient large-scale vaccination campaign is vital in order to control the virus. Especially in high prevalence areas of COVID - 19, it is crucial to implement an effective vaccination strategy. In Italy, programming an efficient COVID-19 mass vaccination campaign has been the main target of the Ministry of Health. AIMS: This paper gives a comprehensive overview of how the mass vaccination campaign is performed in Milan, one of the cities that has been mostly affected by the COVID-19 pandemic in Italy. We analyze the vaccination strategy implemented by Fondazione Ca' Granda - Ospedale Maggiore Policlinico located in Milan. Furthermore, we compare the organization of this campaign in regards of those carried out across EU and UK. MATERIALS AND METHODS: The data derive from an analysis of the different vaccination plans implemented across EU and UK from the 27/12/2020 to the 15/06/2020. In addition, we discuss the data collected from the internal data server of IRCCS Fondazione Ca' Granda - Ospedale Maggiore Policlinico from the 15/02/2021 to the 15/06/2021.The collected data are examined by means of descriptive statistics. RESULTS: From the analysis of the internal data server, we observe that the modular organization of Fiera Milano City guarantees up to 5000 vaccinations/day. Moreover, the precise flow organization of users and a series of strategies adopted to avoid identification errors or vaccine type administration errors are crucial to reach the aforementioned target. CONCLUSIONS: The institution of mass vaccination centers thanks to the optimization of all the involved processes and the meticulous organization of these structures, allows to avoid crowds and guarantees the administration of elevated amounts of vaccines. All these elements assure a rapid vaccination coverage of the population in Lombardy, with a meaningful increase in daily administration doses.

Clinical characteristics of healthcare workers with SARS-CoV-2 infection after vaccination with BNT162b2 vaccine.

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had a significant impact worldwide. Vaccines against COVID-19 appear as a tool able to curb out mortality and reduce the circulation of the virus. Little is known so far about the clinical characteristics of individuals who developed SARS-CoV-2 infection after having received the vaccination, as well as the temporal relationship between vaccine administration and symptoms onset. METHODS: Retrospective cohort study among the 3219 healthcare workers (HCWs) of the Fondazione IRCCS Ospedale Maggiore Policlinico of Milano who received a full immunization with the BNT162b2 vaccine and who developed SARS-CoV-2 infection (documented through positive RT-PCR on nasopharyngeal swab) in March-April 2021. RESULTS: Overall, we have identified 15 HCWs with SARS-CoV-2 infection after vaccination, 7 (46.7%) of them were male and the mean age was 38.4 years (SD 14). In 4 of them, the presence of SARS-CoV-2 anti-nucleocapsid (anti-N) antibodies was assessed before vaccination and resulted positive in 1 case. In all HCWs the presence of SARS-CoV-2 anti-spike (anti-S1) antibodies was assessed, on average 42.2 days after the completion of vaccination, with a mean value of 2055 U/mL (SD 1927.3). SARS-CoV-2 infection was ascertained on average 56.2 days after vaccination. The mean cycle threshold (Ct) of SARS-CoV-2 PCR was 26.4, the lineage was characterized in 9 HCWs. None of the HCWs reported a primary or secondary immunodeficiency. Regarding symptoms, they were reported only by 7 (46.7%) HCWs and appeared on average 55 days after the second dose of vaccination. Of those who reported symptoms, one (14.3%) had fever, 7 (100%) rhinitis/conjunctivitis, 4 (57.1%) taste and smell alterations, none had respiratory symptoms, 4 headache/arthralgia (57.1%) and 1 gastrointestinal symptom (14.3%). All symptoms disappeared in a few days and no other unclassified symptoms were reported. CONCLUSIONS: Infections occurring after vaccination with the BNT162b2 vaccine are mostly asymptomatic and are not associated with the serum titre of anti-S1 antibodies. We did not find a predominance of specific viral variants, with several lineages represented.

Pressure on the Health-Care System and Intensive Care Utilization During the COVID-19 Outbreak in the Lombardy Region of Italy: A Retrospective Observational Study in 43,538 Hospitalized Patients.

During the spring of 2020, the coronavirus disease 2019 (COVID-19) epidemic caused an unprecedented demand for intensive-care resources in the Lombardy region of Italy. Using data on 43,538 hospitalized patients admitted between February 21 and July 12, 2020, we evaluated variations in intensive care unit (ICU) admissions and mortality over the course of 3 periods: the early phase of the pandemic (February 21-March 13), the period of highest pressure on the health-care system (March 14-April 25, when numbers of COVID-19 patients exceeded prepandemic ICU bed capacity), and the declining phase (April 26-July 12). Compared with the early phase, patients aged 70 years or more were less often admitted to an ICU during the period of highest pressure on the health-care system (odds ratio (OR) = 0.47, 95% confidence interval (CI): 0.41, 0.54), with longer ICU delays (incidence rate ratio = 1.82, 95% CI: 1.52, 2.18) and lower chances of dying in the ICU (OR = 0.47, 95% CI: 0.34, 0.64). Patients under 56 years of age had more limited changes in the probability of (OR = 0.65, 95% CI: 0.56, 0.76) and delay to (incidence rate ratio = 1.16, 95% CI: 0.95, 1.42) ICU admission and increased mortality (OR = 1.43, 95% CI: 1.00, 2.07). In the declining phase, all quantities decreased for all age groups. These patterns may suggest that limited health-care resources during the peak phase of the epidemic in Lombardy forced a shift in ICU admission criteria to prioritize patients with higher chances of survival.

The early phase of the COVID-19 epidemic in Lombardy, Italy.

BACKGROUND: In the night of February 20, 2020, the first epidemic of the novel coronavirus disease (COVID-19) outside Asia was uncovered by the identification of its first patient in Lombardy region, Italy. In the following weeks, Lombardy experienced a sudden increase in the number of ascertained infections and strict measures were imposed to contain the epidemic spread. METHODS: We analyzed official records of cases occurred in Lombardy to characterize the epidemiology of SARS-CoV-2 during the early phase of the outbreak. A line list of laboratory-confirmed cases was set up and later retrospectively consolidated, using standardized interviews to ascertained cases and their close contacts. We provide estimates of the serial interval, of the basic reproduction number, and of the temporal variation of the net reproduction number of SARS-CoV-2. RESULTS: Epidemiological investigations detected over 500 cases (median age: 69, IQR: 57-78) before the first COVID-19 diagnosed patient (February 20, 2020), and suggested that SARS-CoV-2 was already circulating in at least 222 out of 1506 (14.7%) municipalities with sustained transmission across all the Lombardy provinces. We estimated the mean serial interval to be 6.6 days (95% CrI, 0.7-19). Our estimates of the basic reproduction number range from 2.6 in Pavia (95% CI, 2.1-3.2) to 3.3 in Milan (95% CI, 2.9-3.8). A decreasing trend in the net reproduction number was observed following the detection of the first case. CONCLUSIONS: At the time of first case notification, COVID-19 was already widespread in the entire Lombardy region. This may explain the large number of critical cases experienced by this region in a very short timeframe. The slight decrease of the reproduction number observed in the early days after February 20, 2020 might be due to increased population awareness and early interventions implemented before the regional lockdown imposed on March 8, 2020.

Nasopharyngeal Testing among Healthcare Workers (HCWs) of a Large University Hospital in Milan, Italy during Two Epidemic Waves of COVID-19.

BACKGROUND: since October 2020, a second SARS-CoV-2 epidemic wave has hit Italy. We investigate the frequency of positive nasopharyngeal swabs among HCWs during the two waves and the association with occupation and demographic characteristics. METHODS: this is a retrospective, observational study conducted in a large university hospital in Milan, Northern Italy. We defined two epidemic waves: 1st (February 2020-July 2020) and 2nd (August 2020-January 2021). Occupational and demographic characteristics of HCWs who underwent nasopharyngeal swabs for SARS-CoV-2 were collected. RESULTS: in the 1st wave, 242 positive subjects (7.2%) were found among 3378 HCWs, whereas in the 2nd wave, the positive subjects were 545 out of 4465 (12.2%). In both epidemic waves positive NPSs were more frequent among HCWs with health-related tasks and lower among students (p < 0.001). However, in the 2nd wave, workers engaged in non-health-related tasks had a peak of 20.7% positivity. Among 160 positive HCWs in the 1st wave who were tested again in the 2nd wave, the rate of reinfection based on SARS-CoV2 RNA cycle quantification value was 0.6%. CONCLUSIONS: during the 2nd epidemic wave, we confirmed a significant impact of COVID-19 among HCWs. The rise of infection rate among HCWs seems to reflect the increasing spread of SARS-CoV-2 among the overall population.

Seroprevalence of and Risk Factors Associated With SARS-CoV-2 Infection in Health Care Workers During the Early COVID-19 Pandemic in Italy.

Importance: Identifying health care settings and professionals at increased risk of SARS-CoV-2 infection is crucial to defining appropriate strategies, resource allocation, and protocols to protect health care workers (HCWs) and patients. Moreover, such information is crucial to decrease the risk that HCWs and health care facilities become amplifiers for SARS-CoV-2 transmission in the community. Objective: To assess the association of different health care professional categories and operational units, including in-hospital wards, outpatient facilities, and territorial care departments, with seroprevalence and odds of SARS-CoV-2 infection. Design, Setting, and Participants: This cross-sectional study was conducted using IgG serological tests collected from April 1 through May 26, 2020, in the Lombardy region in Italy. Voluntary serological screening was offered to all clinical and nonclinical staff providing any health care services or support to health care services in the region. Data were analyzed from June 2020 through April 2021. Exposures: Employment in the health care sector. Main Outcomes and Measures: Seroprevalence of positive IgG antibody tests for SARS-CoV-2 was collected, and odds ratios of experiencing infection were calculated. Results: A total of 140 782 professionals employed in the health sector were invited to participate in IgG serological screening, among whom 82 961 individuals (59.0% response rate) were tested for SARS-CoV-2 antibodies, with median (interquartile range [IQR]; range) age, 50 (40-56; 19-83) years and 59 839 (72.1%) women. Among these individuals, 10 115 HCWs (12.2%; 95% CI, 12.0%-12.4%) had positive results (median [IQR; range] age, 50 [39-55; 20-80] years; 7298 [72.2%] women). Statistically significantly higher odds of infection were found among health assistants (adjusted odds ratio [aOR], 1.48; 95% CI, 1.33-1.65) and nurses (aOR, 1.28; 95% CI, 1.17-1.41) compared with administrative staff and among workers employed in internal medicine (aOR, 2.24; 95% CI, 1.87-2.68), palliative care (aOR, 1.84; 95% CI, 1.38-2.44), rehabilitation (aOR, 1.59; 95% CI, 1.33-1.91), and emergency departments (aOR, 1.56; 95% CI, 1.29-1.89) compared with those working as telephone operators. Statistically significantly lower odds of infection were found among individuals working in forensic medicine (aOR, 0.40; 95% CI, 0.19-0.88), histology and anatomical pathology (aOR, 0.71; 95% CI, 0.52-0.97), and medical device sterilization (aOR, 0.54; 95% CI, 0.35-0.84) compared with those working as telephone operators. The odds of infection for physicians and laboratory personnel were not statistically significantly different from those found among administrative staff. The odds of infection for workers employed in intensive care units and infectious disease wards were not statistically significantly different from those of telephone operators. Conclusions and Relevance: These findings suggest that professionals partially accustomed to managing infectious diseases had higher odds of SARS-CoV-2 infection. The findings further suggest that adequate organization of clinical wards and personnel, appropriate personal protective equipment supply, and training of all workers directly and repeatedly exposed to patients with clinical or subclinical COVID-19 should be prioritized to decrease the risk of infection in health care settings.

SARS-CoV-2 anti-spike antibody titres after vaccination with BNT162b2 in naïve and previously infected individuals.

Great expectations are placed in vaccines against COVID-19 to control the pandemic. We reviewed the antibody titres in a cohort of healthcare workers (HCWs) vaccinated with BNT162b2 to assess the influence of a previous infection on them. We stratified the results according to the individual history of nasopharyngeal swab (NPS) and symptoms. Among 3475 HCWs the highest titres were recorded among those infected more than 6 months before vaccination, independently of symptoms, followed by those infected less than 6 months before vaccination, especially in those with symptoms, and by uninfected HCWs. Vaccination with BNT162b2 can boost immunity acquired through infection, particularly in those infected more than 6 months before vaccination.

Age-specific SARS-CoV-2 infection fatality ratio and associated risk factors, Italy, February to April 2020.

We analysed 5,484 close contacts of coronavirus disease (COVID-19) cases in Italy, all tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infection fatality ratio was 0.43% (95% confidence interval (CI): 0.21-0.79) for individuals younger than 70 years and 10.5% (95% CI: 8.0-13.6) for older individuals. Risk of death after infection was 62% lower (95% CI: 31-80) in clusters identified after 16 March 2020 and 1.8-fold higher for males (95% CI: 1.03-3.16).

Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy.

Importance: In December 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) emerged in China and has spread globally, creating a pandemic. Information about the clinical characteristics of infected patients who require intensive care is limited. Objective: To characterize patients with coronavirus disease 2019 (COVID-19) requiring treatment in an intensive care unit (ICU) in the Lombardy region of Italy. Design, Setting, and Participants: Retrospective case series of 1591 consecutive patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinator center (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network and treated at one of the ICUs of the 72 hospitals in this network between February 20 and March 18, 2020. Date of final follow-up was March 25, 2020. Exposures: SARS-CoV-2 infection confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs. Main Outcomes and Measures: Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Data were recorded by the coordinator center on an electronic worksheet during telephone calls by the staff of the COVID-19 Lombardy ICU Network. Results: Of the 1591 patients included in the study, the median (IQR) age was 63 (56-70) years and 1304 (82%) were male. Of the 1043 patients with available data, 709 (68%) had at least 1 comorbidity and 509 (49%) had hypertension. Among 1300 patients with available respiratory support data, 1287 (99% [95% CI, 98%-99%]) needed respiratory support, including 1150 (88% [95% CI, 87%-90%]) who received mechanical ventilation and 137 (11% [95% CI, 9%-12%]) who received noninvasive ventilation. The median positive end-expiratory pressure (PEEP) was 14 (IQR, 12-16) cm H2O, and Fio2 was greater than 50% in 89% of patients. The median Pao2/Fio2 was 160 (IQR, 114-220). The median PEEP level was not different between younger patients (n = 503 aged ≤63 years) and older patients (n = 514 aged ≥64 years) (14 [IQR, 12-15] vs 14 [IQR, 12-16] cm H2O, respectively; median difference, 0 [95% CI, 0-0]; P = .94). Median Fio2 was lower in younger patients: 60% (IQR, 50%-80%) vs 70% (IQR, 50%-80%) (median difference, -10% [95% CI, -14% to 6%]; P = .006), and median Pao2/Fio2 was higher in younger patients: 163.5 (IQR, 120-230) vs 156 (IQR, 110-205) (median difference, 7 [95% CI, -8 to 22]; P = .02). Patients with hypertension (n = 509) were older than those without hypertension (n = 526) (median [IQR] age, 66 years [60-72] vs 62 years [54-68]; P < .001) and had lower Pao2/Fio2 (median [IQR], 146 [105-214] vs 173 [120-222]; median difference, -27 [95% CI, -42 to -12]; P = .005). Among the 1581 patients with ICU disposition data available as of March 25, 2020, 920 patients (58% [95% CI, 56%-61%]) were still in the ICU, 256 (16% [95% CI, 14%-18%]) were discharged from the ICU, and 405 (26% [95% CI, 23%-28%]) had died in the ICU. Older patients (n = 786; age ≥64 years) had higher mortality than younger patients (n = 795; age ≤63 years) (36% vs 15%; difference, 21% [95% CI, 17%-26%]; P < .001). Conclusions and Relevance: In this case series of critically ill patients with laboratory-confirmed COVID-19 admitted to ICUs in Lombardy, Italy, the majority were older men, a large proportion required mechanical ventilation and high levels of PEEP, and ICU mortality was 26%.

Measles re-emergence in Northern Italy: Pathways of measles virus genotype D8, 2013-2014.

Molecular surveillance and advanced phylogenetic methods are important tools to track the pathways of Measles virus (MV) genotypes, provide evidence for the interruption of endemic transmission and verify the elimination of the disease. The aims of this study were to describe the genetic profile of MV genotype D8 (D8-MV) strains circulating in Northern Italy (Lombardy Region) during the 2013-2014 period and to analyze the transmission chains and estimate the introduction time points using a phylogenetic approach. Forty-four strains of D8-MV identified from 12 outbreaks and 28 cases reported as sporadic were analyzed. Molecular analysis was performed by sequencing the highly variable 450nt region of the N gene of MV genome (N-450), as recommended by the WHO. Phylogenetic analyses and tree time-scaled reconstruction were performed with BEAST software. We could trace back the transmission pathways that resulted in three chains of transmission, two introductions with limited spread (two familiar outbreaks), and two single introductions (true sporadic cases). The D8-Taunton transmission chain, which was involved in 7 outbreaks and 13 sporadic cases, was endemic during the studied period. Furthermore, two novel local variants emerged independently in March 2014 and caused two transmission chains linked to at least 3 outbreaks. Overall, viral diversity was high and strains belonging to 5 different variants were identified. The results of this study clearly demonstrate that multiple lineages of D8-MV co-circulated in Northern Italy. Measles can be considered a re-emerging disease in Italy and additional efforts are necessary to achieve measles elimination goal.

West Nile virus transmission: results from the integrated surveillance system in Italy, 2008 to 2015.

In Italy a national Plan for the surveillance of imported and autochthonous human vector-borne diseases (chikungunya, dengue, Zika virus disease and West Nile virus (WNV) disease) that integrates human and veterinary (animals and vectors) surveillance, is issued and revised annually according with the observed epidemiological changes. Here we describe results of the WNV integrated veterinary and human surveillance systems in Italy from 2008 to 2015. A real time data exchange protocol is in place between the surveillance systems to rapidly identify occurrence of human and animal cases and to define and update the map of affected areas i.e. provinces during the vector activity period from June to October. WNV continues to cause severe illnesses in Italy during every transmission season, albeit cases are sporadic and the epidemiology varies by virus lineage and geographic area. The integration of surveillance activities and a multidisciplinary approach made it possible and have been fundamental in supporting implementation of and/or strengthening preventive measures aimed at reducing the risk of transmission of WNV trough blood, tissues and organ donation and to implementing further measures for vector control.

Surveillance of Mosquitoes and Selected Arthropod-Borne Viruses in the Context of Milan EXPO 2015.

From 1 May 2015 to 31 October 2015 over 20 million visitors from all over the world visited the Universal Exhibition (EXPO) hosted by Milan (Lombardy region, Italy), raising concerns about the possible introduction of mosquito-borne diseases from endemic countries. The entomological surveillance protocol performed in Lombardy over the last three years was implemented in the EXPO area and in the two major regional airports using both Center for Disease Control CO2 and Biogents Sentinel traps. This surveillance aimed to estimate the presence and densities of putative vectors, and also to support investigations, including the vector species involved and area of diffusion, on the local spread of Chikungunya, Dengue and West Nile viruses (WNV) by competent vectors. From 3544 mosquitoes belonging to five different species, 28 pools of Culex spp. and 45 pools of Aedes spp. were screened for the presence of WNV, and for both Chikungunya and flaviviruses, respectively. The entomological surveillance highlighted a low density of potential vectors in the surveyed areas and did not reveal the presence of Chikungunya or Dengue viruses in the local competent vectors inside the EXPO area or in the two airports. In addition, the surveillance reported a low density of Culex spp. mosquitoes, which all tested negative for WNV.

Event-Based Surveillance During EXPO Milan 2015: Rationale, Tools, Procedures, and Initial Results.

More than 21 million participants attended EXPO Milan from May to October 2015, making it one of the largest protracted mass gathering events in Europe. Given the expected national and international population movement and health security issues associated with this event, Italy fully implemented, for the first time, an event-based surveillance (EBS) system focusing on naturally occurring infectious diseases and the monitoring of biological agents with potential for intentional release. The system started its pilot phase in March 2015 and was fully operational between April and November 2015. In order to set the specific objectives of the EBS system, and its complementary role to indicator-based surveillance, we defined a list of priority diseases and conditions. This list was designed on the basis of the probability and possible public health impact of infectious disease transmission, existing statutory surveillance systems in place, and any surveillance enhancements during the mass gathering event. This article reports the methodology used to design the EBS system for EXPO Milan and the results of 8 months of surveillance.

Influenza vaccine effectiveness in Italy: Age, subtype-specific and vaccine type estimates 2014/15 season.

The 2014/15 influenza season in Europe was characterised by the circulation of influenza A(H3N2) viruses with an antigenic and genetic mismatch from the vaccine strain A/Texas/50/2012(H3N2) recommended for the Northern hemisphere for the 2014/15 season. Italy, differently from other EU countries where most of the subtyped influenza A viruses were H3N2, experienced a 2014/15 season characterized by an extended circulation of two influenza viruses: A(H1N1)pdm09 and A(H3N2), that both contributed substantially to morbidity. Within the context of the existing National sentinel influenza surveillance system (InfluNet) a test-negative case-control study was established in order to produce vaccine effectiveness (VE) estimates. The point estimates VE were adjusted by age group (<5; 5-15; 15-64; 65+ years), the presence of at least one chronic condition, target group for vaccination and need help for walking or bathing. In Italy, adjusted estimates of the 2014/15 seasonal influenza VE against medically attended influenza-like illness (ILI) laboratory-confirmed as influenza for all age groups were 6.0% (95%CI: -36.5 to 35.2%), 43.6% (95%CI: -3.7 to 69.3%), -84.5% (95%CI: (-190.4 to -17.2%) and 50.7% (95% CI: -2.5 to 76.3%) against any influenza virus, A(H1N1)pdm09, A(H3N2) and B, respectively. These results suggest evidence of good VE against A(H1N1)pdm09 and B viruses in Italy and evidence of lack of VE against A(H3N2) virus due to antigenic and genetic mismatch between circulating A(H3N2) and the respective 2014/15 vaccine strain.

[Decisional framework for varicella vaccine: challenges in the face of opportunity]. / Modello decisionale per l'adozione del vaccino antivaricella: una sfida di fattibilità.

INTRODUCTION: Decision makers adopt interventions, including vaccines, which are most beneficial to populations. A transparent, unbiased, and comprehensive framework based on evidence-based criteria is a promising tool to guide decision-making on vaccine adoption: we developed a multi-dimensional framework conceived from the DECIDE - Evidence to decision Framework (EtD framework). We validated the framework by conducting a real data and evidence set collection on varicella vaccination and tested it with a multidisciplinary group. METHODS: The EtD framework presented evidence concerning the varicella vaccination organized in six dimensions: Burden of disease, Vaccine characteristics and impact of immunization program, Values and preferences, Resource use, Equity and Feasibility. Two reviewers completed each dimension with information about varicella vaccine. A multidisciplinary group of 42 participants were asked to evaluate the information in the framework, decide whether to introduce varicella vaccine in the national immunization program, assess the usefulness, and propose some impovements of the decision-making tool. RESULTS: From 33 responders (79%) out of 42, 61% supported the adoption of the varicella vaccine as part of the national immunization program. A half (50%) favored the monovalent vaccine while the other half chose the tetravalent vaccine. About 90% of responders found information in the EtD framework comprehensive, easy to understand, and presented in a way that helped make decisions. CONCLUSIONS: Complete and transparent information are welcome. The EtD identified a situation of important divergences between policy makers regarding the introduction and the choice of vaccine. In our case study, for example, a third of the multidisciplinary group did not recommend the adoption of varicella vaccine.