Publications by authors named "Maria Stella"

42 Publications

High coverage of diverse invasive meningococcal serogroup B strains by the 4-component vaccine 4CMenB in Australia, 2007-2011: Concordant predictions between MATS and genetic MATS.

Hum Vaccin Immunother 2021 Apr 13:1-9. Epub 2021 Apr 13.

Queensland Paediatric Infectious Disease Laboratory, Children's Health Queensland Hospitals and Health Service, Queensland Children's Hospital, Brisbane, Australia.

Meningococcal serogroup B (MenB) accounts for an important proportion of invasive meningococcal disease (IMD). The 4-component vaccine against MenB (4CMenB) is composed of factor H binding protein (fHbp), neisserial heparin-binding antigen (NHBA), adhesin A (NadA), and outer membrane vesicles of the New Zealand strain with Porin 1.4. A meningococcal antigen typing system (MATS) and a fully genomic approach, genetic MATS (gMATS), were developed to predict coverage of MenB strains by 4CMenB. We characterized 520 MenB invasive disease isolates collected over a 5-year period (January 2007-December 2011) from all Australian states/territories by multilocus sequence typing and estimated strain coverage by 4CMenB. The clonal complexes most frequently identified were ST-41/44 CC/Lineage 3 (39.4%) and ST-32 CC/ET-5 CC (23.7%). The overall MATS predicted coverage was 74.6% (95% coverage interval: 61.1%-85.6%). The overall gMATS prediction was 81.0% (lower-upper limit: 75.0-86.9%), showing 91.5% accuracy compared with MATS. Overall, 23.7% and 13.1% (MATS) and 26.0% and 14.0% (gMATS) of isolates were covered by at least 2 and 3 vaccine antigens, respectively, with fHbp and NHBA contributing the most to coverage. When stratified by year of isolate collection, state/territory and age group, MATS and gMATS strain coverage predictions were consistent across all strata. The high coverage predicted by MATS and gMATS indicates that 4CMenB vaccination may have an impact on the burden of MenB-caused IMD in Australia. gMATS can be used in the future to monitor variations in 4CMenB strain coverage over time and geographical areas even for non-culture confirmed IMD cases.
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http://dx.doi.org/10.1080/21645515.2021.1904758DOI Listing
April 2021

ANERGY TO SYNERGY-THE ENERGY FUELING THE RXCOVEA FRAMEWORK.

Int J Multiscale Comput Eng 2020 ;18(3):329-333

Department of Chemistry and Courant Institute of Mathematical Sciences, New York University, New York, New York, USA.

We write to introduce our novel group formed to confront some of the issues raised by the COVID-19 pandemic. Information about the group, which we named "cure COVid for Ever and for All" (RxCOVEA), its dynamic membership (changing regularly), and some of its activities-described in more technical detail for expert perusal and commentary-are available upon request.
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http://dx.doi.org/10.1615/intjmultcompeng.2020035097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440281PMC
January 2020

Evaluation of Innate Immune Mediators Related to Respiratory Viruses in the Lung of Stable COPD Patients.

J Clin Med 2020 Jun 10;9(6). Epub 2020 Jun 10.

Divisione di Pneumologia e Laboratorio di Citoimmunopatologia dell'Apparato Cardio Respiratorio, Istituti Clinici Scientifici Maugeri SpA, Società Benefit, IRCCS, Veruno, Via Revislate 13, 28010 Novara, Italy.

Little is known about the innate immune response to viral infections in stable Chronic Obstructive Pulmonary Disease (COPD). Objectives: To evaluate the innate immune mediators related to respiratory viruses in the bronchial biopsies and lung parenchyma of stable COPD patients. We evaluated the immunohistochemical (IHC) expression of Toll-like receptors 3-7-8-9 (TLR-3-7-8-9), TIR domain-containing adaptor inducing IFNβ (TRIF), Interferon regulatory factor 3 (IRF3), Phospho interferon regulatory factor 3  ( pIRF3), Interferon regulatory factor 7 (IRF7), Phospho interferon regulatory factor 7 (pIRF7), retinoic acid-inducible gene I (RIG1), melanoma differentiation-associated protein 5 (MDA5), Probable ATP-dependent RNA helicase DHX58 ( LGP2), Mitochondrial antiviral-signaling protein (MAVS), Stimulator of interferon genes (STING), DNA-dependent activator of IFN regulatory factors (DAI), forkhead box protein A3(FOXA3), Interferon alfa (IFNα), and Interferon beta (IFNβ) in the bronchial mucosa of patients with mild/moderate ( = 16), severe/very severe ( = 18) stable COPD, control smokers (CS) ( = 12), and control non-smokers (CNS) ( = 12). We performed similar IHC analyses in peripheral lung from COPD ( = 12) and CS ( = 12). IFNα and IFNβ were assessed in bronchoalveolar lavage (BAL) supernatant from CNS ( = 8), CS ( = 9) and mild/moderate COPD ( = 12). Viral load, including adenovirus-B, -C, Bocavirus, Respiratory syncytial Virus (RSV),Human Rhinovirus (HRV), Coronavirus, Influenza virus A (FLU-A), Influenza virus B (FLU-B), and Parainfluenzae-1 were measured in bronchial rings and lung parenchyma of COPD patients and the related control group (CS). Among the viral-related innate immune mediators, RIG1, LGP2, MAVS, STING, and DAI resulted well expressed in the bronchial and lung tissues of COPD patients, although not in a significantly different mode from control groups. Compared to CS, COPD patients showed no significant differences of viral load in bronchial rings and lung parenchyma. Some virus-related molecules are well-expressed in the lung tissue and bronchi of stable COPD patients independently of the disease severity, suggesting a "primed" tissue environment capable of sensing the potential viral infections occurring in these patients.
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http://dx.doi.org/10.3390/jcm9061807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356645PMC
June 2020

Culture-Confirmed Invasive Meningococcal Disease in Canada, 2010 to 2014: Characterization of Serogroup B Strains and Their Predicted Coverage by the 4CMenB Vaccine.

mSphere 2020 03 4;5(2). Epub 2020 Mar 4.

GSK, Siena, Italy.

The molecular epidemiology of culture-confirmed invasive meningococcal disease (IMD) in Canada from 2010 to 2014 was studied with an emphasis on serogroup B (MenB) isolates, including their predicted coverage by the 4CMenB vaccine. The mean annual incidence rates of culture confirmed IMD varied from 0.19/100,000 in Ontario to 0.50/100,000 in New Brunswick and 0.59/100,000 in Quebec. In both Quebec and Atlantic region, MenB was significantly more common than other serogroups, while in other provinces, both MenB and serogroup Y (MenY) were almost equally common. The majority of MenB cases (67.0%) were in those aged ≤24 years, while most MenC (75.0%) and MenY (69.6%) cases were in adults more than 24 years old. The 349 MenB isolates were grouped into 103 sequence types (STs), 90 of which belonged to 13 clonal complexes (CCs). A large number of 4CMenB antigen genes were found among the Canadian MenB, which is predicted to encode 50 factor H binding protein (fHbp) types, 40 NHBA types, and 55 PorA genotypes. Provinces and regions were found to have their own unique MenB STs. A meningococcal antigen typing system assay predicted an overall MenB coverage by 4CMenB to be 73.6%, with higher coverage predicted for the two most common STs: 100% for ST154 and 95.9% for ST269, leading to higher coverage in both the Atlantic region and Quebec. Higher coverage (81.4%) was also found for MenB recovered from persons aged 15 to 24 years, followed by strains from infants and children ≤4 years old (75.2%) and those aged 5 to 14 years (75.0%). Laboratory surveillance of invasive meningococcal disease (IMD) is important to our understanding of the evolving nature of the strain types causing the disease and the potential coverage of disease strains by the newly developed vaccines. This study examined the molecular epidemiology of culture-confirmed IMD cases in Canada by examining the strain types and the potential coverage of a newly licensed 4CMenB vaccine on Canadian serogroup B strains. The strain types identified in different parts of Canada appeared to be unique as well as their predicted coverage by the 4CMenB vaccine. These data were compared to data obtained from previous studies done in Canada and elsewhere globally. For effective control of IMD, laboratory surveillance of this type was found to be essential and useful to understand the dynamic nature of this disease.
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http://dx.doi.org/10.1128/mSphere.00883-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056808PMC
March 2020

Does vaccination with 4CMenB convey protection against meningococcal serogroup B strains not predicted to be covered by MATS? A study of the UK clonal complex cc269.

Hum Vaccin Immunother 2020 04 6;16(4):945-948. Epub 2019 Dec 6.

GSK, Siena, Italy.

The Meningococcal Antigen Typing System (MATS) has been developed as an hSBA surrogate to evaluate potential coverage afforded by the 4-component meningococcal serogroup B vaccine (4CMenB: , GSK). We investigated whether the lower value of MATS coverage among invasive Meningococcus serogroup B clonal complex 269 strains from the United Kingdom (53% in 2014-2015 versus 73% in 2007-2008) reflected the lower bactericidal activity of the vaccine against these isolates. A total of 34 MATS-negative strains (31 were cc269 or closely related) were tested against pooled sera from 32 or 72 4CMenB-vaccinated infants in a serum bactericidal antibody assay in presence of human complement (hSBA). All infants had received four 4CMenB doses in the first 2 y of life. Baseline sera comprised 180 pooled samples from healthy-unvaccinated 2-month-old infants. Twenty of the 34 (59%) MATS-negative strains were killed in hSBA with titers ≥4 by pooled sera from vaccinated infants. There were 13/34 strains with hSBA titers ≥4 and at least a 4-fold rise in titer with respect to pooled baseline sera, and 10/34 with hSBA titers ≥8 and at least a 4-fold rise in titer with respect to baseline. These data confirm MATS as a conservative estimate for predicting strain coverage by 4CMenB.
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http://dx.doi.org/10.1080/21645515.2019.1688039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227617PMC
April 2020

Novel Multiplex Immunoassays for Quantification of IgG against Group B Capsular Polysaccharides in Human Sera.

mSphere 2019 08 7;4(4). Epub 2019 Aug 7.

GSK, Siena, Italy

Group B (GBS) infections constitute a major cause of invasive disease during the first three months of life and an unmet medical need that could be addressed by maternal vaccination. The GBS capsular polysaccharides (CPSs) have shown promise as vaccine targets in clinical studies. A highly specific serological assay to quantify maternal and neonatal anti-CPS antibody levels will be instrumental for GBS vaccine licensure. Here, we describe the development and comparison of two novel multiplex immunoassays (MIAs) based on the Luminex technology for the quantification of IgG antibodies recognizing the five most frequent GBS capsular variants (Ia, Ib, II, III, and V) out of the ten types identified. The first assay is based on the use of biotinylated CPSs coupled to streptavidin-derivatized magnetic microspheres (Biotin-CPS MIA), while the second is a sandwich assay with plain CPSs coupled to magnetic microspheres coated with polysaccharide-specific mouse monoclonal antibodies (Sandwich MIA). Both assays showed good specificity, linearity, and precision, although the Biotin-CPS MIA presented higher sensitivity and lower complexity than the Sandwich MIA. A panel of human sera representing a wide range of anti-CPS IgG concentrations was tested in parallel by the two assays, which resulted in comparable titers. Our data support the preservation of antigenic epitopes in the biotinylated polysaccharides and the suitability of the Biotin-CPS MIA for the precise determination of GBS anti-CPS IgG concentrations in human sera. Group B streptococcal infections can cause death in neonates up to 3 months of age. Intrapartum antibiotic prophylaxis in GBS-colonized mothers has limited early infections but has no impact after the first week of life. The development of a maternal vaccine to address this unmet medical need has been identified as a priority by the World Health Organization, and the GBS CPSs are considered the best antigen targets. However, to date there are no accepted standardized assays to measure immune responses to the investigational vaccines and for establishment of serocorrelates of protection. Here, we describe the performance of two microsphere-based pentaplex immunoassays for the determination of antibodies recognizing the five most frequent GBS serotypes. Our data confirm that an assay based on biotinylated polysaccharides coupled to streptavidin microspheres would be suitable for the intended purpose.
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http://dx.doi.org/10.1128/mSphere.00273-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6686225PMC
August 2019

The effect of opioid therapy on sleep quality in patients with chronic non-malignant pain: A systematic review and exploratory meta-analysis.

Sleep Med Rev 2019 06 13;45:105-126. Epub 2019 Apr 13.

Pain Center, Division of Anesthesiology, Lausanne University Hospital (CHUV) and University of Lausanne, Switzerland.

Current guidelines recommend opioid therapy to chronic non-malignant pain (CNP) patients when the benefits for pain and function outweigh risks. This systematic review examined the effects of opioid therapy on sleep - a valued functional outcome- in CNP. Electronic and hand searches of relevant studies up through July 2017 identified 18 eligible studies providing data from 3,746 CNP patients for analysis. Twelve of these studies were randomised controlled trials of up to 12-month in duration. Morphine sulfate, oxycodone and transdermal fentanyl were the most tested therapies (n = 4 each). Only two studies used objective sleep measures in addition to self-report ratings, questionnaires or sleep diaries. Whilst calmer sleep with less body/leg movements and fewer awakenings could be achieved following opioid therapy, these might occur with increased sleep-disordered breathing and a much-shortened rapid eye movement (REM) sleep latency. Both the narrative synthesis and exploratory meta-analysis suggest that opioid therapy in CNP is associated with improved self-reported sleep quality. However, the effect is inconsistent, small (Standardised Mean Difference = 0.36), and may be accompanied by excessive daytime sleepiness. As a Cochrane-recommended assessment revealed "unclear" or "high" overall risk of bias for all studies, future opioid trials of stronger methodology and better reporting are needed to confirm and elucidate the effect.
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http://dx.doi.org/10.1016/j.smrv.2019.03.005DOI Listing
June 2019

Borrelia burgdorferi sensu lato and spotted fever group rickettsiae in small rodents and attached ticks in the Northern Apennines, Italy.

Ticks Tick Borne Dis 2019 06 14;10(4):862-867. Epub 2019 Apr 14.

Department of Veterinary Sciences, University of Turin, Largo P. Braccini 2, 10095, Grugliasco, TO, Italy.

Ticks and ear biopsies were collected from wild small rodents in 2011 and 2012 in the northern Apennines (Italy), up to 1650 m above sea level. Apodemus spp. (n = 83) and Myodes glareolus (n = 22) were infested by Ixodes ricinus (192 larvae and two nymphs), Dermacentor marginatus (179 larvae and 29 nymphs), and Ixodes trianguliceps (three larvae and two nymphs). We detected several Borrelia burgdorferi sensu lato (s.l.) genospecies (B. afzelii, B. burgdorferi sensu stricto, B. garinii, B. lusitaniae, B. valaisiana) in I. ricinus and skin biopsies. The most common genospecies found in I. ricinus was B. valaisiana, while it was B. lusitaniae in tissues. Spotted fever group (SFG) rickettsiae (Rickettsia monacensis, R. slovaca and R. raoultii) infected I. ricinus, D. marginatus and rodent tissues. Rickettsia slovaca was the Rickettsia species most frequently found in our samples. Coinfections by B. burgdorferi s.l. and SFG rickettsiae indicate an overlap of transmission cycles and potential risk for humans to be infected by multiple pathogens, resulting in more severe symptoms. The findings of B. lusitaniae and R. slovaca in bank voles, and of B. valaisiana in small rodents, open new questions about host-pathogen interactions. In addition, our results highlight the importance of small rodents as data sources for studying tick-borne pathogens.
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http://dx.doi.org/10.1016/j.ttbdis.2019.04.005DOI Listing
June 2019

Potential Coverage of the 4CMenB Vaccine against Invasive Serogroup B Isolated from 2009 to 2013 in the Republic of Ireland.

mSphere 2018 08 22;3(4). Epub 2018 Aug 22.

GSK Vaccines, Siena, Italy.

is a common cause of bacterial meningitis in children and young adults worldwide. The 4CMenB vaccine (Bexsero), developed to combat meningococcal serogroup B (MenB) disease, contains subcapsular antigens that may induce immunity against strains of , regardless of serogroup. Owing to differential levels of expression and peptide diversity in vaccine antigens across meningococcal strains, the eningococcal ntigen yping ystem (MATS) was developed to estimate the potential MenB strain coverage of 4CMenB. Prior to introducing the 4CMenB vaccine into routine use, we sought to estimate the potential 4CMenB coverage against invasive MenB strains isolated in the Republic of Ireland (RoI) over four consecutive epidemiological years. MATS was applied to a panel of 105 invasive MenB strains isolated during July 2009 to June 2013. Sequence data characterizing the multilocus sequence typing (MLST) alleles and the major 4CMenB target peptides were extracted from isolate genome sequence data, hosted in the Bacterial Isolate Sequencing database (BIGSdb). MATS data indicated that 4CMenB may induce protective immunity against 69.5% (95% confidence interval [CI], 64.8% to 84.8%) of circulating MenB strains. Estimated coverage was highest against the most prevalent disease-causing lineage, cc41/44, where the most frequently observed sequence types, ST-154 and ST-41 (21% of isolates, collectively), were typically covered by three antigens. No significant temporal trends were observed. Overall, these data provide a baseline of strain coverage prior to the introduction of 4CMenB and indicate that a decrease in invasive meningococcal disease (IMD) is predicted following the introduction of 4CMenB into the routine infant immunization schedule in the RoI. The meningococcal antigen typing system (MATS) is an enzyme-linked immunosorbent assay (ELISA) that measures both the levels of expression and the immune reactivity of the three recombinant 4CMenB antigens. Together with PorA variable-region sequence data, this system provides an estimation of how susceptible MenB isolates are to killing by 4CMenB vaccine-induced antibodies. Assays based on subcapsular antigen phenotype analyses, such as MATS, are important in situations where conventional vaccine coverage estimations are not possible. Subcapsular antigens are typically highly diverse across strains, and vaccine coverage estimations would require unfeasibly large efficacy trials and screening of an exhaustive strain panel for antibody functional activity. Here, MATS was applied to all invasive meningococcal serogroup B (MenB) strains isolated over four consecutive epidemiological years ( = 105) and predicted reasonably high 4CMenB vaccine coverage in the Republic of Ireland.
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http://dx.doi.org/10.1128/mSphere.00196-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106058PMC
August 2018

Meningococcal Antigen Typing System (MATS)-Based Serogroup B Coverage Prediction for the MenB-4C Vaccine in the United States.

mSphere 2017 Nov-Dec;2(6). Epub 2017 Nov 15.

GSK, Siena, Italy.

is the most common cause of bacterial meningitis in children and young adults worldwide. A 4-component vaccine against serogroup B (MenB) disease (MenB-4C [Bexsero]; GSK) combining factor H binding protein (fHBP), neisserial heparin binding protein (NHBA), neisserial adhesin A (NadA), and PorA-containing outer membrane vesicles was recently approved for use in the United States and other countries worldwide. Because the public health impact of MenB-4C in the United States is unclear, we used the meningococcal antigen typing system (MATS) to assess the strain coverage in a panel of strains representative of serogroup B (NmB) disease in the United States. MATS data correlate with killing in the human complement serum bactericidal assay (hSBA) and predict the susceptibility of NmB strains to killing in the hSBA, the accepted correlate of protection for MenB-4C vaccine. A panel of 442 NmB United States clinical isolates (collected in 2000 to 2008) whose data were down weighted with respect to the Oregon outbreak was selected from the Active Bacterial Core Surveillance (ABCs; CDC, Atlanta, GA) laboratory. MATS results examined to determine strain coverage were linked to multilocus sequence typing and antigen sequence data. MATS predicted that 91% (95% confidence interval [CI], 72% to 96%) of the NmB strains causing disease in the United States would be covered by the MenB-4C vaccine, with the estimated coverage ranging from 88% to 97% by year with no detectable temporal trend. More than half of the covered strains could be targeted by two or more antigens. NHBA conferred coverage to 83% (CI, 45% to 93%) of the strains, followed by factor H-binding protein (fHbp), which conferred coverage to 53% (CI, 46% to 57%); PorA, which conferred coverage to 5.9%; and NadA, which conferred coverage to 2.5% (CI, 1.1% to 5.2%). Two major clonal complexes (CC32 and CC41/44) had 99% strain coverage. The most frequent MATS phenotypes (39%) were fHbp and NHBA double positives. MATS predicts over 90% MenB-4C strain coverage in the United States, and the prediction is stable in time and consistent among bacterial genotypes. The meningococcal antigen typing system (MATS) is an enzyme-linked immunosorbent assay (ELISA)-based system that assesses the levels of expression and immune reactivity of the three recombinant MenB-4C antigens and, in conjunction with PorA variable 2 (VR2) sequencing, provides an estimate of the susceptibility of NmB isolates to killing by MenB-4C-induced antibodies. MATS assays or similar antigen phenotype analyses assume importance under conditions in which analyses of vaccine coverage predictions are not feasible with existing strategies, including large efficacy trials or functional antibody screening of an exhaustive strain panel. MATS screening of a panel of NmB U.S. isolates ( = 442) predicts high MenB-4C vaccine coverage in the United States.
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http://dx.doi.org/10.1128/mSphere.00261-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687916PMC
November 2017

Molecular characterization of Neisseria gonorrhoeae on non-cultured specimens from multiple anatomic sites.

Ann Ist Super Sanita 2017 Jul-Sep;53(3):213-217

Dipartimento Malattie Infettive, Istituto Superiore di Sanità, Rome, Italy.

Introduction: The aim of this study was to molecularly characterize Neisseria gonorrhoeae on non-cultured specimens collected from multiple anatomic sites. N. gonorrhoeae multiantigen sequence typing (NG-MAST) together with the gene sequence analysis of antimicrobial resistance (AMR) target genes were used.

Materials And Methods: Seventeen genital and extra-genital samples from eight patients (7 were men who have sex with men, MSM, and 1 women who have sex with men, WSM) with gonorrhoea symptoms were analyzed. For 7, of the 8 patients, conventional culture method has been used to identify gonorrhoea. All the samples were tested with the rapid molecular method CEPHEID. Amplification and sequencing of porB and tbpB, to identify the Sequence Type (ST) by NG-MAST, and penA, mtrR, porB1b, ponA genes were also performed. Antimicrobial susceptibility by Etest, for the available culture positive samples, was carried out.

Results: For 7 patients the ST was obtained and for 6 the complete sequence analysis of the AMR target genes was also defined. For the majority of them, samples collected from multiple sites (oropharynx, rectum, vaginal and urethra) confirm the presence of the same gonorrhoea strain. In particular, for 5 patients the same STs and changes in the AMR target genes were identified.

Conclusion: Molecular characterization on non-cultured or culture negative specimens for gonorrhoea can successfully be applied directly to genital and extra-genital samples. Thus permit to identify the presence of the same strain in patients with gonorrhoea infection in multiple anatomic sites and to predict the antimicrobial susceptibility pattern.
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http://dx.doi.org/10.4415/ANN_17_03_06DOI Listing
June 2018

'Talkin' 'Bout My Generation': Using a Mixed-Methods Approach to Explore Changes in Adolescent Well-Being across Several European Countries.

Front Psychol 2017 18;8:758. Epub 2017 May 18.

Department of Psychology and Cognitive Science, University of TrentoTrento, Italy.

The promotion of positive mental health is a becoming priority worldwide. Despite all the efforts invested in preventive and curative work, it is estimated that one in four persons will experience a mental health condition at some point in their lives. Even more worrying is the fact that up to a half of all mental health problems have their onset before the age of 14. Recent statistics (national and international surveys, meta-analyses, international reports) point out to the fact that child and adolescent mental health problems are on the rise. The present study will try to corroborate these results and further explore their meaning, by employing a sequential mixed methods research design (quantitative-qualitative). The quantitative part will analyze time trends using Health Behaviors in School-aged Children data (four survey cycles: 2002, 2006, 2010, 2014) on mental well-being from four European countries (the Czechia, Germany, Italy, and United Kingdom). The qualitative part will rely on focus groups to explore the perspectives of 13- and 15-year-old boys and girls on gender differences and on the changes in adolescent mental well-being over time, as well as measures through which these issues could be addressed. Thematic analysis will be employed to analyze qualitative data. The results of this study could make a major contribution to our understanding of the current trends in adolescent mental well-being, as well as the ways in which existing data could be linked to international and national health policies.
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http://dx.doi.org/10.3389/fpsyg.2017.00758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436655PMC
May 2017

Meningococcal serogroup B strain coverage of the multicomponent 4CMenB vaccine with corresponding regional distribution and clinical characteristics in England, Wales, and Northern Ireland, 2007-08 and 2014-15: a qualitative and quantitative assessment.

Lancet Infect Dis 2017 07 30;17(7):754-762. Epub 2017 Mar 30.

Meningococcal Reference Unit, Public Health England, Manchester, UK.

Background: The UK introduced 4CMenB-a multicomponent vaccine against serogroup B meningococcal disease-into the national infant immunisation programme in September, 2015. The Meningococcal Antigen Typing System (MATS) was used to estimate coverage by 4CMenB of invasive meningococcal group B isolates obtained during 2007-08 in England and Wales (MATS coverage). We aimed to repeat the MATS survey for invasive meningococcal group B isolates obtained during 2014-15, before 4CMenB introduction; compare strain coverage between 2007-08 and 2014-15; and investigate associations between MATS coverage, age, region, and disease outcomes.

Methods: Invasive serogroup B meningococcal isolates from cases in England, Wales, and Northern Ireland during 2014-15 were assayed using MATS and compared with 2007-08 data. MATS coverage was assessed by geographical region and age group. Clinical characteristics, risk factors, and outcomes were assessed according to MATS coverage for 2014-15 English cases.

Findings: In 2014-15, 165 of 251 (66%; 95% CI 52-80) meningococcal group B isolates were estimated by MATS to be covered by 4CMenB, compared with 391 of 535 (73%; 95% CI 57-87) in 2007-08. The proportion of MATS-positive isolates with one vaccine antigen increased from 23% (122 of 535) in 2007-08 to 31% (78 of 251) in 2014-15, whereas the proportion with more than one antigen fell from 50% (269 of 535) to 35% (87 of 251). This effect reflected changes in circulating strains, particularly ST-269 clonal complex strains. MATS coverage increased with age, varied by geographical region, and was associated with more severe disease.

Interpretation: In 2014-15, two-thirds of meningococcal group B isolates were predicted to be covered by 4CMenB. Temporal changes in MATS coverage underscore the need for continued monitoring of antigen expression and diversity, particularly in countries with 4CMenB programmes.

Funding: Public Health England, GlaxoSmithKline.
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http://dx.doi.org/10.1016/S1473-3099(17)30170-6DOI Listing
July 2017

Recurrent herpes labialis and Herpes simplex virus-1 genitalis: what is the link?

G Ital Dermatol Venereol 2019 Oct 8;154(5):529-532. Epub 2017 Feb 8.

Section of Dermatology, Department of Health Sciences, San Martino University Hospital IRCCS, University of Genoa, Genoa, Italy.

Background: Recently, Herpes simplex virus (HSV)-1 seroprevalence declined among adolescents, rendering young people lacking HSV-1 antibodies more susceptible to genital HSV-1 acquisition, if sexually exposed. The aim of the present study was to identify the possible risk factors for the development of HSV-1 related Herpes genitalis (HG).

Methods: From January 2012 to December 2015, patients with HG attending three Sexually Transmitted Infections Units in Northern Italy were recruited. A genital swab on the lesions for the search of HSV-1/2 DNA through real time polymerase chain reaction (PCR) and a serum sample for HSV-1/2 specific serology were performed. Moreover, patients were asked whether they had personal history of herpes labialis (HL). Patients with PCR proved HSV-1 HG were included as cases; asymptomatic subjects attending STI Units for a blood check were recruited as controls and were checked for HSV-1/2 serology.

Results: The study included 141 cases and 70 controls. Specific HSV-1 antibodies were found in 34.7% of the cases and 67% of the controls. History of recurrent herpes labialis (RHL) was found in 4% of the cases and 31% of the controls. The occurrence of RHL in HSV-1 seropositive patients resulted lower in the case group compared to the control group.

Conclusions: We can speculate about a protective role for RHL against the clinical appearance of HSV-1 HG. The clinical usefulness of our study involved especially the counselling in serodiscordant couples. The presence of HSV-1 antibodies in asymptomatic sexual partners does appear protective for HG manifestation only in presence of RHL history.
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http://dx.doi.org/10.23736/S0392-0488.17.05563-8DOI Listing
October 2019

Predicted Strain Coverage of a New Meningococcal Multicomponent Vaccine (4CMenB) in Spain: Analysis of the Differences with Other European Countries.

PLoS One 2016 7;11(3):e0150721. Epub 2016 Mar 7.

Reference Laboratory for Meningococci, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.

Background: A novel meningococcal multicomponent vaccine, 4CMenB (Bexsero®), has been approved in Europe, Canada, Australia and US. The potential impact of 4CMenB on strain coverage is being estimated by using Meningococcal Antigen Typing System (MATS), an ELISA assay which measures vaccine antigen expression and diversity in each strain. Here we show the genetic characterization and the 4CMenB potential coverage of Spanish invasive strains (collected during one epidemiological year) compared to other European countries and discuss the potential reasons for the lower estimate of coverage in Spain.

Material And Methods: A panel of 300 strains, a representative sample of all serogroup B Neisseria meningitidis notified cases in Spain from 2009 to 2010, was characterized by multilocus sequence typing (MLST) and FetA variable region determination. 4CMenB vaccine antigens, PorA, factor H binding protein (fHbp), Neisseria Heparin Binding Antigen (NHBA) and Neisserial adhesin A (NadA) were molecularly typed by sequencing. PorA coverage was assigned to strain with VR2 = 4. The levels of expression and cross-reactivity of fHbp, NHBA and NadA were analyzed using MATS ELISA.

Findings: Global estimated strain coverage by MATS was 68.67% (95% CI: 47.77-84.59%), with 51.33%, 15.33% and 2% of strains covered by one, two and three vaccine antigens, respectively. The predicted strain coverage by individual antigens was: 42% NHBA, 36.33% fHbp, 8.33% PorA and 1.33% NadA. Coverage within the most prevalent clonal complexes (cc) was 70.37% for cc 269, 30.19% for cc 213 and 95.83% for cc 32.

Conclusions: Clonal complexes (cc) distribution accounts for variations in strain coverage, so that country-by-country investigations of strain coverage and cc prevalence are important. Because the cc distribution could also vary over time, which in turn could lead to changes in strain coverage, continuous detailed surveillance and monitoring of vaccine antigens expression is needed in those countries where the multicomponent vaccine is introduced. This is really important in countries like Spain where most of the strains are predicted to be covered by only one vaccine antigen and the chance for escape mutants to emerge with vaccine use is higher. Based on the observed data, cc213 should receive special attention as it is associated with low predicted strain coverage, and has recently emerged in Spain.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0150721PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4780694PMC
August 2016

Expression of factor H binding protein in meningococcal strains can vary at least 15-fold and is genetically determined.

Proc Natl Acad Sci U S A 2016 Mar 17;113(10):2714-9. Epub 2016 Feb 17.

GSK Vaccines, 53100 Siena, Italy

Factor H binding protein (fHbp) is a lipoprotein of Neisseria meningitidis important for the survival of the bacterium in human blood and a component of two recently licensed vaccines against serogroup B meningococcus (MenB). Based on 866 different amino acid sequences this protein is divided into three variants or two families. Quantification of the protein is done by immunoassays such as ELISA or FACS that are susceptible to the sequence variation and expression level of the protein. Here, selected reaction monitoring mass spectrometry was used for the absolute quantification of fHbp in a large panel of strains representative of the population diversity of MenB. The analysis revealed that the level of fHbp expression can vary at least 15-fold and that variant 1 strains express significantly more protein than variant 2 or variant 3 strains. The susceptibility to complement-mediated killing correlated with the amount of protein expressed by the different meningococcal strains and this could be predicted from the nucleotide sequence of the promoter region. Finally, the absolute quantification allowed the calculation of the number of fHbp molecules per cell and to propose a mechanistic model of the engagement of C1q, the recognition component of the complement cascade.
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http://dx.doi.org/10.1073/pnas.1521142113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791009PMC
March 2016

High predicted strain coverage by the multicomponent meningococcal serogroup B vaccine (4CMenB) in Poland.

Vaccine 2016 Jan 11;34(4):510-515. Epub 2015 Dec 11.

National Reference Centre for Bacterial Meningitis (NRCBM), National Medicines Institute, Warsaw, Poland. Electronic address:

Neisseria meningitidis of serogroup B (MenB) is currently responsible for more than 70% of cases of invasive meningococcal disease (IMD) in Poland and Europe as a whole. The aim of this study was to estimate strain coverage of a multicomponent meningococcal serogroup B vaccine (4CMenB) in Poland; the meningococcal antigen typing system (MATS) was used to test a panel of 196 invasive MenB strains isolated in Poland in 2010 and 2011. The strains were also characterized by MLST and sequencing of porA, factor H-binding protein (fHbp), Neisserial heparin-binding antigen (nhba) and Neisserial adhesin A (nadA) genes. MATS and molecular data were analyzed independently and in combination. The MATS results predicted that 83.7% (95% CI: 78.6-91.0%) of isolates would be covered by the 4CMenB vaccine; 59.2% by one vaccine antigen, 19.9% by two and 4.6% by three antigens. Coverage by each antigen was as follows: fHbp 73.0% (95% CI: 68.9-77.5%), NHBA 28.6% (95% CI: 13.3-47.4%), NadA 1.0% (95% CI: 1.0-2.0%) and PorA 10.2%. Molecular analysis revealed that the most frequent clonal complexes (ccs) were cc32 (33.2%), cc18 (17.9%) and cc41/44 (15.8%) with estimated coverage of 98.5%, 88.6% and 93.5%, respectively. Consistent with findings for other European countries, our study predicts high coverage by the 4CMenB vaccine in Poland.
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http://dx.doi.org/10.1016/j.vaccine.2015.11.070DOI Listing
January 2016

Wound botulism after traumatic open fracture in Italy.

Infez Med 2015 Sep;23(3):280-2

Department of Medical Sciences, University of Turin; Infectious Diseases, Amedeo di Savoia Hospital, Turin, Italy.

Seventeen days after a traumatic open fracture, a Clostridium botulinum wound infection was diagnosed, with self-limiting symptoms. This is the first report of wound botulism in Italy and the authors discuss the possible role of aerosolized contamination of the wound prior to hospital admission.
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September 2015

Befriending death: A mindfulness-based approach to cultivating self-awareness in counselling students.

Authors:
Maria Stella

Death Stud 2016 14;40(1):32-9. Epub 2015 Jun 14.

a Division of Arts and Sciences, City University of Seattle-Vancouver , Vancouver , British Columbia , Canada.

The importance of self-awareness in counselling education is widely recognized; however, strengthening this vital aspect is often left to educators' discretion. The author addresses this deficiency by first exploring four theoretical constructs: mindfulness, emotional regulation, death anxiety, and relationship dynamics. Then, she outlines a practical learning activity on the topic of death. The main exercise involves a guided meditation in which students imagine both a worst-case and best-case scenario of their own death, while practicing mindfulness, followed by a debriefing period and a written self-reflection. This activity can be used by educators to promote greater self-awareness in master's level counselling students.
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http://dx.doi.org/10.1080/07481187.2015.1056566DOI Listing
January 2017

MATS: Global coverage estimates for 4CMenB, a novel multicomponent meningococcal B vaccine.

Vaccine 2015 May 13;33(23):2629-36. Epub 2015 Apr 13.

GSK Vaccines, Cambridge, MA, USA.

Recently approved in the EU, US, Australia, and Canada, 4CMenB (Bexsero(®), GSK Vaccines) is a multi-component meningococcal B (MenB) vaccine containing 3 surface exposed recombinant proteins (fHbp, NadA, and NHBA) and New Zealand strain outer membrane vesicles (NZ OMV) containing PorA 1.4. The accepted correlate of protection to assess response to MenB vaccines, the serum bactericidal assay with human complement, is impractical for large panels of strains with diverse antigenic profile and expression. Therefore, the Meningococcal Antigen Typing System (MATS) was developed to identify MenB strains with a high likelihood of being covered by 4CMenB. MATS is used to assess MenB strain coverage without requiring sera, an advantage for testing large panels of bacterial isolates. MATS provides an accurate, conservative estimate of 4CMenB coverage. In a public-private partnership, 10 reference laboratories around the world were established and standardized to facilitate the timely collection and analysis of regional data. MATS has global public health implications for informing local policy makers of the predicted effect of the implementation of the 4CMenB vaccine. Coverage estimates are similar to or better than other recently approved vaccines, ranging from 66% to 91%. The use of MATS in post-vaccine implementation surveillance could provide data regarding vaccine effectiveness in the field and duration of protection on a global scale that will aid in the development of vaccine booster schedules, if necessary. This MATS approach could potentially be applied rapidly to assess epidemiology of other bacterial pathogens and coverage by other protein-based vaccines.
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http://dx.doi.org/10.1016/j.vaccine.2015.04.015DOI Listing
May 2015

[Technology and medicine].

G Ital Nefrol 2014 Jul-Aug;31(4)

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June 2016

Molecular analysis and associated pathology of beak and feather disease virus isolated in Italy from young Congo African grey parrots (Psittacus erithacus) with an "atypical peracute form" of the disease.

Avian Pathol 2014 16;43(4):333-44. Epub 2014 Jul 16.

a Department of Veterinary Sciences , University of Turin , Grugliasco , Turin , Italy.

This study is the first report on the genetic and pathogenic characterization of beak and feather disease virus (BFDV) occurring in Italy. Twenty BFDV strains isolated in Italy from juvenile Congo African grey parrots (Psittacus erithacus) were investigated. Seventeen strains showed an "atypical peracute form" (aPF) of the disease, and three a chronic form (CF). The birds with aPF had been weaned, were independent as far as food and protection were concerned and apparently were without lesions. The gene coding for the putative coat protein was amplified in all isolates while the BFDV genome was sequenced completely in 10 samples, eight of them belonging to aPF affected birds and two from CF of the disease. All full genomes clustered into the J strain of BFDV, where two new subtypes were identified. Recombination analyses showed evidence of genetic exchanges in two BFDV genomes. In addition, a correlation between viral isolate and origin of the breeding material was shown, while an association between the genetic features of the virus and the clinical form was not observed. Histologically, apoptosis was detected frequently in aPF samples and sporadically in CF samples. Interestingly, BFDV antigens were detected in the nuclei and cytoplasm of such apoptotic cells. The data presented here support the hypothesis that, in the absence of a defined BFDV genetic variant accountable for a specific clinical form of psittacine beak and feather disease, differences in the apoptotic rate between aPF and CF are strictly host related.
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http://dx.doi.org/10.1080/03079457.2014.934660DOI Listing
April 2015

Quantification by LC-MS(E) of outer membrane vesicle proteins of the Bexsero® vaccine.

Vaccine 2014 Mar 23;32(11):1273-9. Epub 2014 Jan 23.

Novartis Vaccines and Diagnostics, Via Fiorentina, 1 53100 Siena, Italy. Electronic address:

Meningococcal disease is a major cause of morbidity and mortality worldwide. Its epidemiology is currently dominated by five capsular serogroups (A, B, C, W, and Y). While effective vaccines already exist for serogroups A, C, W and Y, except for under clonal outbreaks, no vaccine was available against serogroup B. Recently, a four component vaccine, Bexsero(®), designed to prevent infection caused by this serogroup, has been approved in Europe and other Countries for use in individuals from two months of age and older. The active components of this vaccine are three recombinant proteins identified by reverse vaccinology combined with detergent extracted outer membrane vesicles (DOMV) prepared from a New Zealand epidemic strain. Considering their intrinsic complexity, we performed additional characterization of DOMVs on top of the standard quality control testing carried out for batch release. We applied the Hi3 label-free LC-MS(E) methodology to qualitatively and quantitatively characterize the DOMV protein content. We first, successfully investigated the robustness and the accuracy of the methodology for the DOMV characterization and we then applied it to compare six DOMV production lots. Around 100 proteins were quantified from each preparation. When classified according to their predicted cellular localization, about 90% of the total protein amount belongs consistently to the outer membrane compartment. Using nonparametric hypothesis testing and complementary log-log linear regression, the quantifications of a subset of 21 proteins common to all lots and including approximately 90% (85-92%) of the total protein amount quantified in any DOMV lot were found consistent across lots. The relevance of these results is two-fold, showing that the Hi3 quantification methodology is robust for a broad range of proteins and indicating that the manufacturing process currently used for the production of the Bexsero(®) DOMV components is highly reproducible and consistent.
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http://dx.doi.org/10.1016/j.vaccine.2014.01.011DOI Listing
March 2014

Rickettsia slovaca in immature Dermacentor marginatus and tissues from Apodemus spp. in the northern Apennines, Italy.

Ticks Tick Borne Dis 2013 Dec 9;4(6):518-21. Epub 2013 Oct 9.

Dipartimento di Scienze Veterinarie, University of Torino, Italy.

Immature Dermacentor marginatus ticks and tissues from small rodents were tested for infection with Rickettsia slovaca in the northern Apennines, Lucca Province, where tick-borne lymphadenopathy (TIBOLA) was previously reported in people. Prevalence of infestation with D. marginatus was 30.5% (n=131, 95% CI: 22.8-39.2%) in Apodemus spp. and 26.5% (n=34, 95% CI: 12.9-44.4%) in Myodes glareolus, which were captured during 1980 trap nights in 2009 and 2010. Rickettsia slovaca was identified by polymerase chain reaction, targeting the gltA and OmpA genes, in ear biopsies from 8 out of 37 tested Apodemus (22%, 95% CI: 9.8-38.2%), but not from 9 M. glareolus. The prevalence of R. slovaca in D. marginatus feeding on Apodemus spp. was 53% in larvae (n=51, 95% CI: 38.5-67.1%) and 47.5% in nymphs (n=59, 95% CI: 34.3-60.9%). No larvae (0.0%, 95% CI: 0-36.9%), but one nymph removed from M. glareolus was positive (10%, 95% CI: 0.3-44.5%). Prevalence of R. slovaca in host-seeking D. marginatus larvae, collected in the same area, was 42% (n=38; 95% CI: 26.3-59.2%). Prevalence of R. slovaca was greater in larvae feeding on PCR-positive Apodemus than in those feeding on negative mice (78.6% vs. 37.1%). Furthermore, levels of infestation with D. marginatus larvae were greater for R. slovaca-positive mice. The infection of Apodemus spp. was probably the result of repeated bites by transovarially infected larvae. On the other hand, the finding of R. slovaca in mice tissues would be compatible with transmission from these hosts to feeding D. marginatus. Based on such a hypothesis, the most heavily infested Apodemus might play a role as amplifiers of the infection.
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http://dx.doi.org/10.1016/j.ttbdis.2013.07.002DOI Listing
December 2013

A(H1N1)pdm09 hemagglutinin D222G and D222N variants are frequently harbored by patients requiring extracorporeal membrane oxygenation and advanced respiratory assistance for severe A(H1N1)pdm09 infection.

Influenza Other Respir Viruses 2013 Nov 9;7(6):1416-26. Epub 2013 Aug 9.

Department of Infectious Diseases, Laboratory of Microbiology and Virology, Amedeo di Savoia Hospital, Turin, Italy.

Background: In patients with A(H1N1)pdm09 infection, severe lung involvement requiring admission to intensive care units (ICU) has been reported. Mutations at the hemagglutinin (HA) receptor binding site (RBS) have been associated with increased virulence and disease severity, representing a potential marker of critical illness.

Objectives: To assess the contribution of HA-RBS variability in critically ill patients, A(H1N1)pdm09 virus from adult patients with severe infection admitted to ICU for extracorporeal membrane oxygenation support (ECMO) during influenza season 2009-2011 in Piemonte (4·2 million inhabitants), northwestern Italy, was studied.

Patients And Methods: We retrospectively analyzed HA-RBS polymorphisms in ICU patients and compared with those from randomly selected inpatients with mild A(H1N1)pdm09 disease and outpatients with influenza from the local surveillance program.

Results: By HA-RBS direct sequencing of respiratory specimens, D222G and D222N viral variants were identified in a higher proportion in ICU patients (n=8/24, 33·3%) than in patients with mild disease (n=2/34, 6%) or in outpatients (n=0/44) (Fisher's exact test P<0·0001; OR 38·5; CI 95% 4·494-329·9). Eleven ICU patients died (42%), three of them carrying the D222G variant, which was associated with RBS mutation S183P in two. D222G and D222N mutants were identified in upper and lower respiratory samples.

Conclusions: A(H1N1)pdm09 HA substitutions D222G and D222N were harbored in a significantly higher proportion by patients with acute respiratory distress for A(H1N1)pdm09 severe infection requiring ICU admission and ECMO. These data emphasize the importance of monitoring viral evolution for understanding virus-host adaptation aimed at the surveillance of strain circulation and the study of viral correlates of disease severity.
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http://dx.doi.org/10.1111/irv.12146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4634302PMC
November 2013

High rate of respiratory MDR gram-negative bacteria in H1N1-ARDS treated with ECMO.

Intensive Care Med 2013 Oct 6;39(10):1880-1. Epub 2013 Jul 6.

Infectious Diseases, Department of Medical Sciences, University of Turin, Ospedale Amedeo di Savoia, Corso Svizzera 164, 10149, Torino, Italy,

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http://dx.doi.org/10.1007/s00134-013-3012-yDOI Listing
October 2013

Predicted strain coverage of a meningococcal multicomponent vaccine (4CMenB) in Europe: a qualitative and quantitative assessment.

Lancet Infect Dis 2013 May 13;13(5):416-25. Epub 2013 Feb 13.

University of Würzburg, Institute for Hygiene and Microbiology, Würzburg, Germany.

Background: A novel multicomponent vaccine against meningococcal capsular group B (MenB) disease contains four major components: factor-H-binding protein, neisserial heparin binding antigen, neisserial adhesin A, and outer-membrane vesicles derived from the strain NZ98/254. Because the public health effect of the vaccine, 4CMenB (Novartis Vaccines and Diagnostics, Siena, Italy), is unclear, we assessed the predicted strain coverage in Europe.

Methods: We assessed invasive MenB strains isolated mainly in the most recent full epidemiological year in England and Wales, France, Germany, Italy, and Norway. Meningococcal antigen typing system (MATS) results were linked to multilocus sequence typing and antigen sequence data. To investigate whether generalisation of coverage applied to the rest of Europe, we also assessed isolates from the Czech Republic and Spain.

Findings: 1052 strains collected from July, 2007, to June, 2008, were assessed from England and Wales, France, Germany, Italy, and Norway. All MenB strains contained at least one gene encoding a major antigen in the vaccine. MATS predicted that 78% of all MenB strains would be killed by postvaccination sera (95% CI 63-90, range of point estimates 73-87% in individual country panels). Half of all strains and 64% of covered strains could be targeted by bactericidal antibodies against more than one vaccine antigen. Results for the 108 isolates from the Czech Republic and 300 from Spain were consistent with those for the other countries.

Interpretation: MATS analysis showed that a multicomponent vaccine could protect against a substantial proportion of invasive MenB strains isolated in Europe. Monitoring of antigen expression, however, will be needed in the future.

Funding: Novartis Vaccines and Diagnostics.
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http://dx.doi.org/10.1016/S1473-3099(13)70006-9DOI Listing
May 2013

Interlaboratory standardization of the sandwich enzyme-linked immunosorbent assay designed for MATS, a rapid, reproducible method for estimating the strain coverage of investigational vaccines.

Clin Vaccine Immunol 2012 Oct 8;19(10):1609-17. Epub 2012 Aug 8.

Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Diseases Control and Prevention, Atlanta, Georgia, USA.

The meningococcal antigen typing system (MATS) sandwich enzyme-linked immunosorbent assay (ELISA) was designed to measure the immunologic cross-reactivity and quantity of antigens in target strains of a pathogen. It was first used to measure the factor H-binding protein (fHbp), neisserial adhesin A (NadA), and neisserial heparin-binding antigen (NHBA) content of serogroup B meningococcal (MenB) isolates relative to a reference strain, or "relative potency" (RP). With the PorA genotype, the RPs were then used to assess strain coverage by 4CMenB, a multicomponent MenB vaccine. In preliminary studies, MATS accurately predicted killing in the serum bactericidal assay using human complement, an accepted correlate of protection for meningococcal vaccines. A study across seven laboratories assessed the reproducibility of RPs for fHbp, NadA, and NHBA and established qualification parameters for new laboratories. RPs were determined in replicate for 17 MenB reference strains at laboratories A to G. The reproducibility of RPs among laboratories and against consensus values across laboratories was evaluated using a mixed-model analysis of variance. Interlaboratory agreement was very good; the Pearson correlation coefficients, coefficients of accuracy, and concordance correlation coefficients exceeded 99%. The summary measures of reproducibility, expressed as between-laboratory coefficients of variation, were 7.85% (fHbp), 16.51% (NadA), and 12.60% (NHBA). The overall within-laboratory measures of variation adjusted for strain and laboratory were 19.8% (fHbp), 28.8% (NHBA), and 38.3% (NadA). The MATS ELISA was successfully transferred to six laboratories, and a further laboratory was successfully qualified.
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http://dx.doi.org/10.1128/CVI.00202-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3485892PMC
October 2012

Hepatic intra-arterial cetuximab in combination with 5-fluorouracil and cisplatin as salvage treatment for sorafenib-refractory hepatocellular carcinoma.

Anticancer Res 2011 Nov;31(11):3927-33

Department of Oncology, IRCCS S. Maugeri Foundation, 10 Maugeri Street, 27100 Pavia, Italy.

Background: Sorafenib is the only therapy approved for advanced hepatocellular carcinoma no longer eligible for transcatheter arterial chemoembolization. Hepatic intra-arterial chemotherapy has been shown to be an effective and safe therapy for advanced hepatocellular carcinoma. Cetuximab has been administered intravenously to patients with advanced hepatocellular carcinoma, showing encouraging results in terms of its safety and toxicity profile.

Aim: Our purpose was to evaluate the safety and feasibility of hepatic arterial chemotherapy with cetuximab, cisplatin and 5-fluoruracil for patients with advanced hepatocellular carcinoma, not responsive or not eligible for sorafenib therapy.

Patients And Methods: From January 2010 to January 2011, 12 patients received a 2-day course of chemotherapy consisting of repeated daily hepatic arterial administration of 20 mg of cisplatin as 2-h infusion, 5-fluorouracil at 500 mg/m(2) as 5-h infusion and cetuximab 500 mg/m(2) as 12-h infusion. Cycles were repeated every 14 days.

Results: After a mean of four months of therapy, computed tomography revealed five partial responses, five cases of stable disease and two of progressive disease. The toxicity profile was favourable, with no G4 gastrointestinal, hematologic or skin side-effects, or severe deterioration of liver function.

Conclusion: Hepatic intra-arterial chemotherapy with cetuximab is a safe and feasible treatment for advanced hepatocellular carcinoma, with promising results in patients with initial poor prognosis.
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November 2011