oru.sePublications
Change search
Refine search result
12 1 - 50 of 63
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • 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.
  • 1.
    Ahlstrand, Erik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Hematology, Örebro University Hospital, Örebro, Sweden.
    Bäckman, Anders
    Örebro University, School of Medical Sciences. Clinical Research Centre, Örebro University Hospital, Örebro, Sweden.
    Persson, Lennart
    Örebro University Hospital. Department of Infectious diseases, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Tidefelt, Ulf
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Infectious diseases & Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Evaluation of a PCR method to determine the clinical significance of blood cultures with Staphylococcus epidermidis in patients with hematological malignancies2014In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 122, no 6, p. 539-544Article in journal (Refereed)
    Abstract [en]

    The aim was to investigate whether the detection and quantification of Staphylococcus epidermidis DNA in blood could distinguish S. epidermidis blood stream infections (BSIs) from blood culture contaminations in patients with hematological malignancies. The hld gene was chosen to identify S. epidermidis DNA and DNA in blood samples was detected by real-time PCR. Blood samples were obtained simultaneously with blood cultures positive for S. epidermidis (n = 30), during blood culture-negative episodes (n = 10) and episodes of bacteremia with other bacteria than S. epidermidis (n = 4) and from healthy blood donors (n = 10). In addition, DNA from S. epidermidis and a selection of other bacterial species were analyzed. Three different sets of criteria were used to classify episodes with positive blood cultures with S. epidermidis as BSIs or contaminations. All DNA preparations from S. epidermidis (n = 48) were hld-positive, but other bacterial species (n = 13) were negative. Sixteen (53%) of 30 blood samples from patients with blood cultures positive for S. epidermidis were hld-positive, but none of the controls. There was no clear association between a positive hld PCR and episodes interpreted as BSIs. In conclusion, hld PCR failed to distinguish S. epidermidis BSIs from blood culture contaminations in patients with hematological malignancies.

  • 2.
    Bjørkeng, Eva
    et al.
    Research Group for Host-Microbe Interactions, Department of Medical Biology, University of Tromsø, Tromsø, Norway.
    Rasmussen, Gunlög
    Örebro University, School of Medical Sciences.
    Sundsfjord, Arnfinn
    Research Group for Host-Microbe Interactions, Department of Medical Biology, University of Tromsø, Tromsø, Norway; Department of Microbiology and Infection Control, Reference Centre for Detection of Antimicrobial Resistance, University Hospital of North-Norway, Tromsø, Norway.
    Sjöberg, Lennart
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Hegstad, Kristin
    Research Group for Host-Microbe Interactions, Department of Medical Biology, University of Tromsø, Tromsø, Norway; Department of Microbiology and Infection Control, Reference Centre for Detection of Antimicrobial Resistance, University Hospital of North-Norway, Tromsø, Norway.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences. Department of Infectious Diseases and Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Clustering of polyclonal VanB-type vancomycin-resistant Enterococcus faecium in a low-endemic area was associated with CC17-genogroup strains harbouring transferable vanB2-Tn5382 and pRUM-like repA containing plasmids with axe-txe plasmid addiction systems2011In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 119, no 4-5, p. 247-258Article in journal (Refereed)
    Abstract [en]

    VanB-type vancomycin-resistant Enterococcus faecium isolates (n = 17) from 15 patients at the Örebro University hospital in Sweden during a span of 18 months was characterized. All patients had underlying disorders and received broad-spectrum antimicrobial therapy. Pulsed-field gel electrophoresis (PFGE) grouped 14 isolates in three PFGE types and three isolates in unique PFGE patterns. All isolates had multi-locus sequence types [ST17 (n = 5); ST18 (n = 3); ST125 (n = 7); ST262 (n = 1); ST460 (n = 1)] belonging to the successful hospital-adapted clonal complex 17 (CC17), harboured CC17-associated virulence genes, were vanB2-positive and expressed diverse vancomycin minimum inhibitory concentration (MICs; 8 to > 256 mg/L). Isolate 1 had a unique PFGE type and a chromosomal transferable vanB2-Tn5382 element. Interestingly, the other five PFGE types had Tn5382 located on plasmids containing pRUM-like repA and a plasmid addiction system (axe-txe) shown by co-hybridization analysis of PFGE-separated S1-nuclease digested total DNA. The resistance plasmids were mainly of 120-kb and supported intraspecies vanB transfer. Two strains were isolated from patient 6 and we observed a possible transfer of the vanB2-resistance genes from PFGE type III ST460 to a more successful PFGE type I ST125. This latter PFGE type I ST125 became the predominant type afterwards. Our observations support the notion that vanB-type vancomycin-resistant Enterococcus faecium can persist in a low-endemic area through successful clones and plasmids with stability functions in hospital patients with known risk factors.

  • 3.
    Boiko, Iryna
    et al.
    Ternopil Regional Clinical Dermatovenerologic Dispensary, Clinical Laboratory Department, Ternopil, Ukraine; Department of Functional and Laboratory Diagnostics, I. Horbachevsky Ternopil State Medical University, Ternopil, Ukraine; WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Krynsytska, Inna
    Department of Functional and Laboratory Diagnostics, I. Horbachevsky Ternopil State Medical University, Ternopil, Ukraine.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    High prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae and particularly Trichomonas vaginalis diagnosed using US FDA-approved Aptima molecular tests and evaluation of conventional routine diagnostic tests in Ternopil, Ukraine2019In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 127, no 9, p. 627-634Article in journal (Refereed)
    Abstract [en]

    Sexually transmitted infections (STIs) remain major public health problems globally. Appropriate laboratory diagnosis of STIs is rare in Ukraine. We investigated the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) using the US FDA-approved Aptima Combo 2 and Aptima TV assays and compared the results with the conventional routine diagnostic tests (CDTs) in Ukraine. Urogenital swabs from consecutive mostly symptomatic females (n = 296) and males (n = 159) were examined. The prevalences were as follows: 10% (n = 47) of TV, 5.3% (n = 24) of CT and 1.5% (n = 7) of NG. The specificity of some CDTs was high, for example, 100% for NG culture, TV IgG ELISA, CT IgM ELISA and CT microscopy, but lower for other CDTs, that is, from 44% to 99.8%. The sensitivity of all CDTs was suboptimal, that is, 71% (n = 5) for NG microscopy, 57% (n = 4) for NG culture, 53% (n = 8) for CT IgG ELISA, 33% (n = 1) for TV IgG ELISA, 28% (n = 13) for TV microscopy, 25% (n = 1) for CT IgA ELISA, 20% (n = 3) for CT IgM ELISA and 0% (n = 0) for CT microscopy. The prevalences of particularly TV and CT were high, but substantial also for NG, in Ternopil, Ukraine. The sensitivities of all CDTs were low, and widespread implementation of validated, quality-assured and cost-effective molecular diagnostic STI tests in Ukraine is imperative.

  • 4.
    Boiko, Iryna
    et al.
    WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 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 STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Krynytska, Inna
    Department of Functional and Laboratory Diagnostics, I. Horbachevsky Ternopil State Medical University, Ternopil, Ukraine.
    Bezkorovaina, Halyna
    Outpatient Department, Ternopil Regional Clinical Dermatovenerologic Dispensary, Ternopil, Ukraine.
    Frankenberg, Arkadii
    Dnipropetrovsk Regional Clinical Dermatovenerologic Dispensary, Dnipro, Ukraine.
    Onuchyna, Margarita
    Clinical Laboratory Department, Dnipropetrovsk Regional Clinical Dermatovenerologic Dispensary, Dnipro, Ukraine.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Antimicrobial susceptibility of Neisseria gonorrhoeae isolates and treatment of gonorrhoea patients in Ternopil and Dnipropetrovsk regions of Ukraine, 2013-20182019In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 127, no 7, p. 503-509Article in journal (Refereed)
    Abstract [en]

    Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major public health concern globally. However, recent gonococcal AMR data from Eastern Europe are extremely limited and no AMR data for strains spreading in Ukraine have ever been internationally published. We investigated the AMR of N. gonorrhoeae isolates in two regions of Ukraine (Ternopil 2013-2018, Dnipropetrovsk 2013-2014), and, where information was available, the treatment administered to the corresponding gonorrhoea patients. Determination of minimum inhibitory concentration (MIC) of eight antimicrobials was performed using Etest and resistance breakpoints from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) were applied. Overall, 9.3% of the examined 150 isolates were resistant to ciprofloxacin, 6.0% to tetracycline, 2.0% to azithromycin, and 0.7% to benzylpenicillin. No isolates were resistant to ceftriaxone, cefixime, spectinomycin, or gentamicin. However, one (0.7%) isolate showed a MIC value of 0.125 mg/L for both ceftriaxone and cefixime, i.e., bordering resistance. Eighty-eight (67.2%) of 131 patients were administered dual therapy (ceftriaxone 1 g plus doxycycline/clarithromycin/azithromycin/ofloxacin) and 22 (16.8%) ceftriaxone 1 g monotherapy. Worryingly, 21 (16.0%) patients received monotherapy with clarithromycin/doxycycline/azithromycin/ofloxacin/benzylpenicillin. In conclusion, the antimicrobial susceptibility of gonococcal strains spreading in Ternopil and Dnipropetrovsk, Ukraine during 2013-2018 was high. Low levels of resistance to ciprofloxacin, tetracycline, azithromycin, and benzylpenicillin were found, but no resistance to the internationally recommended ceftriaxone, cefixime, or spectinomycin. Ceftriaxone 1 g should remain as empiric first-line treatment, in dual therapy with azithromycin or doxycycline or in monotherapy. Continued and expanded gonococcal AMR surveillance in Ukraine is essential to monitor the susceptibility to particularly extended-spectrum cephalosporins, azithromycin and doxycycline.

  • 5.
    Demirel, Isak
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Säve, Susanne
    School of Natural Sciences, Linnaeus University, Kalmar, Sweden.
    Kruse, Robert
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Persson, Katarina
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Expression of suppressor of cytokine signalling 3 (SOCS3) in human bladder epithelial cells infected with uropathogenic Escherichia coli2013In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 121, no 2, p. 158-167Article in journal (Refereed)
    Abstract [en]

    Suppressor of cytokine signalling (SOCS) proteins inhibit pro-inflammatory signalling mediated by Janus-activated kinase (JAK)-signal transducer and activator of transcription (STAT) pathways. To evade the immune response some pathogens appear to modify the host SOCS proteins. Uropathogenic Escherichia coli (UPEC) are able to subvert the host response evoked by bladder epithelial cells, but the mechanisms are not fully understood. The objective of this study was to investigate whether UPEC can modify the host SOCS and STAT3 response. Real time RT-PCR studies demonstrated an increased SOCS1 and SOCS3 expression in the isolated human bladder epithelial cell lines (RT-4 and 5637) in response to cytokines. UPEC strain IA2 increased SOCS3, but not SOCS1, mRNA levels with a peak at 6 h after infection. The increase of SOCS3 was confirmed at the protein level by Western blotting. The UPEC strain IA2 caused a time-dependent decrease in the phosphorylation of STAT3. This study demonstrates that UPEC are able to affect SOCS3 and STAT3 signalling in human uroepithelial cells. The finding that UPEC are able to induce mediators involved in suppression of host cytokine signalling may help to elucidate how UPEC may circumvent the host response during urinary tract infection.

  • 6.
    Eriksson, Katarina
    et al.
    Department of Obstetrics and Gynecology, Ålands Centralsjukhus, Mariehamn, Finland; Department of Clinical and Experimental Medicine, Faculty of Health Science, Linköpings University, Linköping, Sweden.
    Adolfsson, Annsofie
    Department of Clinical and Experimental Medicine, Faculty of Health Science, Linköpings University, Linköping, Sweden; Department of Obstetrics and Gynecology, Kärnsjukhuset, Skövde, Sweden; School of Life Sciences, University of Skövde, Skövde, Sweden.
    Forsum, Urban
    Department of Clinical and Experimental Medicine, Faculty of Health Science, Linköpings University, Linköping, Sweden.
    Larsson, Per-Göran
    Department of Clinical and Experimental Medicine, Faculty of Health Science, Linköpings University, Linköping, Sweden; Department of Obstetrics and Gynecology, Kärnsjukhuset, Skövde, Sweden; School of Life Sciences, University of Skövde, Skövde, Sweden.
    The prevalence of BV in the population on the Åland Islands during a 15-year period2010In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 118, no 11, p. 903-908Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to describe the prevalence and age distribution of bacterial vaginosis (BV) during an observation period of 15 years in a population study with cross-sectional samples of adult women living on the Åland Islands. The Åland Islands form an archipelago in the Baltic Sea and are a province of Finland. Every fifth year, specific age groups in the adult female population are invited to participate in a screening program for early diagnosis of cervical cancer using a papanicolaou (PAP)-stained vaginal smear. Women in the age groups of 20, 25, 30, 35, 40, 45, 50, 55, and 60 years are called each year. BV diagnosis of the PAP-stained smears uses the classification according to Nugent. The PAP-stained smears from the screening program of cervical cancer 1993, 1998, 2003, and 2008 were used in this study. A total of 3456 slides were investigated and 271 women could be followed for the 15-year observation period. The prevalence of BV declined from 15.6% in 1993 to 8.6% in 2008. The highest prevalence occurred among the age groups of 35 and 50 years. Among the 271 women who could be followed for the 15-year observation period, two-third showed normal/intermediate flora and one-third were infected with BV at least once. As this is a cross-sectional population study spanning 15 years, the prevalence of BV in the female adult population of the Åland Islands can be estimated. The prevalence has declined between 1993 and 2008 from 15.6% to 8.6%.

  • 7.
    Foerster, Sunniva
    et al.
    WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
    Gustafsson, Tomas N.
    Department of Clinical Microbiology, Sunderby Research Unit, Umeå University, Umeå, Sweden.
    Rita Brochado, Anna
    European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
    Desilvestro, Valentino
    World Trade Institute (WTI), University of Bern, Bern, Switzerland.
    Typas, Athanasios
    European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine.
    The first wide-scale drug repurposing screen using the Prestwick Chemical Library (1200 bioactive molecules) against Neisseria gonorrhoeae identifies high in vitro activity of auranofin and many additional drugs2020In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463Article in journal (Refereed)
    Abstract [en]

    Treatment options for gonorrhoea are scarce. Drug repurposing of bioactive molecules approved for other conditions might therefore be of value. We developed a method for wide-scale, systematic drug repurposing screen to identify molecules with activity against Neisseria gonorrhoeae and screened the Prestwick Chemical Library (1200 FDA-approved drugs). As a proof-of-concept, we further examined one promising and interesting screening hit (auranofin; antirheumatic agent). Three WHO gonococcal reference strains (WHO F, O, P) were used for the Library screening. The strains were grown in presence of a fixed concentration of the library drugs in 384-well plates for 12 hours and the remaining bacterial respiration, to reflect growth, was then quantitatively measured using optical density (OD) 450 nm and a resazurin assay. The activity of auranofin was further examined using in vitro susceptibility testing (minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)) against genetically diverse antimicrobial-resistant N. gonorrhoeae strains and time-kill assays. Sixty-eight molecules significantly inhibited bacterial growth of WHO F, O and, P. Auranofin showed potent in vitro bactericidal activity (in MIC-, MBC-, and time-kill assays) against four WHO reference strains. No cross resistance between auranofin and any antimicrobial currently or previously used for gonorrhoea treatment was found when examining 51 selected antimicrobial-resistant gonococcal strains. In conclusion, this is the first wide-scale systematic screening effort for repurposing drugs for future treatment of gonorrhoea. Additional studies examining mechanism(s) of action, resistance development, in vivo anti-gonococcal activity, and pharmacokinetics/pharmacodynamics for gonococcal infections of auranofin and several other significant screening hits would be valuable.

  • 8. Friberg, Örjan
    et al.
    Källman, Jan
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    Olcén, P.
    Introduction: [to prevention of surgical site infections in cardiac surgery]2007In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 115, no 9, p. 987-988Article in journal (Refereed)
  • 9.
    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.

  • 10.
    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.

  • 11.
    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.

  • 12.
    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.

  • 13.
    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.

  • 14.
    Hahn-Strömberg, Victoria
    et al.
    Örebro University, School of Health and Medical Sciences.
    Edvardsson, Henrik
    Bodin, Lennart
    Franzén, Lennart
    Disturbed expression of E-cadherin, beta-catenin and tight junction proteins in colon carcinoma is unrelated to growth pattern and genetic polymorphisms2008In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 116, no 4, p. 253-262Article in journal (Refereed)
    Abstract [en]

    Adhesion proteins are responsible for the structural integrity of epithelial tissue and in tumors this integrity is often lost, resulting in a disorganization of the tissue. In the present study the complexity of the invasive front of colon carcinomas was correlated with cell adhesion protein expression and with polymorphisms in their genes. A complexity index was constructed from 32 colon carcinomas using computer-assisted morphometry estimating fractal dimension and tumor cell clusters followed by tree analysis. Immunohistochemical staining of beta-catenin, E-cadherin, occludin and claudin 2 was used for assessment of protein expression. Genetic screening of tissue from the tumor invasion front with laser microdissection was performed using SSCP and DNA sequencing. Adhesion protein distribution was significantly disturbed in most carcinomas. A single mutation in the gene of beta-catenin was found but there was no correlation between protein expression and genetic polymorphism. Nor was there any correlation between the complexity of the invasive border and protein distribution or genetic alterations. The results indicate that the complexity of colon carcinoma invasion is not dependent on genetic derangements in the genes of adhesion proteins or the protein distribution. Rather, aberrations in the function of other proteins related to the adhesive proteins could be responsible.

  • 15.
    Hahn-Strömberg, Victoria
    et al.
    Örebro University, School of Health and Medical Sciences.
    Edvardsson, Henrik
    Bodin, Lennart
    Franzén, Lennart
    Tumor volume of colon carcinoma is related to the invasive pattern but not to the expression of cell adhesion proteins2009In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 117, no 3, p. 205-211Article in journal (Refereed)
    Abstract [en]

    Tumor volume increases during growth and due to tumor progression various mutations appear that may cause phenotypic changes. The invasive pattern may thus be affected resulting in a more disorganized growth. This phenomenon might be due to mutations in the genome of the adhesion proteins, which are responsible for the structural integrity of epithelial tissue. Tumor volume was assessed in whole mount sections of 33 colon carcinomas using Cavalieri's principle. Images from the entire invasive border were captured and used for calculating the irregularity of the border (Complexity Index). The expression of the adhesion proteins E-cadherin, beta-catenin, Claudin 2 and Occludin was assessed after immunohistochemical staining of two randomly selected areas of the invasive front of the tumor. Statistical significance for differences in volume was obtained for tumor Complexity Index, tumor stage (pT) and lymph node status (pN). Expression of adhesion proteins was significantly perturbed in the tumors compared with normal mucosa but only infrequently correlated to tumor differentiation or invasive pattern. The results show that when tumor volume increases the invasive pattern becomes more irregular which is compatible with tumor progression. A direct contribution of adhesion protein derangement to this process appears to be insignificant.

  • 16.
    Hamad, Tarza
    et al.
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University, Örebro, Sweden; Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Hellmark, Bengt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Clinical Microbiology, Örebro University, Örebro, Sweden.
    Nilsdotter-Augustinsson, Åsa
    Department of Infectious Diseases, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Laboratory Medicine, Clinical Microbiology, Örebro University, Örebro, Sweden.
    Antibiotic susceptibility among Staphylococcus epidermidis isolated from prosthetic joint infections, with focus on doxycycline2015In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 123, no 12, p. 1055-1060Article in journal (Refereed)
    Abstract [en]

    In recent years, coagulase-negative staphylococci such as Staphylococcus epidermidis have gained importance as nosocomial pathogens, especially in immunocompromised patients and prosthetic joint infections (PJIs). These infections are often long lasting and difficult to treat due to the production of bacterial biofilm and the transformation of the bacteria into a stationary growth phase. Rifampicin is able to penetrate the biofilm, but to reduce the risk of development of rifampicin resistance it should be used in combination with an additional antibiotic. In this study we used Etest to investigate the antimicrobial susceptibility of 134 clinical isolates of S.epidermidis obtained from PJIs to six oral antibiotics: doxycycline, rifampicin, linezolid, fusidic acid, clindamycin, and ciprofloxacin. We also performed synergy testing on doxycycline in combination with each of the remaining antibiotics. Ninety-three (69%) of the 134 isolates were susceptible to doxycycline, 94/134 (70%) to rifampicin, 56/134 (42%) to clindamycin, 25/134 (19%) to ciprofloxacin, 81/134 (60%) to fusidic acid, and 100% to linezolid. Thirty-two (80%) of the 40 isolates not fully susceptible to rifampicin were susceptible to doxycycline. Doxycycline in combination with each of the other investigated antibiotics exerted an additive effect on nearly half of the isolates, with the exception of clindamycin, which displayed an even higher percentage of additive effect (69%). To conclude, as the majority of the S.epidermidis isolates were susceptible to doxycycline, this antimicrobial agent may provide a potential alternative for combination therapy together with rifampicin.

  • 17.
    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)
  • 18.
    Hedlund, Linda
    et al.
    Örebro University Hospital, Örebro, Sweden.
    Hellmark, Bengt
    Örebro University Hospital.
    Söderquist, Bo
    Örebro University Hospital.
    Presence of arginine catabolic mobile element among community-acquired meticillin-resistant staphylococcus aureus is linked to a specific genetic background2013In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 121, no 3, p. 221-225Article in journal (Refereed)
    Abstract [en]

    The prevalence of arginine catabolic mobile element (ACME) among diverse and heterogeneous community-associated methicillin-resistant Staphylococcus aureus community-associated Methicillin-resistant S. aureus (CA-MRSA) (n = 114) in a low-endemic area, i.e. Sweden, was investigated. Among the CA-MRSA, represented by 47 different spa types, ACME was only found in 10 isolates with a common genetic background [t008, SCCmec type IV, Panton-Valentine leukocidin (PVL) positive, and indistinguishable or closely related pulsed-field gel electrophoresis (PFGE)-patterns] corresponding to USA300. This strain does not seem to be established in our area as most of the patients contracted the CA-MRSA abroad. Presence of ACME does not seem to be associated with colonization, long-term carriership, or intra-familiar transmission in a higher extent than CA-MRSA in general.

  • 19.
    Hussain, Rashida
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Oliynyk, Igor
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Roomans, Godfried M.
    Örebro University, School of Medicine, Örebro University, Sweden.
    Björkqvist, Maria
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Department of Pediatrics, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Modulation of ENaC, CFTR, and iNOS expression in bronchial epithelial cells after stimulation with Staphylococcus epidermidis (94B080) and Staphylococcus aureus (90B083)2013In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 121, no 9, p. 814-826Article in journal (Refereed)
    Abstract [en]

    Bacteria affect the respiratory epithelium, which is covered by airway surface liquid (ASL) and mucus. Ion concentrations in the ASL are determined by the cystic fibrosis transmembrane conductance regulator (CFTR) and the epithelial Na+ channel (ENaC). Neonatal sepsis is a major risk factor for subsequent pulmonary disease in preterm newborns. Predominating are coagulase-negative staphylococci (e.g., Staphylococccus epidermidis and Staphylococccus aureus). The aim of this study was to investigate modulation of CFTR, ENaC, mucins, proinflammatory cytokines, and inducible nitric oxide synthase (iNOS) in respiratory epithelial cells after S. epidermidis 94B080 and S. aureus 90B083 exposure. Bronchial epithelial cells were incubated with S. epidermidis 94B080 and S. aureus 90B083 (neonatal blood isolates) for 1-36h. Expression of CFTR, ENaC, iNOS, and mucins was analyzed by real-time PCR and Western blotting. Release of cytokines was analyzed by ELISA, and production of NO by the Griess assay. Expression of CFTR significantly decreased after 36h incubation with S. epidermidis and more prominently with S. aureus, whereas S. epidermidis caused a significant increase in the expression of - and -ENaC. Expression of iNOS increased, but NO was not detected. Both staphylococci caused a decrease in the intracellular Ca2+ concentration. S. aureus induced increased secretion of IL-6, IL-8, and transforming nuclear factor (TNF)- in a time-dependent manner as compared with S. epidermidis. In conclusion, expression of ENaC, CFTR, and iNOS is modulated by exposure to S. aureus 90B083 and S. epidermidis 94B080. S. aureus is more potent in causing release of IL-6, IL-8, and TNF- by bronchial epithelial cells as compared with S. epidermidis. The mRNA expression for the mucus proteins MUC2, MUC5AC, and MUC5B could not be measured, neither in the presence nor in the absence of bacteria.

  • 20.
    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.

  • 21.
    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.

  • 22.
    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.

  • 23.
    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.

  • 24.
    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.

  • 25.
    Jönsson, Agnez
    et al.
    WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Foerster, Sunniva
    WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden; Institute for Infectious Diseases, University of Bern, Bern, Switzerland; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Hamasuna, Ryoichi
    Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Lindberg, Magnus
    Örebro University, School of Medical Sciences. Department of Dermatovenerology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Jensen, Jörgen Skov
    Department of Microbiology and Infection Control, Sexually Transmitted Infections, Research and Development, Statens Serum Institut, Copenhagen, Denmark.
    Ohnishi, Makoto
    Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan.
    Unemo, Magnus
    WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    In vitro activity and time-kill curve analysis of sitafloxacin against a global panel of antimicrobial-resistant and multidrug-resistant Neisseria gonorrhoeae isolates2018In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 126, no 1, p. 29-37Article in journal (Refereed)
    Abstract [en]

    Treatment of gonorrhoea is a challenge worldwide because of emergence of resistance in N. gonorrhoeae to all therapeutic antimicrobials available and novel antimicrobials are imperative. The newer-generation fluoroquinolone sitafloxacin, mostly used for respiratory tract infections in Japan, can have a high in vitro activity against gonococci. However, only a limited number of recent antimicrobial-resistant isolates from Japan have been examined. We investigated the sitafloxacin activity against a global gonococcal panel (250 isolates cultured in 1991-2013), including multidrug-resistant geographically, temporally and genetically diverse isolates, and performed time-kill curve analysis for sitafloxacin. The susceptibility to sitafloxacin (agar dilution) and seven additional therapeutic antimicrobials (Etest) was determined. Sitafloxacin was rapidly bactericidal, and the MIC range, MIC50 and MIC90 was ≤0.001-1, 0.125 and 0.25 mg/L, respectively. There was a high correlation between the MICs of sitafloxacin and ciprofloxacin; however, the MIC50 and MIC90 of sitafloxacin were 6-fold and >6-fold lower, respectively. Sitafloxacin might be an option for particularly dual antimicrobial therapy of gonorrhoea and for cases with ceftriaxone resistance or allergy. However, further in vitro and particularly in vivo evaluations of potential resistance, pharmacokinetics/pharmacodynamics and ideal dosing for gonorrhoea, as well as performance of randomized controlled clinical, trials are crucial.

  • 26.
    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.

  • 27.
    Karlsson, Christina
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Helenius, Gisela
    Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Fernandes, Oswaldo
    Department of Thoracic Surgery, Örebro University Hospital, Örebro, Sweden.
    Karlsson, Mats G.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Thoracic Surgery, Örebro University Hospital, Örebro, Sweden.
    Oestrogen receptor ss in NSCLC: prevalence, proliferative influence, prognostic impact and smoking2012In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 120, no 6, p. 451-458Article in journal (Refereed)
    Abstract [en]

    In non-small-cell lung carcinoma (NSCLC) there are gender differences. The female gender is associated with more adenocarcinomas (ADCA), among both smokers and non-smokers compared to men. Women with NSCLC have a better prognosis compared to men, regardless of other factors. A possible role for oestrogen receptor (ER) signalling has been proposed. The role for ER beta in NSCLC is still not clear, especially concerning the impact of smoking. In a material of NSCLC (n = 262), ER beta and cyclins A1 and A2 were studied by immunohistochemistry on formalin-fixed paraffin embedded tissue. In 137 of those cases, frozen material was available, on which expression analysis of ESR2 (ER beta) and cyclin A1 were performed. Data were correlated to histology, gender, smoking habits, stage and clinical outcome. ER beta was expressed in 86% of the cases. ER beta was most frequently expressed in Stage I ADCAs, especially in male subjects. A correlation between ER beta expression and cyclins was observed in ADCA, also with a male predominance. ER beta transcripts had a positive prognostic impact in ADCA. ER beta transcripts were increased in NSCLC among smokers compared to non-smokers. In conclusion, our data support a role for ER beta in lung ADCAs, proposing a role for ER beta in lungcarcinogenesis, especially among smokers.

  • 28.
    Karlsson, Mats G.
    et al.
    Departments of Pathology and Otorhionolaryngology, Medical Center Hospital, Örebro, Sweden.
    Davidsson, Åke
    Departments of Pathology and Otorhionolaryngology, Medical Center Hospital, Örebro, Sweden.
    Hellquist, Henrik B.
    Department of Pathology II, University Hospital, Linköping, Sweden.
    Increase in CD4+ and CD45RO+ memory T cells in the nasal mucosa of allergic patients1994In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 102, no 10, p. 753-758Article in journal (Refereed)
    Abstract [en]

    By means of immunocytochemistry we have investigated subsets of T lymphocytes in frozen sections of nasal mucosa from patients with seasonal allergic rhinitis and healthy control persons. All participants were subjected to time-course provocation during the non-pollen season, and samples were taken during provocation as well as during the natural pollen season. Computerized image analysis was applied for evaluation of the immunostained lymphocytes. CD45RO+ memory T cells outnumbered the remaining leukocyte populations in the mucosa of both allergic patients and controls on all occasions. During the repeat provocation there was no difference in numerical values, with respect to any of the five leukocyte subpopulations studied (CD4, CD8, CD25, CD45RA and CD45RO), between patients and controls. However, during continuous exposure in the pollen season a significant increase in CD4+ cells was observed in allergic patients compared to before provocation (p < 0.05). No changes were observed with respect to CD8+ and CD25+ cells. Similarly, an increase in CD45RO+ memory was found in allergic patients during the pollen season compared to the non-pollen season (p < 0.02). This latter finding was, however, only evident in the patients who did not use nasal corticosteroids. Hence the present investigation has demonstrated an allergen-induced increase in CD4+ and CD45RO+ memory T cells in the mucosa of allergic patients during the pollen season. These events may constitute a cellular basis for local continuous production of certain cytokines, particularly interleukin-4, which is essential for IgE synthesis.

  • 29.
    Kelly, Anne
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Jacobsson, Susanne
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Hussain, Shahida
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Olcen, Per
    Mölling, Paula
    Örebro University Hospital.
    Gene variability and degree of expression of vaccine candidate factor H binding protein in clinical isolates of Neisseria meningitidis2013In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 121, no 1, p. 56-63Article in journal (Refereed)
    Abstract [en]

    The factor H binding protein (fHbp) is currently being evaluated in clinical trials as a vaccine candidate for a meningococcal group B vaccine. We have previously described the prevalence and sequence variation of fHbp (Jacobsson et al., 2009) and here we investigate the expression of the antigen. The present study includes isolates from carriers (n = 62) and patients with invasive Neisseria meningitidis infections (n = 146), of which 62 had a fatal outcome. Among the invasive isolates from patients with fatal and non-fatal infections fHbp allele 1 was most common (42% and 29% respectively), but it was only identified in 3% of the carrier isolates, where allele 16 was most frequent (13%). The Fluorescence-activated cell sorting analysis identified fHbp expression in all except seven isolates and further analysis by Western blot showed that five of these seven samples were indeed negative using a polyclonal anti-fHbp serum. The negative isolates belonged to serogroup B fHbp allele 24, Y allele 104, and W-135 allele 16 (all invasive). Two were non-serogroupable carrier isolates (allele 21 and 101). An interesting finding is that isolates from invasive infections with fatal outcome had lower expression of fHbp or lower affinity for the fHbp antibody compared to isolates from non-fatal invasive infections and carriers.

  • 30.
    Khairullin, Rafil
    et al.
    Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Russia; The State Research Center of Dermatology, Venereology and Cosmetology of The Russian Ministry of Health (SRCDVC), Moscow, Russia.
    Vorobyev, Denis
    The State Research Center of Dermatology, Venereology and Cosmetology of The Russian Ministry of Health (SRCDVC), Moscow, Russia.
    Obukhov, Andrey
    Tuvan Republican Skin and Venereal Diseases Dispensary, Tuva, Russia.
    Kuular, Ural-Herel
    Tuvan Republican Skin and Venereal Diseases Dispensary, Tuva, Russia.
    Kubanova, Anna
    The State Research Center of Dermatology, Venereology and Cosmetology of The Russian Ministry of Health (SRCDVC), Moscow, Russia.
    Kubanov, Alexey
    The State Research Center of Dermatology, Venereology and Cosmetology of The Russian Ministry of Health (SRCDVC), Moscow, Russia.
    Unemo, Magnus
    Örebro University, School of Health Sciences. WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Syphilis epidemiology in 1994-2013, molecular epidemiological strain typing and determination of macrolide resistance in Treponema pallidum in 2013-2014 in Tuva Republic, Russia2016In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 124, no 7, p. 595-602Article in journal (Refereed)
    Abstract [en]

    The incidence of syphilis in the Tuva Republic (geographical centre of Asia), Russia has been exceedingly high historically. No detailed examinations and no molecular investigations of Treponema pallidum strains transmitted in the Tuva Republic, or in general, in Russia, were published internationally. We examined the syphilis epidemiology in 1994-2013, and the molecular epidemiology and macrolide resistance in T. pallidum strains in 2013-2014 in the Tuva Republic. Among 95 mainly primary or secondary syphilis patients, the arp, tpr, tp0548 and 23S rRNA genes in 85 polA gene-positive genital ulcer specimens were characterized. The syphilis incidence in Tuva Republic peaked in 1998 (1562), however declined to 177 in 2013. Among the 70 (82%) completely genotyped specimens, six molecular strain types were found. Strain type 14d/f accounted for 91%, but also 14c/f, 14d/g, 14b/f, 14i/f, 9d/f, and 4d/f were identified. Two (2.4%) specimens contained the 23S rRNA A2058G macrolide resistance mutation. This is the first internationally published typing study regarding T. pallidum in Russia, performed in the Tuva Republic with the highest syphilis incidence in Russia. The two molecular strain types 4d/f and 9d/f have previously been described only in Eastern and Northern China and for the first time, macrolide-resistant syphilis was described in Russia.

  • 31. Lindbäck, Emma
    et al.
    Unemo, Magnus
    Örebro University, Department of Clinical Medicine.
    Akhras, Michael
    Gharizadeh, Baback
    Fredlund, Hans
    Örebro University, Department of Clinical Medicine.
    Pourmand, Nader
    Wretlind, Bengt
    Pyrosequencing of the DNA gyrase gene in Neisseria species: effective indicator of ciprofloxacin resistance in Neisseria gonorrhoeae2006In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 114, no 12, p. 837-841Article in journal (Refereed)
    Abstract [en]

    The quinolone resistance determining region (QRDR) of the gyrA gene in ciprofloxacin-susceptible strains (n=53) and strains of Neisseria spp. with reduced susceptibility (n=70) was determined by the pyrosequencing method. Results showed that the QRDR of the gyrA gene is an effective molecular indicator of resistance to ciprofloxacin in Neisseria gonorrhoeae, and presumably in Neisseria meningitidis, but not in all other Neisseria spp. This sequence was not unique for N. gonorrhoeae and seems unsuitable for species verification of N. gonorrhoeae. However, whether it is also possible to use this region for verification depends on the specificity of the primary screening method used.

  • 32.
    Lindh, Ingrid
    et al.
    Örebro University, School of Science and Technology.
    Kalbina, Irina
    Örebro University, School of Science and Technology.
    Hedberg, Sara Thulin
    Scherbak, Nikolai
    Örebro University, School of Science and Technology.
    Sävenstrand, Helena
    Örebro University, School of Science and Technology.
    Bråve, Andreas
    Hinkula, Jorma
    Strid, Åke
    Örebro University, School of Science and Technology.
    Andersson, Sören
    Örebro University, School of Science and Technology.
    Feeding of mice with Arabidopsis thaliana expressing the HIV-1 subtype C p24 antigen gives rise to systemic immune responses2008In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 116, no 11, p. 985-994Article in journal (Refereed)
    Abstract [en]

    Development of transgenic edible plants, to be used as production, storage and delivery systems for recombinant vaccine antigens, is a promising strategy to obtain cost effective vaccines against infectious diseases, not the least for use in developing countries. Therefore, we used Agrobacterium tumefaciens-mediated gene transfer to introduce the p24 gag gene encoding the nucleocapsid protein from HIV-1 subtype C into the Arabidopsis thaliana plant genome. Eighteen plant lines were confirmed positive for the p24 gene by PCR, four of these lines showed an apparent homozygous phenotype when grown on selective medium and these lines also showed transcription of the p24 gene into its corresponding mRNA. The mRNA in all four cases generated the p24 protein in plants, as verified by western blot analysis. The plants were shown to contain between 0.2 µg and 0.5 µg p24 protein per g of fresh tissue. Analysis of the localisation of the p24 protein showed that stem tissue contained the largest amount of protein, more than twice as much as leaf tissue, whereas no p24 protein was detected in roots. By using Southern blotting, we found that 4, 2-3, 2 and 1 T-DNA insertion events took place in the four lines 1, 2, 7, and 10, respectively. The genetic insertions of line 1 were stable from the T1 to the T4 generation and gave rise to the p24 protein in all cases, as verified by western blotting. In mice fed with fresh transgenic A. thaliana (line 10), anti-gag IgG was obtained in serum after a booster injection with recombinant p37Gag. No immune response was observed after equal booster injection of untreated mice or mice fed with A. thaliana WT plants.

  • 33. Lundbäck, David
    et al.
    Fredlund, Hans
    Örebro University, Department of Clinical Medicine.
    Berglund, Torsten
    Wretlind, Bengt
    Unemo, Magnus
    Örebro University, Department of Clinical Medicine.
    Molecular epidemiology of Neisseria gonorrhoeae- identification of the first presumed Swedish transmission chain of an azithromycin-resistant strain2006In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 114, no 1, p. 67-71Article in journal (Refereed)
    Abstract [en]

    In the present study, 10 azithromycin-resistant Neisseria gonorrhoeae isolates from 6 Swedish male patients in 2004, 3 sporadic Swedish azithromycin-resistant N. gonorrhoeae isolates from recent years and one Swedish N. gonorrhoeae isolate from 2003 that was susceptible to azithromycin but assigned the same serological variant (serovar), i.e. IB-37, as the isolates from 2004 were included. The isolates were characterized phenotypically using antibiograms and serovar determination and genetically with pulsed-field gel electrophoresis (PFGE), entire porB gene sequencing and N. gonorrhoeae multiantigen sequence typing (NG-MAST). The epidemiological information and the results of the thorough phenotypic characterisation and genetic characterisation identified the first presumed domestic transmission of one azithromycin-resistant N. gonorrhoeae strain in Sweden in 2004. This stresses the need for continuous surveillance of the antibiotic susceptibility of N. gonorrhoeae in order to identify emergence of new resistance, monitor the changing patterns of the susceptibility, and be able to update treatment recommendations on a regular basis.

  • 34.
    Månsson, Emeli
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Centre for Clinical Research, Uppsala University, Uppsala, Sweden; County Hospital, Västerås, Sweden.
    Hellmark, Bengt
    Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Sundqvist, Martin
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden.
    Sequence types of Staphylococcus epidermidis associated with prosthetic joint infections are not present in the laminar airflow during prosthetic joint surgery2015In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 123, no 7, p. 589-595Article in journal (Refereed)
    Abstract [en]

    Molecular characterization of Staphylococcus epidermidis isolates from prosthetic joint infections (PJIs) has demonstrated a predominance of healthcare-associated multi-drug resistant sequence types (ST2 and ST215). How, and when, patients acquire these nosocomial STs is not known. The aim was to investigate if sequence types of S. epidermidis associated with PJIs are found in the air during prosthetic joint surgery. Air sampling was undertaken during 17 hip/knee arthroplasties performed in operating theaters equipped with mobile laminar airflow units in a 500-bed hospital in central Sweden. Species identification was performed using MALDI-TOF MS and 16S rRNA gene analysis. Isolates identified as S. epidermidis were further characterized by MLST and antibiotic susceptibility testing. Seven hundred and thirty-five isolates were available for species identification. Micrococcus spp. (n = 303) and coagulase-negative staphylococci (n = 217) constituted the majority of the isolates. Thirty-two isolates of S. epidermidis were found. S. epidermidis isolates demonstrated a high level of allelic diversity with 18 different sequence types, but neither ST2 nor ST215 was found. Commensals with low pathogenic potential dominated among the airborne microorganisms in the operating field during prosthetic joint surgery. Nosocomial sequence types of S. epidermidis associated with PJIs were not found, and other routes of inoculation are therefore of interest in future studies.

  • 35.
    Månsson, Emeli
    et al.
    Örebro University, School of Medical Sciences. Centre for Clinical Research, Hospital of Västmanland, Region Västmanland, Västerås,Sweden; Centre for Clinical Research, Hospital of Västmanland, Uppsala University, Västerås, Sweden.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Clinical Microbiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Nilsdotter-Augustinsson, Åsa
    Department of Infectious Diseases, Department of Clinical and Experimental Medicine, Linköping University, Norrköping, Sweden.
    Särndahl, Eva
    Örebro University, School of Medical Sciences.
    Demirel, Isak
    Örebro University, School of Medical Sciences.
    Staphylococcus epidermidis from prosthetic joint infections induces lower IL-1 release from human neutrophils than isolates from normal flora2018In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 126, no 8, p. 678-684Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to test the hypothesis that Staphylococcus epidermidis isolated from prosthetic joint infections (PJIs) differs from S.epidermidis isolated from normal flora in terms of its capacity to induce activation of caspase-1 and release of IL-1 in human neutrophils. The amount of active caspase-1 was determined over 6h by detecting Ac-YVAD-AMC fluorescence in human neutrophils incubated with S.epidermidis isolates from PJIs (ST2) or normal flora. The amount of IL-1 was detected by ELISA in neutrophil supernatants after 6h of incubation. Mean IL-1 release was lower after incubation with S.epidermidis from PJIs compared to isolates from normal flora, but no statistically significant difference was found in active caspase-1. Substantial inter-individual differences in both active caspase-1 and IL-1 were noted. These results suggest that evasion of innate immune response, measured as reduced capacity to induce release of IL-1 from human neutrophils, might be involved in the predominance of ST2 in S.epidermidis PJIs, but that other microbe-related factors are probably also important.

  • 36.
    Nestor, David
    et al.
    Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University Hospital, Örebro University, Örebro, Sweden; School of Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Malmvall, Bo-Eric
    Futurum - Academy for Health and Care, Jönköping County Council, Jönköping, Sweden.
    Masonda, Yohana Paul
    Department of Laboratory Medicine, Nkinga Referral Hospital Laboratory, Nkinga, Tanzania.
    Msafiri, John
    Department of Laboratory Medicine, Nkinga Referral Hospital Laboratory, Nkinga, Tanzania.
    Sundqvist, Martin
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Detection of extended-spectrum beta-lactamase production in Enterobacteriales from patients with suspected urinary tract infections, Tabora region, Rural Tanzania2018In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 126, no 8, p. 700-702Article in journal (Refereed)
  • 37.
    Norén, Torbjörn
    et al.
    Örebro University Hospital. Örebro University, School of Medical Sciences. Dept Lab Med, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    Örebro University Hospital. Dept Lab Med, Örebro University Hospital, Örebro, Sweden.
    Magnusson, Cecilia
    Dept Infect Control, Ryhov Cty Hosp, Jönköping, Sweden; Dept Infect Dis, Ryhov Cty Hosp, Jönköping, Sweden.
    Eiserman, Maud
    Ryhov Cty Hosp, Jönköping, Sweden.
    Matussek, Andreas
    Div Med Serv, Dept Lab Med, Ryhov Cty Hosp, Jönköping, Sweden.
    Evaluation of the rapid loop-mediated isothermal amplification assay Illumigene for diagnosis of Clostridium difficile in an outbreak situation2014In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 122, no 2, p. 155-160Article in journal (Refereed)
    Abstract [en]

    An outbreak of Clostridium difficile infection (CDI) at Hoglandet Hospital Eksjo in southern Sweden in 2011 was mainly due to a multidrug-resistant PCR ribotype 046 (30% of all samples). Diagnostics used routinely was the Vidas CDAB assay, but to control the outbreak the rapid loop-mediated isothermal amplification (LAMP) assay Illumigene was introduced and both techniques were compared to Toxigenic culture (TC) prospectively. The LAMP assay had a superior sensitivity, that is, 98% compared to 79% for the Vidas CDAB assay. Most importantly, the mean turn-around-time from collecting sample to result was reduced from 59h to 2h enabling early isolation of patients and effective hygiene precautions. This may potentially decrease the morbidity and nosocomial transmissions of C. difficile.

  • 38.
    Oliynyk, Igor
    et al.
    Örebro University, School of Health and Medical Sciences. Örebro University Hospital, Örebro, Sweden; Dept Med Cell Biol, Uppsala Univ, Uppsala, Sweden.
    Varelogianni, Georgia
    Örebro University, School of Health and Medical Sciences. Örebro University Hospital, Örebro, Sweden; Dept Med Cell Biol, Uppsala Univ, Uppsala, Sweden.
    Roomans, Godfried M.
    Örebro University, School of Health and Medical Sciences. Örebro University Hospital, Örebro, Sweden.
    Johannesson, Marie
    Örebro University Hospital, Örebro , Sweden; Department of Paediatrics and Child Health, University of Otago, Wellington Campus, Wellington, New Zealand.
    Effect of duramycin on chloride transport and intracellular calcium concentration in cystic fibrosis and non-cystic fibrosis epithelia2010In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 118, no 12, p. 982-990Article in journal (Refereed)
    Abstract [en]

    The lantibiotic duramycin (Moli1901, Lancovutide) has been suggested as a drug of choice in the treatment for cystic fibrosis (CF). It has been proposed that duramycin may stimulate chloride secretion through Ca2+-activated Cl channels (CaCC). We investigated whether duramycin exhibited any effect on Cl efflux and intracellular Ca2+ concentration ([Ca2+]i) in CF and non-CF epithelial cells. Duramycin did stimulate Cl efflux from CF bronchial epithelial cells (CFBE) in a narrow concentration range (around 1 μM). However, 100 and 250 μM of duramycin inhibited Cl efflux from CFBE cells. An inhibitor of the CF transmembrane conductance regulator (CFTRinh-172) and a blocker of the capacitative Ca2+ entry, gadolinium chloride, inhibited the duramycin-induced Cl efflux. No effect on Cl efflux was observed in non-CF human bronchial epithelial cells (16HBE), human airway submucosal gland cell line, human pancreatic epithelial cells, CF airway submucosal gland epithelial cells, and CF pancreatic cells. The [Ca2+]i was increased by 3 μM duramycin in 16HBE cells, but decreased after 1, and 3 μM of duramycin in CFBE cells. The results suggest that the mechanism responsible for the stimulation of Cl efflux by duramycin is mainly related to unspecific changes of the cell membrane or its components rather than to effects on CaCC.

  • 39.
    Olsen, Birgitta
    et al.
    Örebro University, School of Health and Medical Sciences.
    Hadad, Ronza
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences.
    The Neisseria gonorrhoeae population in Sweden during 2005: phenotypes, genotypes and antibiotic resistance2008In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 116, no 3, p. 181-189Article in journal (Refereed)
    Abstract [en]

    In Sweden, the gonorrhoea incidence has significantly increased since an all-time low in 1996. We aimed to phenotypically and genotypically characterise N. gonorrhoeae isolates (nΩ180) transmitted in Sweden during 2005. All isolates were susceptible to cefixime, ceftriaxone, and spectinomycin. However, 2%, 50% and 75% displayed intermediate susceptibility or resistance to azithromycin, ciprofloxacin and ampicillin, respectively. The isolates were assigned to 28 different serovars using Genetic Systems monoclonal antibodies (Mabs) (discriminatory index, 91.0%) and 46 different serovars using Pharmacia Mabs (index, 94.4%). Furthermore, they displayed 95 porB sequences (index, 97.8%) and 95 N. gonorrhoeae multiantigen sequence typing (NG-MAST) sequence types (STs) (index, 98.0%). 51 (54%) of these STs have not been previously described. 14 ST clusters, comprising between 3 and 15 isolates, were identified that indicate the existence of several transmission chains. The high number of unique STs (nΩ63) may be associated with import of strains from abroad, local emergence of new STs, incomplete epidemiological surveillance, and/or suboptimal diagnostics, including contact tracing. Overall, the Swedish N. gonorrhoeae population was remarkably diversified. Comprehensive knowledge regarding transmission, phenotypes (including antibiotic resistance), but also in many cases highly discriminative and precise genotypic characteristics of the N. gonorrhoeae strains circulating in our societies, is crucial.

  • 40. Olsson, Emma
    et al.
    Friberg, Örjan
    Venizelos, Nikolaos
    Örebro University, School of Health and Medical Sciences.
    Koskela, Anita
    Örebro University, School of Health and Medical Sciences.
    Källman, Jan
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    Coagulase-negative staphylococci isolated from sternal wound infections after cardiac surgery: attachment to and accumulation on sternal fixation stainless steel wires2007In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 115, no 2, p. 142-151Article in journal (Refereed)
    Abstract [en]

    Sternal wound infection (SWI) is a serious complication after cardiac surgery. Coagulase-negative staphylococci (CoNS) have been found to be the most common pathogen involved in this postoperative infection related to implanted foreign materials, i.e. sternal fixation wires made from stainless steel. In this study a rapid and simple assay was developed for studying attachment and accumulation of CoNS on stainless steel wires in vitro using [(3)H] thymidine. The method showed a potential to detect differences in the dynamics of the adherence patterns among various CoNS isolates. However, no differences in attachment and accumulation were found between isolates causing deep SWI after cardiac surgery and contaminant isolates. In addition, there were no differences in the distribution of the ica operon between the two groups, as determined by polymerase chain reaction (PCR). Nevertheless, the ability to produce biofilm was found to be present significantly more frequently among SWI isolates than among contaminants.

  • 41.
    Olsson, Jan
    et al.
    Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Davidsson, Sabina
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Molling, Paula
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Andersson, Swen-Olov
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Andrén, Ove
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Sellin, Mats
    Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Elgh, Fredrik
    Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Antibiotic susceptibility in prostate-derived Propionibacterium acnes isolates2012In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 120, no 10, p. 778-785Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to determine antibiotic susceptibility of Propionibacterium acnes isolates from prostate. Prostate-derived P. acnes isolates (n = 24, Umea & Orebro, Sweden, 20072010) and a panel of control strains (n = 25, Sweden) collected from skin and deep infections were assessed for resistance to penicillin G, piperacillintazobactam, imipenem, gentamicin, azithromycin, erythromycin, vancomycin, ciprofloxacin, moxifloxacin, tetracycline, tigecycline, fusidic acid, clindamycin, rifampicin, linezolid, daptomycin, trimethoprimsulfamethoxazole, and metronidazole. In addition, the isolates were tested for inducible clindamycin resistance. All prostate derived P. acnes isolates displayed wild-type distribution of MIC-values, without evidence of acquired resistance. In the reference panel, 5 of 25 isolates had acquired macrolide resistance with cross-resistance to azithromycin, clindamycin, and erythromycin. In addition, one of these isolates was resistant to tetracycline.

  • 42.
    Palm, Eleonor
    et al.
    Örebro University, School of Medical Sciences.
    Demirel, Isak
    Örebro University, School of Medical Sciences.
    Bengtsson, Torbjörn
    Örebro University, School of Medical Sciences.
    Khalaf, Hazem
    Örebro University, School of Medical Sciences.
    The role of toll-like and protease-activated receptors and associated intracellular signaling in Porphyromonas gingivalis-infected gingival fibroblasts2017In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 125, no 2, p. 157-169Article in journal (Refereed)
    Abstract [en]

    Porphyromonas gingivalis, which is considered a keystone agent in periodontitis, has evolved elaborate mechanisms to grow and survive in a hostile milieu. The gingival fibroblast is the major cell type in the gingiva and is considered to be important in the periodontitis-associated inflammation. As a part of the innate immune response, they produce cytokines such as CXCL8 and interleukin (IL)-6 which are believed to contribute to the destruction of the tooth-supporting tissues. This study investigates how the expression of protease-activated receptors (PAR1, PAR2) and toll-like receptors (TLR2, TLR4) changes with P. gingivalis exposure and how silencing of one receptor affects the expression of the other receptors. The importance of protein kinase C (PKC) and p38 in the regulation of CXCL8 and IL-6 was also examined. Receptors were knockdown with small-interfering RNA. PKC or p38 was blocked prior to stimulation with P. gingivalis. Fibroblasts were able to compensate for PAR1 knockdown with increased expression of PAR2. PKC and p38 were involved in the regulation of P. gingivalis-induced CXCL8 and IL-6. Our results indicate that PAR1 and PAR2 could be implicated in periodontitis and that PKC and P38 play a role in the inflammatory response in P. gingivalis-infected gingival fibroblasts.

  • 43.
    Prag, Gustaf
    et al.
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Falk-Brynhildsen, Karin
    Department of Cardiothoracic and Vascular Surgery, Örebro University Hospital, Örebro, Sweden.
    Jacobsson, Susanne
    Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Hellmark, Bengt
    Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, 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; Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Decreased susceptibility to chlorhexidine and prevalence of disinfectant resistance genes among clinical isolates of Staphylococcus epidermidis2014In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 122, no 10, p. 961-967Article in journal (Refereed)
    Abstract [en]

    Staphylococcus epidermidis, despite regarded as a commensal, is recognized as a nosocomial pathogen usually by acting as an opportunist, especially in infections associated with implanted foreign body materials. Pre-operative antiseptic preparation is an important strategy for reducing the risk of complications such as surgical site infection (SSI). The currently most widely used antiseptic compounds are alcohols and quaternary ammonium compounds (QACs), predominantly chlorhexidine.

    The aim of this study was to investigate if decreased susceptibility to chlorhexidine among S. epidermidis was present in our setting. S. epidermidis (n=143) were obtained from prosthetic joint infections (PJI) (n=61), commensals (n=24), post-operative infections after cardiothoracic surgery (n=31), and the skin of the chest after routine disinfection prior cardiothoracic surgery (n=27). Determination of MIC of chlorhexidine was performed on Müeller Hinton agar plates supplemented with serial dilutions of chlorhexidine. Five QAC resistance genes; qacA/B, smr, qacH, qacJ, and qacG, were detected using PCR.

    Decreased susceptibility to chlorhexidine was found in 54% of PJI isolates, 68% of cardiothoracic isolates, 21% of commensals, and 7% of isolates obtained from the skin of cardiothoracic patients, respectively.

    The qacA/B gene was present in 62/143 isolates (43%), smr in 8/143 (6%) and qacH in one isolate (0.7%). The qacA/B gene was found in 52% of PJI isolates, 61% of cardiothoracic isolates, 25% of commensals, and 19% of isolates obtained from the skin of cardiothoracic patients. In conclusion, decreased susceptibility to chlorhexidine as well as QAC resistance genes was highly prevalent among S. epidermidis causing deep SSIs.

  • 44.
    Rathsman, Sandra
    et al.
    Department of Laboratory Medicine/Microbiology, Örebro University Hospital, Örebro, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Eriksson, Sune
    Department of Laboratory Medicine/Pathology, Örebro University Hospital, Örebro, Sweden.
    Hultgren, Olof
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine/Microbiology, Örebro University Hospital, Örebro, Sweden.
    Åberg, Anna-Karin
    Department of Laboratory Medicine/Microbiology, Örebro University Hospital, Örebro, Sweden.
    Olcén, Per
    Department of Laboratory Medicine/Microbiology, Örebro University Hospital, Örebro, Sweden.
    Elution of antitransglutaminase antibodies from duodenal biopsies: a novel approach in the diagnosis of celiac disease2012In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 120, no 8, p. 666-674Article in journal (Refereed)
    Abstract [en]

    Celiac disease (CeD) is a disease more prevalent and multisymptomatic than was earlier recognized. Whereas prompt initiation of gluten-free diet (GFD) is beneficial in relieving the symptoms, an accurate CeD diagnosis is necessary also to avoid years of restricted diet on uncertain grounds. We propose a new diagnostic method, based on elution of deposited antibodies against transglutaminase (anti-tTG) from duodenal biopsies in patients with symptoms and screening serology analyses suggestive of CeD. The eluates were analyzed in a Phadia 250 fluoroimmunoassay, demonstrating elevated concentrations of anti-tTG in CeD patients, corresponding to serology and histopathology findings. In one case histology was inconclusive, displaying only unspecific inflammation, but eluted anti-tTG was positive. This patient has clinically improved following GFD. We conclude that our novel method represents a new tool in the diagnostic work up in CeD. The detection of deposited anti-tTG at the site of inflammation appears to provide a high sensitivity and specificity using a technique that is quick, simple and reliable. Further studies are needed for optimization and elucidation of suitable applications for this elution method.

  • 45.
    Rumyantseva, Tatiana
    et al.
    Department of Molecular Diagnostics, Central Research Institute for Epidemiology, Moscow, Russian Federation.
    Golparian, Daniel
    WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for Pathogenic Neisseria, , Örebro University Hospital, Örebro, Sweden; Department of Laboratory Medicine, Microbiology, Faculty of Medicine and Health, Örebro University, Sweden.
    Nilsson, Christian S.
    Department of Dermatovenereology, Örebro University Hospital, Örebro, Sweden.
    Johansson, Emma
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. WHO Collaborating Ctr Gonorrhoea & Other STIs, Natl Reference Lab Pathogen Neisseria, Dept Lab Med, Microbiol, Örebro University Hospital, Örebro, Sweden.
    Falk, My
    Department of Dermatovenereology, Örebro University Hospital, Örebro, Sweden.
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. WHO Collaborating Ctr Gonorrhoea & Other STIs, Natl Reference Lab Pathogen Neisseria, Dept Lab Med, Microbiol, Örebro University Hospital, Örebro, Sweden.
    Van Dam, Alje
    Public Health Laboratory, Amsterdam Health Centre, Amsterdam, Netherlands; Department of Medical Microbiology, Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam, Netherlands.
    Guschin, Alexander
    Department of Molecular Diagnostics, Central Research Institute for Epidemiology, Moscow, Russian Federation.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. WHO Collaborating Ctr Gonorrhoea & Other STIs, Natl Reference Lab Pathogen Neisseria, Dept Lab Med, Microbiol, Örebro University Hospital, Örebro, Sweden.
    Evaluation of the new AmpliSens multiplex real-time PCR assay for simultaneous detection of Neisseriagonorrhoeae, Chlamydiatrachomatis, Mycoplasmagenitalium, and Trichomonasvaginalis2015In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 123, no 10, p. 879-886Article in journal (Refereed)
    Abstract [en]

    In this study, we performed an evaluation of the new CE-marked multiplex real-time AmpliSens N.gonorrhoeae/C.trachomatis/M.genitalium/T.vaginalis-MULTIPRIME-FRT PCR assay compared to APTIMA tests, i.e., APTIMA COMBO 2assay, APTIMA Trichomonasvaginalis assay (FDA-approved), and two different APTIMA Mycoplasmagenitalium assays (research use only; one of them only used for discrepancy analysis). Vaginal swabs (n=209) and first-void urine (FVU) specimens from females (n=498) and males (n=554), consecutive attendees (n=1261) at a dermatovenerological clinic in Sweden, were examined. The sensitivity of the AmpliSens PCR assay for detection of C.trachomatis (6.3% prevalence), M.genitalium (5.7% prevalence), N.gonorrhoeae (0.3% prevalence), and T.vaginalis (0.08% prevalence) was 97.5% (95% confidence interval (CI): 91.2-99.6%), 81.9% (95% CI: 70.7-89.7%), 100% (95% CI: 40.2-100%) and 100% (95% CI: 16.5-100%), respectively. The specificity of the AmpliSens PCR assay was 100% (95% CI: 99.6-100%) for all agents. The analytical sensitivity and specificity for N.gonorrhoeae detection was excellent, i.e., 55 international gonococcal strains detected and 135 isolates of 13 non-gonococcal Neisseria species were negative. In conclusion, the multiplex real-time AmpliSens N.gonorrhoeae/C.trachomatis/M.genitalium/T.vaginalis-MULTIPRIME-FRT PCR assay demonstrated high sensitivity and excellent specificity for the detection of C.trachomatis, N.gonorrhoeae, and T.vaginalis, and excellent specificity but suboptimal sensitivity for M.genitalium detection.

  • 46.
    Rumyantseva, Tatiana
    et al.
    Central Research Institute for Epidemiology, Moscow, Russia.
    Shipitsyna, Elena
    Laboratory of Microbiology, D.O. Ott Research Institute of Obstetrics, Gynaecology and Reproductology, St. Petersburg, Russia; Department of Laboratory Medicine, Microbiology, WHO Collaborating Centre for Gonorrhoea and Other STIs, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Guschin, Alexander
    Central Research Institute for Epidemiology, Moscow, Russia.
    Unemo, Magnus
    Örebro University, School of Health Sciences. Department of Laboratory Medicine, Microbiology, WHO Collaborating Centre for Gonorrhoea and Other STIs, Örebro University Hospital, Örebro, Sweden.
    Evaluation and subsequent optimizations of the quantitative AmpliSens Florocenosis/Bacterial vaginosis-FRT multiplex real-time PCR assay for diagnosis of bacterial vaginosis2016In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 124, no 12, p. 1099-1108Article in journal (Refereed)
    Abstract [en]

    Traditional microscopy-based methods for diagnosis of bacterial vaginosis (BV) are underutilized in many settings, and molecular techniques may provide opportunities for rapid, objective, and accurate BV diagnosis. This study evaluated the quantitative AmpliSens Florocenosis/Bacterial vaginosis-FRT multiplex real-time PCR (Florocenosis-BV) assay. Vaginal samples from a previous study including unselected female subjects (n = 163) and using Amsel criteria and 454 pyrosequencing for BV diagnosis were examined with the Florocenosis-BV test and additionally tested for the presence and quantity of Gardnerella vaginalis clades 3 and 4. The Florocenosis-BV assay demonstrated 100% and 98% sensitivity compared with the Amsel criteria and 454 pyrosequencing, respectively, with 91% specificity. The modified Florocenosis-BV assay (detecting also G. vaginalis clades 3 and 4) resulted in 100% sensitivity vs the Amsel criteria and 454 pyrosequencing with specificity of 86% and 88%, respectively. Further optimizations of thresholds for the quantitative parameters used in the kit resulted in 99-100% accuracy vs Amsel criteria and 454 pyrosequencing for selected parameters. The Florocenosis-BV assay is an objective, accurate, sensitive, and specific method for BV diagnosis; however, the performance of the test can be further improved with some minor optimizations.

  • 47.
    Sahdo, Berolla
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Särndahl, Eva
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Elgh, Fredrik
    Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital.
    Propionibacterium acnes activates caspase-1 in human neutrophils2013In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 121, no 7, p. 652-63Article in journal (Refereed)
    Abstract [en]

    Propionibacterium acnes is a Gram-positive, slow-growing, anaerobic bacillus, predominantly found as a commensal on the skin and mucous membranes of adults. It is, however, also considered an opportunistic pathogen; mostly associated with acne vulgaris, but rarely also with severe infections such as infective endocarditis, prosthetic joint infections, and deep sternal wound infections following cardiothoracic surgery. In addition, P. acnes has recently been found in high frequency in prostate tissue from patients with prostatitis and prostate cancer. The NOD-like receptors (NLR) act as intracellular sensors of microbial components, and a number of various bacteria have been found to induce assembling and activation of NLR-inflammasomes; leading to a pro-inflammatory response. The inflammasome-mediated formation of the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18 involves the auto-proteolytic maturation of caspase-1. This study investigated if P. acnes activates inflammasomes. Propionibacterium acnes isolates (n = 29) with diverse origin were used as stimuli for peripheral leukocytes obtained from blood donors (BDs). The activity of inflammasomes was determined by measuring caspase-1 by flow cytometry and cytokine production by ELISA. A significant amount of caspase-1 was found in neutrophils upon P. acnes stimulation, whereas only a modest activation was seen in monocytes. The activation was mainly produced by components of the bacterial cell and no exo-products, because heat-killed and live bacteria caused high activation of caspase-1 as well as cytokine production, whereas the bacterial supernatant elicited minor effect. The response among different BDs varied significantly, almost fivefold. In addition, P. acnes of various origins showed considerable variation, however, the commensal isolates showed a stronger response compared with the invasive. In conclusion, although regarded as a harmless commensal of the skin, P. acnes strongly activates the inflammasome of human peripheral neutrophils.

  • 48.
    Serwin, Agnieszka Beata
    et al.
    Department of Dermatology and Venereology, Medical University of Bialystok, Bialystok, Poland.
    Bulhak-Koziol, Violetta
    Diagnostic and Research Centre for Sexually Transmitted Diseases, Bialystok, Poland.
    Sokolowska, Marianna
    Diagnostic and Research Centre for Sexually Transmitted Diseases, Bialystok, Poland.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Trichomonas vaginalis is very rare among women with vaginal discharge in Podlaskie province, Poland2017In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 125, no 9, p. 840-843Article in journal (Refereed)
    Abstract [en]

    Trichomonas vaginalis is the most common curable sexually transmitted pathogen globally. However, in the European Union (EU), trichomoniasis appears to be a rare condition. The aim of this study was to examine the prevalence of T. vaginalis among females attending an STI centre in Bialystok, Poland, using the highly sensitive and specific APTIMA T. vaginalis assay. Consecutive females, referred by gynaecologists mainly because of abnormal vaginal discharge, were diagnosed using wet mount microscopy, culture and APTIMA T. vaginalis assay. Among 272 women studied, 82% were pre- and 18% postmenopausal. The average age was 36.0 +/- 13.9 (range: 18-86) years. Abnormal discharge (alone or accompanied by itch or vulvovaginal burning) was the most frequent complain in both groups (66.2% and 48.0%). Erythema and discharge were the most frequent abnormal signs (58.6% and 56.0%). Not a single T. vaginalis-positive sample was detected using wet mount microscopy, culture or APTIMA T. vaginalis assay. Despite using the highly sensitive APTIMA T. vaginalis assay for detection, the pathogen could not be identified in females in the studied setting, similar to results from other EU settings. The need for general screening using NAAT for this pathogen while diagnosing vulvovaginal symptoms in females in Poland appears to be low.

  • 49. Shalepo, Kira
    et al.
    Savicheva, Alevtina
    Shipitsyna, Elena
    Unemo, Magnus
    Örebro University, Department of Clinical Medicine.
    Domeika, Marius
    Diagnosis of Chlamydia trachomatis in Russia--in-house PCR assays may be effective but overall optimization and quality assurance are urgently needed2006In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 114, no 7-8, p. 500-507Article in journal (Refereed)
    Abstract [en]

    In the present study, the performance of the cell culture method, two non-Russian direct immunofluorescence (DIF) assays, and three different in-house polymerase chain reaction (PCR) tests used in St. Petersburg, Russia, for detection of Chlamydia trachomatis in urogenital specimens was evaluated. A total of 650 patients were examined and it was most disquieting that previous C. trachomatis positivity with Russian DIF assays could - 7 days later - be confirmed only in 26% of the women and 30% of the men. Overall, the highest diagnostic sensitivity was obtained using PCR analysis. However, the sensitivity varied significantly: from 79% to 100% between the different PCR assays, sex of the patients, and type of samples. The highest sensitivity was obtained for female vaginal and male urine samples (100%). The specificity of the PCR assays varied from 97% to 100%. The sensitivity of cell culture and both the examined DIF assays was low, i.e. it varied from 46% to 56% and 55% to 75%, respectively. Meanwhile, cell culture was 100% specific and the DIFs showed a specificity varying from 99% to 100%. In conclusion, in a Russian perspective, adequate in-house PCR methods may be used quite effectively for detection of C. trachomatis in invasive as well as non-invasive clinical material. Simultaneous analysis of two different specimens from women resulted in a significantly increased detection rate of C. trachomatis. Nevertheless, in Russia the need for optimization and quality assurance of diagnostic methods for C. trachomatis, especially Russian DIF assays, has to be emphasized.

  • 50. Shipitsyna, Elena
    et al.
    Guschin, Alexander
    Maximova, Anna
    Tseslyuk, Mariya
    Savicheva, Alevtina
    Sokolovsky, Evgenij
    Shipulin, German
    Domeika, Marius
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences.
    Comparison of microscopy, culture and in-house PCR and NASBA assays for diagnosis of Neisseria gonorrhoeae in Russia2008In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 116, no 2, p. 133-138Article in journal (Refereed)
    Abstract [en]

    This study aimed to assess the laboratory diagnosis of Neisseria gonorrhoeae in St. Petersburg, Russia. In total, 334 consecutive symptomatic patients were enrolled. Cervical and urethral specimens from women (nΩ286) and urethral specimens from men (nΩ48) were analyzed by microscopy, culture and two in-house NAATs, i.e. polymerase chain reaction (PCR) and nucleic acid sequence-based amplification (NASBA), developed in Russia. All N. gonorrhoeae-positive samples were confirmed using porA pseudogene and 16S rRNA gene sequencing. All methods displayed 100% specificity, i.e. positive predictive values of 100%. Compared to the PCR (most sensitive method in the present study), in women the sensitivity of both microscopy and culture was 31.8%, and that of NASBA was 90.9%. In men, microscopy, culture and NASBA displayed a sensitivity of 75%, 50% and 100%, respectively. The negative predictive values of microscopy, culture, and NASBA were 97.3%, 97.3%, and 99.6% in women, and 97.8%, 95.7%, and 100% in men, respectively. According to the PCR, the prevalences of N. gonorrhoeae were 4.5% (women) and 8.3% (men). In conclusion, both the investigated Russian NAATs displayed a high sensitivity and specificity. However, in general the diagnosis of gonorrhoea in Russia is suboptimal and crucially requires validation, improvements and quality assurance.

12 1 - 50 of 63
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • 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