Syphilis, a re‐emerging public health problem worldwide caused by Treponema pallidum subsp pallidum (T. pallidum), usually induces systemic and chronic inflammation in hosts who do not receive timely therapy after exposing to high‐risk factors such as leprous sexual contact. Before the treatment, rapid and accurate detection of syphilis is essential. However, the existing detection methods, which focus on the treponemal or non‐treponemal antibody test, both have inherent limitations. For instance, both of them cannot distinguish the stage and severity of syphilis. Non‐treponemal test such as RPR, which is generally deemed to be used for assessing treatment response, is influenced by biological false positives. Therefore, it is imperative to seek out a new and effective diagnostic test. With recent advancements in molecular biology and whole‐genome sequencing, the molecular diagnosis has increased in popularity, especially the use of polymerase chain reaction (PCR). Here, we firstly present a mini‐review on the research of PCR detection methods used for syphilis diagnosis over the past decade, and we then compare these methodologies to assess their potential and the challenges faced. This information can provide a fresh perspective to help researchers address the current challenges.

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The data presented in this article are related to the research article entitled “Performance of novel infection phase-dependent antigens in syphilis serodiagnosis and treatment efficacy determination”. The rabbit model [1], [2] is an appropriate animal model for studying syphilis, a classic sexually transmitted disease (STD). Live Treponema pallidum (T. pallidum, Tp) and inactivated T. pallidum were inoculated in the backs of New Zealand rabbits. RT-PCR was performed to determine whether T. pallidum DNA could be detected in different groups. Sixty paired serum samples from patients at follow-up were tested by RPR and recombinant Tp0971-, Tp0768-, Tp0462- and Tp92-based ELISA.