Sequencing of most Treponema pallidum genomes excludes repeat regions in tp0470 and the tp0433 gene, encoding the acidic repeat protein (arp). As a first step to understanding the evolution and function of these genes and the proteins they encode, we developed a protocol to nanopore sequence tp0470 and arp genes from 212 clinical samples collected from ten countries on six continents. Both tp0470 and arp repeat structures recapitulate the whole genome phylogeny, with subclade-specific patterns emerging. The number of tp0470 repeats is on average appears to be higher in Nichols-like clade strains than in SS14-like clade strains. Consistent with previous studies, we found that 14-repeat arp sequences predominate across both major clades, but the combination and order of repeat type varies among subclades, with many arp sequence variants limited to a single subclade. Although strains that were closely related by whole genome sequencing frequently had the same arp repeat length, this was not always the case. Structural modeling of TP0470 suggested that the eight residue repeats form an extended α-helix, predicted to be periplasmic. Modeling of the ARP revealed a C-terminal sporulation-related repeat (SPOR) domain, predicted to bind denuded peptidoglycan, with repeat regions possibly incorporated into a highly charged β-sheet. Outside of the repeats, all TP0470 and ARP amino acid sequences were identical. Together, our data, along with functional considerations, suggests that both TP0470 and ARP proteins may be involved in T. pallidum cell envelope remodeling and homeostasis, with their highly plastic repeat regions playing as-yet-undetermined roles. 

/pdf/high-throughput-nanopore-sequencing-of-treponema-pallidum-eg9hpdc8.pdf

High-throughput nanopore sequencing of Treponema pallidum tandem repeat genes arp and tp0470 reveals clade-specific patterns and recapitulates global whole genome phylogeny

The Treponema pallidum strain distribution among men who have sex with women were similar to the strain distribution men who have sex with men (MSM). The most prevalent strains and percentage of strains belonging to the Nichols lineage are similar to previous studies in Amsterdam focusing on MSM. 

Treponema pallidum strains among women and men who have sex with women in Amsterdam, the Netherlands and Antwerp, Belgium between 2014 – 2020

www.thelancet.com/infection Vol 22 October 2022 1409 level. In addition, CDSS are, in essence, multimodal interventions, and the process of selecting the parameters that should be measured and retrievable from the system for each component of the intervention is essential to ensure a fine-grained evaluation of the trial results. In the near future, it might be worthwhile to use alternative causal-inference methods to evaluate interventions that have already diffused, to avoid the use of interrupted time-series designs, and to overcome the classic pitfalls of the cluster randomisation framework. To that end, real-world data at the individual level could be used to emulate target trials to produce real-world evidence. Future improvements of CDSSs in the hospital setting will come from integrating individual level laboratory and microbiological data, and possibly personal medical history through electronic health records, to personalise CDSS-derived recommendations in complex cases of infection. However, two challenges remain for integrating and evaluating CDSS to improve antimicrobial prescribing. First, paediatrics, and in particular neonatal sepsis, for which extrapolation of results from studies done in adults is not possible, and for which many broad-spectrum antibiotics are used off label. Second, primary care, including nursing homes, which accounts for the bulk of antimicrobial prescribing, and for which even a small effect could prevent a substantial number of antimicrobial exposures, but for which implementation of the interventions is complex.

Sexually transmitted outbreaks and genomic surveillance

Abstract Background We aimed to examine the incidence of syphilis in men who have sex with men (MSM) and identify subgroups of MSM at a higher risk of syphilis infection. Methods We conducted a retrospective cohort study of MSM attending a sexual health clinic in Australia, during 2013–2019, who had at least 2 syphilis serological tests during the study period. The incidence of syphilis was expressed as per 100 person-years. A cox regression analysis was conducted to identify risk factors for syphilis. Results A total of 24 391 individual MSM (75 086 consultations) were included. A total of 1404 new syphilis cases were diagnosed with an incidence of 3.7/100 person-years (95% confidence interval, 3.5–3.9). Syphilis incidence was higher in MSM with human immunodeficiency virus ([HIV] 9.3/100 person-years) than in MSM taking HIV pre-exposure prophylaxis (PrEP) (6.9/100 person-years) or HIV-negative MSM not taking PrEP (2.2/100 person-years). Risk factors associated with high incidence of syphilis included the following: MSM with HIV (adjusted hazard ratio [aHR] 2.7), MSM taking HIV PrEP (aHR 2.1), past history of syphilis infection (aHR 2.4), injecting drug use (aHR 2.7), condomless anal sex (aHR 1.7), >4 sexual partners in the last 12 months (aHR 1.2), and concurrent sexually transmitted infection (chlamydia and gonorrhoea) (aHR 1.6). Conclusions The incidence of syphilis remains high among MSM, particularly in subgroups with associated risk factors for syphilis infections. These data highlight the need for biomedical and behavioral interventions to be targeted to subgroups of MSM at the highest risk of syphilis infection.

https://academic.oup.com/ofid/article-pdf/10/2/ofad017/49090125/ofad017.pdf

Incidence and Risk Factors for Early Syphilis Among Men Who Have Sex With Men in Australia, 2013–2019: A Retrospective Cohort Study

BackgroundThe incidence of syphilis has increased markedly in the past decade in high-income countries, including Australia. To date, however, genomic studies of Treponema pallidum have focused mainly on the northern hemisphere. Here, we aimed to characterise the lineages of T pallidum driving the current syphilis epidemic in Australia.MethodsIn this genomic epidemiological analysis, using phylogenomic and phylodynamic analyses, we analysed 456 high-quality T pallidum genomes collected from clinical samples in Australia between Oct 19, 2005, and Dec 31, 2020, and contextualised this information with publicly available sequence data. We also performed detailed genomic characterisation of putative antimicrobial resistance determinants, in addition to correlating single-locus typing of the TP0548 allele with the T pallidum phylogeny.FindingsPhylogenomic analyses identified four major sublineages circulating in Australia and globally, two belonging to the SS14 lineage, and two belonging to the Nichols lineage. Australian sublineages were further delineated into twelve subgroups, with five of the six largest subgroups associated with men who have sex with men, and the sixth lineage was predominantly associated with heterosexual people. Most Australian T pallidum genomes (398 [87%] of 456) were genotypically macrolide resistant, and TP0548 typing correlated significantly with T pallidum genomic subgroups.InterpretationThese findings show that the current syphilis epidemic in Australia is driven by multiple lineages of T pallidum, rather than one distinct outbreak. Major subgroups of T pallidum in Australia have emerged within the past 30 years, are closely related to global lineages, and circulate across different sexual networks. In conjunction with improved testing and treatment, these data could better inform the control of syphilis in Australia.FundingNational Health and Medical Research Council, Australian Research Council. The incidence of syphilis has increased markedly in the past decade in high-income countries, including Australia. To date, however, genomic studies of Treponema pallidum have focused mainly on the northern hemisphere. Here, we aimed to characterise the lineages of T pallidum driving the current syphilis epidemic in Australia. In this genomic epidemiological analysis, using phylogenomic and phylodynamic analyses, we analysed 456 high-quality T pallidum genomes collected from clinical samples in Australia between Oct 19, 2005, and Dec 31, 2020, and contextualised this information with publicly available sequence data. We also performed detailed genomic characterisation of putative antimicrobial resistance determinants, in addition to correlating single-locus typing of the TP0548 allele with the T pallidum phylogeny. Phylogenomic analyses identified four major sublineages circulating in Australia and globally, two belonging to the SS14 lineage, and two belonging to the Nichols lineage. Australian sublineages were further delineated into twelve subgroups, with five of the six largest subgroups associated with men who have sex with men, and the sixth lineage was predominantly associated with heterosexual people. Most Australian T pallidum genomes (398 [87%] of 456) were genotypically macrolide resistant, and TP0548 typing correlated significantly with T pallidum genomic subgroups. These findings show that the current syphilis epidemic in Australia is driven by multiple lineages of T pallidum, rather than one distinct outbreak. Major subgroups of T pallidum in Australia have emerged within the past 30 years, are closely related to global lineages, and circulate across different sexual networks. In conjunction with improved testing and treatment, these data could better inform the control of syphilis in Australia. 

Francesca Azzatto

Papers

Characterisation of Treponema pallidum lineages within the contemporary syphilis outbreak in Australia: a genomic epidemiological analysis.