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DNA Sequencing Sheds Light on Gonorrhea Transmission Patterns

NEW YORK (GenomeWeb) – A new study in Lancet Infectious Diseases suggests bacterial genome sequencing is an effective method for tracking gonorrhea transmission and identifying potential resistance-related genetic features.

Between 2013 and 2014, gonorrhea prevalence ticked up by 19 percent in England, with that country's cases accounting for nearly 35,000 of the roughly 78 million documented around the world each year.

A UK-led team sequenced the genomes of nearly 1,300 Neisseria gonorrhoeae cultures from isolates collected at a sexual health centers in the UK from early 2011 to mid-2015. By analyzing the genomes alongside sequences from N. gonorrhoeae isolates from other parts of the UK or US, the researchers demonstrated that they could follow gonorrhea transmission events within Brighton and across international borders.

They used the sequence data to look at the genetic diversity and mutation rates in the gonorrhea-causing microbes, and were also able to pick out antimicrobial resistance patterns that matched those found by testing for resistance in N. gonorrhoeae cultures.

"Sequencing can overcome some of the weaknesses in traditional partner notification tracing, while at the same time enabling us to spot risk factors and better target health interventions," co-senior author David Eyre — a researcher affiliated with the John Radcliffe Hospital, the University of Oxford, and the National Institute for Health Research — said in a statement.

In order to untangle gonorrhea transmission using genome sequence data, the researchers focused on 1,267 N. gonorrhoeae-positive cultures produced using samples from patients at clinics and primary care centers in Brighton from 2011 to 2015, including individuals with or without gonorrhea symptoms.

Using Illumina HiSeq instruments, the team attempted to sequence 1,437 isolates picked from those cultures, successfully sequencing the genomes of 1,407 isolates — a set representing 1,061 gonorrhea infections in 907 individuals who experienced between one and seven infections.   

More than one-quarter of the isolates were genetically indistinguishable from isolates involved in at least one of the other cases, the researchers reported, and almost three-quarters of the cases seemed to stem from Brighton-related sources. The remaining cases were not genetically linked to other cases in Brighton, they noted. Instead, their SNP-based transmission nomogran analyses indicated that 225 of the Brighton cases were caused by isolates related to gonorrhea cases in other parts of the UK. Another 115 cases were traced to isolates resembling those associated with cases in the US.

In particular, the team narrowed in on four N. gonorrhoeae lineages with genetic ties to 70 isolates in the US. Of those American isolates, 61 belong to a lineage marked by a penA genotype associated with diminished vulnerability to the antibiotic cefixime.

These and other results suggest that "action to tackle antibiotic-resistant gonorrhea needs to be coordinated across national boundaries," Eyre said. "However, using whole genome sequencing to track transmission of these infections is feasible."

In an accompanying commentary article in Lancet Infectious Diseases, University of Toronto researchers Vanessa Allen and Roberto Melano discussed the study's strengths. For example, while they cautioned that the UK team's transmission nomogram alone cannot corroborate person-to-person gonorrhea transmission, it does offer a genetic means of tracing transmission that's complementary to other clinical and epidemiological information.

"The development of new genomic epidemiological tools for antimicrobial surveillance and analysis of resistance dissemination is key to improvement of the public health response to emerging infectious diseases," they added.