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  • 1.
    Asfaw Idosa, Berhane
    et al.
    Örebro University, School of Medical Sciences.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences.
    Kelly, Anne
    Karolinska University Hospital, Stockholm, Sweden.
    Fredlund, Hans
    Örebro University, School of Medical Sciences.
    Persson, Alexander
    Örebro University, School of Medical Sciences.
    Särndahl, Eva
    Örebro University, School of Medical Sciences.
    Human gene variants that regulate the NLRP3 activity limit the production of Neisseria meningitidis-induced IL-1β and IL-18Manuscript (preprint) (Other academic)
  • 2.
    Asfaw Idosa, Berhane
    et al.
    Örebro University, School of Medical Sciences.
    Persson, Alexander
    Örebro University, School of Medical Sciences.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences.
    Demirel, Isak
    Örebro University, School of Medical Sciences.
    Fredlund, Hans
    Örebro University, School of Medical Sciences.
    Särndahl, Eva
    Örebro University, School of Medical Sciences.
    Kelly, Anne
    Karolinska University Hospital, Stockholm, Sweden.
    LOS-dependent Neisseria meningitidis-induced caspase-1 activation in human neutrophilsManuscript (preprint) (Other academic)
  • 3. Edberg, Andreas
    et al.
    Jurstrand, Margaretha
    Johansson, Eva
    Wikander, Elisabeth
    Höög, Anna
    Ahlqvist, Thomas
    Falk, Lars
    Jensen, Jørgen Skov
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences.
    A comparative study of three different PCR assays for detection of Mycoplasma genitalium in urogenital specimens from men and women2008In: Journal of Medical Microbiology, ISSN 0022-2615, E-ISSN 1473-5644, Vol. 57, no Pt 3, p. 304-309Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to compare conventional 16S rRNA gene PCR, real-time 16S rRNA gene PCR and real-time Mycoplasma genitalium adhesin protein (MgPa) gene PCR as detection methods for M. genitalium infection. The study also determined the prevalence of M. genitalium in male and female patients attending a sexually transmitted infections clinic in a rural area in the west of Sweden. First void urine (FVU) and/or urethral swabs were collected from 381 men, and FVU and/or cervical swabs and/or urethral swabs were collected from 298 women. A total of 213 specimens were used in the PCR comparative study: 98 consecutively sampled specimens from patients enrolled in the prevalence study, 36 consecutively sampled specimens from patients with symptoms of urethritis and 79 specimens from patients positive for M. genitalium by real-time MgPa gene PCR in the prevalence study. A true-positive M. genitalium DNA specimen was defined as either a specimen positive in any two PCR assays or a specimen whose PCR product was verified by DNA sequencing. The prevalence of M. genitalium infection in men and women was 27/381 (7.1 %) and 23/298 (7.7 %), respectively. In the PCR comparative study, M. genitalium DNA was detected in 61/76 (80.3 %) of true-positive specimens by conventional 16S rRNA gene PCR, in 52/76 (68.4 %) by real-time 16S rRNA gene PCR and in 74/76 (97.4 %) by real-time MgPa gene PCR. Real-time MgPa gene PCR thus had higher sensitivity compared with conventional 16S rRNA gene PCR and had considerably increased sensitivity compared with real-time 16S rRNA gene PCR for detection of M. genitalium DNA. Real-time MgPa gene PCR is well suited for the clinical diagnosis of M. genitalium.

  • 4.
    Falk, L.
    et al.
    Dept Local Hlth Care, Linköping Univ, Linköping, Sweden; Dept Dermatol & Venereol, Linköping Univ Hosp, Linköping, Sweden.
    Coble, B-I
    Dept Dermatol & Venereol, Linköping Univ Hosp, Linköping, Sweden.
    Mjornberg, P-A
    Ryhov Cty Hosp, Dept Dermatol & Venereol, Jönköping, Sweden.
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences. Örebro University Hospital, Örebro, Sweden.
    Sampling for Chlamydia trachomatis infection: a comparison of vaginal, first-catch urine, combined vaginal and first-catch urine and endocervical sampling2010In: International Journal of STD and AIDS (London), ISSN 0956-4624, E-ISSN 1758-1052, Vol. 21, no 4, p. 283-287Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to evaluate the sensitivity of patients' self-sampled vaginal specimens, first-catch urine (FCU), combined vaginal/FCU specimens and endocervical specimens for detecting chlamydial infection in women. Women attending sexually transmitted disease clinics, youth clinics and a women's health clinic were enrolled. They self-collected a vaginal specimen with two swabs, which were placed into a sterile tube and into a tube containing a buffer medium, respectively. An FCU sample was collected and aliquoted into both an empty tube and the tube containing the vaginal swab. A clinician collected an endocervical swab. The samples were sent to laboratories for analysis using polymerase chain reaction testing and strand displacement amplification testing, respectively. The sensitivities calculated in all 171 Chlamydia trachomatis-infected women were equal for endocervical specimens (97.1%), vaginal specimens (96.5%) and combined vaginal/FCU specimens (95.3%), whereas the sensitivity for FCU was significantly lower (87.7%). The sensitivity of vaginal specimens for the detection of C. trachomatis is as high as that of combined vaginal/FCU specimens.

  • 5. Falk, L.
    et al.
    Coble, B.-I.
    Mjörnberg, P.-A.
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences.
    Vilket självprovtagningssätt är bäst vid screening av genital klamydia hos kvinnor?2008Conference paper (Other academic)
  • 6. Falk, Lars
    et al.
    Lindberg, Margret
    Jurstrand, Margaretha
    Örebro University, Department of Clinical Medicine.
    Bäckman, Anders
    Örebro University, School of Medical Sciences.
    Olcén, Per
    Fredlund, Hans
    Örebro University, School of Health Sciences.
    Genotyping of Chlamydia trachomatis would improve contact tracing2003In: Sexually Transmitted Diseases, ISSN 0148-5717, E-ISSN 1537-4521, Vol. 30, no 3, p. 205-210Article in journal (Refereed)
    Abstract [en]

    Background: The reported number of genital Chlamydia trachomatis infections has increased 15% annually since 1997 in Sweden. Inaccurate partner notification might be one reason.

    Goal: The goals were to determine if genotyping of C trachomatis would improve partner notification and to study the duration of infection.

    Study Design: Sexual networks were constructed. C trachomatis isolates from 231 individuals attending the Örebro STD clinic during 1 year were typed by sequencing of the omp1 gene.

    Results: All individuals were traced and diagnoses were established in 30 of 161 networks. More than one genotype was seen in seven networks. The mean duration of C trachomatis infection in each network was calculated to be 23 weeks.

    Conclusion: Genotyping could be a useful tool in partner notification when there are discrepant or uncommon genotypes. Limited clinic catchment areas create information difficulties that obstruct accurate contact tracing.

  • 7.
    Golparian, Daniel
    et al.
    World Health Organization Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, Swedish Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Ohlsson, A. K.
    Dept Clin Microbiol, Karolinska Univ Hosp, Stockholm, Sweden.
    Janson, H.
    Dept Clin Microbiol, Cent Hosp Växjö, Växjö, Sweden.
    Lidbrink, P.
    Dept Dermatovenereol, Karolinska Univ Hosp, Stockholm, Sweden.
    Richtner, T.
    Dept Dermatol, Karolinska Inst Södersjukhuset, Stockholm, Sweden.
    Ekelund, O.
    Dept Clin Microbiol, Cent Hosp Växjö, Växjö, Sweden.
    Fredlund, Hans
    Örebro University Hospital. World Health Organization Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, Swedish Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    Örebro University Hospital. World Health Organization Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, Swedish Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Four treatment failures of pharyngeal gonorrhoea with ceftriaxone (500 mg) or cefotaxime (500 mg), Sweden, 2013 and 20142014In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 19, no 30, p. 2-5, article id 20862Article in journal (Refereed)
    Abstract [en]

    We describe four cases in Sweden of verified treatment failures of pharyngeal gonorrhoea with ceftriaxone (500 mg; n=3) or cefotaxime (500 mg; n=1) monotherapy. All the ceftriaxone treatment failures were caused by the internationally spreading multidrug-resistant gonococcal NG-MAST genogroup 1407 clone. Increased awareness of treatment failures is crucial particularly when antimicrobial monotherapy is used. Frequent test of cure and appropriate verification/falsification of suspected treatment failures, as well as implementation of recommended dual antimicrobial therapy are imperative.

  • 8. Hadad, Ronza
    et al.
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences.
    Evaluation of the new COBAS TaqMan CT test v2.0 and impact on the proportion of new variant Chlamydia trachomatis by the introduction of diagnostics detecting new variant C trachomatis in Örebro county, Sweden2008In: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 85, p. 190-193Article in journal (Refereed)
    Abstract [en]

    Background: The new variant of Chlamydia trachomatis (nvCT), discovered in Sweden in 2006, contains a 377-bp cryptic plasmid deletion, which includes the targets for the COBAS Amplicor/TaqMan C trachomatis/Neisseria gonorrhoea and Abbott m2000rt C trachomatis/N gonorrhoea tests.

    Objectives: To evaluate the new real-time COBAS TaqMan CT test v2.0 (CTM CT v2.0) for C trachomatis diagnostics and to investigate whether the proportion of nvCT was affected by the introduction of genetic diagnostics detecting nvCT (LightMix 480HT) in Örebro county, Sweden.

    Methods: CTM CT v2.0 compared with LightMix 480 HT PCR for the diagnosis of C trachomatis was evaluated. Discrepant samples were analysed using BD ProbeTec ET and Abbott m2000rt RealTime CT II. All previously LightMix and cell culture-positive samples were analysed using an nvCT-specific PCR.

    Results: The sensitivity, specificity, negative predictive value and positive predictive value of CTM CT v2.0 for examined samples (n  =  1058) was 100%, 99.8%, 100% and 98.2%, respectively. Of 11 577 consecutive PCR samples, 9.4% (n  =  1084) were positive and 34.3% (n  =  372) of these were nvCT. Of 2306 consecutive culture samples, 5.0% (n  =  116) were C trachomatis positive and 38.8% (n  =  45) of these were nvCT.

    Conclusions: CTM CT v2.0 is a sensitive and specific method for C trachomatis detection. Studies including larger numbers of symptomatic and asymptomatic patients as well as genital and extragenital samples, and in comparison with other internationally validated and, ideally, US Food and Drug Administration-approved C trachomatis nucleic acid amplification tests are imperative. The proportion of nvCT remains high in Örebro county, Sweden, despite the introduction of genetic diagnostics to detect the mutant. 

  • 9. Hadad, Ronza
    et al.
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences.
    Impact on the proportion of the new variant of Chlamydia trachomatis (nvCT) by introduction of diagnostics detecting nvCT and evaluation of Cobas TaqMan48 CT Test v2.0 for C. trachomatis diagnostics in Örebro county, Sweden2008Conference paper (Other academic)
  • 10.
    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.

  • 11.
    Hedberg, Sara Thulin
    et al.
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Törös, Bianca
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Fredlund, Hans
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Olcén, Per
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Genetic characterisation of the emerging invasive Neisseria meningitidis serogroup Y in Sweden, 2000 to 20102011In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 16, no 23, article id 19885Article in journal (Refereed)
    Abstract [en]

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

  • 12.
    Hedberg, Sara Thulin
    et al.
    Örebro University, School of Health and Medical Sciences.
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences.
    Nicolas, Pierre
    Caugant, Dominique A.
    Olcén, Per
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences.
    Antibiotic susceptibility and characteristics of Neisseria meningitidis isolates from the African meningitis belt, 2000 to 2006: phenotypic and genotypic perspectives2009In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 53, no 4, p. 1561-1566Article in journal (Refereed)
    Abstract [en]

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

  • 13.
    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)
  • 14.
    Hedberg, Sara Thulin
    et al.
    Örebro University, School of Health and Medical Sciences.
    Olcén, Per
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences.
    Antibiotic susceptibility of invasive Neisseria meningitidis isolates from 1995 to 2008 in Sweden: the meningococcal population remains susceptible2010In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 42, no 1, p. 61-64Article in journal (Refereed)
    Abstract [en]

    The susceptibility to 7 antibiotics was determined for all Swedish invasive Neisseria meningitidis isolates from 1995 to 2008 (N=717). In general, these remain highly susceptible to the antibiotics recommended for use. Accordingly, penicillin G remains effective for the treatment of invasive meningococcal disease and ciprofloxacin appropriate for prophylaxis.

  • 15.
    Hedberg, Sara Thulin
    et al.
    Örebro University, School of Health and Medical Sciences.
    Olcén, Per
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences.
    Unemo, Magnus
    Örebro University, Department of Health Sciences.
    Combined real-time PCR and pyrosequencing strategy for objective, sensitive, specific, and high throughput identification of reduced susceptibility to penicillins in Neisseria meningitidis2008In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 52, no 2, p. 753-756Article in journal (Refereed)
    Abstract [en]

    A segment of penA in Neisseria meningitidis strains (n = 127), including two nucleotide sites closely associated to reduced susceptibility to penicillins, was amplified and pyrosequenced. All results were in concordance with Sanger sequencing, and a high correlation between alterations in the two Pen(i)-specific sites and reduced susceptibility to penicillins was identified.

  • 16. Hedberg, Sara Thulin
    et al.
    Olcén, Per
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences.
    Prevalence, phenotypic and genotypic characterisation of Neisseria meningitidis comprising reduced susceptibility or resistance to rifampicin and/or ciprofloxacin in Sweden2008Conference paper (Other academic)
  • 17.
    Herrmann, Björn
    et al.
    Section of Clinical Bacteriology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Eden, Desiree
    Section of Clinical Bacteriology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Hadad, Ronza
    WHO Collaborating Centre for Gonorrhoea and Other STIs, Örebro University Hospital, Örebro, Sweden.
    Christerson, Linus
    Section of Clinical Bacteriology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Loré, Britta
    Department of Clinical Microbiology, Falu Lasarett, Falun, Sweden.
    Österlund, Anders
    Communicable Disease Prevention and Control, Sunderby Hospital, Luleå, Sweden.
    Larsson, Inger
    Department of Clinical Microbiology, Sunderby Hospital, Luleå, Sweden.
    Sylvan, Staffan
    Department of Communicable Diseases Control and Prevention, Uppsala County Council, Uppsala, Sweden.
    Fredlund, Hans
    Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other STIs , Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other STIs, Örebro University Hospital, Örebro, Sweden.
    Prevalence Trends of the New Variant of Chlamydia trachomatis in Four Counties of Sweden in 2007-20112012In: Sexually Transmitted Diseases, ISSN 0148-5717, E-ISSN 1537-4521, Vol. 39, no 8, p. 648-650Article in journal (Refereed)
    Abstract [en]

    A new variant of Chlamydia trachomatis (nvCT) was discovered in Sweden in 2006, and it could not be detected by diagnostic systems from Abbott and Roche, whereas the third system used, from Becton Dickinson (BD), detects nvCT. We analyzed 3648 samples from 2 counties that used Roche and 2 counties that used BD methods from 2007 to 2011. After implementation of a Roche method that detects nvCT, its proportion has decreased and converged in the 4 counties but are still at different levels in Roche and BD counties. Future studies are needed to see if nvCT will decline further.

  • 18.
    Idahl, Annika
    et al.
    Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden.
    Jurstrand, Margaretha
    Faculty of Medicine and Health, Clinical Research Centre, Örebro University, Örebro, Sweden.
    Olofsson, Jan I.
    Reproductive Medicine, Department of Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden.
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Mycoplasma genitalium serum antibodies in infertile couples and fertile women2015In: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 91, no 8, p. 589-591Article in journal (Refereed)
    Abstract [en]

    Objectives: The association between Mycoplasma genitalium (M. genitalium) serum antibodies and infertility in women and men, as well as infertility subtypes, was investigated.

    Methods: Stored serum was obtained from two patient cohorts: infertile couples (239 women and 243 men) attending a gynaecological outpatient clinic between October 1997 and February 2001 and 244 age-matched spontaneously pregnant women. An enzyme immunoassay was used to detect serum immunoglobulin G (IgG) antibodies to M. genitalium in these samples. Patient's Chlamydia trachomatis seropositivity had been previously determined. Risks were calculated using multivariate logistic regression.

    Results: M. genitalium serum IgG was more common among women of infertile couples (5.4%) than among fertile controls (1.6%) (OR (95% CI) 3.45 (1.10 to 10.75)), adjusting for C. trachomatis IgG (adjusted OR=3.00 (0.95 to 9.47)). Of the women with tubal factor infertility (TFI) 9.1% had M. genitalium IgG compared with 4.6% of women without TFI (OR=2.07 (0.60 to 7.05)); (AOR=1.20 (0.32 to 74.40)). In patients IgG positive to both microorganisms the OR for having TFI was increased (OR=4.86 (1.22 to 19.36)) compared with those positive to C. trachomatis IgG only (AOR=3.14 (1.58 to 6.20)). No associations were found with other infertility diagnoses. Only two men of the infertile couples were M. genitalium IgG positive (0.8%).

    Conclusions: M. genitalium serum IgG was associated with infertility in women, however insignificant after adjustment for C. trachomatis IgG, but not with infertility subtypes within this study. M. genitalium IgG seroprevalence among men was very low and not associated with male factor infertility.

  • 19. Jacobsson, Susanne
    et al.
    Olcén, Per
    Löfdahl, Margareta
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences.
    Mölling, Paula
    Characteristics of Neisseria meningitidis isolates causing fatal disease2008In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 40, no 9, p. 734-744Article in journal (Refereed)
    Abstract [en]

    The objectives of the present study were to describe a selection of characteristics of all available fatal meningococcal isolates (n=62) and to compare these with all the other invasive isolates (non-fatal, n=474) collected in Sweden from 1995 to 2004 (fatality rate of 12%). The coverage of the fatal isolates by presently discussed outer membrane vesicle (OMV) vaccines was also estimated. The isolates were characterized by serogroup, serotype, genosubtype, multilocus sequence type and antibiogram. Basic epidemiological data were gathered. The results of the fatal isolates showed 55% serogroup B, 27% C, 15% Y and 3% W-135, with a fatality rate of 11% for B, 12% for C, 17% for Y and 8% for W-135. Characteristics associated with higher mortality were age, gender, serogroup Y, serotype 14 and 15 and genosubtypes P1.7,16-29,35 and P1.5-1,10-4,36-2. In contrast, non-14/non-15 serotypes, the genosubtypes P1.5-1,10-8,36-2; P1.7-2,4,37 and P1.7,16,35, as well as reduced sensitivity for penicillin G were associated with decreased mortality. The presently discussed OMV vaccines could, based solely on the complete genosubtype, theoretically cover up to 44% of the fatal serogroup B cases and up to 100% if every variable region by itself is capable to induce protective immunity.

  • 20. Jurstrand, Margareta
    et al.
    Herrmann, B.
    Morin, T.
    Ödmark, S.
    Christersson, L.
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences.
    Characterization of Chlamydia trachomatis genotype E by multi locus sequence typing after the finding of the new variant (nvCt) in a Swedish county 20062008Conference paper (Other academic)
  • 21.
    Jurstrand, Margaretha
    et al.
    Örebro University, Department of Clinical Medicine.
    Falk, Lars
    Fredlund, Hans
    Örebro University Hospital.
    Lindberg, Margareta
    Olcén, Per
    Andersson, Sören
    Persson, Kenneth
    Albert, Jan
    Bäckman, Anders
    Örebro University Hospital.
    Characterization of Chlamydia trachomatis omp1 genotypes among sexually transmitted disease patients in Sweden2001In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 39, no 11, p. 3915-3919Article in journal (Refereed)
    Abstract [en]

    A method for detection and genotyping of genital Chlamydia trachomatis infections based on omp1 gene amplification and sequencing was developed. DNA was extracted from urogenital or urine samples using a Chelex-based method, and an approximately 1,100-bp-long fragment from the omp1 gene was directly amplified and sequenced. Genotyping was performed by BLAST similarity search, and phylogenetic tree analysis was used to illustrate the evolutionary relationships between clinical isolates and reference strains. The method was used to determine the genotypes of C. trachomatis in 237 positive urogenital and/or urine specimens collected at a Swedish sexually transmitted disease clinic during 1 year. The most common genotypes corresponded to serotypes E (47%) and F (17%). The omp1 gene was highly conserved for genotype E (106 of 112 samples without any mutation) and F (41 of 42 samples without any mutation) strains but appear slightly less conserved for genotypes G (n = 6) and H (n = 6), where the sequences displayed one to four nucleotide substitutions relative to the reference sequence. Genotyping of samples collected at the follow-up visit indicated that two patients had become reinfected, while three other patients suffered treatment failure or reinfection. One woman appeared to have a mixed infection with two different C. trachomatis strains. This omp1 genotyping method had a high reproducibility and could be used for epidemiological characterization of sexually transmitted Chlamydia infections.

  • 22.
    Jurstrand, Margaretha
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital, Örebro, Sweden.
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital, Örebro, Sweden.
    The new variant of Chlamydia trachomatis was present as early as 2003 in Orebro County, Sweden, but remained undetected until 20062013In: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 89, no 7, p. 607-608Article in journal (Refereed)
    Abstract [en]

    Objectives In 2006, a new variant of Chlamydia trachomatis (nvCT) was reported in Sweden. Because of a cryptic plasmid deletion, the nvCT was undetectable in several of the genetic diagnostic systems used worldwide at the time. This study aimed to evaluate whether the nvCT was present in specimens obtained from patients attending the outpatient sexually transmitted infection (STI) clinic at orebro University Hospital, orebro, Sweden already in 2002-2003. Methods In 2012, archival (-20 degrees C freezer) urogenital specimens (2002 (n=1083) and in 2003 (n=1143)) obtained from men (2002 (n=398) and 2003 (n=486)) and women (2002 (n=301) and 2003 (n=408)) were analysed with Cobas TaqMan CT test V.2.0. All C trachomatis positive specimens were subsequently examined using a duplex PCR assay that simultaneously detects the deletion on the nvCT cryptic plasmid and the ompA gene of C trachomatis genotype E. Results In total, 68 patients (9.7%) in 2002 and 61 (6.8%) in 2003 were C trachomatis positive. The duplex PCR assay identified 26 C trachomatis genotype E positive patients in 2002 (38%) and 25 in 2003 (41%). No nvCT was found in 2002, but one specimen obtained from a 23-year-old man in June 2003 was positive for the nvCT. Conclusions The nvCT was present as early as 2003 in orebro County, Sweden, which concurs with previously reported statistical estimations of its emergence. Accordingly, the nvCT spread undetected for at least 3years, explaining the high proportion (38%) in orebro County when it was first detected in late 2006.

  • 23. Lennell, A.
    et al.
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences.
    Use of hand disinfection reduces absenteeism from day care centres2008In: Eurosurveillance, ISSN 1560-7917, Vol. 13, no 42, p. Article 6-Article in journal (Other academic)
  • 24. Lennell, Anne
    et al.
    Kühlmann-Berenzon, Sharon
    Geli, Patricia
    Hedin, Katarina
    Petersson, Christer
    Cars, Otto
    Mannerquist, Kerstin
    Burman, Lars G.
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences.
    Alcohol-based hand-disinfection reduced children's absence from Swedish day care centers2008In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 97, no 12, p. 1672-1680Article in journal (Refereed)
    Abstract [en]

    Aim: To determine if the use of alcohol-based hand-disinfection as a complement to regular hand washing at daycare centers (DCCs) can reduce the childhood rate of absenteeism. Methods: Children aged 0–6 years attending DCC were studied in a cluster randomized controlled trial during 30 weeks. Thirty matched pairs of DCCs were included in the study, where one of the DCCs was randomized to intervention and the other to control within each pair. The intervention consisted in children and staff using alcohol-based oily disinfectant gel containing 70% ethanol after regular hand washing. The main outcome was the rate of episodes of absence from DCC due to infection. A regression model was fitted at the individual level and controlling several possible confounders for illness. Absences were reported by the parents. Results: Differences in missing absence reports between the two groups led to only evaluating those 29 DCCs (1431 children) that were able to provide complete reports. In the multivariate regression, the intervention significantly reduced the rate of absenteeism of a child by 12% compared to a child in a control DCC (IRR 95% CI: 0.799–0.965).

  • 25. 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.

  • 26.
    Lucidarme, J.
    et al.
    Meningococcal Reference Unit, Public Health England, Manchester, United Kingdom.
    Scott, K. J.
    Scottish Haemophilus, Legionella, Meningococcus and Pneumococcus Reference Laboratory, Glasgow Royal Infirmary, Glasgow, United Kingdom.
    Ure, R.
    Scottish Haemophilus, Legionella, Meningococcus and Pneumococcus Reference Laboratory, Glasgow Royal Infirmary, Glasgow, United Kingdom.
    Smith, A.
    Scottish Haemophilus, Legionella, Meningococcus and Pneumococcus Reference Laboratory, Glasgow Royal Infirmary, Glasgow, United Kingdom; College of Medical, Veterinary & Life Sciences, Glasgow Dental Hospital & School, University of Glasgow, Glasgow, United Kingdom.
    Lindsay, D.
    Scottish Haemophilus, Legionella, Meningococcus and Pneumococcus Reference Laboratory, Glasgow Royal Infirmary, Glasgow, United Kingdom.
    Stenmark, Bianca
    Örebro University, School of Medical Sciences. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Fredlund, Hans
    Örebro University, School of Health Sciences. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Cameron, J. C.
    Health Protection Scotland, NHS National Services Scotland, Glasgow, United Kingdom.
    Smith-Palmer, A.
    Health Protection Scotland, NHS National Services Scotland, Glasgow, United Kingdom.
    McMenamin, J.
    Health Protection Scotland, NHS National Services Scotland, Glasgow, United Kingdom.
    Gray, S. J.
    Meningococcal Reference Unit, Public Health England, Manchester, United Kingdom.
    Campbell, H.
    Immunisation Department, Public Health England, London, United Kingdom.
    Ladhani, S.
    Immunisation Department, Public Health England, London, United Kingdom.
    Findlow, J.
    Meningococcal Reference Unit, Public Health England, Manchester, United Kingdom.
    Mölling, Paula
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Borrow, R.
    Meningococcal Reference Unit, Public Health England, Manchester, United Kingdom.
    An international invasive meningococcal disease outbreak due to a novel and rapidly expanding serogroup W strain, Scotland and Sweden, July to August 20152016In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 21, no 45, p. 15-23, article id 30395Article in journal (Refereed)
    Abstract [en]

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

  • 27. 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.

  • 28.
    Malm, Kerstin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Andersson, Sören
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Norrgren, Hans
    Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
    Biague, Antonio
    National Public Health Laboratory (LNSP), Bissau, Guinea-Bissau.
    Månsson, Fredrik
    Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
    Ballard, R.
    Center for Global Health, Centers for Disease Control and Protection, Atlanta GA, USA.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Analytical evaluation of nine serological assays for diagnosis of syphilis2015In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 29, no 12, p. 2369-2376Article in journal (Refereed)
    Abstract [en]

    Background: The diagnosis of syphilis is most frequently dependent on antibody detection with serological assays. Assays for both treponemal and non-treponemal antibodies are needed to provide a sensitive and specific diagnosis. For decades, a first screening has been done with non-treponemal assays, followed by treponemal. However, in recent years, following laboratory automation, the reverse sequence screening algorithms have been developed, using a treponemal assay as the initial screening test.

    Objective: To evaluate serological assays for treponemal and non-treponemal antibodies, to use in reverse algorithm screening of syphilis.

    Material and methods: Six treponemal assays (one IgM-specific assay), two non-treponemal assays and one novel dual point-of-care (POC) assay for serological diagnosis of syphilis were evaluated. Serum samples from Guinea-Bissau and Sweden were examined, as well as two performance panels and samples from blood donors. Sensitivity and specificity were calculated for each assay, using different assays as gold standard test.

    Results: The Macro-Vue RPR Card test was the most sensitive non-treponemal test and the TrepSure Anti-Treponema EIA Screen and the SeroDia TP-PA were the most sensitive and specific treponemal assays. Among the automated assays, both the Liaison Treponema Screen and Architect Syphilis TP showed high sensitivity, however, the former had clearly higher specificity.

    Conclusions: In resourced settings, where the reverse sequence algorithm is preferred for screening, an automated treponemal immunoassay for initial screening subsequently followed by the TrepSure test or TP-PA assay as a second treponemal assay appear highly effective. Finally, a quantitative highly sensitive non-treponemal assay, e.g. the Macro-Vue RPR Card test, could then be used as a supplementary test to evaluate activity of the syphilis infection.

  • 29.
    Malm, Kerstin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Andersson, Sören
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Norrgren, Hans
    Lund University, Lund, Sweden.
    Biague, Antonio
    National Public Health Laboratory (LNSP), Bissau, Guinea-Bissau.
    Månsson, Fredrik
    Lund University, Lund, Sweden.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Analytical evaluation of nine serological assays for diagnosis of syphilisManuscript (preprint) (Other academic)
  • 30.
    Malm, Kerstin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Duberg, Ann-Sofi
    Örebro University, School of Medicine, Örebro University, Sweden.
    Sundqvist, Martin
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Andersson, Sören
    Evaluation of a hepatitis C virus core antigen assay to monitor viral load in patients on antiviral therapy and in untreated patientsManuscript (preprint) (Other academic)
  • 31.
    Malm, Kerstin
    et al.
    Örebro University Hospital, Örebro, Sweden.
    Ekermo, Bengt
    Linköping University Hospital, Linköping, Sweden.
    Hillgren, Kristina
    Maria Beroendecentrum, Centre for Dependency Disorders, Stockholm, Sweden.
    Britton, Sven
    Karolinska University Hospital, Solna, Sweden.
    Fredlund, Hans
    Örebro University Hospital, Örebro, Sweden.
    Andersson, Sören
    Örebro University Hospital, Örebro, Sweden.
    Prevalence of human T-lymphotropic virus type 1 and 2 infection in Sweden2012In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 44, no 11, p. 852-9Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Prevalence data on human T-lymphotropic virus types 1 and 2 (HTLV-1/2) in Sweden have not been updated since 1995. The seroprevalence among blood donors at that time was 0.2/10,000. A few years earlier, a high prevalence of HTLV-2 was found in intravenous drug users (IDUs) in Stockholm (3.4%). The objective of this study was to update information on the seroprevalence of HTLV in several study groups.

    METHODS: Serum samples from pregnant women, hepatitis C virus (HCV)-positive individuals, and IDUs in Stockholm were investigated for HTLV-1/2 antibodies. Data from the mandatory HTLV-1/2 screening (2003-2006) of in vitro fertilization (IVF) clients were compiled, as well as data from new blood donors.

    RESULTS: Eight out of 35,000 IVF patients were positive for anti-HTLV-1/2 (seroprevalence 2.3 per 10,000). Of the anti-HCV-positive individuals (n = 355), 1 sample was HTLV-1-positive (28.2 per 10,000). From 1995 to 2007, 18 HTLV-positive new blood donors were identified out of approximately 550,000 individuals tested (0.3 per 10,000). Thirty-five of 1079 tested IDUs were screening reactive.

    CONCLUSIONS: Since the start of screening in 1994, there has been no increased seroprevalence of HTLV-1/2 among blood donors in Sweden. Seroprevalence among Swedish IVF patients is 10 times higher than among blood donors. This finding is comparable to a 2003 European seroprevalence study of pregnant women in 7 countries. However, the possibility that the IVF group includes individuals with a higher risk of acquiring sexually transmitted infections, including HTLV, than the general population cannot be ruled out.

  • 32.
    Mårild, Karl
    et al.
    Örebro University, School of Health and Medical Sciences. Astrid Lindgren Childrens Hosp, Karolinska Univ Hosp, Solna, Sweden.
    Fredlund, Hans
    Örebro University Hospital, Örebro, Sweden.
    Ludvigsson, Jonas F.
    Dept Med, Clin Epidemiol Unit, Karolinska Inst, Stockholm, Sweden.
    Increased risk of hospital admission for influenza in patients with celiac disease: a nationwide cohort study in Sweden2010In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 105, no 11, p. 2465-2473Article in journal (Refereed)
    Abstract [en]

    Objectives: Although earlier studies suggest an increased risk of infectious disease in celiac disease (CD), data on the risk of influenza in patients with CD are limited. We examined the risk of hospital admission for influenza in CD patients, but for comparative reasons also in individuals with small-intestinal inflammation or normal mucosa but positive CD serology.

    Methods: In 2006-2008, we collected duodenal/jejunal biopsy data on CD (Marsh 3: villous atrophy, VA; n=29,008 unique individuals) and inflammation (Marsh 1-2; n=13,200) from all 28 pathology departments in Sweden. A third regional cohort consisted of 3,709 individuals with positive CD serology but normal mucosa (Marsh 0). The biopsies were performed between 1969 and 2008. Through linkage with the Swedish Hospital Discharge Register, we estimated the risk of hospital admission for influenza compared with that of 224,114 age-and sex-matched controls from the general population.

    Results: Individuals with CD were at increased risk of hospital admission for influenza (hazard ratio (HR)=2.1; 95% confidence interval (CI)=1.6-2.7; n=81). The absolute risk of influenza was 30/100,000 person-years (excess risk: 16/100,000 person-years). Furthermore, children with CD were at increased risk of influenza (HR=2.5; 95% CI=1.3-4.8). Whereas individuals with inflammation without VA were also at increased risk of influenza (HR=1.9; 95% CI=1.4-2.5), individuals with normal mucosa but positive CD serology were not (HR=1.2; 95% CI=0.5-3.0).

    Conclusions: This study found an increased risk of hospital admission for influenza in patients with CD.

  • 33.
    Olsen, Birgitta
    et al.
    Örebro University, Department of Clinical Medicine.
    Hadad, Ronza
    Fredlund, Hans
    Örebro University, Department of Clinical Medicine.
    Unemo, Magnus
    Örebro University, Department of Clinical Medicine.
    A view of the Neisseria gonorrhoeae population in Sweden in 2005: phenotypic and genetic characterisation2006Conference paper (Other academic)
    Abstract [en]

    Aims

    To phenotypically and genotypically characterise clinical N. gonorrhoeae isolates transmitted in Sweden during 2005 and to compare with characteristics of N. gonorrhoeae populations in other countries.

    Introduction

    In Sweden, the gonorrhoea incidence decreased from the beginning of the 1970s to 1996. From 1997 the incidence has almost annually increased, mainly due to a rise in domestic cases of young heterosexuals of both sexes and homosexual men. Furthermore, during recent decades resistance to most of the traditional antibiotics used in the treatment of gonorrhoea has rapidly increased worldwide. Availability of effective diagnostics, treatment and surveillance of epidemiological characteristics (antibiotic susceptibility, serovars and genotypes) are main tools for control of the transmission of infection.

    Materials, Methods & Results

    N. gonorrhoeae isolates (n=175) cultured in Sweden in 2005 and received at the Swedish Reference Laboratory for Pathogenic Neisseria were included. Phenotypic characterisation was performed by antibiotic susceptibility testing and serovar determination using both Genetic systems (GS) and Pharmacia (Ph) panels of monoclonal antibodies (MAbs). Genetic characterisation was performed using N. gonorrhoeae multiantigen sequence typing (NG-MAST) that analyses more variable segments of the porB gene (490 bp) and of the tbpB gene (390 bp).

    All isolates were susceptible to cefixime, ceftriaxone, and spectinomycin. The levels of intermediate susceptibility and resistance to azithromycin, ciprofloxacin, and ampicillin were 2.3%, 49.7% and 75.3%, respectively (Table 1). Fifty-seven (33%) of the isolates were -lactamase producing.

    In total, 33 of the isolates were determined as serogroup WI (PorB1a). These were assigned nine different GS-serovars and seven different Ph-serovars. Two of the PorB1a isolates were not serotypeable using Ph MAbs. The remaining 142 isolates were determined as serogroup WII/III (PorB1b). These isolates were assigned 18 different GS-serovars and 38 different Ph-serovars.

    The isolates displayed 66 and 56 divergent NG-MAST porB and tbpB alleles, respectively. These resulted in assignment of 95 different sequence types (STs), of which 34 have not been previously described. ST40 (n=15), ST225 (n=12), ST1813 (n=9), ST5 (n=8), ST753 (n=6), ST323 (n=5), and ST211 (n=4), were the most prevalent STs. Four STs were represented by three isolates, 20 STs by two isolates and 64 STs by single isolates (Figure 1).

    Conclusions

    A highly diverse N. gonorrhoeae population was transmitted in Sweden during 2005, which can reflect importation of strains from abroad, and/or in some geographic areas suboptimal diagnostics and incomplete epidemiological surveillance. However, many clusters of isolates, which can reflect the existence of several transmission chains, were also identified.

    Serovar determination is still fairly effective, rapid, inexpensive, easily performed and remains a valuable primary epidemiological marker of N. gonorrhoeae, which can supplement the superior genetic characterisation.

  • 34.
    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.

  • 35.
    Pellrud, Helena
    et al.
    STD Clinic, Department of Dermatovenereology, Örebro University Hospital, Örebro, Sweden.
    Golparian, Daniel
    WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, Swedish Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Nilsson, Christian Steezko
    STD Clinic, Department of Dermatovenereology, Örebro University Hospital, Örebro, Sweden.
    Falk, My
    STD Clinic, Department of Dermatovenereology, Örebro University Hospital, Örebro, Sweden.
    Fredlund, Hans
    Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, Swedish Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, Swedish Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Trichomonas vaginalis Infections are Rare Among Young Patients Attending an STI Clinic in Sweden2015In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 95, no 3, p. 343-344Article in journal (Refereed)
  • 36.
    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.

  • 37. Shipitsyna, Elena
    et al.
    Roos, Annika
    Datcu, Raluca
    Hallén, Anders
    Fredlund, Hans
    Örebro University Hospital.
    Jensen, Jørgen S
    Engstrand, Lars
    Unemo, Magnus
    Örebro University Hospital, Örebro, Sweden.
    Composition of the vaginal microbiota in women of reproductive age--sensitive and specific molecular diagnosis of bacterial vaginosis is possible?2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 4, article id e60670Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVE: Bacterial vaginosis (BV) is the most common vaginal disorder, characterized by depletion of the normal lactobacillus-dominant microbiota and overgrowth of commensal anaerobic bacteria. This study aimed to investigate the composition of the vaginal microbiota in women of reproductive age (healthy women and women with BV), with the view of developing molecular criteria for BV diagnosis.

    MATERIALS AND METHODS: Vaginal samples from 163 women (79 control, 73 BV and 11 intermediate (Lactobacillary grade II flora) cases) were analyzed using 454 pyrosequencing of the hypervariable regions V3-V4 of the 16S rRNA gene and 16 quantitative bacterial species/genus-specific real-time PCR assays. Sensitivities and specificities of potential BV markers were computed using the Amsel criteria as reference standard for BV. The use of quantitative thresholds for prediction of BV, determined for both relative abundance measured with 454 pyrosequencing and bacterial load measured with qPCR, was evaluated.

    RESULTS: Relative to the healthy women, the BV patients had in their vaginal microbiota significantly higher prevalence, loads and relative abundances of the majority of BV associated bacteria. However, only Gardnerella vaginalis, Atopobium vaginae, Eggerthella, Prevotella, BVAB2 and Megasphaera type 1 detected at or above optimal thresholds were highly predictable for BV, with the best diagnostic accuracy shown for A. vaginae. The depletion of Lactobacillus species combined with the presence of either G. vaginalis or A. vaginae at diagnostic levels was a highly accurate BV predictor.

    CONCLUSIONS: Quantitative determination of the presence of G. vaginalis, A. vaginae, Eggerthella, Prevotella, BVAB2 and Megasphaera type 1 as well as the depletion of Lactobacillus was highly accurate for BV diagnosis. Measurements of abundance of normal and BV microbiota relative to total bacteria in vaginal fluid may provide more accurate BV diagnosis, and be used for test-of-cure, rather than qualitative detection or absolute counts of BV related microorganisms.

  • 38.
    Sjöberg, Lennart
    et al.
    Department of Clinical Microbiology, Örebro Medical Center Hospital, Örebro, Sweden.
    Fredlund, Hans
    Department of Clinical Microbiology, Örebro Medical Center Hospital, Örebro, Sweden.
    Duberg, Ann-Sofie
    Department of Clinical Microbiology, Örebro Medical Center Hospital, Örebro, Sweden.
    A comparison between Bactec aerobic resin and hypertonic blood culture media.1988In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 96, no 8, p. 720-722Article in journal (Refereed)
    Abstract [en]

    The presence of antimicrobial agents in patients' blood is thought to represent an important source of false-negative blood cultures. This has led to the incorporation of agents with inhibitory effects on antimicrobial drugs into culture medium. In the present study, Bactec aerobic resin-containing blood culture medium was compared with Bactec hypertonic blood culture medium. 504 patients receiving cytostatic and/or antibiotic treatment were studied. Sensitivity calculations on detection of bacteremia in these patients gave 0.91 for the resin medium and 0.79 for the hypertonic blood culture system and showed a significant difference (p = 0.016). In addition, the resin-containing system more rapidly detected positive cultures than the hypertonic system.

  • 39.
    Smith-Palmer, A.
    et al.
    Health Protection Scotland, Glasgow, United Kingdom.
    Oates, K.
    NHS Highland, Inverness, United Kingdom.
    Webster, D.
    NHS Grampian, Aberdeen, United Kingdom.
    Taylor, S.
    NHS Shetland, Lerwick, United Kingdom.
    Scott, K. J.
    Scottish Haemophilus, Legionella, Meningococcus and Pneumococcus Reference Laboratory, Glasgow, United Kingdom.
    Smith, G.
    International Health Regulations National Focal Point, Public Health England, London, United Kingdom.
    Parcell, B.
    NHS Grampian, Aberdeen, United Kingdom.
    Lindstrand, A.
    Public Health Agency of Sweden, Solna, Sweden.
    Wallensten, A.
    Public Health Agency of Sweden, Solna, Sweden.
    Fredlund, Hans
    Örebro University, School of Health Sciences. National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sweden.
    Widerström, M.
    Stockholm County Council Medical Officer, Stockholm, Sweden.
    McMenamin, J.
    Health Protection Scotland, Glasgow, United Kingdom.
    Outbreak of Neisseria meningitidis capsular group W among scouts returning from the World Scout Jamboree, Japan, 20152016In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 21, no 45, p. 8-14, article id 30392Article in journal (Refereed)
    Abstract [en]

    The 23rd World Scout Jamboree was held in Japan from 28 July to 8 August 2015 and was attended by over 33,000 scouts from 162 countries. An outbreak of invasive meningococcal disease capsular group W was investigated among participants, with four confirmed cases identified in Scotland, who were all associated with one particular scout unit, and two confirmed cases in Sweden; molecular testing showed the same strain to be responsible for illness in both countries. The report describes the public health action taken to prevent further cases and the different decisions reached with respect to how wide to extend the offer of chemoprophylaxis in the two countries; in Scotland, chemoprophylaxis was offered to the unit of 40 participants to which the four cases belonged and to other close contacts of cases, while in Sweden chemoprophylaxis was offered to all those returning from the Jamboree. The report also describes the international collaboration and communication required to investigate and manage such multinational outbreaks in a timely manner.

  • 40.
    Thulin, Sara
    et al.
    Örebro University, School of Health and Medical Sciences.
    Olcén, Per
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences.
    Total variation in the penA gene of Neisseria meningitidis: correlation between susceptibility to beta-lactam antibiotics and penA gene heterogeneity2006In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 50, no 10, p. 3317-3324Article in journal (Refereed)
    Abstract [en]

    In recent decades, the prevalence of Neisseria meningitidis isolates with reduced susceptibility to penicillins has increased. The intermediate resistance to penicillin (Pen(i)) for most strains is due mainly to mosaic structures in the penA gene, encoding penicillin-binding protein 2. In this study, susceptibility to beta-lactam antibiotics was determined for 60 Swedish clinical N. meningitidis isolates and 19 reference strains. The penA gene was sequenced and compared to 237 penA sequences from GenBank in order to explore the total identified variation of penA. The divergent mosaic alleles differed by 3% to 24% compared to those of the designated wild-type penA gene. By studying the final 1,143 to 1,149 bp of penA in a sequence alignment, 130 sequence variants were identified. In a 402-bp alignment of the most variable regions, 84 variants were recognized. Good correlation between elevated MICs and the presence of penA mosaic structures was found especially for penicillin G and ampicillin. The Pen(i) isolates comprised an MIC of >0.094 microg/ml for penicillin G and an MIC of >0.064 microg/ml for ampicillin. Ampicillin was the best antibiotic for precise categorization as Pen(s) or Pen(i). In comparison with the wild-type penA sequence, two specific Pen(i) sites were altered in all except two mosaic penA sequences, which were published in GenBank and no MICs of the corresponding isolates were described. In conclusion, monitoring the relationship between penA sequences and MICs to penicillins is crucial for developing fast and objective methods for susceptibility determination. By studying the penA gene, genotypical determination of susceptibility in culture-negative cases can also be accomplished.

  • 41.
    Törös, B.
    et al.
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology/Molecular diagnostics R&D, Örebro University Hospital, Örebro, Sweden.
    Thulin [Hedberg], Sara
    Örebro University Hospital. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology/Molecular diagnostics R&D, Örebro University Hospital, Örebro, Sweden.
    Jacobsson, Susanne
    Örebro University Hospital. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology/Molecular diagnostics R&D, Örebro University Hospital, Örebro, Sweden.
    Fredlund, Hans
    Örebro University Hospital. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology/Molecular diagnostics R&D, Örebro University Hospital, Örebro, Sweden.
    Olcén, P.
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology/Molecular diagnostics R&D, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    Örebro University Hospital. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology/Molecular diagnostics R&D, Örebro University Hospital, Örebro, Sweden.
    Surveillance of invasive Neisseria meningitidis with a serogroup Y update, Sweden 2010 to 20122014In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 19, no 42, p. 25-33, article id UNSP 20940Article in journal (Refereed)
    Abstract [en]

    An increase of invasive meningococcal disease caused by Neisseria meningitidis serogroup Y has been noted in Sweden since 2005, and to a lower extent throughout Europe. The present study describes the epidemiology of invasive N. meningitidis isolates in Sweden in the period between 2010 and 2012, with a focus on serogroup Y. We also aimed to find an optimal molecular typing scheme for both surveillance and outbreak investigations. All invasive N. meningitidis isolates in Sweden during the study period (n=208) were genetically characterised. Serogroup Y predominated with 22/57, 31/61 and 44/90 of all invasive isolates (incidence 0.23, 0.33 and 0.46 per 100,000 population) in 2010, 2011 and 2012 respectively. In each of these years, 15/22, 22/31 and 19/44 of serogroup Y isolates were genetically clonal (Y: P1.5-2,10-1,36-2: F4-1: ST-23(cc23), 'porB allele 3-36, fHbp allele 25 and penA allele 22). Our findings further support those of others that currently recommended FetA typing could be replaced by FHbp. Moreover, in line with a previous study that we conducted, the current results indicate that highly variable multilocus variable-number tandem repeat analysis (HV-MLVA) can be used as a first-hand rapid method for small outbreak investigations.

  • 42.
    Törös, Bianca
    et al.
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Hedberg, Sara Thulin
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Jacobsson, Susanne
    Örebro University Hospital. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Fredlund, Hans
    Örebro University Hospital. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Olcén, Per
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    Örebro University Hospital. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Evaluation of molecular typing methods for identification of outbreak-associated Neisseria meningitidis isolates2013In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 121, no 6, p. 503-510Article in journal (Refereed)
    Abstract [en]

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

  • 43.
    Törös, Bianca
    et al.
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Hedberg, Sara [Thulin]
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Jacobsson, Susanne
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Fredlund, Hans
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Olcén, Per
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Surveillance of invasive Neisseria meningitidis with a serogroup Y update, Sweden 2010 to 2012Manuscript (preprint) (Other academic)
    Abstract [en]

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

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

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

  • 44.
    Törös, Bianca
    et al.
    Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Hedberg, Sara Thulin
    Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Jacobsson, Susanne
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Hill, Dorothea M. C.
    Department of Zoology, University of Oxford, Oxford, United Kingdom.
    Olcén, Per
    Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Bratcher, Holly B.
    Department of Zoology, University of Oxford, Oxford, United Kingdom.
    Jolley, Keith A.
    Department of Zoology, University of Oxford, Oxford, United Kingdom.
    Maiden, Martin C. J.
    Department of Zoology, University of Oxford, Oxford, United Kingdom.
    Mölling, Paula
    Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Genome-based characterization of emergent invasive Neisseria meningitidis serogroup Y isolates in Sweden from 1995 to 20122015In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 53, no 7, p. 2154-2162Article in journal (Refereed)
    Abstract [en]

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

  • 45.
    Törös, Bianca
    et al.
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Hedberg, Sara [Thulin]
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Jacobsson, Susanne
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Hill, Dorothea M.C.
    Department of Zoology, University of Oxford, Oxford, United Kingdom.
    Olcén, Per
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Fredlund, Hans
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Bratcher, Holly B.
    Department of Zoology, University of Oxford, Oxford, United Kingdom.
    Jolley, Keith A.
    Department of Zoology, University of Oxford, Oxford, United Kingdom.
    Maiden, Martin C.J.
    Department of Zoology, University of Oxford, Oxford, United Kingdom.
    Mölling, Paula
    National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Whole-genome characterization of emergent invasive Neisseria meningitidis serogroup Y in Sweden from the two recent decadesManuscript (preprint) (Other academic)
    Abstract [en]

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

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

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

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

  • 46.
    Unemo, Magnus
    et al.
    Örebro University, School of Health and Medical Sciences.
    Olcén, Per
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences.
    Hedberg, Sara Thulin
    Real-time PCR and subsequent pyrosequencing for screening of penA mosaic alleles and prediction of reduced susceptibility to expanded-spectrum cephalosporins in Neisseria gonorrhoeae2008Conference paper (Other academic)
  • 47.
    Unemo, Magnus
    et al.
    Örebro University, School of Health and Medical Sciences.
    Olcén, Per
    Örebro University, School of Health and Medical Sciences.
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences.
    Hedberg, Sara Thulin
    Örebro University, School of Health and Medical Sciences.
    Real-time PCR and subsequent pyrosequencing for screening of penA mosaic alleles and prediction of reduced susceptibility to expanded-spectrum cephalosporins in Neisseria gonorrhoeae2008In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 116, no 11, p. 1004-1008Article in journal (Refereed)
  • 48.
    Unemo, Magnus
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sweden; Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Ringlander, Johan
    WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Örebro University, Örebro Sweden; Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Wiggins, Catherine
    Sexually Transmitted Bacteria Reference Unit, Public Health England, London, United Kingdom.
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Örebro University, Örebro Sweden; Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Jacobsson, Susanne
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Örebro University, Örebro Sweden; Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Cole, Michelle
    Sexually Transmitted Bacteria Reference Unit, Public Health England, London, United Kingdom.
    High In Vitro Susceptibility to the Novel Spiropyrimidinetrione ETX0914 (AZD0914) among 873 Contemporary Clinical Neisseria gonorrhoeae Isolates from 21 European Countries from 2012 to 20142015In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 59, no 9, p. 5220-5225Article in journal (Refereed)
    Abstract [en]

    Resistance in Neisseria gonorrhoeae against all antimicrobials available for the treatment of gonorrhea has emerged. The first gonococcal strains with high-level resistance to ceftriaxone, the last option for first-line empirical antimicrobial monotherapy, were recently described. Consequently, new treatment options are essential. In this study, the in vitro activity of the novel spiropyrimidinetrione ETX0914 (AZD0914), a DNA topoisomerase II inhibitor, was investigated among contemporary consecutive clinical N. gonorrhoeae isolates obtained in 21 European countries and compared to the activities of antimicrobials currently or previously recommended for treatment. Consecutive clinical N. gonorrhoeae isolates (n = 873) cultured in 21 European countries from 2012 to 2014 were examined for their susceptibility to ETX0914. The MICs of ETX0914 were determined using the agar dilution method. For comparison, the MICs of ceftriaxone, cefixime, azithromycin, and ciprofloxacin were determined using Etest or the agar dilution method. For ETX0914, the MIC range, modal MIC, MIC50, and MIC90 were <= 0.002 to 0.25 mg/liter, 0.125 mg/liter, 0.064 mg/liter, and 0.125 mg/liter, respectively. The MIC values were substantially lower than those of the fluoroquinolone ciprofloxacin and most other antimicrobials examined. No cross-resistance with any other examined antimicrobial was observed. In conclusion, the in vitro susceptibility to the novel spiropyrimidinetrione ETX0914 (AZD0914) among 873 contemporary clinical isolates from 21 European countries was high, and no cross-resistance to antimicrobials currently or previously used for gonorrhea treatment was indicated. Additional studies investigating the in vitro and in vivo induction and mechanisms of ETX0914 resistance in gonococci, pharmacokinetics/pharmacodynamics in modeling/simulations and in humans, and performance in randomized controlled gonorrhea treatment trials are essential.

  • 49.
    Wallensten, A.
    et al.
    Public Health Agency of Sweden, Solna, Sweden; Department of Medical Sciences, Infectious Diseases, Uppsala University, Uppsala, Sweden.
    Fredlund, Hans
    Örebro University Hospital. Department of Laboratory Medicine Clinical Microbiology, Communicable Disease Control Unit, Örebro University Hospital, Örebro, Sweden.
    Runehagen, A.
    Communicable Diseases Control Unit, Kronoberg County Council, Växjö, Sweden.
    Multiple human-to-human transmission from a severe case of psittacosis, Sweden, January-February 20132014In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 19, no 42, p. 34-39, article id 20937Article in journal (Refereed)
    Abstract [en]

    Proven transmission of Chlamydia psittaci between humans has been described on only one occasion previously. We describe an outbreak which occurred in Sweden in early 2013, where the epidemiological and serological investigation suggests that one patient, severely ill with psittacosis after exposure to wild bird droppings, transmitted the disease to ten others: Two family members, one hospital roommate and seven hospital caregivers. Three cases also provided respiratory samples that could be analysed by PCR. All the obtained C. psittaci sequences were indistinguishable and clustered within genotype A. The finding has implications for the management of severely ill patients with atypical pneumonia, because these patients may be more contagious than was previously thought. In order to prevent nosocomial person-to-person transmission of C. psittaci, stricter hygiene measures may need to be applied.

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