Clearance of Treponema pallidum from oral and anal sites after treatment of secondary syphilis: results from a multi-centre, prospective, cross-sectional study

Background Syphilis is increasing worldwide, and secondary syphilis may represent its most infectious stage. Scarce data exist on Treponema pallidum clearance after treatment. We aimed to determine the frequency and load of T. pallidum mucosal shedding, and time to clearance following treatment of secondary syphilis. Methods Men-who-have-sex-with-men (MSM) and transgender women with secondary syphilis were recruited from Australian clinics between January 27, 2023, and August 19, 2024. Oral, anal or genital lesions were swabbed, and non-lesion samples (blood, oral cavity and anal canal swabs were collected on the day of treatment (baseline). Non-lesion oral cavity and anal canal swabs were repeated 3, 7, 14 and 30 days post-treatment. T. pallidum bacterial load was determined by quantitative PCR. Findings 78 cis-men and one trans-woman, who reported sex with men, were included. At baseline, T. pallidum was detected in the participants' oral cavity, anal canal and blood of 81% (64/79), 70% (55/79) and 24% (19/79), respectively. When detected at oral and anal sites, 22/64 (36%) had oral lesions and 31/55 (59%) had anal lesions, respectively. The median oral and anal bacterial loads decreased significantly from baseline to day 3, [cycle thresholds 35.7–37.7, (1.7–1.2 copies/μL), (p = 0.013), and 30.2–38.2 (3.3–1.0 copies/μL), (p < 0.001), respectively]. T. pallidum cleared from 99% (96/97) of non-lesion, paired samples from 58 participants by day 7, 95% confidence interval (94–100%). Interpretation During secondary syphilis, most MSM had T. pallidum DNA detected in oral and anal mucosa. Bacterial load dropped markedly 3 days post-treatment and cleared in almost all samples by 7 days. Funding Australian National Health and Medical Research Council.