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  • 1.
    Acevedo, Reinaldo
    et al.
    Biologic Evaluation Department, Finlay Institute of Vaccines, Havana, Cuba.
    Bai, Xilian
    Meningococcal Reference Unit, Public Health England, Manchester, UK.
    Borrow, Ray
    Meningococcal Reference Unit, Public Health England, Manchester, UK.
    Caugant, Dominique A.
    Division of Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.
    Carlos, Josefina
    Department of Pediatrics, College of Medicine, University of the East – Ramon Magsaysay Memorial Medical Center, Quezon City, Philippines.
    Ceyhan, Mehmet
    Faculty of Medicine, Department of Pediatric Infectious Diseases, Hacettepe University, Ankara, Turkey.
    Christensen, Hannah
    Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
    Climent, Yanet
    Biologic Evaluation Department, Finlay Institute of Vaccines, Havana, Cuba.
    De Wals, Philippe
    Department of Social and Preventive Medicine, Laval University, Quebec City QC, Canada.
    Dinleyici, Ener Cagri
    Department of Paediatrics, Eskisehir Osmangazi University Faculty of Medicine, Eskisehir, Turkey.
    Echaniz-Aviles, Gabriela
    Center for Research on Infectious Diseases, Instituto Nacional de Salud Pública, Cuernavaca, México.
    Hakawi, Ahmed
    Infectious Diseases Control, Ministry of Health, Riyadh, Saudi Arabia.
    Kamiya, Hajime
    Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Tokyo, Japan.
    Karachaliou, Andromachi
    Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
    Lucidarme, Jay
    Meningococcal Reference Unit, Public Health England, Manchester, UK.
    Meiring, Susan
    Division of Public Health Surveillance and Response, National Institute for Communicable Diseases, Johannesburg, South Africa.
    Mironov, Konstantin
    Central Research Institute of Epidemiology, Moscow, Russian Federation.
    Safadi, Marco A. P.
    Department of Pediatrics, FCM Santa Casa de São Paulo School of Medical Sciences, São Paulo, Brazil.
    Shao, Zhujun
    National Institute for Communicable Disease Control and Prevention, Chinese Centre for Disease Control and Prevention, Beijing, China.
    Smith, Vinny
    Meningitis Research Foundation, Bristol, UK.
    Steffen, Robert
    Department of Epidemiology and Prevention of Infectious Diseases, WHO Collaborating Centre for Travellers’ Health, University of Zurich, Zurich, Switzerland.
    Stenmark, Bianca
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine.
    Taha, Muhamed-Kheir
    Institut Pasteur, National Reference Centre for Meningococci, Paris, France.
    Trotter, Caroline
    Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
    Vazquez, Julio A.
    National Centre of Microbiology, Institute of Health Carlos III, Madrid, Spain.
    Zhu, Bingqing
    National Institute for Communicable Disease Control and Prevention, Chinese Centre for Disease Control and Prevention, Beijing, China.
    The Global Meningococcal Initiative meeting on prevention of meningococcal disease worldwide: Epidemiology, surveillance, hypervirulent strains, antibiotic resistance and high-risk populations2019In: Expert Review of Vaccines, ISSN 1476-0584, E-ISSN 1744-8395, Vol. 18, no 1, p. 15-30Article, review/survey (Refereed)
    Abstract [en]

    Introduction: The 2018 Global Meningococcal Initiative (GMI) meeting focused on evolving invasive meningococcal disease (IMD) epidemiology, surveillance, and protection strategies worldwide, with emphasis on emerging antibiotic resistance and protection of high-risk populations. The GMI is comprised of a multidisciplinary group of scientists and clinicians representing institutions from several continents.

    Areas covered: Given that the incidence and prevalence of IMD continually varies both geographically and temporally, and surveillance systems differ worldwide, the true burden of IMD remains unknown. Genomic alterations may increase the epidemic potential of meningococcal strains. Vaccination and (to a lesser extent) antimicrobial prophylaxis are the mainstays of IMD prevention. Experiences from across the globe advocate the use of conjugate vaccines, with promising evidence growing for protein vaccines. Multivalent vaccines can broaden protection against IMD. Application of protection strategies to high-risk groups, including individuals with asplenia, complement deficiencies and human immunodeficiency virus, laboratory workers, persons receiving eculizumab, and men who have sex with men, as well as attendees at mass gatherings, may prevent outbreaks. There was, however, evidence that reduced susceptibility to antibiotics was increasing worldwide.

    Expert commentary: The current GMI global recommendations were reinforced, with several other global initiatives underway to support IMD protection and prevention.

  • 2.
    Ehlersson, Gustaf
    et al.
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Hellmark, Bengt
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Svartström, Olov
    Department of Clinical Microbiology, Linköping University Hospital, Linköping, Sweden.
    Stenmark, Bianca
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Clinical Microbiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Phenotypic characterisation of coagulase-negative staphylococci isolated from blood cultures in newborn infants, with a special focus on Staphylococcus capitis2017In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, no 10, p. 1576-1582Article in journal (Refereed)
    Abstract [en]

    AIM: This Swedish study determined which species of coagulase-negative staphylococci (CoNS) were found in neonatal blood cultures and whether they included Staphylococcus capitis clones with decreased susceptibility to vancomycin.

    METHODS: CoNS isolates (n = 332) from neonatal blood cultures collected at Örebro University Hospital during 1987-2014 were identified to species level with matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). The antibiotic susceptibility pattern of S. capitis isolates was determined by the disc diffusion test and Etest, and the presence of heterogeneous glycopeptide-intermediate S. capitis (hGISC) was evaluated.

    RESULTS: Staphylococcus epidermidis (67.4%), Staphylococcus haemolyticus (10.5%) and S. capitis (9.6%) were the most common CoNS species. Of the S. capitis isolates, 75% were methicillin-resistant and 44% were multidrug-resistant. No isolate showed decreased susceptibility to vancomycin, but at least 59% displayed the hGISC phenotype. Staphylococcus capitis isolates related to the strain CR01 displaying pulsotype NRCS-A were found.

    CONCLUSION: Staphylococcus epidermidis, S. haemolyticus and S. capitis were the predominant species detected in neonatal blood cultures by MALDI-TOF MS. The number of episodes caused by S. capitis increased during the study period, but no isolates with decreased susceptibility to vancomycin were identified. However, S. capitis isolates related to the strain CR01 displaying pulsotype NRCS-A were found.

  • 3.
    Eriksson, Lorraine
    et al.
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Hedberg, Sara Thulin
    Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University, School of Health Sciences. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Fredlund, Hans
    Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Stenmark, Bianca
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Whole-Genome Sequencing of Emerging Invasive Neisseria meningitidis Serogroup W in Sweden2018In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 56, no 4, article id e01409-17Article in journal (Refereed)
    Abstract [en]

    Invasive disease caused by Neisseria meningitidis serogroup W (MenW) has historically had a low incidence in Sweden, with an average incidence of 0.03 case/100,000 population from 1995 to 2014. In recent years, a significant increase in the incidence of MenW has been noted in Sweden, to an average incidence of 0.15 case/100,000 population in 2015 to 2016. In 2017 (1 January to 30 June), 33% of invasive meningococcal disease cases (7/21 cases) were caused by MenW. In the present study, all invasive MenW isolates from Sweden collected in 1995 to June 2017 (n = 86) were subjected to whole-genome sequencing to determine the population structure and to compare isolates from Sweden with historical and international cases. The increase of MenW in Sweden was determined to be due to isolates belonging to the South American sublineage of MenW clonal complex 11, namely, the novel U.K. 2013 lineage. This lineage was introduced in Sweden in 2013 and has since been the dominant lineage of MenW.

  • 4.
    Hedberg, Sara Thulin
    et al.
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Törös, Bianca
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Fredlund, Hans
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Olcén, Per
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Genetic characterisation of the emerging invasive Neisseria meningitidis serogroup Y in Sweden, 2000 to 20102011In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 16, no 23, article id 19885Article in journal (Refereed)
    Abstract [en]

    Neisseria meningitidis serogroups B and C have beenresponsible for the majority of invasive meningococcaldisease in Europe. Recently, an increase of N. meningitidisdisease due to serogroup Y has been notedin Sweden (in 2010, the proportion was 39%, with anincidence of 0.23 per 100,000 population), as well as inother northern European countries. We aimed to investigatethe clonal pattern of the emerging serogroup Yin Sweden during 2000 to 2010. The serogroup Y isolatesidentified during this time (n=85) were characterisedby multilocus sequence typing and sequencing ofthe fetA, fHbp, penA, porA and porB genes. The mostfrequent clone (comprising 28 isolates) with identicalallele combinations of the investigated genes, waspartly responsible for the observed increased numberof N. meningitidis serogroup Y isolates. It was sulfadiazineresistant, with genosubtype P1.5-2,10-1,36-2,sequence type 23, clonal complex 23, porB allele 3-36,fetA allele F4-1, fHbp allele 25 and penA allele 22. Thefirst case with disease due to this clone was identifiedin 2002: there was a further case in 2004, six during2006 to 2007, eight during 2008 to 2009, with a peakof 12 cases in 2010. An unusual increase of invasivedisease in young adults (aged 20–29 years) caused bythis clone was shown, but no increase in mortality ratewas observed.

  • 5.
    Jacobsson, Susanne
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Neisseria meningitidis, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Stenmark, Bianca
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Neisseria meningitidis, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Hedberg, Sara Thulin
    WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Fredlund, Hans
    WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Neisseria meningitidis carriage in Swedish teenagers associated with the serogroup W outbreak at the World Scout Jamboree, Japan 20152018In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 126, no 4, p. 337-341Article in journal (Refereed)
    Abstract [en]

    The aims of the study were to estimate the carrier state of Neisseria meningitidis in Swedish teenagers and its association with an outbreak at the World Scout Jamboree in 2015 as well as to compare sensitivity of throat versus nasopharyngeal swab for optimal detection of carriage. In total, 1 705 samples (cultures n = 32, throat swabs n = 715, nasopharyngeal swabs n = 958) from 1 020 Jamboree participants were collected and sent to the National Reference Laboratory for Neisseria meningitidis for culture and molecular analysis. The overall positivity for N. meningitidis was 8% (83/1 020), whereas 2% (n = 22) belonged to a known sero/genogroup while the majority (n = 61) were non-groupable. Throat sample is clearly the sampling method of choice, in 56 individuals where both throat and nasopharynx samples were taken, N. meningitidis was detected in both throat and nasopharynx in eight individuals, in 46 individuals N. meningitidis was only detected in the throat and in two individuals only in the nasopharynx. Carriage studies are important to provide knowledge of the current epidemiology and association between carrier isolates and disease-causing isolates in a given population. Therefore, planning for a carriage study in Sweden is in progress.

  • 6.
    Lucidarme, J.
    et al.
    Meningococcal Reference Unit, Public Health England, Manchester, United Kingdom.
    Scott, K. J.
    Scottish Haemophilus, Legionella, Meningococcus and Pneumococcus Reference Laboratory, Glasgow Royal Infirmary, Glasgow, United Kingdom.
    Ure, R.
    Scottish Haemophilus, Legionella, Meningococcus and Pneumococcus Reference Laboratory, Glasgow Royal Infirmary, Glasgow, United Kingdom.
    Smith, A.
    Scottish Haemophilus, Legionella, Meningococcus and Pneumococcus Reference Laboratory, Glasgow Royal Infirmary, Glasgow, United Kingdom; College of Medical, Veterinary & Life Sciences, Glasgow Dental Hospital & School, University of Glasgow, Glasgow, United Kingdom.
    Lindsay, D.
    Scottish Haemophilus, Legionella, Meningococcus and Pneumococcus Reference Laboratory, Glasgow Royal Infirmary, Glasgow, United Kingdom.
    Stenmark, Bianca
    Örebro University, School of Medical Sciences. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Fredlund, Hans
    Örebro University, School of Health Sciences. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Cameron, J. C.
    Health Protection Scotland, NHS National Services Scotland, Glasgow, United Kingdom.
    Smith-Palmer, A.
    Health Protection Scotland, NHS National Services Scotland, Glasgow, United Kingdom.
    McMenamin, J.
    Health Protection Scotland, NHS National Services Scotland, Glasgow, United Kingdom.
    Gray, S. J.
    Meningococcal Reference Unit, Public Health England, Manchester, United Kingdom.
    Campbell, H.
    Immunisation Department, Public Health England, London, United Kingdom.
    Ladhani, S.
    Immunisation Department, Public Health England, London, United Kingdom.
    Findlow, J.
    Meningococcal Reference Unit, Public Health England, Manchester, United Kingdom.
    Mölling, Paula
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Borrow, R.
    Meningococcal Reference Unit, Public Health England, Manchester, United Kingdom.
    An international invasive meningococcal disease outbreak due to a novel and rapidly expanding serogroup W strain, Scotland and Sweden, July to August 20152016In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 21, no 45, p. 15-23, article id 30395Article in journal (Refereed)
    Abstract [en]

    The 23rd World Scout Jamboree in 2015 took place in Japan and included over 33,000 scouts from 162 countries. Within nine days of the meeting ending, six cases of laboratory-confirmed invasive serogroup W meningococcal disease occurred among scouts and their close contacts in Scotland and Sweden. The isolates responsible were identical to one-another by routine typing and, where known (4 isolates), belonged to the ST-11 clonal complex (cc11) which is associated with large outbreaks and high case fatality rates. Recent studies have demonstrated the need for high-resolution genomic typing schemes to assign serogroup W cc11 isolates to several distinct strains circulating globally over the past two decades. Here we used such schemes to confirm that the Jamboree-associated cases constituted a genuine outbreak and that this was due to a novel and rapidly expanding strain descended from the strain that has recently expanded in South America and the United Kingdom. We also identify the genetic differences that define the novel strain including four point mutations and three putative recombination events involving the horizontal exchange of 17, six and two genes, respectively. Noteworthy outcomes of these changes were antigenic shifts and the disruption of a transcriptional regulator.

  • 7.
    Magnusson, Charlotta
    et al.
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Stegger, Marc
    Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark.
    Hellmark, Bengt
    Örebro University, School of Health Sciences.
    Stenmark, Bianca
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Söderquist, Bo
    Örebro University, School of Medical Sciences.
    Staphylococcus aureus isolates from nares of orthopaedic patients in Sweden are mupirocin susceptible2019In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 51, no 6, p. 475-478Article in journal (Refereed)
  • 8.
    Stenmark, Bianca
    et al.
    Örebro University Hospital, Örebro, Sweden.
    Eriksson, Lorraine
    Örebro University, School of Medical Sciences. Örebro University Hospital, Örebro, Sweden.
    Anton, Brian
    New England Biolabs, Beverly, MA, USA.
    Fomenkov, Alexey
    New England Biolabs, Beverly, MA, USA.
    Tooming-Klunderud, Ave
    University of Oslo, Oslo, Norway.
    Thulin Hedberg, Sara
    Örebro University Hospital, Örebro, Sweden.
    Roberts, Richard
    New England Biolabs, Beverly, MA, USA.
    Mölling, Paula
    Örebro University Hospital, Örebro, Sweden.
    Methylome comparison of two meningococcal sub-lineages of serogroup Y cc232018Conference paper (Refereed)
    Abstract [en]

    Introduction: A significant increase in invasive meningococcal disease (IMD) due to serogroup Y Neisseria meningitidis (MenY) ST-23 clonal complex (cc23) emerged in the United States during the 1990s, spreading to Europe shortly thereafter. The largest increase was observed in Sweden with incidence proportions up to 53%. Genome analysis of all MenY isolates causing IMD between 1995 to 2012 in Sweden revealed that a distinct strain (YI) and more specifically a subtype (1) of this strain was found to be responsible for the increase of MenY IMD in Sweden [1]. In this study, we compared the methylomes of subtype 1 to the less successful subtype 2, using Single Molecule Real-Time (SMRT) sequencing technology.

    Methods: Ten genomes belonging to subtype 1 (n=7) and 2 (n=3) and one MenY genome without connection to a specific lineage were sequenced using SMRT sequencing on a PacBio®RS II. The analysis platform SMRT Portal v2 was used to identify modified positions and for the genome-wide analysis of modified motifs. DNA methyltransferase genes associated with the different methyltransferase recognition motifs identified were searched using SEQWARE. The modification-dependent restriction endonucleases MspJI and FspEI were used to determine the m5C recognition sites of the active m5C methylases in the strains.

    Results: The genome-wide analysis of the methylomes identified two m6A modified motifs: GATC and CACNNNNNTAC, but the latter was only found in isolates belonging to subtype 2 due to a transposase inserted in the candidate gene in subtype 1 strains: a Type I restriction system specificity protein (NEIS2535). The motif CACNNNNNTAC was only found in one other meningococcal isolate in REBASE, belonging to cc23, suggesting that this is a cc23 specific motif. Eleven putative restriction modification (RM) systems were found when comparing the sequences of all 11 genomes to DNA methyltransferase genes in REBASE. Five m5C genes were predicted, however, only three of these corresponding to the motifs: GCRYGC, GGNNCC and CCAGR were confirmed as active using MspJI and FspEI cleavage. The apparent CCAGR motif may be the result of two methylases, one recognizing CCWGG and the other CCAGA, but this will have to be verified.

    Conclusion: These results are consistent with previous studies [2] that have shown that the composition of different RM systems are clade specific suggesting that the unique RM system of cc23 isolates will most likely result in a specific DNA methylation pattern unique to this particular cc. However, although the majority of methyltransferases were shared between the two subtypes, there was one difference in a m6A modified motif between these two highly similar cc23 subtypes, which may lead to an altered gene expression pattern.

  • 9.
    Stenmark, Bianca
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Eriksson, Lorraine
    Örebro University, School of Medical Sciences.
    Rydbeck, H.
    University of Oslo, Oslo, Norway.
    Roberts, J.
    New England BioLabs, Ipswich MA, USA.
    Tooming-Klunderud, A.
    University of Oslo, Oslo, Norway.
    Thulin Hedberg, S.
    Örebro University Hospital, Örebro, Sweden.
    Mölling, P.
    Örebro University Hospital, Örebro, Sweden.
    Complete genome and methylome comparison of two Neisseria meningitidis serogroup Y subtypes2017In: 2nd ASM Conference on Rapid Applied Microbial Next-Generation Sequencing and Bioinformatic Pipelines: Final Program with Abstracts, Washington, DC: American Society for Microbiology , 2017, p. 32-33Conference paper (Other academic)
    Abstract [en]

    Background: A significant increase in invasive meningococcal disease (IMD) due to serogroup Y Neisseria meningitidis (MenY) strains emerged in the United States during the 1990s spreading to Europe shortly thereafter. The largest increase was observed in Sweden with incidence proportions up to 53%. cgMLST of all MenY isolates causing IMD between 1995 to 2012 in Sweden revealed that a distinct strain (YI) and more specifically a subtype (1) of this strain was found to be responsible for the increase of MenY IMD in Sweden [1]. The aim was to compare the complete genome and methylome of subtype 1 to the less successful subtype 2 using Single Molecule Real-Time (SMRT) sequencing technology.

    Methods: Ten genomes belonging to subtype 1 (n=7) and 2 (n=3) and one MenY genome without connection to a specific strain were sequenced using SMRT sequencing on a PacBio®RS II. SMRT Portal v2 was used to identify modified positions and for the genome-wide analysis of modified motifs. DNA methyltransferase genes associated with the different methyltransferase recognition motifs identified were searched using the Restriction Enzyme Database REBASE (rebase.neb.com).

    Results: Genomic comparison of the two MenY subtypes revealed that these possessed highly similar genomes, only two genes encoding hypothetical proteins were present in subtype 2 but absent in subtype 1. There were 99 genes with allelic differences and non-synonymous differences were found in genes implicated in adhesion, lipooligosaccharides (LOS) production, pilin production and iron acquisition. The genome-wide analysis of the methylome identified three modified motifs: GATC, GGNNCC and CACNNNNNTAC, the latter was only found in isolates belonging to subtype 2 and a trans-posase was found inserted in the candidate enzyme: a type I restriction system specificity protein (NEIS2535). In general, modifications were found in both cytosine and adenine bases although the latter, 6mA, was the most frequent modification in all isolates and more predominant among subtype 2. Many inactive restriction modification systems were present; however, in order to reveal more active sys-tems, further analysis on 5mC is needed.

    Conclusion: Our preliminary results indicate that there is a difference in methylation motifs as well as positional distribution of modifications between the two MenY subtypes. Since no differences were found in the presence of genes potentially involved in pathogenicity between the two subtypes, and it has been previously established that there was rather a tendency of a milder clinical picture among IMD caused by subtype 1 [2], the emergence of subtype 1 was most probably due to increased transmission or that the human population was more immunologically naïve to this subtype.

    References: 1. Törös B et al. J Clin Microbiol 2015, 53(7):2154-2162. 2. Säll O et al.Epidemiol Infect 2017, 145(10):2137-2143.

  • 10.
    Stenmark, Bianca
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Eriksson, Lorraine
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Thulin Hedberg, Sara
    WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Fredlund, Hans
    WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Whole genome sequencing of the emerging invasive Neisseria meningitidis serogroup W in Sweden2017In: 14th Congress of the EMGM, European Meningococcal and Haemophilus Disease Society: Book of Abstracts, Prague: EMGM , 2017, p. 7-8Conference paper (Other academic)
    Abstract [en]

    Introduction: The incidence of Neisseria meningitidisserogroup W (MenW) causing invasive meningococcal disease has historically been low. In 2015 an increase in MenW was observed in Sweden when an incidence of 0.1/100,000 population (10 cases) was reported, compared to an incidence of 0.02 (2 cases), in 2014. In 2016 the number of cases had almost doubled (18 cases, incidence of 0.2). England and Wales have also reported an increase of MenW from 2009 which was determined to be due to a sublineage in the South American/UK strain, called novel UK-2013 strain1. Both the South American/UK strain cluster and the novel UK-2013 strain belong to clonal complex (cc) 11, which consists of different strains from different serogroups associated with outbreaks that have occurred around the world2.

    Aim: The aim was to determine the population structure of MenW in Sweden compared to historical and international cases.

    Material and methods: All invasive MenW isolates collected in Sweden between 1995 and 2016 (n=71) were whole genome sequenced on the MiSeq (Illumina) using Nextera XT library preparation kit (Illumina) and MiSeq reagent Kit v3, 600 cycles. Reads were de novo assembled using Velvet within SeqSphere (Ridom GmbH). Genomes were uploaded to the Neisseria PubMLST database and genome comparison was performed with the genome comparator tool within pubMLST, comparing 1605 species specific core genes. The generated distance matrices were visualized using SplitsTree4 V4.

    Results: The most common fine type among the Swedish isolates was P1.5-2: F1-1: ST-11 (cc11) (n=31). Theisolates belonged to four different clonal complexes: cc11, cc22, cc60 and cc174, and the majority of isolates (39/71) belonged to cc11. No particular clonal complex dominated during the investigated time period except for cc11 since 2014. Core genome comparison showed that the majority of Swedish MenW isolates clustered with the South American/UK strain (n=26), six isolates clustered with the Hajj-associated strain and seven isolates were not associated to any strain. The majority of Swedish isolates in the South American/UK strain cluster, were from 2015 to 2016 and more specifically belonged to the UK sublineages: 23 isolates in the novel UK-2013 strain and three isolates in the original UK-strain.

    Conclusion: In conclusion, the increase of MenW in Sweden is comprised of isolates belonging to the South American/UK sublineage, more specifically the novel UK-2013 strain currently increasing in England and Wales.

    References:1 Lucidarme J, Scott KJ, Ure R, Smith A, Lindsay D, Stenmark B, et al. An international invasive meningococcal disease outbreak due to a novel and rapidly expanding serogroup W strain, Scotland and Sweden, July to August 2015. Euro Surveill. 2016;21(45):pii=303952 Lucidarme J, Hill DM, Bratcher HB, Gray SJ, du Plessis M, Tsang RS, et al. Genomic resolution of an aggressive, widespread, diverse and expanding meningococcal serogroup B, C and W lineage. The Journal of infection. 2015;71(5):544-52

  • 11.
    Stenmark, Bianca
    et al.
    Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University Hospital, Örebro, Sweden.
    Hellmark, Bengt
    Örebro University, School of Health Sciences.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University Hospital, Örebro, Sweden.
    Genomic analysis of Staphylococcus capitis isolated from blood cultures in neonates at a neonatal intensive care unit in Sweden2019In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 38, no 11, p. 2069-2075Article in journal (Refereed)
    Abstract [en]

    Emergence of a genetically distinct, multidrug-resistant Staphylococcus capitis clone (NRCS-A) present in neonatal intensive care units has recently been extensively reported. The aims of the present study were to investigate which clones of S. capitis isolated from blood in a Swedish neonatal intensive care unit (NICU) have been present since 1987 and to investigate whether the NRCS-A clone has disseminated in Sweden. All S. capitis isolates from blood cultures of neonates (≤ 28 days of age) between 1987 and 2017 (n = 46) were whole-genome sequenced, and core genome multilocus sequence typing (cgMLST) was performed. Single-nucleotide polymorphism (SNP)-based phylogenetic relationships between the S. capitis isolates and in silico predictions of presence of genetic traits specific to the NRCS-A clone were identified. Furthermore, antibiotic susceptibility testing, including screening for heterogeneous glycopeptide-intermediate resistance, was performed. Thirty-five isolates clustered closely to the isolates previously determined as belonging to the NRCS-A clone and had fewer than 81 core genome loci differences out of 1063. Twenty-one of these isolates were multidrug resistant. The NRCS-A clone was found in 2001. Six pairs of isolates had differences of fewer than two SNPs. Genetic traits associated with the NRCS-A clone such as nsr, ebh, tarJ, and CRISPR were found in all 35 isolates. The increasing incidence of S. capitis blood cultures of neonates is predominantly represented by the NRSC-A clone at our NICU in Sweden. Furthermore, there were indications of transmission between cases; adherence to basic hygiene procedures and surveillance measures are thus warranted.

  • 12.
    Stenmark, Bianca
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Hellmark, Bengt
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Söderquist, Bo
    Örebro University, School of Medical Sciences.
    Increase of S. capitis in neonates with bacteremia in Sweden due to the emergence of a multidrug-resistant clone2018Conference paper (Refereed)
    Abstract [en]

    Background: Staphylococcus capitis has traditionally been considered a commensal due to its low pathogenicity in healthy adults; however, it has been shown to cause 20% of all cases of neonatal sepsis in neonatal intensive care units (NICUs). In addition, S. capitis strains with reduced susceptibility to last line anti-staphylococcal agents such as vancomycin and linezolid are emerging in NICUs. The aim of this study was to characterize S. capitis isolated from blood in a Swedish NICU and to investigate if the multidrug-resistant clone NRCS-A has disseminated in Sweden.

    Materials/methods: All S. capitis isolates from neonatal blood cultures collected at Örebro University Hospital during 1987 to the 1st of March 2017 (n=42), were included. Several more episodes of neonatal sepsis with growth of coagulase-negative staphylococci were registered during this time period but probably considered as contaminants and therefore not preserved. Antibiotic susceptibility testing was performed using standardized disc diffusion method on cefoxitin, fusidic acid, clindamycin, erythromycin, gentamicin, rifampicin, trimethroprim/sulfamethoxazole and norfloxacin. Isolates resistant to ≥3 antibiotics were defined as multidrug-resistant. The isolates were whole genome sequenced using the Nextera XT kit (Illumina) on a MiSeq (Illumina). Single nucleotide polymorphisms found with the online tool REALPHY 1.12 in the alignments of shared homologous sites with the reference (the S. capitis NRCS-A strain CR01) were used to create phylogenetic trees.

    Results: Seventeen isolates out of the 42 isolates (40%) were multidrug-resistant (resistant to fusidic acid, cefoxitin and gentamicin) and 33 out of the 42 isolates (79%) clustered with the multi-resistant NRCS-A clone (Figure 1). The earliest isolate within the NRCS-A cluster was from 2001.

    Conclusions: Although prevalent since 2001, the increase of S. capitis in neonates with bacteremia since 2010 in Örebro county is mainly due to the dissemination of the multidrug-resistant NRCS-A clone and therefore warrants increased surveillance of the epidemiology and etiology of neonatal sepsis to prevent the spread of this clone.

  • 13.
    Säll, Olof
    et al.
    Örebro University, School of Medical Sciences. Department of Infectious Diseases, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Stenmark, Bianca
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Glimåker, Martin
    Department of Infectious Diseases, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    Department of Laboratory Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Olcén, Per Olof
    Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Fredlund, Hans
    Department of Laboratory Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Clinical presentation of invasive disease caused by Neisseria meningitidis serogroup Y in Sweden, 1995 to 20122017In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 145, no 10, p. 2137-2143Article in journal (Refereed)
    Abstract [en]

    Over the period 1995-2012, the incidence of invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup Y (NmY) increased significantly in Sweden. This is mainly due to the emergence of a predominant cluster named strain type YI subtype 1, belonging to the ST-23 clonal complex (cc). The aim of this study was to examine the clinical picture of patients with invasive disease caused by NmY and to analyse whether the predominant cluster exhibits certain clinical characteristics that might explain the increased incidence. In this retrospective observational study, the medical records available from patients with IMD caused by Nm serogroup Y in Sweden between 1995 and 2012 were systematically reviewed. Patient characteristics, in-hospital findings and outcome were studied and differences between the dominating cluster and other isolates were analysed. Medical records from 175 of 191 patients were retrieved. The median age was 62 years. The all-cause mortality within 30 days of admission was 9% (15/175) in the whole material; 4% (2/54) in the cohort with strain type YI subtype 1 and 11% (12/121) among patients with other isolates. Thirty-three per cent of the patients were diagnosed with meningitis, 19% with pneumonia, 10% with arthritis and 35% were found to have bacteraemia but no apparent organ manifestation. This survey included cases with an aggressive clinical course as well as cases with a relatively mild clinical presentation. There was a trend towards lower mortality and less-severe disease in the cohort with strain type YI subtype 1 compared with the group with other isolates.

  • 14.
    Thulin Hedberg, Sara
    et al.
    WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Stenmark, Bianca
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Sundqvist, Martin
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Lepp, Tiia
    The Public Health Agency of Sweden, Stockholm, Sweden.
    Fredlund, Hans
    WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Invasive meningococcal disease in Sweden 20162017In: 14th Congress of the EMGM, European Meningococcal and Haemophilus Disease Society: Book of Abstracts, Prague: The European Meningococcal and Haemophilus Disease Society EMGM , 2017, p. 69-69Conference paper (Other academic)
    Abstract [en]

    Invasive meningococcal disease (IMD) is notifiable in Sweden. The reporting system comprises of mandatory notification of cases and mandatory laboratory notification of samples to the Public Health Agency of Sweden, Stockholm. All samples are sent to the National Reference Laboratory for Pathogenic Neisseria, Örebro for further typing and surveillance.

    In 2016, 62 cases of IMD (incidence 0.6/100 000 population) were reported in Sweden. Among the patients 58 % were females and 42 % males, aged from 1 month to95 years with mean age of 42 years. The incidence was highest, as in previous years, in the age group 15-19 years (2.1/100 000 population) followed by elderly ≥80 years (1.8/100 000 population) and infants ≤1 year (1.7/100 000 population). The case fatality rate increased in 2016 to 12.9 % compared with 7.5 % in 2015, eight people died from the disease (MenW, n=3; MenY, n=2; MenB, n=2 and MenC n=1). None of the IMD cases in 2016 had any epidemiological linkage.

    All 62 cases of IMD were laboratory confirmed: 54 were culture-confirmed, three PCR-confirmed and in five cases further typing data are missing because no samples were sent to the National Reference Laboratory for Pathogenic Neisseria. The serogroup distribution was MenW (n=18, 31.5 %), MenY (n=18, 31.5 %), MenB (n=10, 17.5 %), MenC (n=10, 17.5 %) and one non-groupable isolate. The W:P1.5,2:F1-1:ST11 (cc11) (n=15) were predominant among the culture-confirmed meningococci during 2016 followed by Y:P1.5-2,10-1:F4-1:ST23 (cc23) (n=7) och Y:P1.5-1,2-2:F5-8:ST23 (cc23) (n=6). Antibiotic susceptibility testing was performed with Gradient test (Etest, BioMerieux). Decreased susceptibility to penicillin was seen in 30 % of the isolates (MIC >0,064 mg/L) of which one was resistant (MIC=0.5 mg/L). One of the isolates with decreased susceptibility to penicillin was also resistant to ciprofloxacin (MIC=0.125 mg/L). All other isolates were susceptible to cefotaxime, chloramphenicol, ciprofloxacin, rifampicin and meropenem. No β-lactamase producing isolates has so far been found in Sweden.

    To conclude, the incidence of IMD continues to be relatively low in Sweden, however, a shift in the serogroup distribution of N. meningitidisin Sweden is ongoing; the previously dominating disease-causing MenB and MenC have been replaced, first by MenY which emerged in 2009 and since 2015 also by MenW. MenW has gone from only causing invasive disease in a few, 0-6 cases per year from 1990 onwards, to now being the dominating serogroup together with MenY in Sweden 2016.

  • 15.
    Törös, Bianca
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Genome-based characterization of Neisseria meningitidis with focus on the emergent serogroup Y disease2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Neisseria meningitidis, also referred to as meningococcus, is one of the leading causes of epidemic meningitis and septicaemia worldwide. Despite modern treatment, meningococcal disease remains associated with a high mortality (about 10%). Meningococcal disease is mainly restricted to specific hypervirulent lineages and specific capsular groups (serogroups), which have a changing global distribution over time. At the end of the 2000s, the previously unusual serogroup Y emerged, corresponding to half of all of the invasive meningococcal disease (IMD) cases in Sweden by the beginning of the 2010s. The aim of this thesis is to describe the emergence of serogroup Y meningococci genetically in an effort to understand some of the factors involved in the successful spread of this group throughout Sweden. In addition, genetic typing schemes were evaluated for surveillance and outbreak investigation.

    Our results indicate that the currently recommended typing for surveillance of meningococci could be altered to include the factor H-binding protein (fHbp). A highly variable multilocus variable number tandem repeat analysis (HV-MLVA) was able to confirm connected cases in a suspected small outbreak. In addition, a strain type sharing the same porA, fetA, porB, fHbp, penA and multilocus sequence type was found to be the principal cause of the increase in serogroup Y disease. However, a deeper resolution obtained from the core genomes revealed a subtype of this strain, which was mainly responsible for the increase. Finally, when the Swedish serogroup Y genomes were compared internationally, different strains seemed to dominate in different regions. This indicates that the increase was probably not due to one or more point introductions of a strain previously known internationally but more probably multifactorial.

    List of papers
    1. Evaluation of molecular typing methods for identification of outbreak-associated Neisseria meningitidis isolates
    Open this publication in new window or tab >>Evaluation of molecular typing methods for identification of outbreak-associated Neisseria meningitidis isolates
    Show others...
    2013 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 121, no 6, p. 503-510Article in journal (Refereed) Published
    Abstract [en]

    It is essential in an outbreak investigation that strain characterization of Neisseria meningitidis is performed in a rapid and accurate manner. This study evaluated two new molecular typing methods, multiple- locus variable number tandem repeat analysis (MLVA) and repetitive sequence-based PCR (rep-PCR) (DiversiLab; bioMe´rieux) and compared them with current recommended methodologies. This retrospective study included 36 invasive N. meningitidis serogroup C isolates collected in Sweden 2001 through 2009 and previously subjected to outbreak investigation. All strains were typed with highly variable- MLVA (HV-MLVA) and rep-PCR. The isolates were further characterized by multilocus sequence typing (MLST) and sequencing of the fetA, fHbp, penA, porA and porB genes. The results showed that HVMLVA had the highest index of diversity (0.99) and rep-PCR had the highest congruence (40%) with the currently recommended typing methods. The HV MLVA correlated best to the spatiotemporal connections and had the overall highest Adjusted Wallace coefficients, suggesting that HV-MLVA can predict the results of the other typing methods in the study. We therefore suggest that after initial confirmation of species, serogroup and genosubtype, HV-MLVA should be used asthe most discriminatorymethod for first hand investigation of N. meningitidis serogroup C isolates.

    Keywords
    Neisseria meningitidis, molecular typing, repetitive sequence-based PCR, MLVA, epidemiology.
    National Category
    Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
    Research subject
    Microbiology
    Identifiers
    urn:nbn:se:oru:diva-36111 (URN)10.1111/apm.12022 (DOI)000319427100004 ()
    Available from: 2014-08-25 Created: 2014-08-25 Last updated: 2019-03-26Bibliographically approved
    2. Genetic characterisation of the emerging invasive Neisseria meningitidis serogroup Y in Sweden, 2000 to 2010
    Open this publication in new window or tab >>Genetic characterisation of the emerging invasive Neisseria meningitidis serogroup Y in Sweden, 2000 to 2010
    Show others...
    2011 (English)In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 16, no 23, article id 19885Article in journal (Refereed) Published
    Abstract [en]

    Neisseria meningitidis serogroups B and C have beenresponsible for the majority of invasive meningococcaldisease in Europe. Recently, an increase of N. meningitidisdisease due to serogroup Y has been notedin Sweden (in 2010, the proportion was 39%, with anincidence of 0.23 per 100,000 population), as well as inother northern European countries. We aimed to investigatethe clonal pattern of the emerging serogroup Yin Sweden during 2000 to 2010. The serogroup Y isolatesidentified during this time (n=85) were characterisedby multilocus sequence typing and sequencing ofthe fetA, fHbp, penA, porA and porB genes. The mostfrequent clone (comprising 28 isolates) with identicalallele combinations of the investigated genes, waspartly responsible for the observed increased numberof N. meningitidis serogroup Y isolates. It was sulfadiazineresistant, with genosubtype P1.5-2,10-1,36-2,sequence type 23, clonal complex 23, porB allele 3-36,fetA allele F4-1, fHbp allele 25 and penA allele 22. Thefirst case with disease due to this clone was identifiedin 2002: there was a further case in 2004, six during2006 to 2007, eight during 2008 to 2009, with a peakof 12 cases in 2010. An unusual increase of invasivedisease in young adults (aged 20–29 years) caused bythis clone was shown, but no increase in mortality ratewas observed.

    Place, publisher, year, edition, pages
    Saint-Maurice, France: European Centre for the Epidemiological Monitoring of AIDS, 2011
    National Category
    Biomedical Laboratory Science/Technology
    Research subject
    Biomedicine
    Identifiers
    urn:nbn:se:oru:diva-36113 (URN)000291586300002 ()21679677 (PubMedID)2-s2.0-79959480972 (Scopus ID)
    Available from: 2014-08-25 Created: 2014-08-25 Last updated: 2019-03-26Bibliographically approved
    3. Surveillance of invasive Neisseria meningitidis with a serogroup Y update, Sweden 2010 to 2012
    Open this publication in new window or tab >>Surveillance of invasive Neisseria meningitidis with a serogroup Y update, Sweden 2010 to 2012
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    As previously described in this journal, an increase of invasive meningococcal disease caused by Neisseria meningitidis serogroup Y has been noted in Sweden, and to a lower extent throughout Europe. In the present study, we aimed to describe the current epidemiology of invasive N. meningitidis isolates in Sweden, with focus on the still increasing serogroup Y, and to find an optimal molecular typing scheme for both surveillance and outbreak investigations.

    All invasive N. meningitidis isolates in Sweden from 2010 to 2012 (n=208) were genetically characterized.

    The predominant serogroup in Sweden is still serogroup Y, in 2010, 2011 and 2012 corresponding to 22/57, 31/61 and 44/90of all invasive isolates (incidence 0.23, 0.33 and 0.46 per 100,000 population). Of the serogroup Y isolates in 2010, 2011 and 2012: 15/22, 23/32 and 19/44 were genetically clonal (Y: P1.5-2,10-1,36-2: F4-1: ST-23 (cc23), ‘porB allele 3- 36, fHbp allele 25 and penA allele 22), respectively. Our findings further support those of others that currently recommended FetA typing could be replaced by FHbp. Moreover, in line with our previous study, the current results indicate that highly variable multiple-locus variable number tandem repeat analysis (HV-MLVA) can be used as a first-hand rapid method for small outbreak investigations.

    National Category
    Biomedical Laboratory Science/Technology
    Research subject
    Biomedicine
    Identifiers
    urn:nbn:se:oru:diva-36118 (URN)
    Available from: 2014-08-25 Created: 2014-08-25 Last updated: 2017-10-17Bibliographically approved
    4. Whole-genome characterization of emergent invasive Neisseria meningitidis serogroup Y in Sweden from the two recent decades
    Open this publication in new window or tab >>Whole-genome characterization of emergent invasive Neisseria meningitidis serogroup Y in Sweden from the two recent decades
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background and Objective: Invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup Y has increased in Europe, especially in Scandinavia. In Sweden, serogroup Y is the dominating serogroup and in 2012 the serogroup Y disease incidence was 0.46/100,000 population. We have previously shown that a strain type belonging to ST-23 is responsible for the emergence of this serogroup in Sweden. The objective of this study was to compare the meningococcal population structure and phylogeography of Swedish invasive serogroup Y strains to other countries with different disease incidence.

    Materials and Methods: Whole-genome sequencing was performed on invasive serogroup Y isolates from 1995 to 2012 in Sweden (n=186). A comparison of serogroup Y isolates was performed using a collection of isolates from England, Wales and Northern Ireland (n=143), which has relatively low incidence, and two isolates from the USA, where serogroup Y remains one of the major causes of IMD.

    Results: The meningococcal population structures were similar in the investigated regions; however, different strain types were dominating in each geographic region. A number of genes, known or hypothesized to have an impact on meningococcal virulence, were shown to be associated with different strain types and subtypes.

    Conclusions: The emergence of serogroup Y is most likely not associated with a previously described strain type that has been introduced into the Swedish meningococcal population. The reasons for the disease increase are most probably multifactorial; both increased virulence and host adaptive immunity influence infection and transmission. Future genomewide association studies could reveal additional genes associated with serogroup Y meningococcal disease.

    Keywords
    Neisseria meningitidis, genome sequencing, epidemiology, serogroup Y, invasive meningococcal disease
    National Category
    Biomedical Laboratory Science/Technology
    Research subject
    Biomedicine
    Identifiers
    urn:nbn:se:oru:diva-36120 (URN)
    Available from: 2014-08-25 Created: 2014-08-25 Last updated: 2017-10-17Bibliographically approved
  • 16.
    Törös, Bianca
    et al.
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Hedberg, Sara Thulin
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Jacobsson, Susanne
    Örebro University Hospital. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Fredlund, Hans
    Örebro University Hospital. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Olcén, Per
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    Örebro University Hospital. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Evaluation of molecular typing methods for identification of outbreak-associated Neisseria meningitidis isolates2013In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 121, no 6, p. 503-510Article in journal (Refereed)
    Abstract [en]

    It is essential in an outbreak investigation that strain characterization of Neisseria meningitidis is performed in a rapid and accurate manner. This study evaluated two new molecular typing methods, multiple- locus variable number tandem repeat analysis (MLVA) and repetitive sequence-based PCR (rep-PCR) (DiversiLab; bioMe´rieux) and compared them with current recommended methodologies. This retrospective study included 36 invasive N. meningitidis serogroup C isolates collected in Sweden 2001 through 2009 and previously subjected to outbreak investigation. All strains were typed with highly variable- MLVA (HV-MLVA) and rep-PCR. The isolates were further characterized by multilocus sequence typing (MLST) and sequencing of the fetA, fHbp, penA, porA and porB genes. The results showed that HVMLVA had the highest index of diversity (0.99) and rep-PCR had the highest congruence (40%) with the currently recommended typing methods. The HV MLVA correlated best to the spatiotemporal connections and had the overall highest Adjusted Wallace coefficients, suggesting that HV-MLVA can predict the results of the other typing methods in the study. We therefore suggest that after initial confirmation of species, serogroup and genosubtype, HV-MLVA should be used asthe most discriminatorymethod for first hand investigation of N. meningitidis serogroup C isolates.

  • 17.
    Törös, Bianca
    et al.
    Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Hedberg, Sara Thulin
    Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Jacobsson, Susanne
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Hill, Dorothea M. C.
    Department of Zoology, University of Oxford, Oxford, United Kingdom.
    Olcén, Per
    Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Bratcher, Holly B.
    Department of Zoology, University of Oxford, Oxford, United Kingdom.
    Jolley, Keith A.
    Department of Zoology, University of Oxford, Oxford, United Kingdom.
    Maiden, Martin C. J.
    Department of Zoology, University of Oxford, Oxford, United Kingdom.
    Mölling, Paula
    Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Genome-based characterization of emergent invasive Neisseria meningitidis serogroup Y isolates in Sweden from 1995 to 20122015In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 53, no 7, p. 2154-2162Article in journal (Refereed)
    Abstract [en]

    Invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup Y has increased in Europe, especially in Scandinavia. In Sweden, serogroup Y is now the dominating serogroup, and in 2012, the serogroup Y disease incidence was 0.46/100,000 population. We previously showed that a strain type belonging to sequence type 23 was responsible for the increased prevalence of this serogroup in Sweden. The objective of this study was to investigate the serogroup Y emergence by whole-genome sequencing and compare the meningococcal population structure of Swedish invasive serogroup Y strains to those of other countries with different IMD incidence. Whole-genome sequencing was performed on invasive serogroup Y isolates from 1995 to 2012 in Sweden (n = 186). These isolates were compared to a collection of serogroup Y isolates from England, Wales, and Northern Ireland from 2010 to 2012 (n = 143), which had relatively low serogroup Y incidence, and two isolates obtained in 1999 in the United States, where serogroup Y remains one of the major causes of IMD. The meningococcal population structures were similar in the investigated regions; however, different strain types were prevalent in each geographic region. A number of genes known or hypothesized to have an impact on meningococcal virulence were shown to be associated with different strain types and subtypes. The reasons for the IMD increase are multifactorial and are influenced by increased virulence, host adaptive immunity, and transmission. Future genome-wide association studies are needed to reveal additional genes associated with serogroup Y meningococcal disease, and this work would benefit from a complete serogroup Y meningococcal reference genome.

  • 18.
    Törös, Bianca
    et al.
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Jacobsson, Susanne
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Is the Emergence of the N. meningitidis Serogroup W ST-11 Hajj Outbreak Unraveling in the New Era of WGS?2015In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 2, no 10, p. 1294-1295Article in journal (Other academic)
  • 19.
    Wildeman, Peter
    et al.
    Örebro University, School of Medical Sciences. Department of Orthopedics.
    Tevell, Staffan
    Örebro University, School of Medical Sciences. Department of Infectious Diseases, Karlstad, and Centre for Clinical Research, Region Värmland, Karlstad, Sweden.
    Eriksson, Carl
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Campillay Lagos, Amaya
    Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine.
    Stenmark, Bianca
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine.
    Genomic characterization and outcome of prosthetic joint infections caused by Staphylococcus aureusManuscript (preprint) (Other academic)
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