Recent dynamics in Neisseria gonorrhoeae genomic epidemiology in Brazil: antimicrobial resistance and genomic lineages in 2017–20 compared to 2015–16

Author:

Golparian Daniel1,Bazzo Maria Luiza2,Ahlstrand Josefine1,Schörner Marcos André2,Gaspar Pamela Cristina3,de Melo Machado Hanalydia2,Martins Jéssica Motta2,Bigolin Alisson3,Ramos Mauro Cunha4,Ferreira William Antunes5,Pereira Gerson Fernando Mendes3,Miranda Angelica Espinosa3,Unemo Magnus16ORCID, ,de Carvalho Simone Veloso Faria,Costa Maria Rita Rabelo,Dias Luciane Guimarães,Feitosa Joana D'arc Pinheiro,Maciel Mariana Isabella,Neto Sibele Corrêa,Porto Elly Rodrigo,da Fonseca Andrade Lidiane,de Castro e Caldo Lima Glaura Regina,Lozano Viviane Furlan,Bazzo Maria Luiza,de Rocco Felipe,Barazzetti Fernando Hartmann,Kerber Guilherme,de Melo Machado Hanalydia,Martins Jéssica Motta,Buss Ketlyn,Scheffer Mara Cristina,Schörner Marcos André,Zonta Ronaldo,Ramos Mauro Cunha,Nicola Maria Rita Castilhos,Cecconi Maria Cristina,de Noronha Barbara Suely Souza,dos Santos Cleiby Andrade,Lopes Francinete Motta,de Souza Gomes Jairo,Júnior Jamile Izan Lopes Palhesta,Saif Paulo Tadeu Cavalcante,Ferreira Willian Antunes,Freire Miralba,Costa Ramos André Maurício,Carvalho Felipe Nogueira M,Politano Aida,da Silva Roberto José Carvalho,de Araújo Sandra,do Porto Claudio Campos,Bocalon Roberta Alessandra Lima,de Oliveira Machado de Souza Ursula,Mialski Rafael,da Silva Nogueira Keite,Bay Mônica Baumgardt,do Monte Alves Manoella,de Macedo Erianna Yadja Lucina,Campos Juliana Cintra,Junior Luíz Fernando Aires,de Oliveira Camargo Larissa,de Souza Neves Lis Aparecida,Paes Ana Paula Luchetta,Barufaldi Felipe,Reis Henrique Dib Oliveira,D’Oliveira Rocha Luiz Sérgio,Ribeiro Marta Inês Cazentini,da Silva Paulo,Amaral Fabiana Rezende,de Figueiroa François José,Barbosa Anesia Maria Siqueira,Araujo Ana Albertina,Varejão Maria Goretti,de França Mendes Fernanda Garnier,Cavalcanti Valdelucia Oliveira,Ribeiro Paulo Gabriel Lima,Ishigami Bruno,Caheté Lucas,Zoccoli Cássia Maria

Affiliation:

1. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, Department of Laboratory Medicine, Microbiology, Faculty of Medicine and Health, Örebro University , SE-701 85, Örebro , Sweden

2. Molecular Biology, Microbiology and Serology Laboratory, Federal University of Santa Catarina , Florianópolis , Brazil

3. Department of HIV/AIDS, Tuberculosis, and Sexually Transmitted Infection, Secretariat of Health Surveillance and Environment, Ministry of Health of Brazil , Brasília , Brazil

4. Brazilian STD Society , Porto Alegre , Brazil

5. Alfredo da Mata Foundation , Manaus , Brazil

6. Institute for Global Health, University College London (UCL) , London , UK

Abstract

Abstract Objectives Regular quality-assured WGS with antimicrobial resistance (AMR) and epidemiological data of patients is imperative to elucidate the shifting gonorrhoea epidemiology, nationally and internationally. We describe the dynamics of the gonococcal population in 11 cities in Brazil between 2017 and 2020 and elucidate emerging and disappearing gonococcal lineages associated with AMR, compare to Brazilian WGS and AMR data from 2015 to 2016, and explain recent changes in gonococcal AMR and gonorrhoea epidemiology. Methods WGS was performed using Illumina NextSeq 550 and genomes of 623 gonococcal isolates were used for downstream analysis. Molecular typing and AMR determinants were obtained and links between genomic lineages and AMR (determined by agar dilution/Etest) examined. Results Azithromycin resistance (15.6%, 97/623) had substantially increased and was mainly explained by clonal expansions of strains with 23S rRNA C2611T (mostly NG-STAR CC124) and mtr mosaics (mostly NG-STAR CC63, MLST ST9363). Resistance to ceftriaxone and cefixime remained at the same levels as in 2015–16, i.e. at 0% and 0.2% (1/623), respectively. Regarding novel gonorrhoea treatments, no known zoliflodacin-resistance gyrB mutations or gepotidacin-resistance gyrA mutations were found. Genomic lineages and sublineages showed a phylogenomic shift from sublineage A5 to sublineages A1–A4, while isolates within lineage B remained diverse in Brazil. Conclusions Azithromycin resistance, mainly caused by 23S rRNA C2611T and mtrD mosaics/semi-mosaics, had substantially increased in Brazil. This mostly low-level azithromycin resistance may threaten the recommended ceftriaxone-azithromycin therapy, but the lack of ceftriaxone resistance is encouraging. Enhanced gonococcal AMR surveillance, including WGS, is imperative in Brazil and other Latin American and Caribbean countries.

Funder

Örebro County Council Research Committe

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

Brazilian Ministry of Health

Publisher

Oxford University Press (OUP)

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