oru.sePublications
Change search
Refine search result
12345 51 - 100 of 210
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 51.
    Englund, Lena
    et al.
    National Veterinary Institute, Uppsala, Sweden.
    Bille, Jaques
    Centre National de Référence des Listerias, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
    Danielsson Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden..
    Eld, Karin
    National Veterinary Institute, Uppsala, Sweden.
    Gavier-Widén, D.
    National Veterinary Institute, Uppsala, Sweden.
    Rocourt, Jocelyne
    Institut Pasteur, Paris, France.
    Tham, Wilhelm
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden..
    A possible outbreak of listeriosis in a farmed herd of fallow deer (Dama dama)1992In: Listeria 1992: The Eleventh International Symposium on Problems of Listeriosis (ISOPOL XI) / [ed] Peter Gerner-Smidt, ISOPOL, Copenhagen, Denmark: SSI , 1992, p. 43-44Conference paper (Refereed)
  • 52.
    Ericsson, Henrik
    et al.
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Danielsson Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Stålhandske, Per
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Tham, Wilhelm
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Jan, Ursing
    Department of Bacteriology, University of Lund, General Hospital, Malmö, Sweden.
    Subtyping of a frequent phagovar of Listeria monocytogenes in Sweden by use of restriction endonuclease analysis1993In: APMIS: Acta pathologica, microbiologica et immunologica Scandinavica. Supplementum, ISSN 0903-465X, E-ISSN 1600-5503, Vol. 101, no 7-12, p. 971-974Article in journal (Refereed)
    Abstract [en]

    In Sweden, many Listeria monocytogenes strains belonging to serovar 4b and isolated during the last five years from different sources share the same phagovar - 2389:2425:3274:2671:47:108:340. The object of the present study was to investigate if 31 L. monocytogenes serovar 4b strains belonging to this particular phagovar could be differentiated by use of a simple restriction endonuclease analysis (REA). Among the enzymes tested, Xho I was found to be the most useful, since this enzyme could divide the 31 strains into five groups. The profiles of all human clinical isolates were indistinguishable from each other, which indicates that these strains may represent a single clone. The food isolates and the strains of human origin did not share the same profile. This further characterization may be of epidemiological importance as this phagovar of L. monocytogenes has been associated with at least two outbreaks of human listeriosis in Europe.

  • 53.
    Falk-Brynhildsen, Karin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Cardiothoracic and Vascular Surgery, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology ,Örebro University Hospital, Örebro, Sweden.
    Friberg, Örjan
    Örebro University Hospital. Department of Cardiothoracic and Vascular Surgery, Örebro University Hospital, Örebro, Sweden.
    Nilsson, Ulrica
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bacterial growth and wound infection following saphenous vein harvesting in cardiac surgery: a randomized controlled trial of the impact of microbial sealant2014In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 33, no 11, p. 1981-1987Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to compare microbial skin sealant versus bare skin on the leg regarding intraoperative bacterial presence in the surgical wound and time to recolonization of the adjacent skin at the saphenous vein harvesting site. A second aim was to evaluate the incidence of leg wound infection 2 months after surgery. In this randomized controlled trial, 140 patients undergoing coronary artery bypass grafting (CABG) between May 2010 and October 2011 were enrolled. Bacterial samples were taken preoperatively and intraoperatively at multiple time points and locations. OF the patients, 125 (92.6 %) were followed up 2 months postoperatively regarding wound infection. Intraoperative bacterial growth did not differ between the bare skin (n = 68) and the microbial skin sealant group (n = 67) at any time point. At 2 months postoperatively, 7/61 patients (11.5 %) in the skin sealant versus 14/64 (21.9 %) in the bare skin group (p = 0.120) had been treated with antibiotics for a verified or suspected surgical site infection (SSI) at the harvest site. We found almost no intraoperative bacterial presence on the skin or in the subcutaneous tissue, irrespective of microbial skin sealant use. In contrast, we observed a relatively high incidence of late wound infection, indicating that wound contamination occurred postoperatively. Further research is necessary to determine whether the use of microbial skin sealant reduces the incidence of leg wound infection at the saphenous vein harvest site.

  • 54.
    Forde, Brian M.
    et al.
    The University of Queensland, Brisbane, Queensland, Australia.
    Zowawi, Hosam M.
    Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia; The University of Queensland, UQ Centre for Clinical Research (UQCCR), Herston, Queensland, Australia; College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; World Health Organization Collaborating Centre for Infection Prevention and Control, Riyadh, Saudi Arabia; Gulf Cooperation Council Center for Infection Control, Riyadh, Saudi Arabia; King Abdullah International Medical Research Centre, Riyadh, Saudi Arabia.
    Harris, Patrick N. A.
    The University of Queensland, UQ Centre for Clinical Research (UQCCR), Herston, Queensland, Australia; Pathology Queensland, Brisbane, Queensland, Australia.
    Roberts, Leah
    The University of Queensland, Brisbane, Queensland, Australia.
    Ibrahim, Emad
    Microbiology Division, Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar.
    Shaikh, Nissar
    Department of Neurosurgery, Hamad Medical Corporation, Weill Cornell Medical College in Qatar, Ar-Rayyan, Qatar.
    Deshmukh, Anand
    Microbiology Division, Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar.
    Ahmed, Mazen Sid
    Örebro University, School of Science and Technology. Microbiology Division, Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar.
    Al Maslamani, Muna
    Department of Infectious Diseases, Hamad General Hospital, Doha, Qatar.
    Cottrell, Kyra
    The University of Queensland, UQ Centre for Clinical Research (UQCCR), Herston, Queensland, Australia.
    Trembizki, Ella
    The University of Queensland, UQ Centre for Clinical Research (UQCCR), Herston, Queensland, Australia.
    Sundac, Lana
    The University of Queensland, UQ Centre for Clinical Research (UQCCR), Herston, Queensland, Australia; Pathology Queensland, Brisbane, Queensland, Australia.
    Yu, Heidi H.
    Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Victoria, Australia.
    Li, Jian
    Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Victoria, Australia.
    Schembri, Mark A.
    The University of Queensland, Brisbane, Queensland, Australia.
    Whiley, David M.
    The University of Queensland, UQ Centre for Clinical Research (UQCCR), Herston, Queensland, Australia; Pathology Queensland, Brisbane, Queensland, Australia.
    Paterson, David L.
    The University of Queensland, UQ Centre for Clinical Research (UQCCR), Herston, Queensland, Australia.
    Beatson, Scott A.
    The University of Queensland, Brisbane, Queensland, Australia.
    Discovery of mcr-1-Mediated Colistin Resistance in a Highly Virulent Escherichia coli Lineage2018In: mSphere, ISSN 2379-5042, Vol. 3, no 5, article id e00486-18Article in journal (Refereed)
    Abstract [en]

    Resistance to last-line polymyxins mediated by the plasmid-borne mobile colistin resistance gene (mcr-1) represents a new threat to global human health. Here we present the complete genome sequence of an mcr-1-positive multidrug-resistant Escherichia coli strain (MS8345). We show that MS8345 belongs to serotype O2:K1:H4, has a large 241,164-bp IncHI2 plasmid that carries 15 other antibiotic resistance genes (including the extended-spectrum β-lactamase blaCTX-M-1) and 3 putative multidrug efflux systems, and contains 14 chromosomally encoded antibiotic resistance genes. MS8345 also carries a large ColV-like virulence plasmid that has been associated with E. coli bacteremia. Whole-genome phylogeny revealed that MS8345 clusters within a discrete clade in the sequence type 95 (ST95) lineage, and MS8345 is very closely related to the highly virulent O45:K1:H4 clone associated with neonatal meningitis. Overall, the acquisition of a plasmid carrying resistance to colistin and multiple other antibiotics in this virulent E. coli lineage is concerning and might herald an era where the empirical treatment of ST95 infections becomes increasingly more difficult.

    Importance: Escherichia coli ST95 is a globally disseminated clone frequently associated with bloodstream infections and neonatal meningitis. However, the ST95 lineage is defined by low levels of drug resistance amongst clinical isolates, which normally provides for uncomplicated treatment options. Here, we provide the first detailed genomic analysis of an E. coli ST95 isolate that has both high virulence potential and resistance to multiple antibiotics. Using the genome, we predicted its virulence and antibiotic resistance mechanisms, which include resistance to last-line antibiotics mediated by the plasmid-borne mcr-1 gene. Finding an ST95 isolate resistant to nearly all antibiotics that also has a high virulence potential is of major clinical importance and underscores the need to monitor new and emerging trends in antibiotic resistance development in this important global lineage.

  • 55.
    Golparian, Daniel
    et al.
    WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sverige; Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Fernandes, Prabhavathi
    Cempra Pharmaceuticals, Inc., Chapel Hill NC, United States.
    Ohnishi, Makoto
    National Institute of Infectious Diseases, Tokyo, Japan.
    Jensen, Jörgen S
    Department of Microbiological Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark.
    Unemo, Magnus
    Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sverige.
    In vitro activity of the new fluoroketolide solithromycin (CEM-101) against a large collection of clinical Neisseria gonorrhoeae isolates and international reference strains, including those with high-level antimicrobial resistance: potential treatment option for gonorrhea?2012In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 56, no 5, p. 2739-2742Article in journal (Refereed)
    Abstract [en]

    Gonorrhea may become untreatable, and new treatment options are essential. We investigated the in vitro activity of the first fluoroketolide, solithromycin. Clinical Neisseria gonorrhoeae isolates and reference strains (n = 246), including the two extensively drug-resistant strains H041 and F89 and additional isolates with clinical cephalosporin resistance and multidrug resistance, were examined. The activity of solithromycin was mainly superior to that of other antimicrobials (n = 10) currently or previously recommended for gonorrhea treatment. Solithromycin might be an effective treatment option for gonorrhea.

  • 56.
    Golparian, Daniel
    et al.
    WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, Swedish Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Hellmark, Bengt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, Swedish Reference Laboratory for Pathogenic Neisseria, 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. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, Swedish Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Analytical specificity and sensitivity of the novel dual-target GeneProof Neisseria gonorrhoeae PCR kit for detection of N-gonorrhoeae2015In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 123, no 11, p. 955-958Article in journal (Refereed)
    Abstract [en]

    Detection of Neisseria gonorrhoeae relies increasingly on nucleic acid amplification tests (NAATs). The specificity of many gonococcal NAATs has been suboptimal and supplementary testing remains recommended in Europe and several additional countries. The novel dual-target GeneProofNeisseria gonorrhoeae PCR kit, targeting porA pseudogene and 16S rRNA gene, showed a high specificity and sensitivity when isolates of non-gonococcal Neisseria and related species (n=144), and gonococci (n=104) were tested. However, rare gonococcal porA mutants were only detected in the 16S rRNA gene target and two non-gonococcal isolates showed a low-level cross-reactivity in the 16S rRNA gene target. The detection limit for both targets was 1.5 copies per reaction.

  • 57.
    Golparian, Daniel
    et al.
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Shafer, William M.
    Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta GA, United States; Laboratories of Bacterial Pathogenesis, Veterans Affairs Medical Center, Decatur GA, United States.
    Ohnishi, Makoto
    National Institute of Infectious Diseases, Tokyo, Japan.
    Unemo, Magnus
    Örebro University Hospital. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Importance of Multidrug Efflux Pumps in the Antimicrobial Resistance Property of Clinical Multidrug-Resistant Isolates of Neisseria gonorrhoeae2014In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 58, no 6, p. 3556-3559Article in journal (Refereed)
    Abstract [en]

    The contribution of drug efflux pumps in clinical isolates of Neisseria gonorrhoeae that express extensively drug-resistant or multidrug-resistant phenotypes has heretofore not been examined. Accordingly, we assessed the effect on antimicrobial resistance of loss of the three gonococcal efflux pumps associated with a known capacity to export antimicrobials (MtrC-MtrD-MtrE, MacA-MacB, and NorM) in such clinical isolates. We report that the MIC of several antimicrobials, including seven previously and currently recommended for treatment was significantly impacted.

  • 58.
    Gouveia, A. C. Damiao
    et al.
    Research Unit for Reproductive Tract Microbiology, Statens Serum Institut, Copenhagen, Denmark.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, Department of Laboratory Medicine, Microbiology, Öebro University Hospital, Örebro, Sweden.
    Jensen, J. S.
    Research Unit for Reproductive Tract Microbiology, Statens Serum Institut, Copenhagen, Denmark.
    In vitro activity of zoliflodacin (ETX0914) against macrolide-resistan fluoroquinolone-resistant and antimicrobial-susceptible Mycoplasma genitalium strains2018In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 73, no 5, p. 1291-1294Article in journal (Refereed)
    Abstract [en]

    Background: Mycoplasma genitalium is estimated to be the second most common cause of bacterial sexually transmitted infection in Europe. It is of increasing public health concern due to the rapid development of resistance to different antimicrobial classes, including the preferred first- and second-line treatments azithromycin and moxifloxacin. Thus, new antimicrobial agents are urgently needed, especially for the treatment of MDR strains.

    Methods: The in vitro activity of the new spiropyrimidinetrione zoliflodacin against 47 M. genitalium strains was assessed by growing M. genitalium in Vero cell culture and measuring growth by quantitative PCR. The collection included 34 moxifloxacin-susceptible (MIC <1 mg/L) and 13 moxifloxacin-resistant (MIC >= 1 mg/L) strains. Twenty-three of the strains were azithromycin resistant (MIC >= 16 mg/L) and 12 of these strains were MDR.

    Results: Only one (2.1%) strain with substantially increased MIC (4 mg/L) and potential resistance to zoliflodacin was found. Zoliflodacin was overall more potent than moxifloxacin (P = 0.009) and no cross-resistance was observed between the two drug classes of topoisomerase II inhibitors. Differences in the MICs of zoliflodacin and azithromycin were not statistically significant; however, 23 (48.9%) compared with potentially 1 (2.1%) of the strains were resistant to azithromycin and zoliflodacin, respectively.

    Conclusions: Zoliflodacin is a promising candidate for the treatment of M. genitalium and it is important to further develop and evaluate this drug.

  • 59.
    Hadad, Ronza
    et al.
    WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Clinical Microbiology, , Örebro University Hospital, Örebro, Sweden.
    Lagos, Amaya C.
    WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Ljungberg, Johan
    Department of Infectious Diseases, Hospital of Halmstad, Halmstad, Sweden.
    Nilsson, Peter
    Department of Clinical Microbiology & Infection Control, Hospital of Halmstad, Halmstad, Sweden.
    Jensen, Jörgen S.
    Department of Microbiology and Infection Control, Sexually Transmitted Infections, Research and Development, Statens Serum Institut, Copenhagen, Denmark.
    Fredlund, Hans
    WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, 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 Sexually Transmitted Infections, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Macrolide and fluoroquinolone resistance in Mycoplasma genitalium in two Swedish counties, 2011-20152018In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 126, no 2, p. 123-127Article in journal (Refereed)
    Abstract [en]

    Mycoplasma genitalium, causing non-gonococcal non-chlamydial urethritis and associated with cervicitis, has developed antimicrobial resistance (AMR) to both the macrolide azithromycin (first-line treatment) and the fluoroquinolone moxifloxacin (second-line treatment). Our aim was to estimate the prevalence of resistance, based on genetic AMR determinants, to these antimicrobials in the M. genitalium population in two Swedish counties, Örebro and Halland, 2011-2015. In total, 672 M. genitalium positive urogenital samples were sequenced for 23S rRNA and parC gene mutations associated with macrolide and fluoroquinolone resistance, respectively. Of the samples, 18.6% and 3.2% in Örebro and 15.2% and 2.7% in Halland contained mutations associated with macrolide and fluoroquinolone resistance, respectively. The predominating resistance-associated mutations in the 23S rRNA gene was A2059G (n = 39) in Örebro and A2058G (n = 13) and A2059G (n = 13) in Halland. The most prevalent possible resistance-associated ParC amino acid alterations were S83I (n = 4) in Örebro and S83N (n = 2) in Halland. Resistance-associated mutations to both macrolides and fluoroquinolones were found in 0.7% of samples. Our findings emphasize the need for routine AMR testing, at a minimum for macrolide resistance, of all M. genitalium-positive samples and regular national and international surveillance of AMR in M. genitalium, to ensure effective patient management and rational antimicrobial use.

  • 60.
    Hadad, Ronza
    et al.
    WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sverige; Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Jacobsson, Susanne
    Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sverige; Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Pizza, Mariagrazia
    Novartis V&D, Siena, Italy.
    Rappuoli, Rino
    Novartis V&D, Siena, Italy.
    Fredlund, Hans
    Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sverige; Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Olcén, Per
    WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sverige; Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sverige; Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Novel meningococcal 4CMenB vaccine antigens - prevalence and polymorphisms of the encoding genes in Neisseria gonorrhoeae2012In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 120, no 9, p. 750-760Article in journal (Refereed)
    Abstract [en]

    The first cross-protective Neisseria meningitidis vaccine (focus on serogroup B), the protein-based 4 component meningococcus serogroup B (4CMenB), includes the New Zealand outer membrane vesicle and three main genome-derived neisserial antigens (GNAs). These GNAs are fHbp (fused to GNA2091), NHBA (fused to GNA1030) and NadA. In this study, the prevalence and polymorphisms of the nucleotide and amino acid sequences of the 4CMenB antigens in a temporally and geographically diverse collection of N. gonorrhoeae isolates (n similar to=similar to 111) were investigated. All the examined GNA genes, except the nadA gene, were present in all gonococcal isolates. However, 25 isolates contained premature stop codons in the fHbp gene and/or the nhba gene, resulting in truncated proteins. Compared with the 4CMenB antigen sequences in reference strain MC58, the gonococcal strains displayed 67.095.4% and 60.994.9% identity in nucleotide sequence and amino acid sequence, respectively, in the equivalent GNA antigens. The absence of NadA, lack of universal expression of fHbp and NHBA and the uncertainty regarding the surface exposure of fHbp as well as the function of NHBA in N. gonorrhoeae will likely limit the use of the identical 4CMenB antigens in a gonococcal vaccine. However, possible cross-immunity of 4CMenB with gonococci and expression and function of the equivalent gonococcal GNAs, as well as of more appropriate GNAs for a gonococcal vaccine, need to be further examined.

  • 61.
    Hadad, Ronza
    et al.
    Örebro Life Science Center, School of Science and Technology, Örebro University, Örebro, Sweden; Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Marks, Ellen
    Department of Medical Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
    Kalbina, Irina
    Örebro University, School of Science and Technology. Örebro Life Science Center, Örebro University, Örebro, Sweden.
    Schön, Karin
    Department of Medical Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Lycke, Nils
    Department of Medical Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology. Örebro Life Science Center, Örebro University, Örebro, Sweden.
    Andersson, Sören
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Protection against genital tract Chlamydia trachomatis infection following intranasal immunization with a novel recombinant MOMP VS2/4 antigen2016In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 124, p. 1078-1086Article in journal (Refereed)
    Abstract [en]

    The asymptomatic nature of most Chlamydia trachomatis infections and the lack of appropriate effects by current prevention and management call for vaccine development. We evaluated a recombinant subunit vaccine candidate based on the major outer membrane protein variable segments 2 and 4 (MOMP VS2/4). To achieve maximal immunogenicity and ease of production and purification, MOMP VS2/4 was constructed by using highly immunogenic sequences of MOMP only, thereby minimizing the presence of hydrophobic regions, and spacing the immunogenic epitopes with a flexible amino acid sequence. A purification tag was also added. The MOMP VS2/4 was given intranasally, with or without intravaginal boost, with cholera toxin (CT) adjuvant to C57BL/6 mice, which were screened for immunogenicity and protection against a live challenge infection with C. trachomatis serovar D. Bacterial shedding, cell-mediated responses, and antibody responses were monitored. Immunized mice exhibited significantly less bacterial shedding and were better protected against infertility as compared to unimmunized control mice. Immunizations stimulated both systemic and local specific antibody (IgG1, IgG2c, and IgA) responses, and primed T cells that produced interferon-c and interleukins 13 and 17 upon challenge with recall antigen. Thus, MOMP VS2/4, in combination with CT adjuvant, stimulated Th1, Th2, and Th17 effector cells, and generated protective immunity associated with less pathology. We regard MOMP VS2/4 as a promising candidate for further development into a mucosal chlamydial vaccine.

  • 62.
    Hadad, Ronza
    et al.
    Örebro University, School of Science and Technology.
    Schön, Karin
    University of Gothenburg, Gothenburg, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Andersson, Sören
    Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    Örebro University Hospital, Örebro, Sweden.
    Lycke, Nils
    University of Gothenburg, Gothenburg, Sweden.
    Optimization of infection in murine model with Chlamydia trachomatis for vaccine studies2013In: Chlamydia Basic Research Society: 2013 biannual meeting, 2013Conference paper (Refereed)
    Abstract [en]

    Background and Significance: Vaccine studies for Chlamydia trachomatis (Ct) have been hampered by the lack of an ideal murine model. Ct is not ideal for infection and subsequent pathology as it is a human pathogen and C. muridarum (Cm) may not be suitable due to vaccine specificity for Ct. There is currently no standardization of chlamydial infections in murine models concerning mouse strain, infecting agent and dose.

     

    Objectives: To investigate the Ct infection in mice, using different suppliers of mice, doses and the infective agents of Ct serovars D, E and Cm.

     

    Methods: C57BL/6 mice (Taconic; Harlan; in-house breeding mice) were inoculated intravaginally with 103-105 chlamydia  elementary bodies (EB). Vaginal samples were collected at 7-8 days intervals and analyzed using MicroTrak II Chlamydia EIA kit.

     

    Results: Taconic mice inoculated with Ct D with 105 EB showed the strongest infection with 30% of mice infected at day 21 (d21) as seen in figure 1. The number of infected mice and detected antigen (not shown) decreased rapidly after the first time-point (d8). In figure 2 infective agents were analyzed. Ct E did not infect any mice despite using a tenfold increased dose. Cm infection was detectable in 80% of the mice for up to d21.

     

    Conclusions: Ct D infected the mice for a period of 2-3 weeks. There was only a small difference between the suppliers in favor for Harlan mice. Ct D 105 EB was the infectious dose with the highest number of infected mice over time, however the appropriateness of that high bacterial load must be considered. Ct E did not infect these mice and Cm, a mouse pneumonitis strain, infected all mice and had the longest duration of infection. However, for vaccine studies, Cm may not be suitable due to lack of cross reactivity and Ct may still be used however vaginal sampling must be more frequent early on to show significant differences in bacterial shedding between immunized and non-immunized mice. 

  • 63.
    Hahn-Strömberg, Victoria
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Section for Pathology, Örebro University Hospital, Örebro, Sweden.
    Askari, Shlear
    Department of Laboratory Medicine, Section for Pathology, Örebro University Hospital, Örebro, Sweden.
    Befekadu, Rahel
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Section for Pathology, Örebro University Hospital, Örebro, Sweden.
    Matthiessen, Peter
    Örebro University Hospital. Department of Clinical Surgery, Örebro University Hospital, Örebro, Sweden.
    Karlsson, Sune
    Örebro University, Örebro University School of Business.
    Nilsson, Torbjorn K.
    Department of Medical Biosciences/Clinical Chemistry, Umeå University, Umeå, Sweden.
    Polymorphisms in the CLDN1 and CLDN7 genes are related to differentiation and tumor stage in colon carcinoma2014In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 122, no 7, p. 636-642Article in journal (Refereed)
    Abstract [en]

    Tight junction is composed of transmembrane proteins important for maintaining cell polarity and regulating ion flow. Among these proteins are the tissue-specific claudins, proteins that have recently been suggested as tumor markers for several different types of cancer. An altered claudin expression has been observed in colon, prostatic, ovarian, and breast carcinoma. The aim of this study was to analyze the allele frequencies of three common single nucleotide polymorphisms (SNPs) in the genes for claudin 1 and claudin 7 in colon cancer (CC) patients and in a control population of healthy blood donors. Pyrosequencing was used to genotype the CLDN1 SNP rs9869263 (c.369C>T), and the CLDN7 SNPs rs4562 (c.590C>T) and rs374400 (c.606T>G) in DNA from 102 formalin fixed paraffin embedded (FFPE) colon cancer tissue, and 111 blood leukocyte DNA from blood/plasma donors. These results were correlated with clinical parameters such as TNM stage, tumor localization, tumor differentiation, complexity index, sex, and age. We found that there was a significant association between the CLDN1 genotype CC in tumor samples and a higher risk of colon cancer development (OR 3.0, p < 0.001). We also found that the CLDN7 rs4562 (c.590C>T) genotype CT had a higher risk of lymph node involvement (p = 0.031) and a lower degree of tumor differentiation (p = 0.028). In the control population, the allele frequencies were very similar to those in the HapMap cohort for CLDN7. The CLDN1 rs9869263 genotype (c.369C>T) was related to increased risk of colon cancer, and the CLDN7 rs4562 genotype (c.590C>T) was related to tumor differentiation and lymph node involvement in colon carcinoma. Further studies are warranted to ascertain their potential uses as biomarkers predicting tumor development, proliferation, and outcome in this disease.

  • 64.
    Halfvarson, Jonas
    et al.
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Brislawn, Colin J.
    Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland WA, USA.
    Lamendella, Regina
    Juniata College, Huntingdon PA, USA.
    Vázquez-Baeza, Yoshiki
    Department of Computer Science and Engineering, University of California, San Diego CA, USA.
    Walters, William A.
    Max Planck Institute, Tübingen, Germany.
    Bramer, Lisa M.
    National Security Directorate, Pacific Northwest National Laboratory, Richland WA, USA.
    D'Amato, Mauro
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; BioDonostia Health Research Institute, San Sebastian, Spain; IKERBASQUE Basque Foundation for Science.
    Bonfiglio, Ferdinando
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    McDonald, Daniel
    Department of Pediatrics, University of California, San Diego CA, USA.
    Gonzalez, Antonio
    Center for Microbiome Innovation, University of California, San Diego CA, USA.
    McClure, Erin E.
    Juniata College, Huntingdon PA, USA.
    Dunklebarger, Mitchell F.
    Juniata College, Huntingdon PA, USA.
    Knight, Rob
    Department of Computer Science and Engineering, University of California, San Diego CA, USA; Department of Pediatrics, University of California, San Diego CA, USA; Center for Microbiome Innovation, University of California, San Diego CA, USA.
    Jansson, Janet K.
    Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland WA, USA.
    Dynamics of the human gut microbiome in inflammatory bowel disease2017In: Nature Microbiology, E-ISSN 2058-5276, Vol. 2, no 5, article id 17004Article in journal (Refereed)
    Abstract [en]

    Inflammatory bowel disease (IBD) is characterized by flares of inflammation with a periodic need for increased medication and sometimes even surgery. The aetiology of IBD is partly attributed to a deregulated immune response to gut microbiome dysbiosis. Cross-sectional studies have revealed microbial signatures for different IBD subtypes, including ulcerative colitis, colonic Crohn's disease and ileal Crohn's disease. Although IBD is dynamic, microbiome studies have primarily focused on single time points or a few individuals. Here, we dissect the long-term dynamic behaviour of the gut microbiome in IBD and differentiate this from normal variation. Microbiomes of IBD subjects fluctuate more than those of healthy individuals, based on deviation from a newly defined healthy plane (HP). Ileal Crohn's disease subjects deviated most from the HP, especially subjects with surgical resection. Intriguingly, the microbiomes of some IBD subjects periodically visited the HP then deviated away from it. Inflammation was not directly correlated with distance to the healthy plane, but there was some correlation between observed dramatic fluctuations in the gut microbiome and intensified medication due to a flare of the disease. These results will help guide therapies that will redirect the gut microbiome towards a healthy state and maintain remission in IBD.

  • 65.
    Hamasuna, Ryoichi
    et al.
    Department of Urology, University of Occupational and Environmental Health, Kitakyushu, Japan.
    Ohnishi, Makoto
    Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan.
    Matsumoto, Masahiro
    Department of Urology, University of Occupational and Environmental Health, Kitakyushu, Japan.
    Okumura, Ryo
    Rare Disease & LCM Laboratories, Group I, R&D Division, Daiichi Sankyo Co. Ltd., Tokyo, Japan.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Matsumoto, Tetsuro
    Department of Urology, University of Occupational and Environmental Health, Kitakyushu, Japan.
    In Vitro Activity of Sitafloxacin and Additional Newer Generation Fluoroquinolones Against Ciprofloxacin-Resistant Neisseria gonorrhoeae Isolates2018In: Microbial Drug Resistance, ISSN 1076-6294, E-ISSN 1931-8448, Vol. 24, no 1, p. 30-34Article in journal (Refereed)
    Abstract [en]

    Emergence of antimicrobial resistance in Neisseria gonorrhoeae is a major public health concern globally, and new antimicrobials for treatment of gonorrhea are imperative. In this study, the in vitro activity of sitafloxacin, a fluoroquinolone mainly used for respiratory tract or urogenital infections in Japan, and additional newer generation fluoroquinolones were determined against ciprofloxacin-resistant N. gonorrhoeae isolates. Minimum inhibitory concentrations (MICs) of ciprofloxacin, levofloxacin, moxifloxacin, sitafloxacin, pazufloxacin, and tosufloxacin against 47 N. gonorrhoeae isolates cultured in 2009 in Japan were determined by agar dilution method. The quinolone resistance-determining region (QRDR) of gyrA and parC was sequenced. The in vitro potency of sitafloxacin was substantially higher compared with all other tested fluoroquinolones. The MICs of sitafloxacin ranged from 0.03 to 0.5 mg/L for 35 ciprofloxacin-resistant N. gonorrhoeae isolates (ciprofloxacin MICs from 2 to 32 mg/L). No identified mutations in GyrA and ParC QRDR resulted in higher sitafloxacin MIC than 0.5 mg/L. Sitafloxacin had a high activity against N. gonorrhoeae isolates, including strains with mutations in DNA gyrase and topoisomerase IV, resulting in high-level resistance to ciprofloxacin and all other newer generation fluoroquinolones examined. However, it was still to a lower extent affected by GyrA and ParC QRDR mutations resulting in sitafloxacin MICs of up to 0.5 mg/L. This indicates that sitafloxacin should not be considered for empirical first-line monotherapy of gonorrhea. However, sitafloxacin could be valuable in a dual antimicrobial therapy and for cases with ceftriaxone resistance or allergy.

  • 66.
    Hedberg, Sara Thulin
    et al.
    Örebro University, School of Health and Medical Sciences.
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences.
    Nicolas, Pierre
    Caugant, Dominique A.
    Olcén, Per
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences.
    Antibiotic susceptibility and characteristics of Neisseria meningitidis isolates from the African meningitis belt, 2000 to 2006: phenotypic and genotypic perspectives2009In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 53, no 4, p. 1561-1566Article in journal (Refereed)
    Abstract [en]

    Up-to-date information regarding the antibiotic susceptibility of Neisseria meningitidis strains from African countries is highly limited. Our aim was to comprehensively describe the antibiotic susceptibilities of a selection of N. meningitidis isolates recovered between 2000 and 2006 from 18 African countries, mainly those within the meningitis belt. Susceptibilities to 11 antibiotics were determined using Etest for 137 N. meningitidis isolates (stringently selected from 693 available isolates). The isolates were also characterized by serogrouping, multilocus sequence typing, genosubtyping, and penA allele identification. All N. meningitidis isolates were susceptible to ceftriaxone, chloramphenicol, and ciprofloxacin. No isolate produced beta-lactamase. Only three isolates (2%) displayed reduced susceptibility to penicillin G. The two isolates with the highest penicillin G MICs were the only isolates showing reduced susceptibility to ampicillin and cefuroxime. One of these isolates was also resistant to penicillin V. One percent of isolates displayed reduced susceptibility to rifampin, while 52% of the isolates were resistant to tetracycline, 74% were resistant to erythromycin, and 94% were resistant to sulfadiazine. The MICs of rifampin and tetracycline seemed to be associated with the serogroup of the isolates. In total, 18 sequence types (STs), 10 genosubtypes, and 8 different penA alleles were identified; the most common were ST-7, P1.20,9,35-1, and penA4, respectively. A high level of correlation was found between ST, genosubtype, and penA allele. In conclusion, N. meningitidis isolates from the African meningitis belt remain highly susceptible to the antibiotics used. Regarding beta-lactam antibiotics, rare isolates showed a reduced susceptibility to penicillins, but the expanded-spectrum cephalosporins are not affected at present.

  • 67.
    Hedberg, Sara Thulin
    et al.
    Örebro University, School of Health and Medical Sciences.
    Olcén, Per
    Fredlund, Hans
    Mölling, Paula
    Real-time PCR detection of five prevalent bacteria causing acute meningitis2009In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 117, no 11, p. 856-860Article in journal (Refereed)
  • 68.
    Hellmark, Bengt
    et al.
    Örebro University, School of Health and Medical Sciences.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences.
    Simultaneous species identification and detection of rifampicin resistance in staphylococci by sequencing of the rpoB gene2008In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 28, no 2, p. 183-190Article in journal (Refereed)
    Abstract [en]

    In recent years, coagulase-negative staphylococci (CoNS) have been increasingly recognised as causative agents of various infections, especially in immunocompromised patients and related to implanted foreign body materials. In this study, rpoB sequencing was used for simultaneous species identification and detection of rifampicin resistance in clinical staphylococci isolates. Forty-nine (96%) out of 51 isolates, representing 17 different Staphylococcus species according to the initial phenotypic species identification, were identified to the species level using rpoB sequencing. Furthermore, the two remaining isolates were Kocuria sp. and Corynebacterium sp. respectively, according to 16S rRNA sequencing. Comparison with the phenotypic diagnostics also revealed that 8 (16%) of the 49 isolates differed regarding identified species. Discrepant analysis confirmed the result of the rpoB sequencing for all except 2 of these isolates, which could not be distinguished as single species using 16S rRNA sequencing. Regarding detection of rifampicin resistance, isolates obtained pre- and post-treatment with rifampicin were examined. These isolates comprised S. aureus (7 patients) and S. lugdunensis (1 patient). Rifampicin resistance was mainly detected following short-term treatment with rifampicin in combination with isoxazolyl-penicillin, or long-term treatment with rifampicin and ciprofloxacin. Each rifampicin-resistant isolate displayed an identical rpoB sequence as their corresponding rifampicin-susceptible isolates except for one (n = 6) or two (n = 1) nonsynonymous single nucleotide polymorphisms, or insertion of one codon (n = 1). In conclusion, rpoB sequencing is a rapid, objective and accurate method of species identification and simultaneous detection of rifampicin resistance in staphylococci.

  • 69.
    Heymans, Raymond
    et al.
    Public Health Laboratory, Cluster of Infectious Diseases, Health Service of Amsterdam, Amsterdam, The Netherlands.
    Bruisten, Sylvia M.
    Public Health Laboratory, Cluster of Infectious Diseases, Health Service of Amsterdam, Amsterdam, Netherlands; Department of Experimental Virology, University of Amsterdam, Amsterdam, The Netherlands.
    Golparian, Daniel
    WHO Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    Örebro University Hospital. Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. WHO Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    de Vries, Henry J. C.
    STI Outpatient Clinic, Cluster of Infectious Diseases, Health Service of Amsterdam, Amsterdam, Netherlands; Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands; Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
    van Dam, Alje P.
    Public Health Laboratory, Cluster of Infectious Diseases, Health Service of Amsterdam, Amsterdam, Netherlands; Department of Medical Microbiology, Onze Lieve Vrouwe Gasthuis General Hospital, Amsterdam, The Netherlands.
    Clonally Related Neisseria gonorrhoeae Isolates with Decreased Susceptibility to the Extended-Spectrum Cephalosporin Cefotaxime in Amsterdam, the Netherlands2012In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 56, no 3, p. 1516-1522Article in journal (Refereed)
    Abstract [en]

    From 2006 to 2008, Neisseria gonorrhoeae isolates were identified with decreased susceptibility to the extended-spectrum cephalosporin (ESC) cefotaxime among visitors of the Amsterdam sexually transmitted infections (STI) clinic, the Netherlands. Spread, clonality, and characteristics of 202 isolates were examined using antibiograms, conventional penA mosaic gene PCR, and N. gonorrhoeae multiple-locus variable-number tandem repeat analysis (NG-MLVA). A strictly defined subset was further characterized by N. gonorrhoeae multiantigen sequence typing (NG-MAST) and sequencing of ESC resistance determinants (penA, mtrR, and porB1b). Seventy-four N. gonorrhoeae isolates with a cefotaxime MIC of >0.125 mu g/ml (group A), 54 with a cefotaxime MIC of 0.125 mu g/ml (group B), and a control group of 74 with a cefotaxime MIC of <0.125 mu g/ml (group C) were included. Fifty-three clonally related penA mosaic-positive isolates (penicillin-binding protein 2 type XXXIV) were identified in group A (n = 47 isolates; 64%) and B (n = 6 isolates; 11%). The 53 penA mosaic-positive isolates were predominantly NG-MAST ST1407 (87%) and contained an mtrR promoter A deletion (98%) and porB1b alterations G101K/A102N. All were assigned to the same NG-MLVA cluster that comprised in total 56 isolates. A correlation was found between decreased cefotaxime susceptibility and ST1407 that was highly prevalent among visitors of the Amsterdam STI clinic. The rapid spread of this strain, which also has been identified in many other countries, might be facilitated by high-risk sexual behavior and should be monitored closely to identify potential treatment failure. Quality-assured surveillance of ESC susceptibility on the national and international levels and exploration of new drugs and/or strategies for treatment of gonorrhea are crucial.

  • 70.
    Heymans, Raymond
    et al.
    Public Health Laboratory, Cluster of Infectious Diseases, Health Service of Amsterdam, Amsterdam, Netherlands.
    Golparian, Daniel
    Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sverige; Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Bruisten, Sylvia M.
    Public Health Laboratory, Cluster of Infectious Diseases, Health Service of Amsterdam, Amsterdam, Netherlands; Department of Experimental Virology, University of Amsterdam, Amsterdam, Netherlands.
    Schouls, Leo M.
    Laboratory for Infectious Diseases and Perinatal Screening, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.
    Unemo, Magnus
    Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sverige; Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Evaluation of Neisseria gonorrhoeae Multiple-Locus Variable-Number Tandem-Repeat Analysis, N. gonorrhoeae Multiantigen Sequence Typing, and Full-Length porB Gene Sequence Analysis for Molecular Epidemiological Typing2012In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 50, no 1, p. 180-183Article in journal (Refereed)
    Abstract [en]

    The performance characteristics of Neisseria gonorrhoeae multilocus variable-number tandem-repeat analysis were evaluated, by comparison with N. gonorrhoeae multiantigen sequence typing and full-length porB sequence typing. Assessment of the relatedness of intra- and interpatient isolates showed that all three genotyping techniques display a high resolution and typeability.

  • 71. Hjelmevoll, Stig Ove
    et al.
    Olsen, Merethe Elise
    Ericson Sollid, Johanna U.
    Haaheim, Håkon
    Unemo, Magnus
    Örebro University, Department of Clinical Medicine.
    Skogen, Vegard
    A fast real-time polymerase chain reaction method for sensitive and specific detection of the Neisseria gonorrhoeae porA pseudogene2006In: Journal of Molecular Diagnostics, ISSN 1525-1578, E-ISSN 1943-7811, Vol. 8, no 5, p. 574-581Article in journal (Refereed)
    Abstract [en]

    Ever since the advent of molecular methods, the diagnostics of Neisseria gonorrhoeae has been troubled by false negative and false positive results compared with culture. Commensal Neisseria species and Neisseria meningitidis are closely related to N. gonorrhoeae and may cross-react when using molecular tests comprising too-low specificity. We have devised a real-time polymerase chain reaction (PCR), including an internal amplification control, that targets the N. gonorrhoeae porA pseudogene. DNA was automatically isolated on a BioRobot M48. Our subsequent PCR method amplified all of the different N. gonorrhoeae international reference strains (n = 34) and N. gonorrhoeae clinical isolates (n = 176) but not isolates of the 13 different nongonococcal Neisseria species (n = 68) that we tested. Furthermore, a panel of gram-negative bacterial (n = 18), gram-positive bacterial (n = 23), fungal (n = 1), and viral (n = 4) as well as human DNA did not amplify. The limit of detection was determined to be less than 7.5 genome equivalents/PCR reaction. In conclusion, the N. gonorrhoeae porA pseudogene real-time PCR developed in the present study is highly sensitive, specific, robust, rapid and reproducible, making it suitable for diagnosis of N. gonorrhoeae infection.

  • 72. Hjelmevoll, Stig Ove
    et al.
    Olsen, Merethe Elise
    Sollid, Johanna U. Ericson
    Haaheim, Håkon
    Melby, Kjetil K.
    Moi, Harald
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences.
    Skogen, Vegard
    Clinical validation of a real-time polymerase chain reaction detection of Neisseria gonorrheae porA pseudogene versus culture techniques2008In: Sexually Transmitted Diseases, ISSN 0148-5717, E-ISSN 1537-4521, Vol. 35, no 5, p. 517-520Article in journal (Refereed)
    Abstract [en]

    Background: Diagnosing Neisseria gonorrheae using nucleic acid amplification tests (NAATs) might increase the sensitivity, compared to cultivation. However, using NAATs has also been problematic mainly due to the close genetic relationships between different Neisseria species, resulting in false positive diagnoses. This study was conducted to clinically validate a previously published real-time polymerase chain reaction (PCR) method targeting the porA pseudogene in N. gonorrheae in comparison to culture techniques.

    Methods: In total, 360 samples, urethra (n = 109), rectum (n = 84), pharynx (n = 119), and cervix (n = 48) from 185 males and 57 females, were analyzed using porA pseudogene PCR and cultivation. Sequencing of the entire porA pseudogene and the 16S rRNA gene were used to resolve discrepant results.

    Results: Of the 360 samples, 37 were positive by both culture and PCR, however, the PCR identified 15 additional confirmed positive samples. The PCR method showed a sensitivity, specificity, positive predictive value, and negative predictive value of 100% in a preselected population. The preselected population had a true gonorrhea prevalence of 17.4%.

    Conclusions: The present porA pseudogene real-time PCR comprises a valuable supplement to the traditional culture techniques for diagnosis of N. gonorrheae, especially for samples from extragenital sites such as pharynx and rectum.

  • 73.
    Hokynar, Kati
    et al.
    Virology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Rantakokko-Jalava, Kaisu
    Department of Clinical Microbiology, Turku University Hospital, Turku, Finland; Department of Virology, University of Turku, Turku, Finland.
    Hakanen, Antti
    Department of Clinical Microbiology, Turku University Hospital, Turku, Finland; Department of Virology, University of Turku, Turku, Finland.
    Havana, Marika
    YNLAB Finland, Helsinki, Finland.
    Mannonen, Laura
    Virology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Jokela, Pia
    Virology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Kurkela, Satu
    Virology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Lappalainen, Maija
    Virology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. World Health Organization (WHO) Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections (STIs), National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Puolakkainen, Mirja
    Virology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
    The Finnish New Variant of Chlamydia trachomatis with a Single Nucleotide Polymorphism in the 23S rRNA Target Escapes Detection by the Aptima Combo 2 Test2019In: Microorganisms, ISSN 2076-2607, Vol. 7, no 8, article id E227Article in journal (Refereed)
    Abstract [en]

    In 2019, more than 200 cases of Chlamydia trachomatis negative/equivocal by the Aptima Combo 2 assay (AC2, target: 23S rRNA) with slightly elevated relative light units (RLUs), but positive by the Aptima Chlamydia trachomatis assay (ACT, target: 16S rRNA) have been detected in Finland To identify the cause of the AC2 CT false-negative specimens, we sequenced parts of the CT 23S rRNA gene in 40 specimens that were AC2 negative/equivocal but ACT positive. A single nucleotide polymorphism (SNP; C1515T in the C. trachomatis 23S rRNA gene) was revealed in 39 AC2/ACT discordant specimens. No decrease in the number of mandatorily notified C. trachomatis cases was observed nationally in Finland in 2010-2019. When RLUs obtained for AC2 negative specimens were retrospectively evaluated in 2011-2019, a continuous increase in the proportion of samples with RLUs 10-19 was observed since 2014, and a slight increase in the proportion of samples with RLUs 20-84 in 2017-2019, indicating that the Finnish new variant of C. trachomatis might have been spreading nationally for several years. This emphasizes that careful surveillance of epidemiology, positivity rate and test performance are mandatory to detect any changes affecting detection of infections.

  • 74. Holmberg, A.
    et al.
    Lood, R.
    Mörgelin, M.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    Holst, E.
    Collin, M.
    Christensson, B.
    Rasmussen, M.
    Biofilm formation by Propionibacterium acnes is a characteristic of invasive isolates2009In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 15, no 8, p. 787-795Article in journal (Refereed)
    Abstract [en]

    Propionibacterium acnes is a common and probably underestimated cause of delayed joint prosthesis infection. Bacterial biofilm formation is central in the pathogenesis of infections related to foreign material, and P. acnes has been shown to form biofilm both in vitro and in vivo. Here, biofilm formation by 93 P. acnes isolates, either from invasive infections (n = 45) or from the skin of healthy people (n = 48), was analysed. The majority of isolates from deep infections produced biofilm in a microtitre model of biofilm formation, whereas the skin isolates were poor biofilm producers (p <0.001 for a difference). This indicates a role for biofilm formation in P. acnes virulence. The type distribution, as determined by sequencing of recA, was similar among isolates isolated from skin and from deep infections, demonstrating that P. acnes isolates with different genetic backgrounds have pathogenic potential. The biofilm formed on plastic and on bone cement was analysed by scanning electron microscopy (EM) and by transmission EM. The biofilm was seen as a 10-mum-thick layer covering the bacteria and was composed of filamentous as well as more amorphous structures. Interestingly, the presence of human plasma in solution or at the plastic surface inhibits biofilm formation, which could explain why P. acnes primarily infect plasma-poor environments of, for example, joint prostheses and cerebrospinal shunts. This work underlines the importance of biofilm formation in P. acnes pathogenesis, and shows that biofilm formation should be considered in the diagnosis and treatment of invasive P. acnes infections.

  • 75.
    Hurvell, Bengt
    et al.
    Bacteriological Laboratory, National Veterinary Institute, Uppsala, Sweden.
    Danielsson Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Zoonotic aspects of Yersinia enterocolitica with special reference to its ability to grow at low tempearture1980Conference paper (Other academic)
  • 76.
    Hurvell, Bengt
    et al.
    Bacteriological Laboratory, National Veterinary Institute, Uppsala, Sweden.
    Danielsson Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Olsson, Eva
    Department of Bacteriology and Epizootiology, Faculty of Veterinary Medicin, Swedish University of Veterinary Medicine, BMC, Uppsala, Sweden.
    Zoonotic aspects of Yersinia enterocolitica with special reference to its ability to grow at low temperature1981In: Psychrotrophic microorganisms in spoilage and pathogenicity: based on the proceedings of the XIth International symposium on food microbiology organised by the Committee on food microbiology and hygiene of the International union of microbiological societies held at Aalborg, Denmark on 6-11 July, 1980 / [ed] T.A. Roberts, G. Hobbs, J.H.B. Christian, N. Skovgaard, London: Academic Press, 1981, p. 393-399Chapter in book (Refereed)
  • 77.
    Idelevich, E. A.
    et al.
    Institute of Medical Microbiology, University Hospital Münster, Münster, Germany.
    Seifert, H.
    Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany; German Centre for Infection Research, Partner Site Bonn-Cologne, Cologne, Germany.
    Sundqvist, Martin
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Scudeller, L.
    Clinical Epidemiology Unit, Scientific Direction, Fondazione IRCCS, Policlinico San Matteo Pavia Fondazione IRCCS, Pavia, Italy.
    Amit, S.
    Department of Clinical Microbiology and Infectious Diseases, Hadassah Medical Centre, Jerusalem, Israel.
    Balode, A.
    Pauls Stradins Clinical University Hospital, Riga, Latvia.
    Bilozor, A.
    Microbiology Laboratory, Diagnostic Clinic, East-Tallinn Central Hospital, Tallinn, Estonia.
    Drevinek, P.
    Department of Medical Microbiology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
    Tufan, Z. Kocak
    Infectious Diseases and Clinical Microbiology Department, Medical School of Ankara Yildirim Beyazit University, Ankara, Turkey.
    Koraqi, A.
    Clinical Microbiology Laboratory, University Hospital Centre ‘Mother Theresa’, Tirana, Albania.
    Lamy, B.
    Laboratory of Clinical Microbiology, Centre Hospitalier Universitaire de Nice, Université Côte d’Azur, INSERM U1065 (C3M), Nice, France.
    Marekovic, I.
    Department of Clinical and Molecular Microbiology, University Hospital Centre Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia.
    Miciuleviciene, J.
    Vilnius City Clinical Hospital, Vilnius, Lithuania.
    Premru, M. Mueller
    Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
    Pascual, A.
    Unidad de Enfermedades Infecciosas, Microbiologia y Medicina Preventiva, Hospital Universitario Virgen Macarena, Departamento de Microbiología, Universidad de Sevilla, Instituto de Biomedicina de Sevilla (IBiS), Sevilla, Spain.
    Pournaras, S.
    Laboratory of Clinical Microbiology, Attikon Hospital, National and Kapodistrian University of Athens, Athens, Greece.
    Saegeman, V.
    Department of Infection Control and Epidemiology, University Hospitals Leuven, Leuven, Belgium.
    Schønheyder, H. C.
    Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark.
    Schrenzel, J.
    Bacteriology Laboratory, Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland.
    Strateva, T.
    Department of Medical Microbiology, Faculty of Medicine, Medical University of Sofia, Sofia, Bulgaria.
    Tilley, R.
    Department of Microbiology, University Hospitals Plymouth NHS Trust, Plymouth, UK.
    Wiersinga, W. J.
    Department of Infectious Diseases and Centre for Experimental Molecular Medicine, Amsterdam UMC, location AMC, University of Amsterdam, Amsterdam, the Netherlands.
    Zabicka, D.
    National Medicines Institute, Warsaw, Poland.
    Carmeli, Y.
    Division of Epidemiology, Tel Aviv Sourasky Medical Centre, Tel Aviv, Israel.
    Becker, K.
    Institute of Medical Microbiology, University Hospital Münster, Münster, Germany.
    Microbiological diagnostics of bloodstream infections in Europe-an ESGBIES survey2019In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 25, no 11, p. 1399-1407Article in journal (Refereed)
    Abstract [en]

    Objectives: High-quality diagnosis of bloodstream infections (BSI) is important for successful patient management. As knowledge on current practices of microbiological BSI diagnostics is limited, this project aimed to assess its current state in European microbiological laboratories.

    Methods: We performed an online questionnaire-based cross-sectional survey comprising 34 questions on practices of microbiological BSI diagnostics. The ESCMID Study Group for Bloodstream Infections, Endocarditis and Sepsis (ESGBIES) was the primary platform to engage national coordinators who recruited laboratories within their countries.

    Results: Responses were received from 209 laboratories in 25 European countries. Although 32.5% (68/209) of laboratories only used the classical processing of positive blood cultures (BC), two-thirds applied rapid technologies. Of laboratories that provided data, 42.2% (78/185) were able to start incubating BC in automated BC incubators around-the-clock, and only 13% (25/192) had established a 24-h service to start immediate processing of positive BC. Only 4.7% (9/190) of laboratories validated and transmitted the results of identification and antimicrobial susceptibility testing (AST) of BC pathogens to clinicians 24 h/day. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry from briefly incubated sub-cultures on solid media was the most commonly used approach to rapid pathogen identification from positive BC, and direct disc diffusion was the most common rapid AST method from positive BC.

    Conclusions: Laboratories have started to implement novel technologies for rapid identification and AST for positive BC. However, progress is severely compromised by limited operating hours such that current practice of BC diagnostics in Europe complies only partly with the requirements for optimal BSI management.

  • 78.
    Ison, Catherine A.
    et al.
    Sexually Transmitted Bacteria Reference Unit, Health Protection Agency, London, UK.
    Golparian, Daniel
    WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Saunders, Pamela
    Sexually Transmitted Bacteria Reference Unit, Health Protection Agency, London, UK.
    Chisholm, Stephanie
    Sexually Transmitted Bacteria Reference Unit, Health Protection Agency, London, UK.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Evolution of Neisseria gonorrhoeae is a continuing challenge for molecular detection of gonorrhoea: false negative gonococcal porA mutants are spreading internationally2013In: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 89, no 3, p. 197-201Article in journal (Refereed)
    Abstract [en]

    Objectives: Identification of genetic targets specific to Neisseria gonorrhoeae for use in molecular detection methods has been a challenge. The porA pseudogene in N gonorrhoeae has been commonly used but recently gonococcal isolates giving a negative result in these PCRs have been reported. Here we describe the characterisation of two such gonococcal isolates received by the reference service at the Health Protection Agency, London, England.

    Methods: Phenotypic characterisation was achieved using conventional biochemical and immunological tests, matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF-MS), antimicrobial susceptibility testing, serovar determination and detection of meningococcal PorA using monoclonal antibody 4BG4-E7. Genetic species confirmation was determined using commercial and in house PCRs and 16S rRNA gene sequencing. Molecular typing using the N gonorrhoeae multi-antigen sequence typing (NG-MAST) and multilocus sequence typing (MLST) was performed. The DNA sequence of the full-length gonococcal porA pseudogene was determined and compared with published sequences.

    Results: Both isolates were confirmed, biochemically and immunologically as N gonorrhoeae, but repeatedly gave negative results with two in house real-time PCR assays for the porA pseudogene. Further characterisation of these isolates identified the presence of a meningococcal porA sequence and showed these isolates belong to serovar Bropyst, and to NG-MAST sequence type (ST) 5967 and MLST ST1901.

    Conclusions: Gonococcal isolates that give false negative results with porA pseudogene PCR assays have now been identified in four countries, three of which are in Europe, and do not appear clonal. This report highlights the genetic diversity of N gonorrhoeae, which remains a challenge for the molecular detection methods.

  • 79.
    Ito, Teruyo
    et al.
    Dept Bacteriol, Juntendo Univ, Tokyo, Japan .
    Hiramatsu, Keiichi
    Rockefeller University, New York NY, USA .
    Tomasz, Alexander
    Rockefeller University, New York NY, USA .
    de Lencastre, Herminia
    Rockefeller University, New York NY, USA; Inst Tecnol Quim & Biol, University Nova Lisboa, Oeiras, Portugal.
    Perreten, Vincent
    Inst Vet Bacteriol, University Bern, Bern, Switzerland.
    Holden, Matthew T. G.
    Wellcome Trust Sanger Inst, Hinxton, England.
    Coleman, David C.
    Dublin Dent University Hospital, Univ Dublin, Dublin, Ireland; Trinity College, Dublin, Ireland.
    Goering, Richard
    Medical Center, University of Nebraska, Omaha NE, USA.
    Giffard, Philip M.
    Menzies School of Heallth Research, Darwin NT, Australia.
    Skov, Robert L.
    Statens Serum Institut, Copenhagen, Denmark .
    Zhang, Kunyan
    Univ Calgary, Calgary AB, Canada.
    Westh, Henrik
    Faculty of Health, Copenhagen University, Copenhagen, Denmark; Hvidovre Hospital, Copenhagen University, Copenhagen, Denmark.
    O'Brien, Frances
    Curtin Univ Technol, Perth WA, Australia.
    Tenover, Fred C.
    Cepheid, Sunnyvale CA, USA.
    Oliveira, Duarte C.
    Inst Tecnol Quim & Biol, University Nova Lisboa, Oeiras, Portugal; Faculty of Ciencias & Tecnol, Dept Life Sciences, CREM, University Nova Lisboa, Caparica, Portugal .
    Boyle-Vavra, Susan
    Faculty of Ciencias & Tecnol, Dept Life Sciences, CREM, University Nova Lisboa, Caparica, Portugal .
    Laurent, Frederic
    French Natl Reference Ctr Staphylococci, Hosp Civils Lyon, Lyon, France.
    Kearns, Angela M.
    Staphylococcus Reference Unit, Heallth Protecttion Agency, London, England.
    Kreiswirth, Barry
    Pubicl Health Research Institute, New York NY, USA .
    Ko, Kwan Soo
    School of Medicine, Sungkyunkwan University, Seoul, South Korea .
    Grundmann, Hajo
    Nationall Insitute of Public Health & Environment, Utrecht, Netherlands .
    Sollid, Johanna E.
    Tromsø University, Tromsø, Norway .
    John, Joseph F. Jr.
    Ralph H Johnson VA Med Ctr, Charleston SC, USA.
    Daum, Robert
    University of Chicago, Chicago IL, USA.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden.
    Buist, Girbe
    Guidelines for Reporting Novel mecA Gene Homologues2012In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 56, no 10, p. 4997-4999Article in journal (Other academic)
  • 80.
    Jacobsson, Susanne
    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 Sexually Transmitted Infections, Department of Laboratory Medicine.
    Boiko, Iryna
    Clinical Laboratory Department, Ternopil Regional Clinical Dermatovenerologic Dispensary, Ternopil, Ukraine.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine.
    Blondeel, Karel
    Department of Reproductive Health and Research, World Health Organization (WHO), Geneva, Switzerland.
    Kiarie, James
    Department of Reproductive Health and Research, World Health Organization (WHO), Geneva, Switzerland.
    Toskin, Igor
    Department of Reproductive Health and Research, World Health Organization (WHO), Geneva, Switzerland.
    Peeling, Rosanna W.
    London School of Hygiene and Tropical Medicine (LSHTM), London, UK.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine.
    WHO laboratory validation of Xpert((R)) CT/NG and Xpert((R)) TV on the GeneXpert system verifies high performances2018In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 126, no 12, p. 907-912Article in journal (Refereed)
    Abstract [en]

    Effective tests for diagnosis of sexually transmitted infections (STIs), used point of care to inform treatment and management decisions, are urgently needed. We evaluated the analytical sensitivity and specificity of the Xpert((R)) CT/NG and Xpert((R)) TV tests, examining 339 samples spiked with phenotypically and/or genetically diverse strains of Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis, and other related species that may cross-react. The APTIMA Combo 2 test and APTIMA TV test were used as reference tests. The analytical sensitivity for all three agents in the Xpert((R)) CT/NG and Xpert((R)) TV tests was <= 10(2) genome equivalents/reaction. The analytical specificity of both tests was high. False-positive results were identified in the Xpert((R)) TV test when challenging with high concentrations of Trichomonas tenax, Trichomonas gallinae, Trichomonas stableri, and Trichomonas aotus. However, the clinical relevance of these cross-reactions can likely be neglected, because these species have not been identified in urogenital samples from humans. In conclusion, the analytical sensitivity and specificity of the user-friendly Xpert((R)) CT/NG and Xpert((R)) TV tests on the GeneXpert system were high. The results support the use of specimens from also extra-genital sites, for example, pharynx and rectum. However, appropriate clinical validations are additionally required.

  • 81.
    Jacobsson, Susanne
    et al.
    Örebro University Hospital. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Golparian, Daniel
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Alm, Richard A.
    Infection IMed, AstraZeneca RandD Boston, Waltham MA, United States.
    Huband, Michael
    Infection IMed, AstraZeneca RandD Boston, Waltham MA, United States.
    Mueller, John
    Infection IMed, AstraZeneca RandD Boston, Waltham MA, United States.
    Jensen, Jorgen Skov
    Statens Serum Institut, Copenhagen, Denmark.
    Ohnishi, Makoto
    National Institute of Infectious Diseases, Tokyo, Japan.
    Unemo, Magnus
    Örebro University Hospital. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    High In Vitro Activity of the Novel Spiropyrimidinetrione AZD0914, a DNA Gyrase Inhibitor, against Multidrug-Resistant Neisseria gonorrhoeae Isolates Suggests a New Effective Option for Oral Treatment of Gonorrhea2014In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 58, no 9, p. 5585-5588Article in journal (Refereed)
    Abstract [en]

    We evaluated the activity of the novel spiropyrimidinetrione AZD0914 (DNA gyrase inhibitor) against clinical gonococcal isolates and international reference strains (n = 250), including strains with diverse multidrug resistance and extensive drug resistance. The AZD0914 MICs were substantially lower than those of most other currently or previously recommended antimicrobials. AZD0914 should be further evaluated, including in vitro selection, in vivo emergence and mechanisms of resistance, pharmacokinetics/pharmacodynamics in humans, optimal dosing, and performance, in appropriate randomized and controlled clinical trials.

  • 82.
    Jacobsson, Susanne
    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 Sexually Transmitted Infections, Department of Laboratory Medicine.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine.
    Scangarella-Oman, Nicole
    GlaxoSmithKline, Collegeville PA, USA.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine.
    In vitro activity of the novel triazaacenaphthylene gepotidacin (GSK2140944) against MDR Neisseria gonorrhoeae2018In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 73, no 8, p. 2072-2077Article in journal (Refereed)
    Abstract [en]

    Objectives: Increased antimicrobial resistance surveillance and new effective antimicrobials are crucial to maintain treatable gonorrhoea. We examined the in vitro activity of gepotidacin, a novel triazaacenaphthylene, and the effect of efflux pump inactivation on clinical Neisseria gonorrhoeae isolates and international reference strains (n = 252) and compared gepotidacin with antimicrobials currently or previously recommended for gonorrhoea treatment.

    Methods: MICs (mg/L) were determined by agar dilution (gepotidacin) or by Etest (seven other antimicrobials). The gyrA and parC genes were sequenced and the impact of inactivation of the MtrCDE, MacAB and NorM efflux pumps on gepotidacin MICs was examined.

    Results: Gepotidacin showed potent in vitro activity against all gonococcal isolates (n = 252; MIC <= 4 mg/L). The modal MIC, MIC50 , MIC90 and MIC range of gepotidacin were 0.5, 0.5, 1 and 0.032-4 mg/L, respectively. Inactivation of the MtrCDE efflux pump, but not MacAB or NorM, decreased the gepotidacin MICs for most strains. No significant cross-resistance between gepotidacin and any other antimicrobials, including the fluoroquinolone ciprofloxacin, was identified. However, the ParC D86N mutation (possibly together with additional antimicrobial resistance mutation), which is associated with fluoroquinolone resistance, was associated with increased gepotidacin MICs.

    Conclusions: Gepotidacin demonstrated high in vitro activity against gonococcal strains, indicating that gepotidacin could potentially be an effective option for gonorrhoea treatment, particularly in a dual antimicrobialtherapy regimen and for patients with resistance or allergy to extended-spectrum cephalosporins. Nevertheless, elucidating in vitro and in vivo resistance emergence and mechanisms in detail, together with further gonorrhoea clinical studies, ideally also including chlamydia and Mycoplasma genitalium are essential.

  • 83.
    Jacobsson, Susanne
    et al.
    Örebro University, School of Health and Medical Sciences.
    Mölling, Paula
    Örebro University, Örebro, Sweden.
    Olcén, Per
    Seroprevalence of antibodies against fHbp and NadA, two potential vaccine antigens for Neisseria meningitidis2009In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 27, no 42, p. 5755-5759Article in journal (Refereed)
    Abstract [en]

    The IgG antibody levels directed against fHbp and NadA, two potential vaccine antigens for Neisseria meningitidis, were examined in order to investigate the extent of natural immunisation against these antigens in different age groups. As a comparison, the IgG antibody levels against Haemophilus influenzae type b were examined. In the two youngest age groups, below 10 years of age, relatively low levels of both anti-fHbp and anti-NadA were measured. A 15-fold higher geometric mean concentration of anti-fHbp was noted in the age group 20-29 years as compared to the age group 15-19 years. The peak concentration was found at 30-39 years, followed by decreased levels with age. Anti-NadA showed a certain increase up to 9 years followed by an even increase up to 40-49 years.

  • 84.
    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.

  • 85.
    Jayaprakash, Kartheyaene
    et al.
    Örebro University, School of Medical Sciences.
    Demirel, Isak
    Örebro University, School of Medical Sciences.
    Gunaltay, Sezin
    Örebro University, School of Medical Sciences.
    Khalaf, Hazem
    Örebro University, School of Medical Sciences.
    Bengtsson, Torbjörn
    Örebro University, School of Medical Sciences.
    PKC, ERK/p38 MAP kinases and NF-B targeted signalling play a role in the expression and release of IL-1β  and CXCL8 in Porphyromonas gingivalis-infected THP1 cells2017In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 125, no 7, p. 623-633Article in journal (Refereed)
    Abstract [en]

    Porphyromonas gingivalis is a keystone pathogen in periodontitis and is gaining importance in cardiovascular pathogenesis. Protease-activated receptors (PARs), toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD) on monocytes recognize the structural components on P. gingivalis, inducing inflammatory intermediates. Here, we elucidate the modulation of PARs, TLRs, NODs, and the role of MAPK and NF-B in IL-1 and CXCL8 release. THP1 cells were stimulated with P. gingivalis wild-type W50 and its isogenic gingipain mutants: Rgp mutant E8 and Kgp mutant K1A. We observed modulation of PARs, TLRs, NOD, IL-1 and CXCL8 expression by P. gingivalis. Gingipains hydrolyse IL-1 and CXCL8, which is more evident for IL-1 accumulation at 24 h. Inhibition of PKC (protein kinase C), p38 and ERK (extracellular signal-regulated kinases) partially reduced P. gingivalis-induced IL-1 at 6 h, whereas PKC and ERK reduced CXCL8 at both 6 and 24 h. Following NF-B inhibition, P. gingivalis-induced IL-1 and CXCL8 were completely suppressed to basal levels. Overall, TLRs, PARs and NOD possibly act in synergy with PKC, MAPK ERK/p38 and NF-B in P. gingivalis-induced IL-1 and CXCL8 release from THP1 cells. These pro-inflammatory cytokines could affect leucocytes in circulation and exacerbate other vascular inflammatory conditions such as atherosclerosis.

  • 86.
    Jayaprakash, Kartheyaene
    et al.
    Department of Medical Sciences, Örebro University, Örebro, Sweden.
    Demirel, Isak
    Örebro University, School of Medical Sciences.
    Khalaf, Hazem
    Örebro University, School of Medical Sciences.
    Bengtsson, Torbjörn
    Örebro University, School of Medical Sciences.
    Porphyromonas gingivalis-induced inflammatory responses in THP1 cells are altered by native and modified low-density lipoproteins in a strain-dependent manner2018In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 126, no 8, p. 667-677Article in journal (Refereed)
    Abstract [en]

    Strong epidemiological evidence supports an association between cardiovascular and periodontal disease and furthermore, the periodontopathogen Porphyromonas gingivalis has been identified in blood and from atheromatous plaques. Blood exposed to P.gingivalis shows an increased protein modification of low-density lipoprotein (LDL). In this study, we investigate the inflammatory responses of THP1 cells incubated with P.gingivalis and the effects of native or modified LDL on these responses. Reactive oxygen species (ROS) and IL-1 were observed in THP1 cells following infection with P.gingivalis ATCC33277 and W50. Caspase 1 activity was quantified in THP1 cells and correlated with IL-1 accumulation. Oxidized LDL (oxLDL) induced IL-1 release and CD36 expression on THP1 cells. Modified LDL co-stimulated with ATCC33277 exhibited regulatory effects on caspase 1 activity, IL-1 release and CD36 expression in THP1 cells, whereas W50 induced more modest responses in THP1 cells. In summary, we show that P.gingivalis is capable of inducing pro-inflammatory responses in THP1 cells, and native and modified LDL could alter these responses in a dose- and strain-dependent manner. Strain-dependent differences in THP1 cell responses could be due to the effect of P.gingivalis proteases, presence or absence of capsule and proteolytic transformation of native and modified LDL.

  • 87.
    Jeverica, Samo
    et al.
    Fac Med, Inst Microbiol & Immunol, Univ Ljubljana, Ljubljana, Slovenia.
    Golparian, Daniel
    WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for Pathogenic Neisseria, Department of Lab. Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Hanzelka, Brian
    Vertex Pharmaceut Inc, Boston MA, USA.
    Fowlie, Andrew J.
    Vertex Pharmaceut Inc, Boston MA, USA.
    Maticic, Mojca
    Clin Infect Dis & Febrile Illnesses, Univ Med Ctr Ljubljana, Ljubljana, Slovenia..
    Unemo, Magnus
    Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for Pathogenic Neisseria, Department of Lab. Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    High in vitro activity of a novel dual bacterial topoisomerase inhibitor of the ATPase activities of GyrB and ParE (VT12-008911) against Neisseria gonorrhoeae isolates with various high-level antimicrobial resistance and multidrug resistance2014In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 69, no 7, p. 1866-1872Article in journal (Refereed)
    Abstract [en]

    Clinical resistance to the currently recommended extended-spectrum cephalosporins (ESCs), the last remaining options for empirical antimicrobial monotherapy of gonorrhoea globally, has been reported. New antimicrobials are essential to avoid the emergence of untreatable gonorrhoea. We have investigated the in vitro activity of a novel dual bacterial topoisomerase inhibitor of the ATPase activities of GyrB and ParE (Vertex aminobenzimidazole VT12-008911), compared with antimicrobials currently or previously recommended for gonorrhoea treatment.

    MICs were determined using agar dilution (VT12-008911) or Etest (seven antimicrobials) for international reference strains (naEuroS=aEuroS28) and clinical Neisseria gonorrhoeae isolates (naEuroS=aEuroS220). The latter included three extensively drug-resistant isolates with high-level ceftriaxone resistance, additional isolates with clinical ESC resistance and a high number of isolates with ciprofloxacin resistance and multidrug resistance.

    The MIC50, MIC90 and MIC range of VT12-008911 were 0.064, 0.125 and a parts per thousand currency sign0.002-0.25 mg/L, respectively. One-hundred and seventy (69%) isolates were ciprofloxacin resistant; however, only 54 of those isolates had a VT12-008911 MIC > 0.064 mg/L (47 and 7 with MICaEuroS=aEuroS0.125 mg/L and MICaEuroS=aEuroS0.25 mg/L, respectively). The in vitro activity of VT12-008911 was superior to that of ciprofloxacin and all additional antimicrobials investigated. Time-kill curve analysis showed that VT12-008911 exhibited potent time-dependent bactericidal activity, at or very close to the MIC, against N. gonorrhoeae.

    In vitro results suggest that VT12-008911 might be an effective treatment option for gonorrhoea. However, it will be important to detail the pharmacokinetics/pharmacodynamics, toxicity, selection and mechanisms of VT12-008911 resistance in N. gonorrhoeae and, finally, to perform well-designed in vivo randomized clinical trials.

  • 88.
    Jeverica, Samo
    et al.
    Fac Med, Inst Microbiol & Immunol, Univ Ljubljana, Ljubljana, Slovenia.
    Golparian, Daniel
    WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Maticic, Mojca
    Clin Infect Dis & Febrile Illnesses, Univ Med Ctr Ljubljana, Ljubljana, Slovenia.
    Potocnik, Marko
    Dept Dermatovenereol, Univ Med Ctr Ljubljana, Ljubljana, Slovenia.
    Mlakar, Bostjan
    Surg Ctr Zdrav Splet, Ljubljana, Slovenia.
    Unemo, Magnus
    Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Phenotypic and molecular characterization of Neisseria gonorrhoeae isolates from Slovenia, 2006-12: rise and fall of the multidrug-resistant NG-MAST genogroup 1407 clone?2014In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 69, no 6, p. 1517-1525Article in journal (Refereed)
    Abstract [en]

    To determine the phenotypic and molecular characteristics of Neisseria gonorrhoeae isolates obtained between 2006 and 2012 in Slovenia.

    Gonococcal isolates obtained between 2006 and 2012 in Slovenia (naEuroS=aEuroS194) were investigated with Etest for susceptibility to cefixime, ceftriaxone, penicillin, ciprofloxacin, azithromycin, tetracycline, gentamicin and spectinomycin. All isolates were examined with N. gonorrhoeae multiantigen sequence typing for molecular epidemiology and sequencing of the major extended-spectrum cephalosporin (ESC) resistance determinants (penA, mtrR and penB) was performed.

    The overall prevalence of decreased susceptibility or resistance to cefixime and ceftriaxone (MIC a parts per thousand yen0.125 mg/L) was 11% and 5%, respectively. The decreased susceptibility or resistance showed an epidemic peak in 2011 (33% for cefixime and 11% for ceftriaxone), decreasing to 6% and 4%, respectively, in 2012. ST1407 (9% of isolates), ST21 (6%) and ST225 (6%) were the most common sequence types (STs) during 2006-12. Genogroup G1407 (ST1407 most prevalent ST), an internationally spread clone with decreased susceptibility or resistance to ESCs, was most prevalent (48%) in 2009. However, the G1407 prevalence then declined: in 2010, 30%; in 2011, 28%; and in 2012, 8%. Instead, in 2012 the ESC- and ciprofloxacin-susceptible G21 was the predominant genogroup (26%).

    The prevalence of gonococcal resistance to ESCs in Slovenia has been high, but fluctuating. Fortunately, in 2012 some ESC- and ciprofloxacin-susceptible clones, such as genogroups G21, G1195 and G2992, appeared to have mainly replaced the multidrug-resistant G1407 clone, a replacement also seen in several European countries.

  • 89.
    Johansson, Joel
    Örebro University, School of Health and Medical Sciences.
    Undersökning av antikroppar riktade mot Mo- MLVs fusionsprotein Env i IAS (Isomerization Arrested Stage) form2008Report (Other academic)
    Abstract [sv]

    Retrovirus invaderar nya celler genom membranfusion, en process som drivs av membranproteinet Env (Envelope). Env är det enda virala proteinet på virusutsidan och därför en potentiell angreppspunkt för neutraliserande antikroppar. Genom att aktivera Env proteinet hos Mo-MLV (Moloney murine leukemia virus) i närvaro av en alkylator blockeras isomerisering av en disulfid-bindning mellan proteinets två subenheter SU och TM. Alkyleringen låser env i en intermediär form som kallas IAS (isomerisation arrested state). För att undersöka om Env i IAS form är ett lämpligt antigen för produktion av neutraliserande antikroppar har vi immuniserat balb/c-möss med denna renade IAS-Env-trimerer och etablerat antikroppsproducerande hybridom från mjältceller från utvalda möss. Antikroppar i musserum och medium från hybridomkulturer undersöktes med immunfällning, ELISA, och XC cell-cell fusion. En preliminär karaktärisering av antikroppar från tre hybridomkolonier visar viss hämning av XC cell-cellfusion, d.v.s. neutraliserande verkan in vitro

  • 90.
    Johansson, Karin
    et al.
    Department of Laboratory Medicine, Molecular Diagnostics, Örebro University Hospital, Örebro, Sweden.
    Karlsson, Hanna
    Department of Laboratory Medicine, Molecular Diagnostics, Örebro University Hospital, Örebro, Sweden.
    Norén, Torbjörn
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Clostridium difficile infection diagnostics: evaluation of the C. DIFF Quik Chek Complete assay, a rapid enzyme immunoassay for detection of toxigenic C. difficile in clinical stool samples2016In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 124, no 11, p. 1016-1020Article in journal (Refereed)
    Abstract [en]

    Diagnostic testing for Clostridium difficile infection (CDI) has, in recent years, seen the introduction of rapid dual-EIA (enzyme immunoassay) tests combining species-specific glutamate dehydrogenase (GDH) with toxin A/B. In a prospective study, we compared the C. DIFF Quik Chek Complete test to a combination of selective culture (SC) and loop-mediated isothermal amplification (LAMP) of the toxin A gene. Of 419 specimens, 68 were positive in SC including 62 positive in LAMP (14.7%). The combined EIA yielded 82 GDH positives of which 47 were confirmed toxin A/B positive (11%) corresponding to a sensitivity and specificity of 94% for GDH EIA compared to SC and for toxin A/B EIA a sensitivity of 71% and a specificity of 99% compared to LAMP. Twenty different PCR ribotypes were evenly distributed except for UK 081 where only 25% were toxin A/B positive compared to LAMP. We propose a primary use of a combined GDH toxin A/B EIA permitting a sensitive 1-h result of 379 of 419 (90%, all negatives plus GDH and toxin EIA positives) referred specimens. The remaining 10% being GDH positive should be tested for toxin A/B gene on the same day and positive results left to a final decision by the physician.

  • 91.
    Johansson, Magnus
    Örebro University, School of Medical Sciences.
    Development of an edible Tick-borne encephalitis vaccine2017Conference paper (Other academic)
  • 92.
    Johansson, Magnus
    et al.
    Örebro University, School of Medical Sciences.
    Frelin, Lars
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Maravelia, Panagiota
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Asghar, Naveed
    Melik, Wessam
    Örebro University, School of Medical Sciences.
    Caro-Perez, Noelia
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Pasetto, Anna
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Ahlen, Gustaf
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Sallberg, Matti
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Immunogenicity of a New Flaviviral-Based DNA Launched Suicidal Replicon for Protective Vaccination Against Hepatitis C2019In: Molecular Therapy, ISSN 1525-0016, E-ISSN 1525-0024, Vol. 27, no 4, p. 139-139Article in journal (Other academic)
  • 93.
    Johansson, Åsa
    et al.
    Department of Clinical Microbiology, Central Hospital, Växjö, Sweden.
    Ekelöf, Josefine
    Sch Nat Sci, Linnaeus Univ, Kalmar, Sweden.
    Giske, Christian G.
    Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institute, Stockholm, Sweden; Karolinska Univ Hosp, Stockholm, Sweden.
    Sundqvist, Martin
    Örebro University Hospital. Department of Clinical Microbiology, Central Hospital, Växjö, Sweden; Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    The detection and verification of carbapenemases using ertapenem and Matrix Assisted Laser Desorption Ionization-Time of Flight2014In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 14, article id 89Article in journal (Refereed)
    Abstract [en]

    Background: The increase in carbapenemase producing Enterobacteriaceae and Pseudomonas aeruginosa is a significant threat to modern medicine. A rapid detection of carbapenemase production in Klebsiella pneumoniae and Pseudomonas aeruginosa is of importance for the institution of correct antibiotic treatment and infection control measures.

    Results: Standardised inoculums of K. pneumoniae or P. aeruginosa were incubated at 37 degrees C with ertapenem in 15 and 120 min followed by centrifugation. The supernatant was applied on a steel target plate, covered with HCCA matrix and analysed using a Microflex(TM) (Bruker Daltonics) in the mass range of 4-600 Da. The assay detected and separated KPC from other carbapenemases in K. pneumoniae after only 15 min incubation. In P. aeruginosa, however, only 8/14 isolates of VIM-producing P. aeruginosa were detected. None of the tested carbapenemase negative isolates displayed a pattern of hydrolysis of ertapenem.

    Conclusions: This assay allows for a very rapid detection and verification of KPC (45 min including the preparation steps) and MBL production (150 min) in K. pneumoniae and can be performed using standard matrix. However, the study revealed the need for optimization of the substrate/species combination in assays for the detection of carbapenemases in P. aeruginosa using MALDI-TOF.

  • 94.
    Johansson, Åsa
    et al.
    Dept of Clinical Microbiology, Växjö Central Hospital, Växjö, Sweden.
    Larsen, Anders Rhod
    Natl Reference Lab Staphylococci, Statens Serum Inst, Copenhagen, Denmark.
    Skov, Robert
    Natl Reference Lab Staphylococci, Statens Serum Inst, Copenhagen, Denmark.
    Sundqvist, Martin
    Örebro University Hospital. v; Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Importance of a Diverse Isolate Collection When Defining Genotype-Specific Mass Spectra in Staphylococcus aureus2014In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 52, no 7, p. 2738-2739Article in journal (Refereed)
  • 95.
    Jönsson, Agnez
    et al.
    WHO Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology.
    Foerster, Sunniva
    WHO Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Cole, Michelle J.
    Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, National Infection Service, Public Health England, London, UK.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology.
    Performance characteristics of newer MIC gradient strip tests compared with the Etest for antimicrobial susceptibility testing of Neisseria gonorrhoeae2018In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 126, no 10, p. 822-827Article in journal (Refereed)
    Abstract [en]

    For Neisseria gonorrhoeae susceptibility testing, Etest, comparable to agar dilution, is frequently used. In recent years, newer MIC gradient strip tests have been commercialized. However, these tests have not been appropriately evaluated for gonococci. We evaluated the sensitivity, specificity, accuracy, quality, availability of antimicrobials and cost of the MIC Test Strip (Liofilchem), M.I.C.Evaluator (Oxoid) and Ezy MIC Strip (HiMedia), compared to the reference Etest (bioMérieux), for gonococcal susceptibility testing. The MICs of eight antimicrobials in 103 gonococcal international reference strains (n = 29) and clinical isolates (n = 74) were examined. Coefficient of determination (R2), complete agreement, essential agreement, SIR categorical agreement, sensitivity, specificity and accuracy were calculated. R2 of the MICs for the antimicrobials ranged between 0.674–0.996, 0.617–0.993, and 0.643–0.994 for the MIC Test Strip, M.I.C.Evaluator strips and Ezy MIC Strips respectively. The essential agreement (SIR categorical agreement) was 99.6% (88.6%), 100% (87.1%) and 93.0% (83.1%) respectively. M.I.C.Evaluator strips for gonococcal key antimicrobials were lacking and the Ezy MIC Strips showed an inconsistent accuracy, quality and some strips were contaminated. The Liofilchem MIC Test Strips had limitations, but might be relatively accurate alternatives to Etest for gonococci. Strict quality assurance (at manufacturing and testing laboratory), including quality controls, are required.

  • 96.
    Kadi, Fawzi
    Örebro University, School of Health and Medical Sciences.
    Cellular and molecular mechanisms responsible for the action of testosterone on human skeletal muscle: a basis for illegal performance enhancement2008In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 154, no 3, p. 522-528Article in journal (Refereed)
    Abstract [en]

    The popularity of testosterone among drug users is due to its powerful effects on muscle strength and mass. Important mechanisms behind the myotrophic effects of testosterone were uncovered both in athletes using steroids for several years and in short-term controlled studies. Both long-term and short-term steroid usage accentuates the degree of fibre hypertrophy in human skeletal muscle by enhancing protein synthesis. A mechanism by which testosterone facilitates the hypertrophy of muscle fibres is the activation of satellite cells and the promotion of myonuclear accretion when existing myonuclei become unable to sustain further enhancement of protein synthesis. Interestingly, long-term steroid usage also enhances the frequency of fibres with centrally located myonuclei, which implies the occurrence of a high regenerative activity. Under the action of testosterone, some daughter cells generated by satellite cell proliferation may escape differentiation and return to quiescence, which help to replenish the satellite cell reserve pool. However, whether long-term steroid usage induces adverse effects of satellite cells remains unknown. Testosterone might also favour the commitment of pluripotent precursor cells into myotubes and inhibit adipogenic differentiation. The effects of testosterone on skeletal muscle are thought to be mediated via androgen receptors expressed in myonuclei and satellite cells. Some evidence also suggests the existence of an androgen-receptor-independent pathway. Clearly, testosterone abuse is associated with an intense recruitment of multiple myogenic pathways. This provides an unfair advantage over non-drug users. The long-term consequences on the regenerative capacity of skeletal muscle are unknown.

  • 97.
    Kalbina, Irina
    et al.
    Örebro University, School of Science and Technology.
    Marks, Ellen
    University of Gothenburg, Gothenburg, Sweden.
    Lycke, Nils
    University of Gothenburg, Gothenburg, Sweden.
    Lindh, Ingrid
    Örebro University, School of Science and Technology.
    Unemo, Magnus
    Örebro University Hospital, Örebro, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Andersson, Sören
    Örebro University Hospital, Örebro, Sweden.
    Construction, immunogenicity and protective efficacy in mice of a prototype chimeric Chlamydia trachomatis MOMP vaccine candidate antigen2011Conference paper (Refereed)
    Abstract [en]

    A chimeric gene construct of Chlamydia trachomatis serovar E major outer membrane protein (MOMP) was designed, and expressed as a candidate vaccine antigen. The construct was based on known T and B cell epitopes located in the variable segment (VS) 2 and 4 loops of MOMP, and successfully expressed and purified in a recombinant Escherichia coli system. BALB/c mice were immunized intranasally with the chimeric MOMP antigen and Cholera toxin (CT) adjuvant, three immunizations with 10 days intervals. A final boost with the identical antigen preparation was given intravaginally. Challenge with live C. trachomatis serovar D was performed 10 days after boost. Antibodies in serum and vaginal washes were determined with the identical chimeric MOMP construct as antigen in ELISAs. All mice in vaccine groups (N=10/group and experiment) developed a strong antigen-specific IgG response in serum, and some also had detectable antigen-specific IgG in vaginal washes. An IgA response, albeit weaker, was detected in some of the mice both in serum and in vaginal washes.

    After challenge with C. trachomatis, 80 and 100% of the mice became infected in two experiments, respectively. However, the vaccinated groups cleared the infection significantly faster than control groups (all vaccinated mice healthy day 24 [90% day 16], compared to day 40 for controls).

    Thus, the new chimeric MOMP antigen construct gave rise to a significant immune response in mice (s-IgG). It also conferred substantial protection to infection caused by genital C. trachomatis infection of a different subtype.

  • 98.
    Karlsson, Mattias
    et al.
    Örebro University, School of Science and Technology.
    Jass, Jana
    Örebro University, School of Science and Technology.
    CXCL8 regulation of urothelial cells by lactobacilli2011Conference paper (Other academic)
    Abstract [en]

    Background

    CXLC8 is an important cytokine that attracts immune cells such as neutrophils and macrophages during infections. This cytokine is released from many cell types including epithelial cells such as the urothelial cells found in the urinary tract. CXCL8 release is dramatically increased when urothelial cells meet bacteria such as uropathogenic Escherichia coli, which are the main cause of urinary tract infections. CXCL8 is needed during the course of the infection; nevertheless, high levels have been associated with chronic inflammation and cancer, and are in those cases considered detrimental to health. Lactobacillus is a diverse group of lactic acid bacteria and a major component of our microbiota. Many are also commercially available as probiotics, and even if they have shown effectiveness as preventative supplements for both infections and supporting bowel regularity, much is left to learn about their mode of action. We know that many probiotics are immunomodulators and affect immune cell function, especially in immune cells. However, less is known about their effect on epithelial cell immune function and the possible variation immunomodulation between different Lactobacillus species.   

     

    Results

    To test the CXCL8 modulating abilities of Lactobacillus, numerous species were used for screening urothelial cell CXCL8 release. We wanted to assess the role of lactobacilli on resting cells, but also how they affect CXCL8 in cells that are already stimulated with E. coli similar to the case of a urinary tract infection. We found that most lactobacilli had a marginal effect on cytokine release in resting cells not challenged with E. coli. However, E. coli-challenged cells subsequently exposed to lactobacilli showed a significant increase or decrease of CXCL8 levels. Many of the tested species changed cytokine levels severalfold in both directions. Comparing the effects between species using evolutionary trees based on 16S rRNA did not reveal any grouping of effects based on the genetic similarity between the different taxa.

     

    Conclusion

    Many lactobacilli have the ability to alter the levels of secreted CXCL8, especially in E. coli-challenged cells. Interestingly, we could not group the effect on CXCL8 based on their evolutionary relationship suggesting that the effects on CXCL8 is analogous in its nature and have evolved independently in many of the tested species. However, as for probiotic activity which is often strain specific, CXCL8 modulating features are also likely to be associated with individual strains. Although we cannot explain the big differences between bacteria, both up- and downregulation of CXCL8 is interesting from a therapeutical perspective. Many pathogens, including uropathogenic E. coli actively inhibit signals that lead to cytokine release and immune migration, and it can in those cases be beneficial to increase CXCL8, whereas decreased cytokine levels might be advantageous in other conditions such as chronic inflammation.  

  • 99.
    Katouli, Mohammad
    et al.
    Laboratory for Bacteriology, Microbiology and Tumorbiology Centre, Karolinska Institute, Stockholm, Sweden.
    Bark, Tor
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Svenberg, Torgny E.
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Möllby, R.
    Laboratory for Bacteriology, Microbiology and Tumorbiology Centre, Karolinska Institute, Stockholm, Sweden.
    Composition and diversity of intestinal coliform flora influence bacterial translocation in rats after hemorrhagic  stress1994In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 2, no 11, p. 4768-4774Article in journal (Refereed)
    Abstract [en]

    Coliform bacteria are the most frequently reported bacteria to translocate afterhemorrhage. We investigated the correlation between composition and diversity of the cecal coliform flora and the degree of translocation in a rat model of hemorrhagic stress. Two groups of nine rats each were bled to 60 and 50 mm Hg mean arterial blood pressure, respectively. A sham-operated group without bleeding (n = 9) and a noninstrumented group (n = 6) served as controls. From each rat, 40 coliform isolates from the cecum and up to 16 from positive mesenteric lymph node (MLN) cultures were tested with an automated biochemical fingerprinting method. The phenotypic diversity of coliforms in each cecal sample was calculated as Simpson's diversity index (DI), and similarities between bacterial types in different samples were calculated as population similarity coefficients. Three rats in the sham-operated group and seven in each of the bled groups showed bacterial translocation. Of the different biochemical phenotypes (BPTs) found in the cecum of bled rats (mean, 6.5 BPTs), only a few were detected in MLNs (mean, 1.9 BPTs per MLN), with Escherichia coli being the dominant species. The translocating E. coli strains were mainly of two BPTs. Rats showing no translocation either did not carry these strains or had a high diversity of coliforms in the cecum. Furthermore, translocation of these coliform types was independent of their proportion in the cecum. In bled rats, the diversityof coliforms (mean DI, 0.53) was significantly higher than that in control groups (mean DI, 0.30; P = 0.004), suggesting that hemorrhage stimulates an increase in diversity of cecal coliforms. Rats with similar coliform flora and subjected to the same treatment showed similar patterns of translocation. Our results suggest that the composition of the coliformflora is an important factor in translocation and that certain coliform strains have the ability to translocate and survive in MLNs more easily than others.

  • 100.
    Katouli, Mohammad
    et al.
    Laboratory for Bacteriology, Microbiology and Tumorbiology Centre, Karolinska Institute, Stockholm,Sweden.
    Nettelbladt, Carl Gustaf
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Muratov, Vladislaw
    Laboratory for Bacteriology, Microbiology and Tumorbiology Centre, Karolinska Institute, Stockholm,Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Bark, Tor
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Svenberg, Torgny E.
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Möllby, R.
    Laboratory for Bacteriology, Microbiology and Tumorbiology Centre, Karolinska Institute, Stockholm,Sweden.
    Selective translocation of coliform bacteria adhering to caecal epithelium of rats during catabolic stress1997In: Journal of Medical Microbiology, ISSN 0022-2615, E-ISSN 1473-5644, Vol. 46, no 7, p. 571-578Article in journal (Refereed)
    Abstract [en]

    Adult conventional rats were starved for 48 h with or without haemorrhage at 24 h, and translocation of caecal coliforms to mesenteric lymph nodes (MLNs) was measured. Translocation was detected in three of 11 rats without haemorrhage, in 6 of 11 starved and sham-operated rats and in 12 of 22 rats after haemorrhage. In contrast, only one of 13 non-instrumented and fed control rats showed translocation. Translocation was associated with more coliforms adhering to caecal epithelium in rats. Coliform isolates from caecum, caecal epithelium and MLNs were characterised and grouped into different biochemical phenotypes (BPTs) by a biochemical fingerprinting method. Of 291 BPTs detected in the caecum of all rats, 108 were also found on caecal epithelium; 36 BPTs were detected in MLNs, of which 17 were not detected either in the caecum or on the caecal epithelium of the corresponding rats. One isolate from each of these 36 BPTs was selected and compared to the others. Four common (C) BPTs (i.e., C1-C4) were identified among them. Strains of C1 formed the majority of isolates from the caecum (79%), caecal epithelium(71%) and MLNs (91%). In contrast, C2-C4 had a significantly lower incidence both in the caecum and on the caecal epithelium, but not in the MLNs. These findings indicate that not all caecal coliforms adhere to the epithelium during catabolic stress and that for translocation to occur, other bacterial properties besides adhesion are needed. It is also concluded that coliforms with a low incidence in the caecum can translocate with the same efficiency as those with a high incidence.

12345 51 - 100 of 210
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf