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Golparian, D., Harris, S. R., Sánchez-Busó, L., Hoffmann, S., Shafer, W. M., Bentley, S. D., . . . Unemo, M. (2020). Genomic evolution of Neisseria gonorrhoeae since the preantibiotic era (1928-2013): antimicrobial use/misuse selects for resistance and drives evolution. BMC Genomics, 21(1), Article ID 116.
Open this publication in new window or tab >>Genomic evolution of Neisseria gonorrhoeae since the preantibiotic era (1928-2013): antimicrobial use/misuse selects for resistance and drives evolution
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2020 (English)In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 21, no 1, article id 116Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Multidrug-resistant Neisseria gonorrhoeae strains are prevalent, threatening gonorrhoea treatment globally, and understanding of emergence, evolution, and spread of antimicrobial resistance (AMR) in gonococci remains limited. We describe the genomic evolution of gonococci and their AMR, related to the introduction of antimicrobial therapies, examining isolates from 1928 (preantibiotic era) to 2013 in Denmark. This is, to our knowledge, the oldest gonococcal collection globally.

METHODS: Lyophilised isolates were revived and examined using Etest (18 antimicrobials) and whole-genome sequencing (WGS). Quality-assured genome sequences were obtained for 191 viable and 40 non-viable isolates and analysed with multiple phylogenomic approaches.

RESULTS: Gonococcal AMR, including an accumulation of multiple AMR determinants, started to emerge particularly in the 1950s-1970s. By the twenty-first century, resistance to most antimicrobials was common. Despite that some AMR determinants affect many physiological functions and fitness, AMR determinants were mainly selected by the use/misuse of gonorrhoea therapeutic antimicrobials. Most AMR developed in strains belonging to one multidrug-resistant (MDR) clade with close to three times higher genomic mutation rate. Modern N. gonorrhoeae was inferred to have emerged in the late-1500s and its genome became increasingly conserved over time.

CONCLUSIONS: WGS of gonococci from 1928 to 2013 showed that no AMR determinants, except penB, were in detectable frequency before the introduction of gonorrhoea therapeutic antimicrobials. The modern gonococcus is substantially younger than previously hypothesized and has been evolving into a more clonal species, driven by the use/misuse of antimicrobials. The MDR gonococcal clade should be further investigated for early detection of strains with predispositions to develop and maintain MDR and for initiation of public health interventions.

Place, publisher, year, edition, pages
BioMed Central, 2020
Keywords
Antimicrobial resistance, Evolution, Genomic epidemiology, Neisseria gonorrhoeae, Temporal analysis, Whole-genome sequencing
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-79946 (URN)10.1186/s12864-020-6511-6 (DOI)32013864 (PubMedID)2-s2.0-85078901790 (Scopus ID)
Available from: 2020-02-19 Created: 2020-02-19 Last updated: 2020-02-19Bibliographically approved
Boiko, I., Golparian, D., Krynytska, I., Bezkorovaina, H., Frankenberg, A., Onuchyna, M., . . . Unemo, M. (2019). Antimicrobial susceptibility of Neisseria gonorrhoeae isolates and treatment of gonorrhoea patients in Ternopil and Dnipropetrovsk regions of Ukraine, 2013-2018. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 127(7), 503-509
Open this publication in new window or tab >>Antimicrobial susceptibility of Neisseria gonorrhoeae isolates and treatment of gonorrhoea patients in Ternopil and Dnipropetrovsk regions of Ukraine, 2013-2018
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2019 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 127, no 7, p. 503-509Article in journal (Refereed) Published
Abstract [en]

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

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
Neisseria gonorrhoeae, Gonorrhoea, antimicrobial resistance (AMR), ceftriaxone, azithromycin, Ukraine
National Category
Immunology in the medical area Microbiology in the medical area
Identifiers
urn:nbn:se:oru:diva-75208 (URN)10.1111/apm.12948 (DOI)000473620900002 ()30903707 (PubMedID)
Available from: 2019-07-26 Created: 2019-07-26 Last updated: 2019-07-26Bibliographically approved
Bruni, M. P., Freitas da Silveira, M., Stauffert, D., Bicca, G. L., Caetano Dos Santos, C., da Rosa Farias, N. A., . . . Unemo, M. (2019). Aptima Trichomonas vaginalis assay elucidates significant underdiagnosis of trichomoniasis among women in Brazil according to an observational study. Sexually Transmitted Infections, 95(2), 129-132
Open this publication in new window or tab >>Aptima Trichomonas vaginalis assay elucidates significant underdiagnosis of trichomoniasis among women in Brazil according to an observational study
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2019 (English)In: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 95, no 2, p. 129-132Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Trichomonas vaginalis (TV) infection is the most common non-viral STI globally and can result in adverse pregnancy outcomes and exacerbated HIV acquisition/transmission. Nucleic acid amplification tests (NAATs) are the most sensitive diagnostic tests, with high specificity, but TV NAATs are rarely used in Brazil. We investigated the TV prevalence and compared the performance of the US Food and Drug Association-cleared Aptima TV assay with microscopy (wet mount and Gram-stained) and culture for TV detection in women in Pelotas, Brazil in an observational study.

METHODS: From August 2015 to December 2016, 499 consecutive asymptomatic and symptomatic sexually active women attending a Gynaecology and Obstetrics Outpatient Clinic were enrolled. Vaginal fluid and swab specimens were collected and wet mount microscopy, Gram-stained microscopy, culture and the Aptima TV assay performed.

RESULTS: The median age of enrolled women was 36.5 years (range: 15-77). The majority were white, had a steady sexual partner and low levels of education. The TV detection rate was 4.2%, 2.4%, 1.2% and 0% using the Aptima TV assay, culture, wet mount microscopy and Gram-stained microscopy, respectively. The sensitivity of culture and wet mount microscopy was only 57.1% (95% CI 36.5 to 75.5) and 28.6% (95% CI 13.8 to 50.0), respectively.

CONCLUSIONS: was found among women in Pelotas, Brazil and the routine diagnostic test (wet mount microscopy) and culture had low sensitivities. More sensitive diagnostic tests (NAATs) and enhanced testing of symptomatic and asymptomatic at-risk women are crucial to mitigate the transmission of TV infection, TV-associated sequelae and enhanced HIV acquisition and transmission.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
Keywords
Aptima, Brazil, culture, nucleic acid amplification test (NAAT), trichomonas infection, trichomonas vaginalis, wet mount microscopy
National Category
Obstetrics, Gynecology and Reproductive Medicine Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-68678 (URN)10.1136/sextrans-2018-053635 (DOI)000471868700012 ()30154157 (PubMedID)2-s2.0-85052888876 (Scopus ID)
Note

Funding Agencies:

Programa de Apoio a Pos-Graduacao (PROAP)  

Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brasilia, DF, Brazil  

Örebro County Council Research Committee  

Foundation for Medical Research at Örebro University Hospital, Örebro, Sweden 

Available from: 2018-09-03 Created: 2018-09-03 Last updated: 2019-11-08Bibliographically approved
Sánchez-Busó, L., Golparian, D., Parkhill, J., Unemo, M. & Harris, S. R. (2019). Genetic variation regulates the activation and specificity of Restriction-Modification systems in Neisseria gonorrhoeae. Scientific Reports, 9(1), Article ID 14685.
Open this publication in new window or tab >>Genetic variation regulates the activation and specificity of Restriction-Modification systems in Neisseria gonorrhoeae
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, no 1, article id 14685Article in journal (Refereed) Published
Abstract [en]

Restriction-Modification systems (RMS) are one of the main mechanisms of defence against foreign DNA invasion and can have an important role in the regulation of gene expression. The obligate human pathogen Neisseria gonorrhoeae carries one of the highest loads of RMS in its genome; between 13 to 15 of the three main types. Previous work has described their organization in the reference genome FA1090 and has inferred the associated methylated motifs. Here, we studied the structure of RMS and target methylated motifs in 25 gonococcal strains sequenced with Single Molecule Real-Time (SMRT) technology, which provides data on DNA modification. The results showed a variable picture of active RMS in different strains, with phase variation switching the activity of Type III RMS, and both the activity and specificity of a Type I RMS. Interestingly, the Dam methylase was found in place of the NgoAXI endonuclease in two of the strains, despite being previously thought to be absent in the gonococcus. We also identified the real methylation target of NgoAXII as 5'-GCAGA-3', different from that previously described. Results from this work give further insights into the diversity and dynamics of RMS and methylation patterns in N. gonorrhoeae.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-77256 (URN)10.1038/s41598-019-51102-2 (DOI)000489701600021 ()31605008 (PubMedID)2-s2.0-85073164375 (Scopus ID)
Note

Funding Agency:

Wellcome Foundation for Medical Research at Örebro University Hospital, Örebro, Sweden 098051

Available from: 2019-10-14 Created: 2019-10-14 Last updated: 2019-10-25Bibliographically approved
Gianecini, R. A., Golparian, D., Zittermann, S., Litvik, A., Gonzalez, S., Oviedo, C., . . . Galarza, P. (2019). Genome-based epidemiology and antimicrobial resistance determinants of Neisseria gonorrhoeae isolates with decreased susceptibility and resistance to extended-spectrum cephalosporins in Argentina in 2011-16. Journal of Antimicrobial Chemotherapy, 74(6), 1551-1559
Open this publication in new window or tab >>Genome-based epidemiology and antimicrobial resistance determinants of Neisseria gonorrhoeae isolates with decreased susceptibility and resistance to extended-spectrum cephalosporins in Argentina in 2011-16
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2019 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 74, no 6, p. 1551-1559Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Our aim was to describe the molecular epidemiology and antimicrobial resistance determinants of isolates of Neisseria gonorrhoeae with decreased susceptibility and resistance to extended-spectrum cephalosporins (ESCs) in Argentina in 2011-16.

METHODS: Gonococcal isolates (n = 158) with decreased susceptibility and resistance to ESCs collected in 2011-16 across Argentina were subjected to WGS and antimicrobial susceptibility testing for six antimicrobials.

RESULTS: In total, 50% of the isolates were resistant to cefixime, 1.9% were resistant to ceftriaxone, 37.3% were resistant to azithromycin and 63.9% of the isolates showed an MDR phenotype. Resistance and decreased susceptibility to ESCs was mainly associated with isolates possessing the mosaic penA-34.001, in combination with an mtrR promoter A deletion, and PorB1b amino acid substitutions G120K/A121N. Phylogenetic analysis revealed two main clades of circulating strains, which were associated with the N. gonorrhoeae multiantigen sequence typing (NG-MAST) ST1407 and closely related STs, and characterized by a high prevalence rate, wide geographical distribution and temporal persistence.

CONCLUSIONS: N. gonorrhoeae isolates with decreased susceptibility and resistance to ESCs in Argentina have emerged and rapidly spread mainly due to two clonal expansions after importation of one or two strains, which are associated with the international MDR NG-MAST ST1407 clone. The identification of the geographical dissemination and characteristics of these predominant clones may help to focus action plans and public health policies to control the spread of ESC resistance in Argentina. Dual antimicrobial therapy (ceftriaxone plus azithromycin) for gonorrhoea needs to be considered in Argentina.

Place, publisher, year, edition, pages
Oxford University Press, 2019
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-72874 (URN)10.1093/jac/dkz054 (DOI)000482076800014 ()30820563 (PubMedID)2-s2.0-85066839578 (Scopus ID)
Note

Funding Agencies:

Programa de Becas de Formacion en el Exterior en Ciencia y Tecnologia (Grant Bec.Ar - CIT 2017), Argentina  

Örebro County Council Research Committee  

Foundation for Medical Research at Örebro University Hospital, Örebro, Sweden 

Available from: 2019-03-04 Created: 2019-03-04 Last updated: 2019-11-12Bibliographically approved
Boiko, I., Golparian, D., Krynsytska, I. & Unemo, M. (2019). High prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae and particularly Trichomonas vaginalis diagnosed using US FDA-approved Aptima molecular tests and evaluation of conventional routine diagnostic tests in Ternopil, Ukraine. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 127(9), 627-634
Open this publication in new window or tab >>High prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae and particularly Trichomonas vaginalis diagnosed using US FDA-approved Aptima molecular tests and evaluation of conventional routine diagnostic tests in Ternopil, Ukraine
2019 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 127, no 9, p. 627-634Article in journal (Refereed) Published
Abstract [en]

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

Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Inc., 2019
Keywords
Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Aptima Combo 2 assay, Aptima Trichomonas vaginalis assay, Ukraine
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-74783 (URN)10.1111/apm.12975 (DOI)000481445100004 ()31225920 (PubMedID)2-s2.0-85070737441 (Scopus ID)
Available from: 2019-06-25 Created: 2019-06-25 Last updated: 2019-11-15Bibliographically approved
Foerster, S., Drusano, G., Golparian, D., Neely, M., Piddock, L. J. V., Alirol, E. & Unemo, M. (2019). In vitro antimicrobial combination testing of and evolution of resistance to the first-in-class spiropyrimidinetrione zoliflodacin combined with six therapeutically relevant antimicrobials for Neisseria gonorrhoeae. Journal of Antimicrobial Chemotherapy, 74(12), 3521-3529
Open this publication in new window or tab >>In vitro antimicrobial combination testing of and evolution of resistance to the first-in-class spiropyrimidinetrione zoliflodacin combined with six therapeutically relevant antimicrobials for Neisseria gonorrhoeae
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2019 (English)In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 74, no 12, p. 3521-3529Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Resistance in Neisseria gonorrhoeae to all gonorrhoea therapeutic antimicrobials has emerged. Novel therapeutic antimicrobials are imperative and the first-in-class spiropyrimidinetrione zoliflodacin appears promising. Zoliflodacin could be introduced in dual antimicrobial therapies to prevent the emergence and/or spread of resistance. We investigated the in vitro activity of and selection of resistance to zoliflodacin alone and in combination with six gonorrhoea therapeutic antimicrobials against N. gonorrhoeae.

METHODS: The international gonococcal reference strains WHO F (WT) and WHO O, WHO V and WHO X (strains with different AMR profiles) were examined. Zoliflodacin was evaluated alone or combined with ceftriaxone, cefixime, spectinomycin, gentamicin, tetracycline, cethromycin or sitafloxacin in chequerboard assays, time-kill curve analysis and selection-of-resistance studies.

RESULTS: Zoliflodacin alone or in combination with all six antimicrobials showed rapid growth inhibition against all examined strains. The time-kill curve analysis indicated that tetracycline or cethromycin combined with zoliflodacin can significantly decrease the zoliflodacin kill rate in vitro. The frequency of selected zoliflodacin-resistance mutations was low when evaluated as a single agent and further reduced for all antimicrobial combinations. All resistant mutants contained the GyrB mutations D429N, K450T or K450N, resulting in zoliflodacin MICs of 0.5-4 mg/L.

CONCLUSIONS: Zoliflodacin, alone or in combination with sexually transmitted infection therapeutic antimicrobials, rapidly kills gonococci with infrequent resistance emergence. Zoliflodacin remains promising for gonorrhoea oral monotherapy and as part of dual antimicrobial therapy with low resistance emergence potential. A Phase III trial evaluating efficacy and safety of zoliflodacin for uncomplicated gonorrhoea treatment is planned in 2019.

Place, publisher, year, edition, pages
Oxford University Press, 2019
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-78560 (URN)10.1093/jac/dkz376 (DOI)000501732800016 ()31730160 (PubMedID)2-s2.0-85075070269 (Scopus ID)
Note

Funding Agencies:

Global Antibiotic Research & Development Partnership (GARDP)  

Örebro County Council Research Committee, Örebro, Sweden  

Foundation for Medical Research at Örebro University Hospital, Örebro, Sweden 

Available from: 2019-12-13 Created: 2019-12-13 Last updated: 2020-01-14Bibliographically approved
Foerster, S., Drusano, G., Golparian, D., Neely, M., Piddock, L., Alirol, E. & Unemo, M. (2019). IN VITRO COMBINATION TESTING AND SELECTION OF RESISTANCE TO ZOLIFLODACIN COMBINED WITH SIX ANTIMICROBIALS FOR N. GONORRHOEAE. Sexually Transmitted Infections, 95(Suppl. 1), A50-A50
Open this publication in new window or tab >>IN VITRO COMBINATION TESTING AND SELECTION OF RESISTANCE TO ZOLIFLODACIN COMBINED WITH SIX ANTIMICROBIALS FOR N. GONORRHOEAE
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2019 (English)In: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 95, no Suppl. 1, p. A50-A50Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-79390 (URN)10.1136/sextrans-2019-sti.135 (DOI)000506050100132 ()
Available from: 2020-01-27 Created: 2020-01-27 Last updated: 2020-01-27Bibliographically approved
Seth-Smith, H., Egli-Gany, D., Golparian, D., Dona, V., Endimiani, A., Unemo, M. & Low, N. (2019). NEISSERIA GONORRHOEAE GENOMIC DIVERSITY IN HIGH RISK GROUPS IN SWITZERLAND. Sexually Transmitted Infections, 95(Supl. 1), A281-A281
Open this publication in new window or tab >>NEISSERIA GONORRHOEAE GENOMIC DIVERSITY IN HIGH RISK GROUPS IN SWITZERLAND
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2019 (English)In: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 95, no Supl. 1, p. A281-A281Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background: Neisseria gonorrhoeae cases are increasing in Europe, with decreasing susceptibility to first line antibiotics. Whole genome sequencing (WGS) provides detailed information about gonococcal molecular epidemiology and prediction of antimicrobial resistance (AMR), especially if linked to epidemiological data. The aim of this study was to examine molecular, clinical and social epidemiological aspects of gonorrhoea infections in Switzerland.

Methods: In 2015–2016, we cultured urethral, cervical, vaginal, rectal, and pharyngeal specimens from patients in three clinics predominantly attended by men who have sex with men (MSM) and female sex workers (FSW). MSM also completed a sexual behaviour questionnaire. Minimal inhibitory concentrations (MIC) were assessed by Etest, interpreted using EUCAST breakpoints except azithromycin (2 mg/L); WGS used an Illumina Miseq.

Results: We sequenced 140 isolates from 116 participants, MSM (107, 92%, mean age 35.8 years) and FSW (6, 5%, mean age 25.3 years). Amongst MSM, 48/105 respondents (45.7%) reported recent sex abroad. Three patients (two MSM and one FSW) carried different strains at different body sites. The isolates show large genomic diversity, with 69 NG-MAST types and 37 MLST sequence types, largely embedded within characterised European Union clusters. NG-MAST 1407 was identified in n=4 isolates from two patients (FSW, not travel-associated and MSM, sex elsewhere in Europe). Mosaic penAXXXIV was seen in these isolates, and also in an NG-MAST 13488 from an MSM, which was also not travel associated. One isolate (heterosexual male, not travel-associated) with elevated cefixime MIC (0.19mg/ml) carried a mosaic penAX in an NG-MAST 10557 background. Ciprofloxacin resistance was seen in these six isolates, and overall in 59/140 (42%), all containing GyrA mutations S91F and D95A/G/N.

Conclusion: Switzerland has a high diversity of circulating gonorrhoea, generally related to European clusters. Multidrug resistant isolates were not identified in this study, but NG-MAST 1407 and penA mosaics, associated with elevated cephalosporin MICs, are circulating.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-79394 (URN)10.1136/sextrans-2019-sti.705 (DOI)000506050104031 ()
Available from: 2020-01-27 Created: 2020-01-27 Last updated: 2020-01-27Bibliographically approved
Sánchez-Busó, L., Golparian, D., Corander, J., Grad, Y. H., Ohnishi, M., Flemming, R., . . . Harris, S. R. (2019). The impact of antimicrobials on gonococcal evolution. Nature Microbiology, 4(11), 1941-1950
Open this publication in new window or tab >>The impact of antimicrobials on gonococcal evolution
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2019 (English)In: Nature Microbiology, E-ISSN 2058-5276, Vol. 4, no 11, p. 1941-1950Article in journal (Refereed) Published
Abstract [en]

The sexually transmitted pathogen Neisseria gonorrhoeae is regarded as being on the way to becoming an untreatable superbug. Despite its clinical importance, little is known about its emergence and evolution, and how this corresponds with the introduction of antimicrobials. We present a genome-based phylogeographical analysis of 419 gonococcal isolates from across the globe. Results indicate that modern gonococci originated in Europe or Africa, possibly as late as the sixteenth century and subsequently disseminated globally. We provide evidence that the modern gonococcal population has been shaped by antimicrobial treatment of sexually transmitted infections as well as other infections, leading to the emergence of two major lineages with different evolutionary strategies. The well-described multidrug-resistant lineage is associated with high rates of homologous recombination and infection in high-risk sexual networks. A second, multisusceptible lineage is more associated with heterosexual networks, with potential implications for infection control.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Infectious Medicine Microbiology in the medical area
Identifiers
urn:nbn:se:oru:diva-75565 (URN)10.1038/s41564-019-0501-y (DOI)000493113000021 ()31358980 (PubMedID)2-s2.0-85069945957 (Scopus ID)
Funder
Wellcome trust, 098051
Note

Funding Agencies:

Foundation for Medical Research at Orebro University Hospital, Örebro, Sweden  

European Research Council (ERC) 745258

Smith Family Foundation  

United States Department of Health & Human Services

National Institutes of Health (NIH) - USA

NIH National Institute of Allergy & Infectious Diseases (NIAID) 1R01AI132606-01

Available from: 2019-08-09 Created: 2019-08-09 Last updated: 2019-11-15Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-0688-2521

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