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Use of whole genome sequencing to investigate an increase in Neisseria gonorrhoeae infection among women in urban areas of Australia.

ABSTRACT: Increasing rates of gonorrhoea have been observed among women within the Australian state of New South Wales. Here, we applied whole genome sequencing (WGS) to better understand the associated networks and transmission dynamics. Ninety-four isolates of a particular N. gonorrhoeae genotype (G122) associated with women (years 2012 to 2014) underwent phylogenetic analysis using core single nucleotide polymorphisms. WGS data revealed five main clusters, all of which were heterogeneous in terms of patient age and site of infection. The relatively high cervical/vaginal infections in each cluster was indicative of transmission in the general heterosexual population, noting that there is typically high rates of condom use for vaginal sex among local commercial sex workers. WGS also enabled the identification of groups of individuals belonging to tighter transmission chains within clusters, and hence may present a new tool for targeting public health interventions. The enhanced resolution of WGS provides a ready means of confirming suspected changes in N. gonorrhoeae epidemiology, but also enables key features to be identified or new questions to be raised regarding the composition of the associated sexual networks.

SUBMITTER: Buckley C

PROVIDER: S-EPMC5784116 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Use of whole genome sequencing to investigate an increase in Neisseria gonorrhoeae infection among women in urban areas of Australia.

Buckley Cameron C Forde Brian M BM Trembizki Ella E Lahra Monica M MM Beatson Scott A SA Whiley David M DM

Scientific reports 20180124 1

Increasing rates of gonorrhoea have been observed among women within the Australian state of New South Wales. Here, we applied whole genome sequencing (WGS) to better understand the associated networks and transmission dynamics. Ninety-four isolates of a particular N. gonorrhoeae genotype (G122) associated with women (years 2012 to 2014) underwent phylogenetic analysis using core single nucleotide polymorphisms. WGS data revealed five main clusters, all of which were heterogeneous in terms of pa ...[more]

PMID: 29367612

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Project description:BACKGROUND:New approaches are urgently required to address increasing rates of gonorrhoea and the emergence and global spread of antibiotic-resistant Neisseria gonorrhoeae. We used whole-genome sequencing to study transmission and track resistance in N gonorrhoeae isolates. METHODS:We did whole-genome sequencing of isolates obtained from samples collected from patients attending sexual health services in Brighton, UK, between Jan 1, 2011, and March 9, 2015. We also included isolates from other UK locations, historical isolates from Brighton, and previous data from a US study. Samples from symptomatic patients and asymptomatic sexual health screening underwent nucleic acid amplification testing; positive samples and all samples from symptomatic patients were cultured for N gonorrhoeae, and resulting isolates were whole-genome sequenced. Cefixime susceptibility testing was done in selected isolates by agar incorporation, and we used sequence data to determine multi-antigen sequence types and penA genotypes. We derived a transmission nomogram to determine the plausibility of direct or indirect transmission between any two cases depending on the time between samples: estimated mutation rates, plus diversity noted within patients across anatomical sites and probable transmission pairs, were used to fit a coalescent model to determine the number of single nucleotide polymorphisms expected. FINDINGS:1407 (98%) of 1437 Brighton isolates between Jan 1, 2011, and March 9, 2015 were successfully sequenced. We identified 1061 infections from 907 patients. 281 (26%) of these infections were indistinguishable (ie, differed by zero single nucleotide polymorphisms) from one or more previous cases, and 786 (74%) had evidence of a sampled direct or indirect Brighton source. We observed multiple related samples across geographical locations. Of 1273 infections in Brighton (including historical data), 225 (18%) were linked to another case elsewhere in the UK, and 115 (9%) to a case in the USA. Four lineages initially identified in Brighton could be linked to 70 USA sequences, including 61 from a lineage carrying the mosaic penA XXXIV allele, which is associated with reduced cefixime susceptibility. INTERPRETATION:We present a whole-genome-sequencing-based tool for genomic contact tracing of N gonorrhoeae and demonstrate local, national, and international transmission. Whole-genome sequencing can be applied across geographical boundaries to investigate gonorrhoea transmission and to track antimicrobial resistance. FUNDING:Oxford National Institute for Health Research Health Protection Research Unit and Biomedical Research Centre.

Project description:BackgroundTracking the spread of the Neisseria gonorrhoeae strains with decreased susceptibility or resistance to cephalosporins is a major priority for global surveillance programmes. Whole-genome sequencing (WGS) has been widely used by increasing countries in North America, Europe, and Pacific to determine the decreased susceptible or resistance determinants of Neisseria gonorrhoeae, track the spread of these determinants throughout the gonococcal population at national or regional level. However, no studies to date have examined the genomic epidemiology of gonorrhea in Asia where the antimicrobial resistant strains of Neisseria gonorrhoeae appears to have emerged before disseminating the strains globally.MethodsWe obtained clinical isolates and data from the China Gonococcal Resistance Surveillance Programme (China-GRSP) from 2012 to 2013. We sequenced the genomes of 435 clinical isolates of Neisseria gonorrhoeae, including 112 (25.6%) isolates with decreased susceptibility to ceftriaxone (Cfx-DS). We assessed the association between antimicrobial resistance genotype and phenotype. We also compared our data with the whole genome data of the isolates from the USA and the UK in the GenBank.FindingsThe most prevalent MLST STs in our gonococcal population were MLST ST7827 (n = 74), followed by ST7365 (n = 58), ST1600 (n = 38), ST7367 (n = 35), and ST7363 (n = 29). MLST ST1901 which was reported as the predominant ST in the US was not found in our population. A total of 2512 strains, including additional 2077 published NG strains, were further included for phylogenetic analysis. It generated two distinct lineages - lineage 1 and lineage 2. Analysis of MLST ST1901 in the database indicate that most of MLST ST1901 isolates in the lineage2.6 were Cfx-DS isolates while all isolates in the lineage 2.1 were sensitive to ceftriaxone (77/110 vs. 0/13; p < 0.001). ST1901/lineage 2.6 is a ceftriaxone resistant clone which cannot distinguished by MLST genotyping. In the isolates from our study, the MICs of ceftriaxone for ST7363/lineage 2.6 isolates ranged from 0.008-0.125 mg/L (mean ± SD; 0.054 ± 0.043 mg/L) while those for ST7363/lineage 2.8 isolates ranged from 0.032-0.250 mg/L (0.134 ± 0.085 mg/L). All ST7363/lineage 2.8 isolates contained penA mosaic alleles.InterpretationTo our knowledge, current study is the first WGS-based analysis of gonococcal population at national level in Asia. China harbors the different predominant clones associated with decreased susceptibility to ceftriaxone from those clones circulated in other regions. The findings from the study can be not only used as baseline data for future studies in China but also contributable to our understanding on spread of N. gonorrhoeae and its resistant strains at regional and global levels.FundingThe Chinese Academy Medical Sciences (CAMS) Initiative for Innovative Medicine.

Dataset Information

Use of whole genome sequencing to investigate an increase in Neisseria gonorrhoeae infection among women in urban areas of Australia.

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Use of whole genome sequencing to investigate an increase in Neisseria gonorrhoeae infection among women in urban areas of Australia.

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