Detection of Treponema pallidum DNA for diagnosis, resistance identification, and treatment outcome prediction in early syphilis among men who have sex with men.

Abstract

Objectives: We investigated the use of Treponema pallidum DNA (TP-DNA) for diagnosis, resistance identification, and treatment outcome prediction in early syphilis among men who have sex with men (MSM).

Methods: MSM seeking care for sexually transmitted infections were prospectively enrolled from September 2021 to August 2024. Oral rinse, rectal swab, and urethral swab samples were tested for TP-DNA. Resistance-associated mutations (RAMs) to macrolides and tetracyclines were identified. Treatment responses were compared between syphilis cases with detected TP-DNA and those without.

Results: Of 656 MSM enrolled, TP-DNA was most frequently detected in oral rinse samples (37.8% [193/510]), followed by rectal swab (20.2% [103/510]) and urethral swab samples (11.6%, 59/510) in clinic visits for early syphilis. TP-DNA was detected in 45.7% (233/510) of early syphilis cases and 0.7% (1/141) of cases without syphilis, resulting in a specificity of 99.3% (95% CI: 96.1-100%) and sensitivity of 45.7% (95% CI: 41.3-50.1%). Secondary syphilis cases had the highest yield of TP-DNA detection (67.6% [117/173]), followed by primary (48.7% [19/39]) and early latent syphilis cases (32.6% [97/298]). The Ct values of T. pallidum PCR in oral rinse samples were significantly lower in cases of higher rapid plasma reagin (RPR) titres (p < 0.001). The rate of T. pallidum harbouring RAMs to macrolides was 58.9% (139/236), increasing over 6-month intervals, from 32.4% (12/37) in 2021 to 77.8% (21/27) in 2023. Cases of detected TP-DNA had greater serological responses to treatments than those without: 80.3% (159/198) vs. 67.0% (156/233) at month 6 (p 0.002) and 84.1% (143/170) vs. 70.3% (137/195) at month 12 (p = 0.002).

Discussion: T. pallidum PCR showed high specificity for the diagnosis of early syphilis, which correlated with RPR titres and treatment response, and lower Ct values in oral rinse samples correlated with higher RPR titres. The high prevalence of T. pallidum strains with RAMs to macrolides argues against using azithromycin to treat syphilis in Taiwan.