DDI - Artigos em revistas internacionais
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Browsing DDI - Artigos em revistas internacionais by Author "Abad, Raquel"
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- Europe-wide expansion and eradication of multidrug-resistant Neisseria gonorrhoeae lineages: a genomic surveillance studyPublication . Sánchez-Busó, Leonor; Cole, Michelle J.; Spiteri, Gianfranco; Day, Michaela; Jacobsson, Susanne; Golparian, Daniel; Sajedi, Noshin; Yeats, Corin A.; Abudahab, Khalil; Underwood, Anthony; Bluemel, Benjamin; Aanensen, David M.; Unemo, Magnus; Pleininger, Sonja; Indra, Alexander; De Baetselier, Irith; Vanden Berghe, Wim; Hunjak, Blaženka; Blažić, Tatjana Nemeth; Maikanti-Charalambous, Panayiota; Pieridou, Despo; Zákoucká, Hana; Žemličková, Helena; Hoffmann, Steen; Cowan, Susan; Schwartz, Lasse Jessen; Peetso, Rita; Epstein, Jevgenia; Viktorova, Jelena; Ndeikoundam, Ndeindo; Bercot, Beatrice; Bébéar, Cécile; Lot, Florence; Buder, Susanne; Jansen, Klaus; Miriagou, Vivi; Rigakos, Georgios; Raftopoulos, Vasilios; Balla, Eszter; Dudás, Mária; Ásmundsdóttir, Lena Rós; Sigmundsdóttir, Guðrún; Hauksdóttir, Guðrún Svanborg; Gudnason, Thorolfur; Colgan, Aoife; Crowley, Brendan; Saab, Sinéad; Stefanelli, Paola; Carannante, Anna; Parodi, Patrizia; Pakarna, Gatis; Nikiforova, Raina; Bormane, Antra; Dimina, Elina; Perrin, Monique; Abdelrahman, Tamir; Mossong, Joël; Schmit, Jean-Claude; Mühlschlegel, Friedrich; Barbara, Christopher; Mifsud, Francesca; Van Dam, Alje; Van Benthem, Birgit; Visser, Maartje; Linde, Ineke; Kløvstad, Hilde; Caugant, Dominique; Młynarczyk-Bonikowska, Beata; Azevedo, Jacinta; Borrego, Maria-José; Nascimento, Marina Lurdes Ramos; Pavlik, Peter; Klavs, Irena; Murnik, Andreja; Jeverica, Samo; Kustec, Tanja; Vázquez Moreno, Julio; Diaz, Asuncion; Abad, Raquel; Velicko, Inga; Unemo, Magnus; Fifer, Helen; Shepherd, Jill; Patterson, LynseyBackground: Genomic surveillance using quality-assured whole-genome sequencing (WGS) together with epidemiological and antimicrobial resistance (AMR) data is essential to characterise the circulating Neisseria gonorrhoeae lineages and their association to patient groups (defined by demographic and epidemiological factors). In 2013, the European gonococcal population was characterised genomically for the first time. We describe the European gonococcal population in 2018 and identify emerging or vanishing lineages associated with AMR and epidemiological characteristics of patients, to elucidate recent changes in AMR and gonorrhoea epidemiology in Europe. Methods: We did WGS on 2375 gonococcal isolates from 2018 (mainly Sept 1-Nov 30) in 26 EU and EEA countries. Molecular typing and AMR determinants were extracted from quality-checked genomic data. Association analyses identified links between genomic lineages, AMR, and epidemiological data. Findings: Azithromycin-resistant N gonorrhoeae (8·0% [191/2375] in 2018) is rising in Europe due to the introduction or emergence and subsequent expansion of a novel N gonorrhoeae multi-antigen sequence typing (NG-MAST) genogroup, G12302 (132 [5·6%] of 2375; N gonorrhoeae sequence typing for antimicrobial resistance [NG-STAR] clonal complex [CC]168/63), carrying a mosaic mtrR promoter and mtrD sequence and found in 24 countries in 2018. CC63 was associated with pharyngeal infections in men who have sex with men. Susceptibility to ceftriaxone and cefixime is increasing, as the resistance-associated lineage, NG-MAST G1407 (51 [2·1%] of 2375), is progressively vanishing since 2009-10. Interpretation: Enhanced gonococcal AMR surveillance is imperative worldwide. WGS, linked to epidemiological and AMR data, is essential to elucidate the dynamics in gonorrhoea epidemiology and gonococcal populations as well as to predict AMR. When feasible, WGS should supplement the national and international AMR surveillance programmes to elucidate AMR changes over time. In the EU and EEA, increasing low-level azithromycin resistance could threaten the recommended ceftriaxone-azithromycin dual therapy, and an evidence-based clinical azithromycin resistance breakpoint is needed. Nevertheless, increasing ceftriaxone susceptibility, declining cefixime resistance, and absence of known resistance mutations for new treatments (zoliflodacin, gepotidacin) are promising.
- Genetic Meningococcal Antigen Typing System (gMATS): A genotyping tool that predicts 4CMenB strain coverage worldwidePublication . Muzzi, Alessandro; Brozzi, Alessandro; Serino, Laura; Bodini, Margherita; Abad, Raquel; Caugant, Dominique; Comanducci, Maurizio; Lemos, Ana Paula; Gorla, Maria Cecilia; Křížová, Pavla; Mikula, Claudia; Mulhall, Robert; Nissen, Michael; Nohynek, Hanna; Simões, Maria João; Skoczyńska, Anna; Stefanelli, Paola; Taha, Muhamed-Kheir; Toropainen, Maija; Tzanakaki, Georgina; Vadivelu-Pechai, Kumaran; Watson, Philip; Vazquez, Julio A.; Rajam, Gowrisankar; Rappuoli, Rino; Borrow, Ray; Medini, DuccioBackground: The Meningococcal Antigen Typing System (MATS) was developed to identify meningococcus group B strains with a high likelihood of being covered by the 4CMenB vaccine, but is limited by the requirement for viable isolates from culture-confirmed cases. We examined if antigen genotyping could complement MATS in predicting strain coverage by the 4CMenB vaccine. Methods: From a panel of 3912 MATS-typed invasive meningococcal disease isolates collected in England and Wales in 2007-2008, 2014-2015 and 2015-2016, and in 16 other countries in 2000-2015, 3481 isolates were also characterized by antigen genotyping. Individual associations between antigen genotypes and MATS coverage for each 4CMenB component were used to define a genetic MATS (gMATS). gMATS estimates were compared with England and Wales human complement serum bactericidal assay (hSBA) data and vaccine effectiveness (VE) data from England. Results: Overall, 81% of the strain panel had genetically predictable MATS coverage, with 92% accuracy and highly concordant results across national panels (Lin's accuracy coefficient, 0.98; root-mean-square deviation, 6%). England and Wales strain coverage estimates were 72-73% by genotyping (66-73% by MATS), underestimating hSBA values after four vaccine doses (88%) and VE after two doses (83%). The gMATS predicted strain coverage in other countries was 58-88%. Conclusions: gMATS can replace MATS in predicting 4CMenB strain coverage in four out of five cases, without requiring a cultivable isolate, and is open to further improvement. Both methods underestimated VE in England. Strain coverage predictions in other countries matched or exceeded England and Wales estimates.
- Increase of invasive meningococcal serogroup W disease in Europe, 2013 to 2017Publication . Krone, Manuel; Gray, Steve; Abad, Raquel; Skoczyńska, Anna; Stefanelli, Paola; van der Ende, Arie; Tzanakaki, Georgina; Mölling, Paula; João Simões, Maria; Křížová, Pavla; Emonet, Stéphane; Caugant, Dominique A.; Toropainen, Maija; Vazquez, Julio; Waśko, Izabela; Knol, Mirjam J.; Jacobsson, Susanne; Rodrigues Bettencourt, Célia; Musilek, Martin; Born, Rita; Vogel, Ulrich; Borrow, RayBackground: The total incidence of invasive meningococcal disease (IMD) in Europe has been declining in recent years; however, a rising incidence due to serogroup W (MenW), predominantly sequence type 11 (ST-11), clonal complex 11 (cc11), was reported in some European countries. Aim: The aim of this study was to compile the most recent laboratory surveillance data on MenW IMD from several European countries to assess recent trends in Europe. Methods: In this observational, retrospective study, IMD surveillance data collected from 2013–17 by national reference laboratories and surveillance units from 13 European countries were analysed using descriptive statistics. Results: The overall incidence of IMD has been stable during the study period. Incidence of MenW IMD per 100,000 population (2013: 0.03; 2014: 0.05; 2015: 0.08; 2016: 0.11; 2017: 0.11) and the proportion of this serogroup among all invasive cases (2013: 5% (116/2,216); 2014: 9% (161/1,761); 2015: 13% (271/2,074); 2016: 17% (388/2,222); 2017: 19% (393/2,112)) continuously increased. The most affected countries were England, the Netherlands, Switzerland and Sweden. MenW was more frequent in older age groups (≥ 45 years), while the proportion in children (< 15 years) was lower than in other age groups. Of the culture-confirmed MenW IMD cases, 80% (615/767) were caused by hypervirulent cc11. Conclusion: During the years 2013–17, an increase in MenW IMD, mainly caused by MenW cc11, was observed in the majority of European countries. Given the unpredictable nature of meningococcal spread and the epidemiological potential of cc11, European countries may consider preventive strategies adapted to their contexts.
- Public health surveillance of multidrug-resistant clones of Neisseria gonorrhoeae in Europe: a genomic surveyPublication . Harris, Simon R.; Cole, Michelle J.; Spiteri, Gianfranco; Sánchez-Busó, Leonor; Golparian, Daniel; Jacobsson, Susanne; Goater, Richard; Abudahab, Khalil; Yeats, Corin A.; Bercot, Beatrice; Borrego, Maria José; Crowley, Brendan; Stefanelli, Paola; Tripodo, Francesco; Abad, Raquel; Aanensen, David M.; Unemo, Magnus; Euro-GASP study groupBackground: Traditional methods for molecular epidemiology of Neisseria gonorrhoeae are suboptimal. Whole-genome sequencing (WGS) offers ideal resolution to describe population dynamics and to predict and infer transmission of antimicrobial resistance, and can enhance infection control through linkage with epidemiological data. We used WGS, in conjunction with linked epidemiological and phenotypic data, to describe the gonococcal population in 20 European countries. We aimed to detail changes in phenotypic antimicrobial resistance levels (and the reasons for these changes) and strain distribution (with a focus on antimicrobial resistance strains in risk groups), and to predict antimicrobial resistance from WGS data. Methods: We carried out an observational study, in which we sequenced isolates taken from patients with gonorrhoea from the European Gonococcal Antimicrobial Surveillance Programme in 20 countries from September to November, 2013. We also developed a web platform that we used for automated antimicrobial resistance prediction, molecular typing (N gonorrhoeae multi-antigen sequence typing [NG-MAST] and multilocus sequence typing), and phylogenetic clustering in conjunction with epidemiological and phenotypic data. Findings: The multidrug-resistant NG-MAST genogroup G1407 was predominant and accounted for the most cephalosporin resistance, but the prevalence of this genogroup decreased from 248 (23%) of 1066 isolates in a previous study from 2009–10 to 174 (17%) of 1054 isolates in this survey in 2013. This genogroup previously showed an association with men who have sex with men, but changed to an association with heterosexual people (odds ratio=4·29). WGS provided substantially improved resolution and accuracy over NG-MAST and multilocus sequence typing, predicted antimicrobial resistance relatively well, and identified discrepant isolates, mixed infections or contaminants, and multidrug-resistant clades linked to risk groups. Interpretation: To our knowledge, we provide the first use of joint analysis of WGS and epidemiological data in an international programme for regional surveillance of sexually transmitted infections. WGS provided enhanced understanding of the distribution of antimicrobial resistance clones, including replacement with clones that were more susceptible to antimicrobials, in several risk groups nationally and regionally. We provide a framework for genomic surveillance of gonococci through standardised sampling, use of WGS, and a shared information architecture for interpretation and dissemination by use of open access software.
- Ten years of external quality assessment (EQA) of Neisseria gonorrhoeae antimicrobial susceptibility testing in Europe elucidate high reliability of dataPublication . Cole, Michelle J.; Quaye, Nerteley; Jacobsson, Susanne; Day, Michaela; Fagan, Elizabeth; Ison, Catherine; Pitt, Rachel; Seaton, Shila; Woodford, Neil; Stary, Angelika; Pleininger, Sonja; Crucitti, Tania; Hunjak, Blaženka; Maikanti, Panayiota; Hoffmann, Steen; Viktorova, Jelena; Buder, Susanne; Kohl, Peter; Tzelepi, Eva; Siatravani, Eirini; Balla, Eszter; Hauksdóttir, Guðrún Svanborg; Rose, Lisa; Stefanelli, Paola; Carannante, Anna; Pakarna, Gatis; Mifsud, Francesca; Cassar, Rosann Zammit; Linde, Ineke; Bergheim, Thea; Steinbakk, Martin; Mlynarczyk-Bonikowska, Beata; Borrego, Maria-José; Shepherd, Jill; Pavlik, Peter; Jeverica, Samo; Vazquez, Julio; Abad, Raquel; Weiss, Sabrina; Spiteri, Gianfranco; Unemo, MagnusBackground: Confidence in any diagnostic and antimicrobial susceptibility testing data is provided by appropriate and regular quality assurance (QA) procedures. In Europe, the European Gonococcal Antimicrobial Susceptibility Programme (Euro-GASP) has been monitoring the antimicrobial susceptibility in Neisseria gonorrhoeae since 2004. Euro-GASP includes an external quality assessment (EQA) scheme as an essential component for a quality-assured laboratory-based surveillance programme. Participation in the EQA scheme enables any problems with the performed antimicrobial susceptibility testing to be identified and addressed, feeds into the curricula of laboratory training organised by the Euro-GASP network, and assesses the capacity of individual laboratories to detect emerging new, rare and increasing antimicrobial resistance phenotypes. Participant performance in the Euro-GASP EQA scheme over a 10 year period (2007 to 2016, no EQA in 2013) was evaluated. Methods: Antimicrobial susceptibility category and MIC results from the first 5 years (2007-2011) of the Euro-GASP EQA were compared with the latter 5 years (2012-2016). These time periods were selected to assess the impact of the 2012 European Union case definitions for the reporting of antimicrobial susceptibility. Results: Antimicrobial susceptibility category agreement in each year was ≥91%. Discrepancies in susceptibility categories were generally because the MICs for EQA panel isolates were on or very close to the susceptibility or resistance breakpoints. A high proportion of isolates tested over the 10 years were within one (≥90%) or two (≥97%) MIC log2 dilutions of the modal MIC, respectively. The most common method used was Etest on GC agar base. There was a shift to using breakpoints published by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in the latter 5 years, however overall impact on the validity of results was limited, as the percentage categorical agreement and MIC concordance changed very little between the two five-year periods. Conclusions: The high level of comparability of results in this EQA scheme indicates that high quality data are produced by the Euro-GASP participants and gives confidence in susceptibility and resistance data generated by laboratories performing decentralised testing.
- WGS analysis and molecular resistance mechanisms of azithromycin-resistant (MIC >2 mg/L) Neisseria gonorrhoeae isolates in Europe from 2009 to 2014Publication . Jacobsson, Susanne; Golparian, Daniel; Cole, Michelle; Spiteri, Gianfranco; Martin, Irene; Bergheim, Thea; Borrego, Maria José; Crowley, Brendan; Crucitti, Tania; Van Dam, Alje P.; Hoffmann, Steen; Jeverica, Samo; Kohl, Peter; Mlynarczyk-Bonikowska, Beata; Pakarna, Gatis; Stary, Angelika; Stefanelli, Paola; Pavlik, Peter; Tzelepi, Eva; Abad, Raquel; Harris, Simon R.; Unemo, MagnusOBJECTIVES: To elucidate the genome-based epidemiology and phylogenomics of azithromycin-resistant (MIC >2 mg/L) Neisseria gonorrhoeae strains collected in 2009-14 in Europe and clarify the azithromycin resistance mechanisms. METHODS: Seventy-five azithromycin-resistant (MIC 4 to >256 mg/L) N. gonorrhoeae isolates collected in 17 European countries during 2009-14 were examined using antimicrobial susceptibility testing and WGS. RESULTS: Thirty-six N. gonorrhoeae multi-antigen sequence typing STs and five phylogenomic clades, including 4-22 isolates from several countries per clade, were identified. The azithromycin target mutation A2059G (Escherichia coli numbering) was found in all four alleles of the 23S rRNA gene in all isolates with high-level azithromycin resistance (n = 4; MIC ≥256 mg/L). The C2611T mutation was identified in two to four alleles of the 23S rRNA gene in the remaining 71 isolates. Mutations in mtrR and its promoter were identified in 43 isolates, comprising isolates within the whole azithromycin MIC range. No mutations associated with azithromycin resistance were found in the rplD gene or the rplV gene and none of the macrolide resistance-associated genes [mef(A/E), ere(A), ere(B), erm(A), erm(B), erm(C) and erm(F)] were identified in any isolate. CONCLUSIONS: Clonal spread of relatively few N. gonorrhoeae strains accounts for the majority of the azithromycin resistance (MIC >2 mg/L) in Europe. The four isolates with high-level resistance to azithromycin (MIC ≥256 mg/L) were widely separated in the phylogenomic tree and did not belong to any of the main clades. The main azithromycin resistance mechanisms were the A2059G mutation (high-level resistance) and the C2611T mutation (low- and moderate-level resistance) in the 23S rRNA gene.
