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.

Applications of genomics to slow the spread of multidrug‐resistant Neisseria gonorrhoeae

“…Beyond inferring likely transmission links, phylogenetic analyses utilizing a molecular clock enable additional inferences. Calculating the time to most recent common ancestor (TMRCA) of isolates from pairs of known contacts in Sheffield, UK enabled estimation of the average duration of infection in this primarily heterosexual population to be 3.4 months …”

“…Typing of bacterial strains has long been a complement to typical epidemiological practices when investigating an outbreak. While WGS is generally concordant with traditional typing methods like MLST and NG‐MAST, it can provide increased resolution and rule out potential transmission links that may be inferred by these methods . For example, in a study of N. gonorrhoeae specimens from Brighton, UK, 8.8% of isolates collected within 28 days of each other had the same NG‐MAST type, but only 3.6% of isolates were compatible with direct or indirect transmission according to WGS results .…”

“…While WGS is generally concordant with traditional typing methods like MLST and NG-MAST, it can provide increased resolution and rule out potential transmission links that may be inferred by these methods. 107 For example, in a study of N. gonorrhoeae specimens from Brighton, UK, 8.8% of isolates collected within 28 days of each other had the same NG-MAST type, but only 3.6% of isolates were compatible with direct or indirect transmission according to WGS results. 24 In British Columbia, monitoring of a database of HIV genotypes allowed for the identification of a growing transmission cluster and timely public health follow-up; 108 N. gonorrhoeae WGS may similarly allow for identification of expanding lineages and prevention of further onward transmission.…”

“…Calculating the time to most recent common ancestor (TMRCA) of isolates from pairs of known contacts in Sheffield, UK enabled estimation of the average duration of infection in this primarily heterosexual population to be 3.4 months. 107 WGS can also be used to track the spread of resistance across geographic boundaries. For example, a cluster of cefixime resistant gonococcus mediated by mosaic penA XXXIV spreads from the west coast to the east coast of the United States.…”

Linking an unchained malady

“…Didelot et al 3 used a different approach to study transmission in two different settings: 132 isolates of N. gonorrhoeae multiantigen sequence type (NGMAST) ST12 that were collected in a single clinic in Sheffield, UK (1995UK ( −2000, from a mostly heterosexual population, and 105 NGMAST ST225 iso lates that were collected in 13 different clinics in London, UK (June−November 2004), from a mostly MSM population. Traditional typ ing approaches, such as NGMAST (which is based on the sequences of two surface pro teins), provide little useful information on transmission for isolates that share the same typing profile.…”