title: Genomic Analysis and Comparison of Two Gonorrhea Outbreaks.
abstract: Gonorrhea is a sexually transmitted disease causing growing concern, with a substantial increase in reported incidence over the past few years in the United Kingdom and rising levels of resistance to a wide range of antibiotics. Understanding its epidemiology is therefore of major biomedical importance, not only on a population scale but also at the level of direct transmission. However, the molecular typing techniques traditionally used for gonorrhea infections do not provide sufficient resolution to investigate such fine-scale patterns. Here we sequenced the genomes of 237 isolates from two local collections of isolates from Sheffield and London, each of which was resolved into a single type using traditional methods. The two data sets were selected to have different epidemiological properties: the Sheffield data were collected over 6 years from a predominantly heterosexual population, whereas the London data were gathered within half a year and strongly associated with men who have sex with men. Based on contact tracing information between individuals in Sheffield, we found that transmission is associated with a median time to most recent common ancestor of 3.4 months, with an upper bound of 8 months, which we used as a criterion to identify likely transmission links in both data sets. In London, we found that transmission happened predominantly between individuals of similar age, sexual orientation, and location and also with the same HIV serostatus, which may reflect serosorting and associated risk behaviors. Comparison of the two data sets suggests that the London epidemic involved about ten times more cases than the Sheffield outbreak.
  
  
  OBJECTIVE
  The recent increases in gonorrhea incidence and antibiotic resistance are cause for public health concern. Successful intervention requires a better understanding of transmission patterns, which is not uncovered by traditional molecular epidemiology techniques. Here we studied two outbreaks that took place in Sheffield and London, United Kingdom. We show that whole-genome sequencing provides the resolution to investigate direct gonorrhea transmission between infected individuals. Combining genome sequencing with rich epidemiological information about infected individuals reveals the importance of several transmission routes and risk factors, which can be used to design better control measures.
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom x.didelot@imperial.ac.uk sh16@sanger.ac.uk.
authors.forename: Xavier
authors.identifier: http://orcid.org/0000-0003-1885-500X
authors.initials: X
authors.lastname: Didelot
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom Department of Biology, Drexel University, Philadelphia, Pennsylvania, USA.
authors.forename: Janina
authors.initials: J
authors.lastname: Dordel
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Lilith K
authors.initials: LK
authors.lastname: Whittles
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Collins
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bilek
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom International AIDS Vaccine Initiative, Human Immunology Laboratory, Imperial College London, London, United Kingdom.
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Bishop
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom Modelling and Economics Unit, Centre for Infectious Disease Surveillance and Control, Public Health England, London, United Kingdom MRC Centre for Outbreak Analysis and Modelling, School of Public Health, Imperial College London, London, United Kingdom NIHR Health Protection Research Unit in Modelling Methodology, School of Public Health, Imperial College London, London, United Kingdom.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: White
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom Centre for Genomic Pathogen Surveillance, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
authors.forename: David M
authors.initials: DM
authors.lastname: Aanensen
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
authors.forename: Julian
authors.identifier: http://orcid.org/0000-0002-7069-5958
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Spratt
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom x.didelot@imperial.ac.uk sh16@sanger.ac.uk.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Harris
mesh_terms: D000328:Adult; D004196:Disease Outbreaks; D005260:Female; D016680:Genome, Bacterial; D023281:Genomics; D006069:Gonorrhea / Q000453:epidemiology* / Q000382:microbiology* / Q000635:transmission; D020010:Heterosexuality; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D015994:Incidence; D008131:London / Q000453:epidemiology; D008297:Male; D058889:Molecular Typing; D009344:Neisseria gonorrhoeae / Q000235:genetics* / Q000302:isolation & purification; D010802:Phylogeny; D012307:Risk Factors; D012747:Sexual Partners; D000072339:Sexual and Gender Minorities; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult