Phylodynamic Analysis and Implication of HCV Genotype 4 Variability on Antiviral Drug Response and T-Cell Recognition.

Therapies for HCV care could change the prevalence and the geographic distribution of genotypes due to differences in Sustained Virologic Response (SVR). In this scenario, uncommon genotypes/subtypes, such as genotype 4, could spread from high-risk groups, replacing genotypes eradicated by antiviral drugs. Genotype eradication is also strongly influenced by the CD8+ T cell response. In this study, the genetic variability in HCV genotype 4 strains obtained from a cohort of 67 patients naïve to DAA therapy was evaluated. We found that the presence of resistance-associated substitutions (RAS) was able to affect drug responses. Next, using a prediction tool, viral mutations were identified by their ability, or lack thereof, to reduce the binding affinity with HLA, which affects T cell recognition. The Bayesian coalescent analysis suggested two different circulation clusters, one in risk groups (IDUs and MSM) and the other due to migration flows, dated to 1940 and 1915, respectively. Most of the RAS overlapped with HLA and a lack of binding mutations was observed in 96% of strains. This study describes the introduction of HCV genotype 4 in a region of the Mediterranean basin and evaluates how HCV genotype 4's genetic variability could affect the response of antiviral drugs and CD8+ T cell recognition.

Surveillance Data for Eight Consecutive Influenza Seasons in Sicily, Italy.

Influenza A and B outbreaks occur each year with different activity and molecular patterns. To date, knowledge of seasonal epidemiology remains a prerequisite not only to put in place the most effective immunization strategy against influenza but also to identify population groups at higher risk of developing serious complications. A retrospective analysis of influenza surveillance data from 2010 to 2018 aimed to explore the epidemiology of influenza in Sicily, at the primary care and hospital level. Overall, 6,740 patients with acute respiratory infection were tested, of which 3,032 (45.0%) were positive for influenza. The relative proportion of type A and B viruses markedly varied across seasons. Type A similarly spreads among children and adults, whereas type B was more commonly identified among pediatric population aged 5-9 years. The median age of confirmed influenza cases differed by health-care setting, increasing according to disease severity (range: 8-54 years). Among influenza-confirmed cases, more than 80% of hospitalized patients had an underlying medical condition. Cardiovascular disease, lung disease, diabetes, and obesity were some of the most frequent. Overall, patients admitted to an intensive care unit were more likely to have multiple comorbidities and being infected with influenza infection strongly increased the risk of severe clinical outcomes. Understanding of the epidemiology of influenza and the molecular features of circulating viruses is of paramount importance to optimize prevention and control strategies. Knowledge of predictors for the occurrence of severe forms of the disease may help to address adequate preventive measures to high-risk population groups.

A mid-term estimate of 2018/2019 vaccine effectiveness to prevent laboratory confirmed A(H1N1)pdm09 and A(H3N2) influenza cases in Sicily (Italy).

Influenza season started in Italy during the month of October 2018, approaching the epidemic peak in January 2019. This report aim to explore the mid-term virologic surveillance data of the 2018-2019 influenza season in Sicily and to estimate the effectiveness of seasonal influenza vaccine (VE) against A(H1N1)pdm09 and A(H3N2) influenza viruses. A test-negative design was used to evaluate influenza VE. In Sicily, almost all influenza infections were sustained by influenza type A viruses, of which 62.3% were A(H3N2) and 36.3% A(H1N1)pdm09. A reduction of laboratory confirmed influenza cases in Sicilian population immunized against influenza were observed. In particular, an overall significant protective values were observed for any influenza A viruses (Adj-VE = 44.0%; 95%CI: 11.2-64.7%), especially among 15-64 years old age group (Adj-VE = 59.5%; 95%CI: 0.03-83.1) and among the elderly (Adj-VE = 73.6%; 95% CI: 29.4-90.2).

Case-based surveillance of measles in Sicily during 2012-2017: The changing molecular epidemiology and implications for vaccine strategies.

Following the indication of the World Health Organization, a national plan for the elimination of measles was approved in Italy and this included the improvement of the molecular surveillance of measles viruses and the interruption of indigenous transmission of the disease. Nevertheless, large outbreaks continue to occur in almost all regions of the country, including Sicily. Here we describe the epidemiology and molecular dynamics of measles viruses as a result of the measles surveillance activity carried out by the "Reference Laboratory for Measles and Rubella" in Sicily over a 5-year period. Biological samples of 259 suspected measles cases were tested for viral RNA detection and a total of 223 (86.1%) were classified as laboratory confirmed. The median age of confirmed measles cases was 21.0 years and about half of them were adults aged 19 years and older. Overall, one-third of the patients showed clinical complications and these latter were more common among adults than children (44.9% vs. 25.7%). The vast majority of measles cases were unvaccinated (94.2%, n = 210). The phylogenetic analysis of 221 measles virus nucleotide sequences revealed sporadic detections of genotypes D4 and H1, while endemic circulation of genotypes D8 and B3 was documented. Genotype D8 was associated with epidemics occurred between 2013 and 2016, whereas genotype B3 was more recently introduced into Sicily characterizing the current measles outbreak. The results of this study confirm the autochthonous co-circulation of viral variants belonging to different genotypes during the study period, and emphasizes the need of measles surveillance programmes in order to investigate the viral dynamics, the pathways of disease transmission, and to eventually adapt the development of successfull vaccine formulations.

Trends of influenza B during the 2010-2016 seasons in 2 regions of north and south Italy: The impact of the vaccine mismatch on influenza immunisation strategy.

Influenza A and B viruses are responsible for respiratory infections, representing globally seasonal threats to human health. The 2 viral types often co-circulate and influenza B plays an important role in the spread of infection. A 6-year retrospective surveillance study was conducted between 2010 and 2016 in 2 large administrative regions of Italy, located in the north (Liguria) and in the south (Sicily) of the country, to describe the burden and epidemiology of both B/Victoria and B/Yamagata lineages in different healthcare settings. Influenza B viruses were detected in 5 of 6 seasonal outbreaks, exceeding influenza A during the season 2012-2013. Most of influenza B infections were found in children aged ≤ 14 y and significant differences were observed in the age-groups infected by the different lineages. B/Victoria strains prevailed in younger population than B/Yamagata, but also were more frequently found in the community setting. Conversely, B/Yamagata viruses were prevalent among hospitalized cases suggesting their potential role in the development of more severe disease. The relative proportions of viral lineages varied from year to year, resulting in different lineage-level mismatch for the B component of trivalent influenza vaccine. Our findings confirmed the need for continuous virological surveillance of seasonal epidemics and bring attention to the adoption of universal influenza immunization program in the childhood. The use of tetravalent vaccine formulations may be useful to improve the prevention and control of the influenza burden in general population.