Generic Portal

TY - JOUR

T1 - Europe-wide expansion and eradication of multidrug-resistant Neisseria gonorrhoeae lineages

T2 - 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 - Centre for Genomic Pathogen Surveillance and the Euro-GASP study group

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, C. cile

AU - Lot, Florence

AU - Buder, Susanne

AU - Jansen, Klaus

AU - Miriagou, Vivi

AU - Rigakos, Georgios

AU - Raftopoulos, Vasilios

AU - Balla, Eszter

AU - Dudás, M. ria

AU - Ásmundsdóttir, Lena R. s

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 - Parodi, Patrizia

AU - Pakarna, Gatis

AU - Nikiforova, Raina

AU - Bormane, Antra

AU - Dimina, Elina

AU - Perrin, Monique

AU - Abdelrahman, Tamir

AU - Mossong, Joël

AU - Schmit, Jean-Claude

AU - Mühlschlegel, Friedrich

AU - Barbara, Christopher

AU - Mifsud, Francesca

AU - van Dam, Alje

AU - van Benthem, Birgit

AU - Visser, Maartje

AU - Linde, Ineke

AU - Kløvstad, Hilde

AU - Caugant, Dominique

AU - Młynarczyk-Bonikowska, Beata

AU - Azevedo, Jacinta

AU - Borrego, Maria-José

AU - Nascimento, Marina Lurdes Ramos

AU - Pavlik, Peter

AU - Klavs, Irena

AU - Murnik, Andreja

AU - Jeverica, Samo

AU - Kustec, Tanja

AU - Vázquez Moreno, Julio

AU - Diaz, Asuncion

AU - Abad, Raquel

AU - Velicko, Inga

AU - Fifer, Helen

AU - Shepherd, Jill

AU - Patterson, Lynsey

N1 - Funding Information: This study was supported by the European Centre for Disease Prevention and Control, the Centre for Genomic Pathogen Surveillance, the Li Ka Shing Foundation (Big Data Institute, University of Oxford), the Wellcome Genome Campus, the Foundation for Medical Research at Örebro University Hospital, and grants from Wellcome (098051 and 099202). LSB was funded by Conselleria de Sanitat Universal i Salut Pública, Generalitat Valenciana (Plan GenT CDEI-06/20-B), Valencia, Spain, and Ministry of Science, Innovation and Universities (PID2020–120113RA-I00), Spain, at the time of analysing and writing this manuscript. Publisher Copyright: © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

PY - 2022/6/1

Y1 - 2022/6/1

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.

UR - http://www.scopus.com/inward/record.url?scp=85133254121&partnerID=8YFLogxK

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

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

M3 - Article

C2 - 35659907

VL - 3

SP - e452-e463

JO - The Lancet. Microbe

JF - The Lancet. Microbe

SN - 2666-5247

IS - 6

ER -