How to interpret syphilis testing

Rates of syphilis, including congenital syphilis, have been rising worldwide. Syphilis is particularly difficult to diagnose given its non-specific symptoms and the inability to culture <i>Treponema pallidum</i> on regular media. Therefore, various diagnostic methods and complementary testing algorithms have been devised with the aim of accurately diagnosing syphilis. These diagnostic methods include direct detection techniques, useful in diagnosing early primary syphilis before seroconversion, and serological testing divided into treponemal (TT) and non-treponemal (NTT) tests. TTs detect <i>Treponema pallidum</i>-specific antibodies but cannot differentiate active from past infections, while NTT titres correlate with disease activity. In neonates being evaluated for congenital syphilis, maternal antibody transfer complicates this interpretation, necessitating careful correlation with clinical findings and maternal history. We explore these aforementioned tests with cases highlighting how they can be used and interpreted in different clinical scenarios.