Europe-wide expansion and eradication of multidrug-resistant Neisseria gonorrhoeae lineages: a genomic surveillance study

Leonor Sánchez-Busó; Michelle J. Cole; Gianfranco Spiteri; Michaela Day; Susanne Jacobsson; Daniel Golparian; Noshin Sajedi; Corin A. Yeats; Khalil Abudahab; Anthony Underwood; Benjamin Bluemel; David M. Aanensen; Magnus Unemo; Sonja Pleininger; Alexander Indra; Irith De Baetselier; Wim Vanden Berghe; Blaženka Hunjak; Tatjana Nemeth Blažić; Panayiota Maikanti-Charalambous; Despo Pieridou; Hana Zákoucká; Helena Žemličková; Steen Hoffmann; Susan Cowan; Lasse Jessen Schwartz; Rita Peetso; Jevgenia Epstein; Jelena Viktorova; Ndeindo Ndeikoundam; Beatrice Bercot; Cécile Bébéar; Florence Lot; Susanne Buder; Klaus Jansen; Vivi Miriagou; Georgios Rigakos; Vasilios Raftopoulos; Eszter Balla; Mária Dudás; Lena Rós Ásmundsdóttir; Guðrún Sigmundsdóttir; Guðrún Svanborg Hauksdóttir; Thorolfur Gudnason; Aoife Colgan; Brendan Crowley; Sinéad Saab; Paola Stefanelli; Anna Carannante; Lynsey Patterson; Centre for Genomic Pathogen Surveillance and the Euro-GASP study group

doi:10.1016/S2666-5247(22)00044-1

Europe-wide expansion and eradication of multidrug-resistant Neisseria gonorrhoeae lineages: a genomic surveillance study

Leonor Sánchez-Busó, Michelle J. Cole, Gianfranco Spiteri, Michaela Day, Susanne Jacobsson, Daniel Golparian, Noshin Sajedi, Corin A. Yeats, Khalil Abudahab, Anthony Underwood, Benjamin Bluemel, David M. Aanensen^*, Magnus Unemo^*, Sonja Pleininger, Alexander Indra, Irith De Baetselier, Wim Vanden Berghe, Blaženka Hunjak, Tatjana Nemeth Blažić, Panayiota Maikanti-CharalambousDespo Pieridou, Hana Zákoucká, Helena Žemličková, Steen Hoffmann, Susan Cowan, Lasse Jessen Schwartz, Rita Peetso, Jevgenia Epstein, Jelena Viktorova, Ndeindo Ndeikoundam, Beatrice Bercot, Cécile Bébéar, Florence Lot, Susanne Buder, Klaus Jansen, Vivi Miriagou, Georgios Rigakos, Vasilios Raftopoulos, Eszter Balla, Mária Dudás, Lena Rós Ásmundsdóttir, Guðrún Sigmundsdóttir, Guðrún Svanborg Hauksdóttir, Thorolfur Gudnason, Aoife Colgan, Brendan Crowley, Sinéad Saab, Paola Stefanelli, Anna Carannante, Lynsey Patterson, Centre for Genomic Pathogen Surveillance and the Euro-GASP study group

^*Corresponding author for this work

School of Medicine, Dentistry and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

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Abstract

BACKGROUND: Genomic surveillance using quality-assured whole-genome sequencing (WGS) together with epidemiological and antimicrobial resistance (AMR) data is essential to characterise the circulating Neisseria gonorrhoeae lineages and their association to patient groups (defined by demographic and epidemiological factors). In 2013, the European gonococcal population was characterised genomically for the first time. We describe the European gonococcal population in 2018 and identify emerging or vanishing lineages associated with AMR and epidemiological characteristics of patients, to elucidate recent changes in AMR and gonorrhoea epidemiology in Europe.

METHODS: We did WGS on 2375 gonococcal isolates from 2018 (mainly Sept 1-Nov 30) in 26 EU and EEA countries. Molecular typing and AMR determinants were extracted from quality-checked genomic data. Association analyses identified links between genomic lineages, AMR, and epidemiological data.

FINDINGS: Azithromycin-resistant N gonorrhoeae (8·0% [191/2375] in 2018) is rising in Europe due to the introduction or emergence and subsequent expansion of a novel N gonorrhoeae multi-antigen sequence typing (NG-MAST) genogroup, G12302 (132 [5·6%] of 2375; N gonorrhoeae sequence typing for antimicrobial resistance [NG-STAR] clonal complex [CC]168/63), carrying a mosaic mtrR promoter and mtrD sequence and found in 24 countries in 2018. CC63 was associated with pharyngeal infections in men who have sex with men. Susceptibility to ceftriaxone and cefixime is increasing, as the resistance-associated lineage, NG-MAST G1407 (51 [2·1%] of 2375), is progressively vanishing since 2009-10.

INTERPRETATION: Enhanced gonococcal AMR surveillance is imperative worldwide. WGS, linked to epidemiological and AMR data, is essential to elucidate the dynamics in gonorrhoea epidemiology and gonococcal populations as well as to predict AMR. When feasible, WGS should supplement the national and international AMR surveillance programmes to elucidate AMR changes over time. In the EU and EEA, increasing low-level azithromycin resistance could threaten the recommended ceftriaxone-azithromycin dual therapy, and an evidence-based clinical azithromycin resistance breakpoint is needed. Nevertheless, increasing ceftriaxone susceptibility, declining cefixime resistance, and absence of known resistance mutations for new treatments (zoliflodacin, gepotidacin) are promising.

FUNDING: European Centre for Disease Prevention and Control, Centre for Genomic Pathogen Surveillance, Örebro University Hospital, Wellcome.

Original language	English
Pages (from-to)	e452-e463
Journal	The Lancet Microbe
Volume	3
Issue number	6
Early online date	10 May 2022
DOIs	https://doi.org/10.1016/S2666-5247(22)00044-1
Publication status	Published - Jun 2022

Keywords

Anti-Bacterial Agents/pharmacology
Azithromycin/pharmacology
Cefixime/therapeutic use
Ceftriaxone/pharmacology
Drug Resistance, Bacterial/genetics
Europe/epidemiology
Genomics
Gonorrhea/drug therapy
Homosexuality, Male
Humans
Male
Microbial Sensitivity Tests
Neisseria gonorrhoeae/genetics
Sexual and Gender Minorities

ASJC Scopus subject areas

Microbiology
Microbiology (medical)
Infectious Diseases
Virology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/S2666-5247(22)00044-1Licence: CC BY

Europe-wide expansion and eradication of multidrug-resistant Neisseria gonorrhoeae lineages: a genomic surveillance study
Copyright 2021 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 2.9 MBLicence: CC BY

Cite this

Sánchez-Busó, L., Cole, M. J., Spiteri, G., Day, M., Jacobsson, S., Golparian, D., Sajedi, N., Yeats, C. A., Abudahab, K., Underwood, A., Bluemel, B., Aanensen, D. M., Unemo, M., Pleininger, S., Indra, A., De Baetselier, I., Vanden Berghe, W., Hunjak, B., Blažić, T. N., ... Centre for Genomic Pathogen Surveillance and the Euro-GASP study group (2022). Europe-wide expansion and eradication of multidrug-resistant Neisseria gonorrhoeae lineages: a genomic surveillance study. The Lancet Microbe, 3(6), e452-e463. https://doi.org/10.1016/S2666-5247(22)00044-1

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title = "Europe-wide expansion and eradication of multidrug-resistant Neisseria gonorrhoeae lineages: a genomic surveillance study",

abstract = "BACKGROUND: Genomic surveillance using quality-assured whole-genome sequencing (WGS) together with epidemiological and antimicrobial resistance (AMR) data is essential to characterise the circulating Neisseria gonorrhoeae lineages and their association to patient groups (defined by demographic and epidemiological factors). In 2013, the European gonococcal population was characterised genomically for the first time. We describe the European gonococcal population in 2018 and identify emerging or vanishing lineages associated with AMR and epidemiological characteristics of patients, to elucidate recent changes in AMR and gonorrhoea epidemiology in Europe.METHODS: We did WGS on 2375 gonococcal isolates from 2018 (mainly Sept 1-Nov 30) in 26 EU and EEA countries. Molecular typing and AMR determinants were extracted from quality-checked genomic data. Association analyses identified links between genomic lineages, AMR, and epidemiological data.FINDINGS: Azithromycin-resistant N gonorrhoeae (8·0% [191/2375] in 2018) is rising in Europe due to the introduction or emergence and subsequent expansion of a novel N gonorrhoeae multi-antigen sequence typing (NG-MAST) genogroup, G12302 (132 [5·6%] of 2375; N gonorrhoeae sequence typing for antimicrobial resistance [NG-STAR] clonal complex [CC]168/63), carrying a mosaic mtrR promoter and mtrD sequence and found in 24 countries in 2018. CC63 was associated with pharyngeal infections in men who have sex with men. Susceptibility to ceftriaxone and cefixime is increasing, as the resistance-associated lineage, NG-MAST G1407 (51 [2·1%] of 2375), is progressively vanishing since 2009-10.INTERPRETATION: Enhanced gonococcal AMR surveillance is imperative worldwide. WGS, linked to epidemiological and AMR data, is essential to elucidate the dynamics in gonorrhoea epidemiology and gonococcal populations as well as to predict AMR. When feasible, WGS should supplement the national and international AMR surveillance programmes to elucidate AMR changes over time. In the EU and EEA, increasing low-level azithromycin resistance could threaten the recommended ceftriaxone-azithromycin dual therapy, and an evidence-based clinical azithromycin resistance breakpoint is needed. Nevertheless, increasing ceftriaxone susceptibility, declining cefixime resistance, and absence of known resistance mutations for new treatments (zoliflodacin, gepotidacin) are promising.FUNDING: European Centre for Disease Prevention and Control, Centre for Genomic Pathogen Surveillance, {\"O}rebro University Hospital, Wellcome.",

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author = "Leonor S{\'a}nchez-Bus{\'o} and Cole, {Michelle J.} and Gianfranco Spiteri and Michaela Day and Susanne Jacobsson and Daniel Golparian and Noshin Sajedi and Yeats, {Corin A.} and Khalil Abudahab and Anthony Underwood and Benjamin Bluemel and Aanensen, {David M.} and Magnus Unemo and Sonja Pleininger and Alexander Indra and {De Baetselier}, Irith and {Vanden Berghe}, Wim and Bla{\v z}enka Hunjak and Bla{\v z}i{\'c}, {Tatjana Nemeth} and Panayiota Maikanti-Charalambous and Despo Pieridou and Hana Z{\'a}kouck{\'a} and Helena {\v Z}emli{\v c}kov{\'a} and Steen Hoffmann and Susan Cowan and Schwartz, {Lasse Jessen} and Rita Peetso and Jevgenia Epstein and Jelena Viktorova and Ndeindo Ndeikoundam and Beatrice Bercot and C{\'e}cile B{\'e}b{\'e}ar and Florence Lot and Susanne Buder and Klaus Jansen and Vivi Miriagou and Georgios Rigakos and Vasilios Raftopoulos and Eszter Balla and M{\'a}ria Dud{\'a}s and {\'A}smundsd{\'o}ttir, {Lena R{\'o}s} and Gu{\dh}r{\'u}n Sigmundsd{\'o}ttir and Hauksd{\'o}ttir, {Gu{\dh}r{\'u}n Svanborg} and Thorolfur Gudnason and Aoife Colgan and Brendan Crowley and Sin{\'e}ad Saab and Paola Stefanelli and Anna Carannante and Lynsey Patterson and {Centre for Genomic Pathogen Surveillance and the Euro-GASP study group}",

year = "2022",

month = jun,

doi = "10.1016/S2666-5247(22)00044-1",

language = "English",

volume = "3",

pages = "e452--e463",

journal = "The Lancet Microbe",

issn = "2666-5247",

publisher = "Elsevier Ltd",

number = "6",

}

Sánchez-Busó, L, Cole, MJ, Spiteri, G, Day, M, Jacobsson, S, Golparian, D, Sajedi, N, Yeats, CA, Abudahab, K, Underwood, A, Bluemel, B, Aanensen, DM, Unemo, M, Pleininger, S, Indra, A, De Baetselier, I, Vanden Berghe, W, Hunjak, B, Blažić, TN, Maikanti-Charalambous, P, Pieridou, D, Zákoucká, H, Žemličková, H, Hoffmann, S, Cowan, S, Schwartz, LJ, Peetso, R, Epstein, J, Viktorova, J, Ndeikoundam, N, Bercot, B, Bébéar, C, Lot, F, Buder, S, Jansen, K, Miriagou, V, Rigakos, G, Raftopoulos, V, Balla, E, Dudás, M, Ásmundsdóttir, LR, Sigmundsdóttir, G, Hauksdóttir, GS, Gudnason, T, Colgan, A, Crowley, B, Saab, S, Stefanelli, P, Carannante, A, Patterson, L & Centre for Genomic Pathogen Surveillance and the Euro-GASP study group 2022, 'Europe-wide expansion and eradication of multidrug-resistant Neisseria gonorrhoeae lineages: a genomic surveillance study', The Lancet Microbe, vol. 3, no. 6, pp. e452-e463. https://doi.org/10.1016/S2666-5247(22)00044-1

TY - JOUR

T1 - Europe-wide expansion and eradication of multidrug-resistant Neisseria gonorrhoeae lineages: a genomic surveillance study

AU - Sánchez-Busó, Leonor

AU - Cole, Michelle J.

AU - Spiteri, Gianfranco

AU - Day, Michaela

AU - Jacobsson, Susanne

AU - Golparian, Daniel

AU - Sajedi, Noshin

AU - Yeats, Corin A.

AU - Abudahab, Khalil

AU - Underwood, Anthony

AU - Bluemel, Benjamin

AU - Aanensen, David M.

AU - Unemo, Magnus

AU - Pleininger, Sonja

AU - Indra, Alexander

AU - De Baetselier, Irith

AU - Vanden Berghe, Wim

AU - Hunjak, Blaženka

AU - Blažić, Tatjana Nemeth

AU - Maikanti-Charalambous, Panayiota

AU - Pieridou, Despo

AU - Zákoucká, Hana

AU - Žemličková, Helena

AU - Hoffmann, Steen

AU - Cowan, Susan

AU - Schwartz, Lasse Jessen

AU - Peetso, Rita

AU - Epstein, Jevgenia

AU - Viktorova, Jelena

AU - Ndeikoundam, Ndeindo

AU - Bercot, Beatrice

AU - Bébéar, Cécile

AU - Lot, Florence

AU - Buder, Susanne

AU - Jansen, Klaus

AU - Miriagou, Vivi

AU - Rigakos, Georgios

AU - Raftopoulos, Vasilios

AU - Balla, Eszter

AU - Dudás, Mária

AU - Ásmundsdóttir, Lena Rós

AU - Sigmundsdóttir, Guðrún

AU - Hauksdóttir, Guðrún Svanborg

AU - Gudnason, Thorolfur

AU - Colgan, Aoife

AU - Crowley, Brendan

AU - Saab, Sinéad

AU - Stefanelli, Paola

AU - Carannante, Anna

AU - Patterson, Lynsey

AU - Centre for Genomic Pathogen Surveillance and the Euro-GASP study group

PY - 2022/6

Y1 - 2022/6

N2 - BACKGROUND: Genomic surveillance using quality-assured whole-genome sequencing (WGS) together with epidemiological and antimicrobial resistance (AMR) data is essential to characterise the circulating Neisseria gonorrhoeae lineages and their association to patient groups (defined by demographic and epidemiological factors). In 2013, the European gonococcal population was characterised genomically for the first time. We describe the European gonococcal population in 2018 and identify emerging or vanishing lineages associated with AMR and epidemiological characteristics of patients, to elucidate recent changes in AMR and gonorrhoea epidemiology in Europe.METHODS: We did WGS on 2375 gonococcal isolates from 2018 (mainly Sept 1-Nov 30) in 26 EU and EEA countries. Molecular typing and AMR determinants were extracted from quality-checked genomic data. Association analyses identified links between genomic lineages, AMR, and epidemiological data.FINDINGS: Azithromycin-resistant N gonorrhoeae (8·0% [191/2375] in 2018) is rising in Europe due to the introduction or emergence and subsequent expansion of a novel N gonorrhoeae multi-antigen sequence typing (NG-MAST) genogroup, G12302 (132 [5·6%] of 2375; N gonorrhoeae sequence typing for antimicrobial resistance [NG-STAR] clonal complex [CC]168/63), carrying a mosaic mtrR promoter and mtrD sequence and found in 24 countries in 2018. CC63 was associated with pharyngeal infections in men who have sex with men. Susceptibility to ceftriaxone and cefixime is increasing, as the resistance-associated lineage, NG-MAST G1407 (51 [2·1%] of 2375), is progressively vanishing since 2009-10.INTERPRETATION: Enhanced gonococcal AMR surveillance is imperative worldwide. WGS, linked to epidemiological and AMR data, is essential to elucidate the dynamics in gonorrhoea epidemiology and gonococcal populations as well as to predict AMR. When feasible, WGS should supplement the national and international AMR surveillance programmes to elucidate AMR changes over time. In the EU and EEA, increasing low-level azithromycin resistance could threaten the recommended ceftriaxone-azithromycin dual therapy, and an evidence-based clinical azithromycin resistance breakpoint is needed. Nevertheless, increasing ceftriaxone susceptibility, declining cefixime resistance, and absence of known resistance mutations for new treatments (zoliflodacin, gepotidacin) are promising.FUNDING: European Centre for Disease Prevention and Control, Centre for Genomic Pathogen Surveillance, Örebro University Hospital, Wellcome.

AB - BACKGROUND: Genomic surveillance using quality-assured whole-genome sequencing (WGS) together with epidemiological and antimicrobial resistance (AMR) data is essential to characterise the circulating Neisseria gonorrhoeae lineages and their association to patient groups (defined by demographic and epidemiological factors). In 2013, the European gonococcal population was characterised genomically for the first time. We describe the European gonococcal population in 2018 and identify emerging or vanishing lineages associated with AMR and epidemiological characteristics of patients, to elucidate recent changes in AMR and gonorrhoea epidemiology in Europe.METHODS: We did WGS on 2375 gonococcal isolates from 2018 (mainly Sept 1-Nov 30) in 26 EU and EEA countries. Molecular typing and AMR determinants were extracted from quality-checked genomic data. Association analyses identified links between genomic lineages, AMR, and epidemiological data.FINDINGS: Azithromycin-resistant N gonorrhoeae (8·0% [191/2375] in 2018) is rising in Europe due to the introduction or emergence and subsequent expansion of a novel N gonorrhoeae multi-antigen sequence typing (NG-MAST) genogroup, G12302 (132 [5·6%] of 2375; N gonorrhoeae sequence typing for antimicrobial resistance [NG-STAR] clonal complex [CC]168/63), carrying a mosaic mtrR promoter and mtrD sequence and found in 24 countries in 2018. CC63 was associated with pharyngeal infections in men who have sex with men. Susceptibility to ceftriaxone and cefixime is increasing, as the resistance-associated lineage, NG-MAST G1407 (51 [2·1%] of 2375), is progressively vanishing since 2009-10.INTERPRETATION: Enhanced gonococcal AMR surveillance is imperative worldwide. WGS, linked to epidemiological and AMR data, is essential to elucidate the dynamics in gonorrhoea epidemiology and gonococcal populations as well as to predict AMR. When feasible, WGS should supplement the national and international AMR surveillance programmes to elucidate AMR changes over time. In the EU and EEA, increasing low-level azithromycin resistance could threaten the recommended ceftriaxone-azithromycin dual therapy, and an evidence-based clinical azithromycin resistance breakpoint is needed. Nevertheless, increasing ceftriaxone susceptibility, declining cefixime resistance, and absence of known resistance mutations for new treatments (zoliflodacin, gepotidacin) are promising.FUNDING: European Centre for Disease Prevention and Control, Centre for Genomic Pathogen Surveillance, Örebro University Hospital, Wellcome.

KW - Anti-Bacterial Agents/pharmacology

KW - Azithromycin/pharmacology

KW - Cefixime/therapeutic use

KW - Ceftriaxone/pharmacology

KW - Drug Resistance, Bacterial/genetics

KW - Europe/epidemiology

KW - Genomics

KW - Gonorrhea/drug therapy

KW - Homosexuality, Male

KW - Humans

KW - Male

KW - Microbial Sensitivity Tests

KW - Neisseria gonorrhoeae/genetics

KW - Sexual and Gender Minorities

U2 - 10.1016/S2666-5247(22)00044-1

DO - 10.1016/S2666-5247(22)00044-1

M3 - Article

C2 - 35659907

SN - 2666-5247

VL - 3

SP - e452-e463

JO - The Lancet Microbe

JF - The Lancet Microbe

IS - 6

ER -

Europe-wide expansion and eradication of multidrug-resistant Neisseria gonorrhoeae lineages: a genomic surveillance study

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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