First National Genomic Epidemiological Study of Neisseria gonorrhoeae Strains Spreading Across Sweden in 2016

Abstract

The increasing transmission and antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a global health concern with worrying trends of decreasing susceptibility to also the last-line extended-spectrum cephalosporin (ESC) ceftriaxone. A dramatic increase of reported gonorrhea cases has been observed in Sweden from 2016 and onward. The aim of the present study was to comprehensively investigate the genomic epidemiology of all cultured N. gonorrhoeae isolates in Sweden during 2016, in conjunction with phenotypic AMR and clinical and epidemiological data of patients. In total, 1279 isolates were examined. Etest and whole-genome sequencing (WGS) were performed, and epidemiological data obtained from the Public Health Agency of Sweden. Overall, 51.1%, 1.7%, and 1.3% resistance to ciprofloxacin, cefixime, and azithromycin, respectively, was found. No isolates were resistant to ceftriaxone, however, 9.3% of isolates showed a decreased susceptibility to ceftriaxone and 10.5% to cefixime. In total, 44 penA alleles were found of which six were mosaic (n = 92). Using the typing schemes of MLST, NG-MAST, and NG-STAR; 133, 422, and 280 sequence types, respectively, and 93 NG-STAR clonal complexes were found. The phylogenomic analysis revealed two main lineages (A and B) with lineage A divided into two main sublineages (A1 and A2). Resistance and decreased susceptibility to ESCs and azithromycin and associated AMR determinants, such as mosaic penA and mosaic mtrD, were predominantly found in sublineage A2. Resistance to cefixime and azithromycin was more prevalent among heterosexuals and MSM, respectively, and both were predominantly spread through domestic transmission. Continuous surveillance of the spread and evolution of N. gonorrhoeae, including phenotypic AMR testing and WGS, is essential for enhanced knowledge regarding the dynamic evolution of N. gonorrhoeae and gonorrhea epidemiology.

Keywords: Neisseria gonorrhoeae; Sweden; antimicrobial resistance; molecular epidemiology; whole-genome sequencing.

FIGURE 1

Phylogenomic tree including genomic lineages, molecular typing and phenotypic antimicrobial resistance (AMR) of cultured Neisseria gonorrhoeae isolates (n = 1278) in Sweden 2016. One isolate was excluded from the phylogeny due to low coverage (<70%). Nodes denote sexual orientation (blue, homosexual males; yellow, females; green, heterosexual males; red, bisexual males; white, not reported). Bars for phenotypic antimicrobial susceptibility (or presence/absence of AMR determinants): green, susceptible (or AMR determinant absent); red, resistant (or AMR determinant present); and pink, decreased susceptibility. See line-listed details about the isolates and each determinant, including their color coding, at: https://microreact.org/project/Hadad_et_al_Swe2016. MLST, multi-locus sequence typing; NG-STAR CC, Neisseria gonorrhoeae sequence typing for antimicrobial resistance clonal complex; CFM, cefixime; CRO, ceftriaxone; AZM, azithromycin; CIP, ciprofloxacin.

FIGURE 2

Summary of patient characteristics (A–C) and Neisseria gonorrhoeae sequence types (D–F) of sublineages A1 and A2 and lineage B. Figures (D–F) Include sequence types of ≥10 isolates. MSM, men who have sex with men; MLST, multi-locus sequence typing; ST, sequence type; NG-STAR CC, Neisseria gonorrhoeae sequence typing for antimicrobial resistance clonal complex.