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  • 1. Berglund, T
    et al.
    Unemo, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment.
    Giesecke, J
    Fredlund, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment.
    Re-emergence of domestic gonorrhoea in Sweden.2001In: Int J STD AIDS,2001, 2001, p. 94-94Conference paper (Refereed)
  • 2.
    Berglund, Torsten
    et al.
    Unit for Infectious Disease Epidemiology, Microbiology and Tumour Biology Centre, Karolinska Institute, Stockholm, Sweden and Unit for Infectious Disease Epidemiology, Swedish Institute for Infectious Disease Control, Solna, Sweden.
    Unemo, Magnus
    Department of Clinical Microbiology and Immunology, Örebro Medical Centre Hospital, Örebro, Sweden.
    Olcén, Per
    Department of Clinical Microbiology and Immunology, Örebro Medical Centre Hospital, Örebro, Sweden.
    Giesecke, Johan
    Unit for Infectious Disease Epidemiology, Microbiology and Tumour Biology Centre, Karolinska Institute, Stockholm, Sweden and Unit for Infectious Disease Epidemiology, Swedish Institute for Infectious Disease Control, Solna, Sweden.
    Fredlund, Hans
    Department of Clinical Microbiology and Immunology, Örebro Medical Centre Hospital, Örebro, Sweden and Unit for Infectious Disease Control, Department of Clinical Microbiology and Immunology, Örebro Medical Centre Hospital, Örebro, Sweden.
    One year of Neisseria gonorrhoeae isolates in Sweden: the prevalence study of antibiotic susceptibility shows relation to the geographic area of exposure2002In: International Journal of STD and AIDS (London), ISSN 0956-4624, E-ISSN 1758-1052, Vol. 13, no 2, p. 109-114Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to compare epidemiological data with antibiotic susceptibility patterns, so as to characterize the risk of infection with a highly resistant Neisseria gonorrhoeae strain. N. gonorrhoeae strains isolated in Sweden from February 1998 through January 1999 were tested for antibiotic susceptibility. Epidemiological data were received from each clinician reporting a case of gonorrhoea and these data were linked to the N. gonorrhoeae strains. A total of 348 N. gonorrhoeae isolates, representing 89% of all Swedish cases diagnosed during the 12-month period, were tested for antibiotic susceptibility. Of all isolates, 24% were β-lactamase-producing, and 18% had decreased susceptibility to ciprofloxacin (MIC>0.064 mg/l). All isolates were fully susceptible to ceftriaxone and spectinomycin. More than 99% of the isolates were fully susceptible to azithromycin. The antibiotic susceptibility varied with the places where patients were exposed to infection. When exposed in Asia, 63% of the isolates showed reduced susceptibility to ciprofloxacin, compared with 0-8.5% of the isolates from patients exposed in other places (RR=8.5, P<0.001). Ciprofloxacin cannot be recommended as the first choice of treatment if the place of exposure was in Asia.

  • 3.
    Clarke, S. C.
    et al.
    Scottish Meningococcus and Pneumococcus Reference Laboratory, North Glasgow University Hospitals NHS Trust, Stobhill Hospital, Scotland, UK and Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow, Scotland, UK.
    Diggle, M. A.
    Scottish Meningococcus and Pneumococcus Reference Laboratory, North Glasgow University Hospitals NHS Trust, Stobhill Hospital, Scotland, UK.
    Mölling, Paula
    National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sweden.
    Olcén, Per
    National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sweden.
    Analysis of PorA variable region 3 in meningococci: implications for vaccine policy?2003In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 21, no 19-20, p. 2468-2473Article in journal (Refereed)
    Abstract [en]

    Outer membrane protein (OMP) vaccines are being developed against Neisseria meningitidis serogroup B which may provide protection against common circulating serotypes and serosubtypes in some countries. However, limited data is available in Europe from genosubtyping meningococci. We therefore undertook a retrospective analysis of the three main variable regions, VR1, VR2 as well as VR3, of the porA gene from N. meningitidis isolated from different countries, mainly from Scotland and Sweden. Analysis of this gene showed that, amongst 226 strains studied, there were a total of 78 different strains. No new VR1 or VR2 alleles were found but five new VR3 alleles are described. Our data indicates the importance of analysing the VR3 region of PorA in addition to VR1 and VR2 and also highlights, in general terms, the need for genosubtyping meningococci. Such analyses have major implications for the design of new meningococcal vaccines.

  • 4.
    Fjeldsoe-Nielsen, H
    et al.
    H:S Hvidovre Hospital.
    Unemo, Magnus
    Örebro University Hospital.
    Fredlund, Hans
    Örebro University Hospital.
    Hjorth, SV
    Danish Neisseria gonorrhoeae Reference Laboratory.
    Berthelsen, LM
    Danish Neisseria gonorrhoeae Reference Laboratory.
    Palmer, HM
    Scottish Neisseria gonorrhoeae Reference Laboratory.
    Friis-Möller, A
    H:S Hvidovre Hospital.
    Phenotypic and genotypic characterization of prolyliminopeptidase-negative Neisseria gonorrhoeae isolates in Denmark.2005In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 24, no 4, p. 280-283Article in journal (Refereed)
    Abstract [en]

    In the study presented here 26 recent Danish clinical isolates of prolyliminopeptidase (PIP)-negative Neisseria gonorrhoeae were phenotypically and genotypically characterized to investigate whether one or more PIP-negative strains are circulating in the Danish community. The profiles of these isolates were compared with those of three isolates from a recent outbreak of PIP-negative N. gonorrhoeae infection in the UK. Twenty-five of the Danish isolates and all three UK isolates had similar antibiograms and were designated serovar IB-4. Genotypic characterization by pulsed-field gel electrophoresis, porB1b gene sequencing, and opa-typing revealed that these isolates were indistinguishable or closely related. The results indicate that at least one PIP-negative N. gonorrhoeae strain is currently circulating in the Danish community, and this strain is indistinguishable from the one that caused an outbreak in the UK.

  • 5.
    Issa, Mohamed
    et al.
    Department of Microbiology and Parasitology, College of Medicine, Juba University, Sudan and Reference Laboratory of Meningitis, Department of Bacteriology, National Health Laboratory, Khartoum, Sudan.
    Mölling, Paula
    National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Bäckman, Anders
    National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Sulaiman, Nageeb
    Reference Laboratory of Meningitis, Department of Bacteriology, National Health Laboratory, Khartoum, Sudan.
    Olcén, Per
    National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    PCR of Cerebrospinal Fluid for Diagnosis of Bacterial Meningitis During Meningococcal Epidemics: an Example from Sudan2003In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 35, no 10, p. 719-723Article in journal (Refereed)
    Abstract [en]

    Meningococcal disease is feared due to its rapid progression and high case fatality rate, especially in the African meningitis belt, where epidemics of meningococcal meningitis appear cyclically. Culture, direct microscopy and antigen detection are the basic methods for diagnosis and species identification of bacterial meningitis. These methods are known to have limitations, especially in developing countries. The aim of the present study was to document the application of PCR technology for the diagnosis of bacterial meningitis in cerebrospinal fluid (CSF) samples (n = 52) collected during epidemics in Sudan. In the application of PCR for detection of the causative agent of bacterial meningitis (based on the 16S rRNA gene), bacterial DNA was identified in 49 samples. Common bacterial species causing bacterial meningitis could be detected in 31 of the CSF samples (27 meningococci), while 18 contained DNA, mainly from normally contaminating bacteria. A specific PCR for group A meningococci (based on the sacC gene) was positive in 27 of the CSF samples. The results show that PCR technology is a sharpedged tool for confirmation of a diagnosis of meningococcal meningitis and for obtaining a direct genogrouping of group A meningococci in CSF. It is important to stress the use of direct and specific PCRs to avoid interference by contaminating bacteria, a great problem in samples from areas in the meningitis belt.

  • 6.
    Issa, Mohamed
    et al.
    Dept. of Microbiology/Parasitology, College of Medicine, Juba University, Juba, Sudan and Reference Laboratory for Meningitis, Department of Bacteriology, National Health Laboratory, Khartoum, Sudan.
    Mölling, Paula
    National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Bäckman, Anders
    National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Mosaad, Mohamed
    Reference Laboratory for Meningitis, Department of Bacteriology, National Health Laboratory, Khartoum, Sudan.
    Sulaiman, Nageeb
    Reference Laboratory for Meningitis, Department of Bacteriology, National Health Laboratory, Khartoum, Sudan.
    Olcén, Per
    National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Neisseria meningitidis serogroup W-135 isolated from healthy carriers and patients in Sudan after the Hajj in 20002003In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 35, no 4, p. 230-233Article in journal (Refereed)
    Abstract [en]

    The first epidemic in the world of meningococcal disease due to serogroup W-135 was reported during the Hajj in 2000, with subsequent spread. The aims of the present study were to investigate whether the Hajj 2000 Neisseria meningitidis serogroup W-135 had also been carried to Sudan in the eastern part of the African meningitis belt, by examining healthy Sudanese pilgrims (Hajj 2000) and members of their families, and whether the strain was causing meningitis. The phenotypic character of W-135 meningococci from Sudanese carriers (n = 5) and patients (n = 2) 1 y later was similar to W-135 strains associated with Hajj 2000. The present study, using the combination of the 2 molecular techniques; sequencing of the porA gene for variable regions (VR1, VR2 and VR3) and pulsed-field gel electrophoresis of the entire genome (using SpeI and NheI), shows that the Hajj 2000 serogroup W-135 clone (P1.5,2,36-2 of the ET-37 complex) most probably was introduced into Sudan, by pilgrims returning from the Hajj 2000. This strain has not been diagnosed before in Sudan. Close epidemiological surveillance is required to identify a possible new emerging meningitis epidemic.

  • 7.
    Jacobsson, Susanne
    et al.
    National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Issa, Mohamed
    Reference Laboratory of Meningitis, Department of Bacteriology, National Health Laboratory, Khartoum, Sudan and Department of Microbiology and Parasitology, College of Medicine, Juba University, Sudan.
    Unemo, Magnus
    National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Bäckman, Anders
    National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Sulaiman, Nageeb
    Reference Laboratory of Meningitis, Department of Bacteriology, National Health Laboratory, Khartoum, Sudan.
    Olcén, Per
    National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Molecular characterisation of group A Neisseria meningitidis isolated in Sudan 1985–20012003In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 111, no 11, p. 1060-1066Article in journal (Refereed)
    Abstract [en]

    A total of 33 group A Neisseria meningitidis (Mc) isolates, collected in Sudan between 1985 and 2001, were studied in order to describe the changes over time in a country within the meningitis belt of Africa. The isolates were characterised by traditional phenotypic methods (serogrouping, serotyping, serosubtyping and antibiogram) and molecular techniques (genosubtyping, pulsed-field gel electrophoresis [PFGE] with restriction endonucleases SpeI and NheI, and multilocus sequence typing [MLST]). Three clones of group A Mc were identified: one before 1988 (sulphadiazine sensitive, serotype 4, genosubtype P1.7,13-1,35-1, sequence type 4 [ST-4]); another during and after the 1988 epidemic (sulphadiazine resistant, serotype 4, genosubtype P1.20,9,35-1, ST-5); and a third causing the 1999 epidemic (sulphadiazine resistant, serotype 4, genosubtype P1.20,9,35-1, ST-7). The first clone showed major differences compared to the other two. The second and third clones had many similarities with differences in only a single gene (pgm) in the MLST (47 of the 450 bp) but significant other differences according to the PFGE patterns. Within the clones, genosubtyping and MLST gave identical information (except one base substitution in the aroE gene in one isolate). However, the PFGE patterns showed changes over time within the clones, where SpeI revealed somewhat more diversity than NheI.

  • 8.
    Jacobsson, Susanne
    et al.
    National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Thulin, Sara
    National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Comanducci, Maurizio
    IRIS, Chiron srl, Siena, Italy.
    Rappuoli, Rino
    IRIS, Chiron srl, Siena, Italy.
    Olcén, Per
    National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Sequence constancies and variations in genes encoding three new meningococcal vaccine candidate antigens2006In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 24, no 12, p. 2161-2168Article in journal (Refereed)
    Abstract [en]

    By the strategy “reverse vaccinology” a number of new antigens have been identified in Neisseria meningitidis, which are potential candidates for a highly needed broad-spectrum meningococcal vaccine. In the present study we examined the prevalence, sequence constancies and variations of the genes encoding three of these new antigens designated, genome-derived neisserial antigen (GNA) 1870, GNA1946 and GNA2132. All three genes were present in all N. meningitidis isolates tested. Concerning gna1870, three major variants of the gene sequences and deduced amino acid sequences were identified and 56% of the deduced amino acids were conserved in all isolates. In gna1946, 98% of the deduced amino acids were conserved and in gna2132, 54% of the deduced amino acids were conserved. Based on gene prevalence and conservation, all three antigens are promising candidates for an effective meningococcal vaccine against all N. meningitidis irrespective of serogroup.

  • 9.
    Lundbäck, David
    et al.
    Örebro University Hospital.
    Fredlund, Hans
    Örebro University Hospital.
    Berglund, Torsten
    Karolinska Institutet.
    Wretlind, Bengt
    Karolinska Institutet.
    Unemo, Magnus
    Örebro University Hospital.
    Molecular epidemiology of Neisseria gonorrhoeae-identification of the first presumed Swedish transmission chain of an azithromycin-resistant strain.2006In: 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.

  • 10.
    Thulin, Sara
    et al.
    Örebro University Hospital.
    Olcén, Per
    Örebro University Hospital.
    Fredlund, Hans
    Örebro University Hospital.
    Unemo, Magnus
    Örebro University Hospital.
    Total variation in the penA gene of Neisseria meningitides: Correlation between susceptibility to beta-lactam antibiotics and penA gene heterogeneity.2006In: 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 (Peni) for most strains is due mainly to mosaic structures in the penA gene, encoding penicillin-binding protein 2. In this study, susceptibility to ß-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 Peni isolates comprised an MIC of >0.094 µg/ml for penicillin G and an MIC of >0.064 µg/ml for ampicillin. Ampicillin was the best antibiotic for precise categorization as Pens or Peni. In comparison with the wild-type penA sequence, two specific Peni 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.

  • 11.
    Unemo, Magnus
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Genotypic and phenotypic characterisation of Neisseria gonorrhoeae2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The bacterium Neisseria gonorrhoeae (the gonococcus) is the aetiological agent of gonorrhoea, which remains a major sexually transmitted infection/disease (STI/STD) worldwide. The incidence of gonorrhoea was previously high in many countries, Sweden included. The incidence in Sweden culminated in 1970 with 487 cases per 100,000 inhabitants. After that, the incidence declined almost every year until an all-time low of 2.4 was observed in 1996. ln 1997 the incidence of gonorrhoea began to significantly increase in Sweden, due mainly to a larger number of domestic cases of young heterosexuals of both sexes and homosexual men. This observation, in combination with the widespread use of suboptimal methods for characterisation and, in some countries, for diagnosis of the bacterium, as well as the rapid increase of resistance to several antibiotics, has intensified the research in the field of N. gonorrhoeae.

    In the present thesis (paper 1), a high prevalence of decreased susceptibility or resistance to several of the traditionally used gonorrhoea antibiotics was identified and correlated to the geographic area of exposure, especially Asia. Nevertheless, effective antibiotics for treating gonorrhoea are at hand. A substantial genetic heterogeneity within identical serological variants (serovars), i.e. intraserovar, as well as interserovar of N. gonorrhoeae strains circulating within the community was revealed, emphasising the importance of using highly discriminative (DNA-based) epidemiological characterisation methods for the bacteria (papers II-V). Effective DNA-based characterisation methods, i.e. pulsed-field gel electrophmesis (PFGE) of genomic DNA digested with rarely cutting restriction endonucleases and porB gene sequencing, were adapted, optimised and evaluated against conventional phenotypic methods, as epidemiological tools on Swedish N. gonorrhoeae isolates. These molecular techniques showed a significantly higher discriminatory ability, reproducibility, and objectivity than the serovar determinations using the Genetic Systems (OS) or the Pharmacia panel (Ph) ofmonoclonal antibodies (MAbs) (papers II & III). According to a comparison of serologic and genetic parB-based typing of N. gonorrhoeae, the precise amino acid residues of porB, critical for the reactivity of several of the GS MAbs, were difficult to identity (paper IV). In papers IV & V, a determination of genetic group (genogroup) and genetic variant (genovar) was developed based on real-time PCR of the entire porB gene with subsequent sequence analysis in real-time by synthesis, i.e. pyrosequencing technology, of short, highly polymorphic porB gene segments. This method provides a rapid, high-throughput, objective, highly discriminative, typeable, portable for interlaboratory comparisons, and reproducible molecular characterisation for N. gonorrhoeae. Genogroup and genovar determination can complement or even replace the internationally established serovar determination in routine use for following the transmission of individual strains in the community and confirming presumed epidemiological connections or discriminating isolates of suspected clusters of gonorrhoea cases.

    List of papers
    1. One year of Neisseria gonorrhoeae isolates in Sweden: the prevalence study of antibiotic susceptibility shows relation to the geographic area of exposure
    Open this publication in new window or tab >>One year of Neisseria gonorrhoeae isolates in Sweden: the prevalence study of antibiotic susceptibility shows relation to the geographic area of exposure
    Show others...
    2002 (English)In: International Journal of STD and AIDS (London), ISSN 0956-4624, E-ISSN 1758-1052, Vol. 13, no 2, p. 109-114Article in journal (Refereed) Published
    Abstract [en]

    The aim of this study was to compare epidemiological data with antibiotic susceptibility patterns, so as to characterize the risk of infection with a highly resistant Neisseria gonorrhoeae strain. N. gonorrhoeae strains isolated in Sweden from February 1998 through January 1999 were tested for antibiotic susceptibility. Epidemiological data were received from each clinician reporting a case of gonorrhoea and these data were linked to the N. gonorrhoeae strains. A total of 348 N. gonorrhoeae isolates, representing 89% of all Swedish cases diagnosed during the 12-month period, were tested for antibiotic susceptibility. Of all isolates, 24% were β-lactamase-producing, and 18% had decreased susceptibility to ciprofloxacin (MIC>0.064 mg/l). All isolates were fully susceptible to ceftriaxone and spectinomycin. More than 99% of the isolates were fully susceptible to azithromycin. The antibiotic susceptibility varied with the places where patients were exposed to infection. When exposed in Asia, 63% of the isolates showed reduced susceptibility to ciprofloxacin, compared with 0-8.5% of the isolates from patients exposed in other places (RR=8.5, P<0.001). Ciprofloxacin cannot be recommended as the first choice of treatment if the place of exposure was in Asia.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26456 (URN)10.1258/0956462021924730 (DOI)11004 (Local ID)11004 (Archive number)11004 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    2. Pulsed-field gel electrophoresis as an epidemiologic tool for Neisseria gonorrhoeae: Identification of clusters within serovars
    Open this publication in new window or tab >>Pulsed-field gel electrophoresis as an epidemiologic tool for Neisseria gonorrhoeae: Identification of clusters within serovars
    2002 (English)In: Sexually Transmitted Diseases, ISSN 0148-5717, E-ISSN 1537-4521, Vol. 29, no 1, p. 25-31Article in journal (Refereed) Published
    Abstract [en]

    Background: The increasing incidence of gonorrhea in Sweden in 1998 was due to mostly domestic cases. Among these, two core groups were identified: homosexual men with serovar IB-2 and young heterosexuals with serovar IB-3.

    Goals: To explore the genetic homogeneity/heterogeneity within the predominant serovars, IB-2 and IB-3, of Neisseria gonorrhoeae in Sweden by pulsed-field gel electrophoresis (PFGE) and to compare these results to epidemiologic information, as well as examine the genetic diversity within and between the 25 other represented serovars of N gonorrhoeae.

    Study Design: By PFGE, 237 N gonorrhoeae isolates were examined, and the results were compared with epidemiologic data for the IB-2 and IB-3 isolates.

    Results: In 79% of the domestic IB-2 cases involving homosexuals and 66% of the domestic IB-3 cases involving young heterosexuals, the isolates were genetically indistinguishable by PFGE. A high genetic diversity was identified within and between the 27 included serovars.

    Conclusions: Examination by means of PFGE indicated that one N gonorrhoeae clone each of the serovars IB-2 and IB-3 created the majority of the two core groups of domestic cases.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26457 (URN)11773875 (PubMedID)11005 (Local ID)11005 (Archive number)11005 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    3. Molecular epidemiology of Neisseria gonorrhoeae: sequence analysis of the porB gene confirms presence of two circulating strains
    Open this publication in new window or tab >>Molecular epidemiology of Neisseria gonorrhoeae: sequence analysis of the porB gene confirms presence of two circulating strains
    Show others...
    2002 (English)In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 40, no 10, p. 3741-3749Article in journal (Refereed) Published
    Abstract [en]

    The phenotypic and genotypic characteristics of Neisseria gonorrhoeae strains fluctuate over time both locally and globally, and highly discriminative and precise characterization of the strains is essential. Conventional characterization of N. gonorrhoeae strains for epidemiological purposes is mostly based on phenotypic methods, which have some inherent limitations. In the present study sequence analysis of porB1b gene sequences was used for examination of the genetic relationships among N. gonorrhoeae strains. Substantial genetic heterogeneity was identified in the porB genes of serovar IB-2 isolates (8.1% of the nucleotide sites were polymorphic) and serovar IB-3 isolates (5.2% of the nucleotide sites were polymorphic) as well as between isolates of different serovars. The highest degree of diversity was identified in the gene segments encoding the surface-exposed loops of the mature PorB protein. Phylogenetic analysis of the porB1b gene sequences confirmed previous findings that have indicated the circulation of one N. gonorrhoeae strain each of serovar IB-2 and serovar IB-3 in the Swedish community. These strains caused the majority of the cases in two domestic core groups comprising homosexual men and young heterosexuals, respectively, and were also detected in other patients. The phylogenetic analyses of porB gene sequences in the present study showed congruence, but not complete identity, with previous results obtained by pulsed-field gel electrophoresis of the same isolates. In conclusion, porB gene sequencing can be used as a molecular epidemiological tool for examination of genetic relationships among emerging and circulating N. gonorrhoeae strains, as well as for confirmation or discrimination of clusters of gonorrhea cases.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26455 (URN)10.1128/​JCM.40.10.3741-3749.2002 (DOI)11003 (Local ID)11003 (Archive number)11003 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    4. Comparison of serologic and genetic porB-based typing of Neisseria gonorrhoeae: consequences for future characterization
    Open this publication in new window or tab >>Comparison of serologic and genetic porB-based typing of Neisseria gonorrhoeae: consequences for future characterization
    2003 (English)In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 41, no 9, p. 4141-4147Article in journal (Refereed) Published
    Abstract [en]

    Due to temporal changes in the epidemiology of gonorrhea, a precise characterization of Neisseria gonorrhoeae is essential. In the present study genetic heterogeneity in the porB genes of N. gonorrhoeae was examined, and serovar determination was compared to porB gene sequencing. Among 108 N. gonorrhoeae isolates, phylogenetic analysis of the entire porB alleles (924 to 993 bp) identified 87 unique sequences. By analyzing only the four to six most heterogeneous porB gene regions (174 to 363 bp), 86 out of these 87 genetic variants were identified. Consequently, analysis of shorter highly variable regions of the porB gene generates high-level discriminatory ability as well as fast, objective, reproducible, and portable data for epidemiological characterization of N. gonorrhoeae. Regarding putative antigenic epitopes of PorB for Genetic Systems monoclonal antibodies (MAbs), some of the previous findings were confirmed, but new findings were also observed. For several of the MAbs, however, the precise amino acid residues of PorB critical for single-MAb reactivity were difficult to identify. In addition, repeated serovar determination of 108 N. gonorrhoeae isolates revealed discrepancies for 34 isolates, mostly due to nonreproducible reactivity with single MAbs. Thus, the prospects of a genetic typing system with congruent translation of the serovar determination seem to be limited. In conclusion, analysis of short highly variable regions of the porB gene could form the basis for a fast molecular epidemiological tool for the examination of emergence and transmission of N. gonorrhoeae strains within the community.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26458 (URN)10.1128/​JCM.41.9.4141-4147.2003 (DOI)11006 (Local ID)11006 (Archive number)11006 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    5. Genetic variant (genovar) determination of Neisseria gonorrhoeae by pyrosequencing of highly polymorphic segments of the porB gene
    Open this publication in new window or tab >>Genetic variant (genovar) determination of Neisseria gonorrhoeae by pyrosequencing of highly polymorphic segments of the porB gene
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    For prevention and control of gonorrhea, an objective, highly discriminating, and reproducible molecular epidemiological characterization of Neisseria gonorrhoeae is essential. In the present study, in the pursuance of providing such qualities, pyrosequencing technology, a fast real-time DNA sequence analysis, was applied to six short, highly polymorphic porB gene segments, with subsequent genetic variant (genovar) determination of the bacterial isolates. The DNA sequencing templates were obtained by real-time PCR amplification, which also included fluorescence melting curve analysis of the entire porB gene in order to determine the genogroup (porB1a or porB1b allele) prior to pyrosequencing analysis. The PSQ 96 MA system used allowed rapid (approximately 1.5 h) determination of 96 sequences of 20 to 65 correct nucleotides each. The results were reproducible and mostly in concordance with the results of conventional Sanger dideoxy-sequencing, with the exception of shorter read lengths and some uncertainty in determining the correct number of identical nucleotides in homopolymeric segments. The number of sequence variants identified in each one of the six highly polymorphic segments of the porB1a and porB1b alleles (encoding surface exposed amino acid loops of the mature porB protein) ranged from 5 to 11 and 8 to 39, respectively. Among porB1a isolates (n=22) and porB1b isolates (n=65), 22 and 64 unique genovars were identified. All isolates were typeable. The current results provide evidence of a high discriminatory ability, practically the same as sequencing of the entire porB gene. In conclusion, the fast and high-throughput pyrosequencing technology can be used for molecular epidemiological characterization of N. gonorrhoeae.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84322 (URN)
    Available from: 2012-10-04 Created: 2012-10-04 Last updated: 2012-10-04Bibliographically approved
  • 12.
    Unemo, Magnus
    et al.
    National Reference Laboratory for Pathogenic Neisseria, Örebro Medical Centre Hospital, Örebro, Sweden.
    Berglund, Torsten
    Units for Infectious Disease Epidemiology, Microbiology and Tumour Biology Centre, Karolinska Institutet, Stockholm, and Swedish Institute for Infectious Disease Control, Solna, Sweden.
    Olcén, Per
    National Reference Laboratory for Pathogenic Neisseria, Örebro Medical Centre Hospital, Örebro, Sweden.
    Fredlund, Hans
    National Reference Laboratory for Pathogenic Neisseria and Unit for Infectious Disease Control, Department of Clinical Microbiology and Immunology, Örebro Medical Centre Hospital, Örebro, Sweden.
    Pulsed-field gel electrophoresis as an epidemiologic tool for Neisseria gonorrhoeae: Identification of clusters within serovars2002In: Sexually Transmitted Diseases, ISSN 0148-5717, E-ISSN 1537-4521, Vol. 29, no 1, p. 25-31Article in journal (Refereed)
    Abstract [en]

    Background: The increasing incidence of gonorrhea in Sweden in 1998 was due to mostly domestic cases. Among these, two core groups were identified: homosexual men with serovar IB-2 and young heterosexuals with serovar IB-3.

    Goals: To explore the genetic homogeneity/heterogeneity within the predominant serovars, IB-2 and IB-3, of Neisseria gonorrhoeae in Sweden by pulsed-field gel electrophoresis (PFGE) and to compare these results to epidemiologic information, as well as examine the genetic diversity within and between the 25 other represented serovars of N gonorrhoeae.

    Study Design: By PFGE, 237 N gonorrhoeae isolates were examined, and the results were compared with epidemiologic data for the IB-2 and IB-3 isolates.

    Results: In 79% of the domestic IB-2 cases involving homosexuals and 66% of the domestic IB-3 cases involving young heterosexuals, the isolates were genetically indistinguishable by PFGE. A high genetic diversity was identified within and between the 27 included serovars.

    Conclusions: Examination by means of PFGE indicated that one N gonorrhoeae clone each of the serovars IB-2 and IB-3 created the majority of the two core groups of domestic cases.

  • 13.
    Unemo, Magnus
    et al.
    Örebro University Hospital.
    Norlén, Olov
    Örebro University Hospital.
    Fredlund, Hans
    Örebro University Hospital.
    The por A pseudogene of Neisseria gonorrhoeae - low level of genetic polymorphism and a few, mainly identical, inactivating mutations.2005In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 113, no 6, p. 410-419Article in journal (Refereed)
    Abstract [en]

    N. meningitidis is the only Neisseria species known to express two outer membrane porins, PorA and PorB. However, a porA pseudogene has been identified in N. gonorrhoeae. The present study investigated the prevalence and genetic polymorphism of this porA pseudogene in 87 different N. gonorrhoeae strains. The porA pseudogene was identified in all isolates. The pseudogene comprised 12 (5.5%), of which 10 were located in the promoter spacer, and 11 (1.0%) polymorphic nucleotide sites in the upstream segment containing the promoter region, i.e. the putative -10 and -35 sequences and the promoter spacer in-between, and the hypothetical PorA coding sequence, respectively. A phylogenetic analysis of the upstream segment and the hypothetical coding sequence identified 36 sequence variants, of which 30 were not previously described. All strains comprised at least two identical confirmed inactivating deletions, of which one was located in the promoter region and one in the hypothetical PorA coding sequence. In conclusion, the porA pseudogene and its few inactivating mutations are widespread in the N. gonorrhoeae population and the homology with the N. meningitidis porA gene reflects their common evolutionary origin. The highly conserved N. gonorrhoeae porA pseudogene may reflect an evolutionary neutral molecular clock and may be a suitable genetic target for diagnosis of N. gonorrhoeae.

  • 14.
    Unemo, Magnus
    et al.
    National Reference Laboratory for Pathogenic Neisseria, Örebro Medical Centre Hospital, Örebro, Sweden.
    Olcén, Per
    National Reference Laboratory for Pathogenic Neisseria, Örebro Medical Centre Hospital, Örebro, Sweden.
    Albert, Jan
    Department of Clinical Virology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden .
    Fredlund, Hans
    National Reference Laboratory for Pathogenic Neisseria and Unit for Infectious Disease Control, Department of Clinical Microbiology, Örebro University Hospital, Örebro.
    Comparison of serologic and genetic porB-based typing of Neisseria gonorrhoeae: consequences for future characterization2003In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 41, no 9, p. 4141-4147Article in journal (Refereed)
    Abstract [en]

    Due to temporal changes in the epidemiology of gonorrhea, a precise characterization of Neisseria gonorrhoeae is essential. In the present study genetic heterogeneity in the porB genes of N. gonorrhoeae was examined, and serovar determination was compared to porB gene sequencing. Among 108 N. gonorrhoeae isolates, phylogenetic analysis of the entire porB alleles (924 to 993 bp) identified 87 unique sequences. By analyzing only the four to six most heterogeneous porB gene regions (174 to 363 bp), 86 out of these 87 genetic variants were identified. Consequently, analysis of shorter highly variable regions of the porB gene generates high-level discriminatory ability as well as fast, objective, reproducible, and portable data for epidemiological characterization of N. gonorrhoeae. Regarding putative antigenic epitopes of PorB for Genetic Systems monoclonal antibodies (MAbs), some of the previous findings were confirmed, but new findings were also observed. For several of the MAbs, however, the precise amino acid residues of PorB critical for single-MAb reactivity were difficult to identify. In addition, repeated serovar determination of 108 N. gonorrhoeae isolates revealed discrepancies for 34 isolates, mostly due to nonreproducible reactivity with single MAbs. Thus, the prospects of a genetic typing system with congruent translation of the serovar determination seem to be limited. In conclusion, analysis of short highly variable regions of the porB gene could form the basis for a fast molecular epidemiological tool for the examination of emergence and transmission of N. gonorrhoeae strains within the community.

  • 15.
    Unemo, Magnus
    et al.
    National Reference Laboratory for Pathogenic Neisseria, Örebro Medical Centre Hospital, Örebro, Sweden.
    Olcén, Per
    National Reference Laboratory for Pathogenic Neisseria, Örebro Medical Centre Hospital, Örebro, Sweden.
    Berglund, Torsten
    Department of Medical Epidemiology, Karolinska Institute and Unit for Infectious Disease Epidemiology, Swedish Institute for Infectious Disease Control, Solna, Sweden.
    Albert, Jan
    Department of Clinical Virology, Karolinska Institute, Huddinge University Hospital, Stockholm .
    Fredlund, Hans
    National Reference Laboratory for Pathogenic Neisseria, Örebro Medical Centre Hospital, Örebro, Sweden and Unit for Infectious Disease Control, Department of Clinical Microbiology, Örebro University Hospital, Örebro .
    Molecular epidemiology of Neisseria gonorrhoeae: sequence analysis of the porB gene confirms presence of two circulating strains2002In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 40, no 10, p. 3741-3749Article in journal (Refereed)
    Abstract [en]

    The phenotypic and genotypic characteristics of Neisseria gonorrhoeae strains fluctuate over time both locally and globally, and highly discriminative and precise characterization of the strains is essential. Conventional characterization of N. gonorrhoeae strains for epidemiological purposes is mostly based on phenotypic methods, which have some inherent limitations. In the present study sequence analysis of porB1b gene sequences was used for examination of the genetic relationships among N. gonorrhoeae strains. Substantial genetic heterogeneity was identified in the porB genes of serovar IB-2 isolates (8.1% of the nucleotide sites were polymorphic) and serovar IB-3 isolates (5.2% of the nucleotide sites were polymorphic) as well as between isolates of different serovars. The highest degree of diversity was identified in the gene segments encoding the surface-exposed loops of the mature PorB protein. Phylogenetic analysis of the porB1b gene sequences confirmed previous findings that have indicated the circulation of one N. gonorrhoeae strain each of serovar IB-2 and serovar IB-3 in the Swedish community. These strains caused the majority of the cases in two domestic core groups comprising homosexual men and young heterosexuals, respectively, and were also detected in other patients. The phylogenetic analyses of porB gene sequences in the present study showed congruence, but not complete identity, with previous results obtained by pulsed-field gel electrophoresis of the same isolates. In conclusion, porB gene sequencing can be used as a molecular epidemiological tool for examination of genetic relationships among emerging and circulating N. gonorrhoeae strains, as well as for confirmation or discrimination of clusters of gonorrhea cases.

  • 16.
    Unemo, Magnus
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment.
    Olcén, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment.
    Falk, L
    Berglund, T
    Fredlund, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment.
    Sequencing of the porB gene of Neisseria gonorrhoeae (Ng); sequence variability inventory and comparative alignments for cluster confirmation.2001In: Int J STD AIDS,2001, 2001, p. 94-94Conference paper (Refereed)
  • 17.
    Unemo, Magnus
    et al.
    National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro.
    Olcén, Per
    National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro.
    Jonasson, Jon
    Unit for Infectious Disease Control, Department of Clinical Microbiology, Örebro University Hospital, Örebro.
    Fredlund, Hans
    Östergötlands Läns Landsting, LMÖ - Laboratoriemedicin i Östergötland.
    Genetic variant (genovar) determination of Neisseria gonorrhoeae by pyrosequencing of highly polymorphic segments of the porB geneManuscript (preprint) (Other academic)
    Abstract [en]

    For prevention and control of gonorrhea, an objective, highly discriminating, and reproducible molecular epidemiological characterization of Neisseria gonorrhoeae is essential. In the present study, in the pursuance of providing such qualities, pyrosequencing technology, a fast real-time DNA sequence analysis, was applied to six short, highly polymorphic porB gene segments, with subsequent genetic variant (genovar) determination of the bacterial isolates. The DNA sequencing templates were obtained by real-time PCR amplification, which also included fluorescence melting curve analysis of the entire porB gene in order to determine the genogroup (porB1a or porB1b allele) prior to pyrosequencing analysis. The PSQ 96 MA system used allowed rapid (approximately 1.5 h) determination of 96 sequences of 20 to 65 correct nucleotides each. The results were reproducible and mostly in concordance with the results of conventional Sanger dideoxy-sequencing, with the exception of shorter read lengths and some uncertainty in determining the correct number of identical nucleotides in homopolymeric segments. The number of sequence variants identified in each one of the six highly polymorphic segments of the porB1a and porB1b alleles (encoding surface exposed amino acid loops of the mature porB protein) ranged from 5 to 11 and 8 to 39, respectively. Among porB1a isolates (n=22) and porB1b isolates (n=65), 22 and 64 unique genovars were identified. All isolates were typeable. The current results provide evidence of a high discriminatory ability, practically the same as sequencing of the entire porB gene. In conclusion, the fast and high-throughput pyrosequencing technology can be used for molecular epidemiological characterization of N. gonorrhoeae.

  • 18.
    Unemo, Magnus
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Olcén, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Jonasson, Jon
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Fredlund, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Molecular typing of Neisseria gonorrhoeae isolates by pyrosequencing of highly polymorphic segments of the porB gene2004In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 42, no 7, p. 2926-2934Article in journal (Refereed)
    Abstract [en]

    For prevention and control of gonorrhea, an objective, highly discriminating, and reproducible molecular epidemiological characterization of Neisseria gonorrhoeae is essential. In the present study, in pursuance of providing such qualities, pyrosequencing technology, a fast real-time DNA sequence analysis, was applied to six short, highly polymorphic porB gene segments, with subsequent genetic variant (genovar) determination of the bacterial isolates. The sequencing templates were obtained by real-time PCR amplification, which also included fluorescence melting curve analysis of the entire porB gene in order to determine the genogroup (porB1a or porB1b allele) prior to pyrosequencing analysis. The PSQ 96 MA system used allowed rapid (in approximately 1.5 h) determination of 96 sequences of 20 to 65 correct nucleotides each. The results were reproducible and mostly in concordance with the results of conventional Sanger dideoxy sequencing, with the exception of shorter read lengths and some uncertainty in determining the correct number of identical nucleotides in homopolymeric segments. The number of sequence variants identified in each of the six highly polymorphic segments of the porB1a and porB1b alleles (encoding surface-exposed amino acid loops of the mature PorB protein) ranged from 5 to 11 and from 8 to 39, respectively. Among porB1a isolates (n = 22) and porB1b isolates (n = 65), 22 and 64 unique genovars, respectively, were identified. All isolates were typeable. The present results provide evidence of a high discriminatory ability, practically the same as that for sequencing of the entire porB gene. In conclusion, the fast and high-throughput pyrosequencing technology can be used for molecular epidemiological characterization of N. gonorrhoeae.

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