Timing of primary syphilis treatment and impact on the development of treponemal antibodies: a cross-sectional clinic-based study

Serology is negative in a proportion of primary syphilis cases where Treponema pallidum PCR testing is positive. We aimed to identify discordant, T. pallidum PCR-positive, serology-negative primary syphilis cases and any clinical or laboratory factors associated with failure to subsequently seroconvert.Serodiscordant primary syphilis cases that were T. pallidum PCR-positive and serology-negative (including rapid plasma reagin, T. pallidum particle agglutination, T. pallidum enzyme immunoassay or T. pallidum chemiluminescence assay) were identified from the Melbourne Sexual Health Centre electronic records between April 2011 and December 2019. Clinical and laboratory associations were examined.There were 814 primary syphilis cases in the study period and 38 (4.7%) were serodiscordant, 35 in men who have sex with men. Thirty-two had follow-up serology performed a median of 24 days later, of which 16 (50%) seroconverted, mostly (81%) within 6 weeks. Failure to seroconvert was significantly associated with treatment on day 1. Of the 12 cases treated on day 1, 10 (83%) failed to seroconvert compared with 6 of 20 (30%) among those who were treated after day 1.Earlier treatment of primary syphilis can prevent the development of serological markers. T. pallidum PCR can identify primary syphilis lesions before the development of serological markers and improve diagnosis of early primary syphilis lesions. Serology alone will miss a proportion of primary syphilis infections and should be repeated if a diagnosis of syphilis is being considered.