Differential diagnosis on measles and rubella discarded cases highlights a sharp increase in parvovirus B19 infections in Milan, Northern Italy, in the first months of 2024.

In line with European trends, since 2023 Lombardy (Northern Italy) is experiencing a resurgence of measles and an increased number of reported cases of fever and rash. Measles discarded cases observed in our region within the context of measles and rubella surveillance from the first few months of 2024 (N = 30) were investigated for parvovirus B19 (B19V) and other rash-associated viruses. Thirteen cases tested positive for B19V DNA, representing a significant increase from previous years (on average 3 cases per year, p < 0.001) and ~40% of all B19V DNA-positive patients we detected since 2017. In 2024, B19V DNA-positive subjects spanned all ages, and the virus was predominant among adolescents and adults (84.6%). Two B19V infected patients were hospitalised, and likely cross-reacting anti-measles virus IgM were found in both. Our data align with the recent reports from the ECDC and various European countries, which are experiencing a surge in B19V infections, and underline the importance of comprehensive measles and rubella surveillance systems that can adapt to changing epidemiological trends.

Increased reports of measles in the Metropolitan City of Milan, northern Italy, September 2023 to March 2024.

Since late 2023, the Metropolitan City of Milan and surrounding areas (northern Italy) have been experiencing a resurgence of measles, with most cases detected starting from January 2024. During this brief period, we observed measles in travellers from endemic areas, participants in international events, vaccinees and healthcare workers. Indigenous cases have also been identified. Even though we have not yet identified large and disruptive outbreaks, strengthening surveillance and vaccination activities is pivotal to help limit the impact of measles spread.

Preliminary results on an autochthonous dengue outbreak in Lombardy Region, Italy, August 2023.

In August 2023, six locally acquired dengue virus 1 infections were detected in Lodi province, Lombardy Region, in northern Italy, where the vector Aedes albopictus is present. Four cases were hospitalised, none died. The viruses clustered with Peruvian and Brazilian strains collected between 2021 and 2023. This preliminary report highlights the importance of continued integrated surveillance of imported vector-borne virus infections and the potential for tropical disease outbreaks in highly populated regions of northern Italy where competent vectors are present.

[Reduction of adverse outcome due to COVID-19 infection in a high-risk population: evaluation of an informative intervention through active call by General Practitioners]. / Riduzione degli outcome sfavorevoli dovuti all'infezione da COVID-19 su una popolazione ad alto rischio: valutazione di un intervento informativo mediante chiamata attiva da parte dei medici di medicina generale.

BACKGROUND: currently, individuals at risk of adverse outcomes for COVID-19 can access to vaccination and pharmacological interventions. But, during the first epidemic wave, there were no treatments or therapeutic strategies available to reduce adverse outcomes in patients at risk. OBJECTIVES: to assess the impact of an intervention at 15-month follow-up developed by the Agency for Health Protection of the Metropolitan Area of Milan (ATS Milan) based on telephone triage and consultation by the General Practitioners (GPs) for patient with high-risk for adverse outcomes. DESIGN: intervention on population. SETTING AND PARTICIPANTS: a total of 127,292 patients in the ATS aged ≥70 years and with comorbidities associated with an increased risk of dying from COVID-19 infection were identified. Using a specific information system, patients were assigned to their GPs for telephone triage and consultation. GPs inform them about the risks of the disease, non-pharmacological prevention measures, and precautions in contacts with family members and other persons. No specific clinical intervention was carried out, only an information/training intervention was performed. MAIN OUTCOME MEASURES: by the end of May 2020, 48.613 patients had been contacted and 78.679 had not been contacted. Hazard Ratios (HRs) of infection hospitalisation and death at 3 and 15 months were estimated using Cox regression models adjusted by confounder. RESULTS: no differences in gender, age class distribution, prevalence of specific diseases, and Charlson Index were found between the two groups (treated such as called patients and not called). Called patients had a higher propensity for influenza and antipneumococcal vaccination and have more comorbidities and greater access to pharmacological therapies. Non-called patients have a greater risk for COVID-19 infection: HR was 3.88 (95%CI 3.48-4.33) at 3 months and 1.28 (95%CI 1.23-1.33) at 15 months; for COVID-19 hospitalization HR was 2.66 (95%CI 2.39-2,95) at 3 months and 1.31 (95%CI 1.25-1.37) at 15 months; for overall mortality HR was 2,52 (95%CI 2.35-2:72) at 3 months and 1.23 (95%CI 1.19-1.27) at 15 months. CONCLUSIONS: the results of this study show a reduction in hospitalization and deaths and support, in case of pandemic events, the implementation of new care strategies based on adapted stratification systems in order to protect the population's health. This study presents some limits: it is not randomized; a selection bias is present (called patients were those most in contact with the GPs); the intervention is indication-based (on march 2020, the actual benefit of protection and distancing for high-risk groups was unclear), and the adjustment is not able to fully control for confounding. However, this study points out the importance to develop information systems and improve methods to best protect the health of the population in setting of territorial epidemiology.

First SARS-CoV-2 vaccine booster and influenza vaccination: risk assessment of COVID-19 hospitalisation and death.

BACKGROUND: the influenza and SARS-CoV-2 viruses share a common respiratory symptomatology and transmission mode. COVID-19 and influenza R0 overlapped in the first epidemic wave. In autumn 2021-winter 2022, the influenza epidemic had a delayed onset compared to pre-COVID-19 years and lower incidence rates than in the pre-pandemic period. The SARS-CoV-2 and influenza vaccination campaign overlapped in 2021-2022. OBJECTIVES: to evaluate in the SARS-CoV-2 vaccinated cohort the effect of different timing of influenza vaccination on hospitalisations for COVID-19 and overall mortality. DESIGN: prospective cohort study. SETTING AND PARTICIPANTS: subjects aged 65 years or older who were administered the first booster dose of SARS-COV-2 vaccine between 01.10.2021 and 01.03.2022. Based on the date of influenza vaccination, subjects were divided into the following 4 different mutually exclusive groups: 1. two vaccinations in the same vaccination session; 2. influenza vaccination following SARS-CoV-2 vaccination; 3. influenza vaccination preceding SARS-CoV-2 vaccination; 4. no influenza vaccination. Using Cox regression models, hazard ratio (HR) and corresponding 95% confidence intervals (95% CI) of hospitalisation and death were estimated for the influenza-vaccinated subjects compared to influenza-unvaccinated subjects. MAIN OUTCOME MEASURES: ordinary hospital admissions for COVID-19 and general mortality. RESULTS: the cohort included 618,964 subjects: 16.3% received two vaccinations in the same vaccination session, 8.5% received the influenza vaccination after SARS-CoV-2 vaccination, 33.9% received it before and 41.1% did not receive an influenza vaccination. Those vaccinated against both SARS-CoV-2 and influenza had a combined HR of 0.73 (0.62-0.86) of hospitalisation for COVID-19 and 0.55 (0.49-0.62) of overall mortality compared to those vaccinated against SARS-CoV-2 only. CONCLUSIONS: influenza vaccination combined with SARS-CoV-2 vaccination increases the protective effect against hospitalisations and overall mortality compared to SARS-CoV-2 vaccination alone. Both organisational and communication actions aimed to promote and encourage vaccination are required.

Characterization of Vaccine Breakthrough Cases during Measles Outbreaks in Milan and Surrounding Areas, Italy, 2017-2021.

Despite the existence of an effective live-attenuated vaccine, measles can appear in vaccinated individuals. We investigated breakthrough measles cases identified during our surveillance activities within the measles/rubella surveillance network (MoRoNet) in Milan and surrounding areas (Northern Italy). Between 2017 and 2021, we confirmed measles virus (genotypes B3 or D8) infections in 653 patients and 51 of these (7.8%) were vaccinees. Among vaccinated individuals whose serum was available, a secondary failure was evidenced in 69.4% (25/36) of cases while 11 patients (30.6%) were non-responders. Non-responders were more frequently hospitalized and had significantly lower Ct values in both respiratory and urine samples. Median age and time since the last immunization were similar in the two groups. Importantly, we identified onward transmissions from vaccine failure cases. Vaccinees were involved in 20 outbreaks, in 10 of them they were able to transmit the virus, and in 8 of them, they were the index case. Comparing viral hemagglutinin sequences from vaccinated and non-vaccinated subjects did not show a specific mutation pattern. These results suggest that vaccination failure was likely due to the poor immune response of single individuals and highlights the importance of identifying breakthrough cases and characterizing their clinical and virologic profiles.

Genome analysis of Legionella pneumophila ST23 from various countries reveals highly similar strains.

Legionella pneumophila serogroup 1 (Lp1) sequence type (ST) 23 is one of the most commonly detected STs in Italy where it currently causes all investigated outbreaks. ST23 has caused both epidemic and sporadic cases between 1995 and 2018 and was analysed at genomic level and compared with ST23 isolated in other countries to determine possible similarities and differences. A core genome multi-locus sequence typing (cgMLST), based on a previously described set of 1,521 core genes, and single-nucleotide polymorphisms (SNPs) approaches were applied to an ST23 collection including genomes from Italy, France, Denmark and Scotland. DNAs were automatically extracted, libraries prepared using NextEra library kit and MiSeq sequencing performed. Overall, 63 among clinical and environmental Italian Lp1 isolates and a further seven and 11 ST23 from Denmark and Scotland, respectively, were sequenced, and pangenome analysed. Both cgMLST and SNPs analyses showed very few loci and SNP variations in ST23 genomes. All the ST23 causing outbreaks and sporadic cases in Italy and elsewhere, were phylogenetically related independent of year, town or country of isolation. Distances among the ST23s were further shortened when SNPs due to horizontal gene transfers were removed. The Lp1 ST23 isolated in Italy have kept their monophyletic origin, but they are phylogenetically close also to ST23 from other countries. The ST23 are quite widespread in Italy, and a thorough epidemiological investigation is compelled to determine sources of infection when this ST is identified in both LD sporadic cases and outbreaks.

A Comparison Between Omicron and Earlier COVID-19 Variants' Disease Severity in the Milan Area, Italy.

Background: In the context of the fourth wave of the COVID-19 pandemic in Italy, which occurred in correspondence with the outbreak of the Omicron variant, it became fundamental to assess differences in the risk of severe disease between the Omicron variant and the earlier SARS-CoV-2 variants that were still in circulation despite Omicron becoming prevalent. Methods: We collected data on 2,267 genotyped PCR-positive swab tests and assessed whether the presence of symptoms, risk of hospitalization, and recovery times were significantly different between Omicron and the earlier variants. Multivariable models adjusted for sex, age class, citizenship, comorbidities, and symptomatology allowed assessing the difference in outcomes between Omicron and the earlier variants according to vaccination status and timing of administration. Results: Compared to the earlier variants in the same period, Omicron was less symptomatic, resulted in fewer hospital admissions for those who were unvaccinated and for those who were already immunized after the booster dose, and was associated with quicker recovery, yet not in subjects with three vaccination doses. Conclusion: Despite being milder, Omicron's higher transmissibility and vaccine resistance should not lead to underrating its damage potential, especially with regard to hospital and health service saturation.

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.

Type 1 Diabetes Patients' Practice, Knowledge and Attitudes towards Influenza Immunization.

Diabetic patients are at higher risk of developing infectious diseases and severe complications, compared to the general population. Almost no data is available in the literature on influenza immunization in people with type 1 diabetes mellitus (T1DM). As part of a broader project on immunization in diabetic patients, we conducted a cross-sectional study to: (i) report on seasonal influenza coverage rates in T1DM patients, (ii) explore knowledge, attitudes, and practices (KAPs) towards seasonal influenza in this population, and (iii) identify factors associated with vaccine uptake, including the role of family doctors and diabetologists. A survey was administered to 251 T1DM patients attending the Diabetes Clinic at San Raffaele Research Hospital in Milan, Italy and individual-level coverage data were retrieved from immunization registries. Self-reported seasonal influenza immunization coverage was 36%, which decreased to 21.7% when considering regional immunization registries, far below coverage target of 75%. More than a third (36.2%) of T1DM patients were classified as pro-vaccine, 30.7% as hesitant, 17.9% as uninformed, and 15.1% as anti-vaccine. Diabetologists resulted to be the most trusted source of information on vaccines' benefits and risks (85.3%) and should be more actively involved in preventive interventions. Our study highlights the importance of developing tailored vaccination campaigns for people with diabetes, including hospital-based programs involving diabetes specialists.

[Epidemiology and surveillance of hepatitis E in Italy: data from the SEIEVA surveillance system 2007-2019]. / Epidemiologia e sorveglianza dell'epatite E in Italia: dati dalla sorveglianza SEIEVA 2007-2019.

BACKGROUND: hepatitis E is a disease spread all over the world, with endemic levels varying according to ecological and socioeconomic factors. In developing countries, large epidemics spread mainly through contaminated water; in developed countries, hepatitis E has always been considered a sporadic disease, closely associated to the travels to endemic areas, especially in Southeastern Asia. In the last years, this perception is significantly changing, because of an increasing number of autochthonous cases reported in many European countries. OBJECTIVES: to describe the epidemiological picture of hepatitis E in Italy from 2007 to 2019. DESIGN: descriptive study based on the cases reported to the special surveillance of acute viral hepatitis (SEIEVA); case-control analytical study for the analysis of risk factors associated with hepatitis E. SETTING AND PARTICIPANTS: hepatitis E cases reported to SEIEVA in the period 2007-2019. MAIN OUTCOME MEASURES: number of cases notified by year, percentages of cases exposed to known risk factors, odds ratios. RESULTS: from January 2007 to June 2019, 385 hepatitis E cases were notified to SEIEVA. The annual number increased from 12 in 2007 to 49 in 2018, the increasing trend continued in 2019, when 39 cases were observed in the first 6 months of the year. Northern and Central Regions reported most of the cases; only a few were diagnosed in Southern Regions. Based on SEIEVA data, the trend of hepatitis E notifications has increased according to the increasing propensity to the differentiated diagnosis, at least until 2018. However, only 46% of suspected cases are tested to detect the presence of anti-HEV IgM antibodies, during the observation period; the percentage of tested cases is significantly lower in the South than in Northern and Central Italy (p<0.001). The reported cases have a median age of 48 years (range: 5-87) and are mostly males (80%); 32% was observed in foreign citizens mainly from endemic areas of South Asia (Bangladesh, India, and Pakistan). In 72.5% of cases, the infection was contracted in Italy. The most frequent risk factor is the consumption of raw or undercooked pork meat, especially sausages (70% of cases), significantly associated with hepatitis E risk (OR 3.0; IC95% 1.4-6.1). Other important risk factors are wild boar sausages consumption (40% of cases, OR 4.6, not statistically significant), and travels to endemic areas during the six weeks before the disease (31% of cases, OR 3.2; IC95% 1.6-6.4). CONCLUSIONS: hepatitis E can now be considered as endemic even in industrialized countries. In Italy, from 2007 an increasing number of cases has been reported. However, the real impact of HEV infection is still underestimated due to the limited number of clinical centres which perform tests for the search of anti-HEV IgM antibodies in cases of acute hepatitis. An ad hoc surveillance has been activated in January 2019 in some Local Health Units/Regions and extended to a national level starting from January 2020. This initiative is necessary in order to better dimension the burden of the disease associated with HEV infection, to study its epidemiology, and to increase awareness of this infection among health professionals.

Strategy to reduce adverse health outcomes in subjects highly vulnerable to COVID-19: results from a population-based study in Northern Italy.

OBJECTIVES: This study describes a new strategy to reduce the impact of COVID-19 on the elderly and other clinically vulnerable subjects, where general practitioners (GPs) play an active role in managing high-risk patients, reducing adverse health outcomes. DESIGN: Retrospective cohort study. SETTING: Population-based study including subjects resident in the province of Milan and Lodi. PARTICIPANTS: 127 735 residents older than 70 years, with specific chronic conditions. INTERVENTIONS: We developed a predictive algorithm for overall mortality risk based on demographic and clinical characteristics. All residents older than 70 years were classified as being at low or high risk of death from COVID-19 infection according to the algorithm. The high-risk group was assigned to their GPs for telephone triage and consultation. The high-risk cohort was divided into two groups based on GP intervention: patients who were not contacted and patients who were contacted by their GPs. OUTCOME MEASURES: Overall mortality, COVID-19 morbidity and hospitalisation. RESULTS: Patients with increased risk of death from COVID-19 were 127 735; 495 669 patients were not at high risk and were not included in the intervention. Out of the high-risk subjects, 79 110 were included but not contacted by their GPs, while 48 625 high-risk subjects were included and contacted. Overall mortality, morbidity and hospitalisation was higher in high-risk patients compared with low-risk populations. High-risk patients contacted by their GPs had a 50% risk reduction in COVID-19 mortality, and a 70% risk reduction in morbidity and hospitalisation for COVID-19 compared with non-contacted patients. CONCLUSIONS: The study showed that, during the COVID-19 outbreak, involvement of GPs and changes in care management of high-risk groups produced a significant reduction in all adverse health outcomes.

Large community-acquired Legionnaires' disease outbreak caused by Legionella pneumophila serogroup 1, Italy, July to August 2018.

In July 2018, a large outbreak of Legionnaires' disease (LD) caused by Legionella pneumophila serogroup 1 (Lp1) occurred in Bresso, Italy. Fifty-two cases were diagnosed, including five deaths. We performed an epidemiological investigation and prepared a map of the places cases visited during the incubation period. All sites identified as potential sources were investigated and sampled. Association between heavy rainfall and LD cases was evaluated in a case-crossover study. We also performed a case-control study and an aerosol dispersion investigation model. Lp1 was isolated from 22 of 598 analysed water samples; four clinical isolates were typed using monoclonal antibodies and sequence-based typing. Four Lp1 human strains were ST23, of which two were Philadelphia and two were France-Allentown subgroup. Lp1 ST23 France-Allentown was isolated only from a public fountain. In the case-crossover study, extreme precipitation 5-6 days before symptom onset was associated with increased LD risk. The aerosol dispersion model showed that the fountain matched the case distribution best. The case-control study demonstrated a significant eightfold increase in risk for cases residing near the public fountain. The three studies and the matching of clinical and environmental Lp1 strains identified the fountain as the source responsible for the epidemic.

Hepatitis A epidemic in men who have sex with men (MSM) in Milan, Italy.

BACKGROUND AND AIM OF THE WORK: Hepatitis A is an infectious disease characterized by fecal-oral transmission; however, a rise in sexually-transmitted cases has been observed, particularly among "men who have sex with men". In Europe, a Hepatitis A epidemic occurred among men who have sex with men between 2016 and 2018. The aim of this study is to describe this Hepatitis A epidemic in the city of Milan and to analyze the incidence of Sexually Transmitted Diseases co-infection among Hepatitis A cases. METHODS: Hepatitis A cases were traced and identified. Epidemiological data were collected and Hepatitis A vaccination was investigated. Cases were georeferenced, calculating incidence rates for each Milan Municipality. Viral genotypic analysis was carried out. RESULTS: 353 cases were reported in Milan. Incidence rates resulted significantly higher in males (RR 18.1 CI9 5% 11.5 - 28.4). 70 cases reported foreign travel. 172 cases reported "Men  who have Sex with Men" behaviour. Genotypic analysis revealed correlation with strains of the European "Men who have Sex with Men" epidemic. Georeferencing showed asymmetric case distribution. Only 12 cases reported Hepatitis A vaccination. The Relative Risk for syphilis infection among Hepatitis A cases was 133.9 (95% CI 81.7 - 219.7) and 29.7 (95%CI 9.5 - 92.7) for gonorrhea. CONCLUSIONS: Most genotyped cases (93.7%) correlated to the European Hepatitis A epidemic among Men who have Sex with Men. Georeferencing showed a greater incidence of Hepatitis A cases in areas characterized by the homosexual community. The higher incidence of Sexually Transmitted Diseases co-infection in Hepatitis A cases correlated to clusters responsible for the European Hepatitis A epidemic, suggests increased sexual promiscuity among Men who have Sex with Men. These data support the need for Hepatitis A vaccination programs and sensitization of Men who have Sex with Men to the adoption of safe sexual practices.

Tuberculosis among asylum seekers in Milan, Italy: epidemiological analysis and evaluation of interventions.

In countries of the European Union, tuberculosis (TB) mainly affects marginalised people, including asylum seekers. Migratory flows from high-incidence countries to Italy have increased up to 2017, posing challenges to the national health system. This study sought to assess TB and latent TB infection (LTBI) prevalence among asylum seekers in Milan during the biennium 2016-2017 and to evaluate interventions in place.A two-level active surveillance and screening system was developed for both TB and LTBI. Asylum seekers underwent an initial screening with a tuberculin skin test (TST) and a questionnaire at the receiving sites. At the Regional TB Reference Centre, those with a positive result underwent chest radiography. People aged <35 years with negative chest radiography results underwent further testing by interferon-γ release assay. If results of the assay were positive, LTBI treatment was offered. TB and LTBI prevalence were compared with literature data.A total of 5324 asylum seekers, mostly young (10-39 years; 98%), male (84%) and from sub-Saharan Africa (69%), were enrolled in the study. 69 active TB cases were diagnosed and 863 LTBI-positive individuals were detected. TB prevalence was high (1236 per 100 000 population) and LTBI prevalence was 28%. Despite losses (41%) during the transition from initial screening sites and the diagnostic centre, a good TB cure rate (84%) and optimal LTBI treatment completion (94%) were achieved.Our study shows that TB incidence is high among asylum seekers in Milan and that well-coordinated screening measures are critical for early diagnosis and treatment. It also proves that rolling out successful at-scale interventions for both prophylaxis and disease management is feasible.

Ongoing large measles outbreak with nosocomial transmission in Milan, northern Italy, March-August 2017.

A large measles outbreak has been ongoing in Milan and surrounding areas. From 1 March to 30 June 2017, 203 measles cases were laboratory-confirmed (108 sporadic cases and 95 related to 47 clusters). Phylogenetic analysis revealed the co-circulation of two different genotypes, D8 and B3. Both genotypes caused nosocomial clusters in two hospitals. The rapid analysis of epidemiological and phylogenetic data allowed effective surveillance and tracking of transmission pathways.