Sustained transmission of high-level azithromycin-resistant Neisseria gonorrhoeae in England: an observational study

Abstract

Public Health England.

Emergence of Neisseria gonorrhoeae Strains Harboring a Novel Combination of Azithromycin-Attenuating Mutations

“…DNA sequence analysis revealed that all 14 isolates harbored the mosaic-mtr and the A2059G mutation in all four copies of their 23S rRNA gene. While investigators from many countries have reported on the A2059G mutation or the mosaic-mtr, none described these two haplotypes together (5,10,(12)(13)(14)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). The 14 isolates in this study are the first known isolates to have possessed both the A2059G mutation and the mosaic-mtr.…”

“…Although the A2059A mutation confers resistance to azithromycin, it has been posited that this same mutation exerts a fitness cost on N. gonorrhoeae isolates (14). This may explain why isolates with this genotype failed to transmit and persist in the population.…”

“…In the United States, the percentage of isolates with reduced cephalosporin susceptibility declined after 2012; however, the number and percentage of gonococcal isolates with reduced susceptibility to azithromycin have steadily increased since then (11). The increase in the number of N. gonorrhoeae isolates displaying elevated MICs to azithromycin is typically associated with the accumulation of genetic mutations in the multiple transferable resistance (mtr) locus or in the 23S rRNA gene (10,(12)(13)(14).…”

A dynamic power-law sexual network model of gonorrhoea outbreaks

“…55 In a sexual network model, the rate of transmission to an uninfected individual depends on the infection 56 status of their sexual partners, rather than on the prevalence of infection in the pool of potential partners, 57 as in compartmental models. Compartmental models that do not explicitly represent partnerships 58 have been shown to underestimate the importance of core groups of highly sexually active individuals 59 in sustaining STI transmission, while overestimating the contribution of long-term partnerships and 60 low-activity individuals [19]. Furthermore, several studies have shown that, in order to explain observed 61 patterns of infection, it is important to take into account not only the network structure but also the 62 duration of partnerships, and the gaps between them [20,21].…”

“…to be applied to the reconstruction of transmission in gonorrhoea outbreaks [38,[58][59][60]. 267 We estimated that on average the mean and variance of the generation time distribution were equal to 268 63 days and 6980 days 2 , respectively ( Fig 4B), which can be emulated using a Gamma distribution with 269 shape and scale parameters equal to 0.57 and 110.48, respectively.…”