The Laboratory Diagnosis of Syphilis

J Clin Microbiol. 2021 Sep 20;59(10):e0010021. doi: 10.1128/JCM.00100-21. Epub 2021 May 12.


Syphilis is a multisystem infection caused by the spirochete Treponema pallidum. Currently, cases of possible syphilis are commonly investigated using the treponemal serological tests T. pallidum IgG chemiluminescence immunoassay (CLIA) and the T. pallidum particle agglutination (TPPA). The nontreponemal rapid plasma reagin (RPR) flocculation test is used to assess disease activity. There has been a resurgence of syphilis diagnoses in Australia. Large foci of infection have been identified in isolated communities. The remoteness of these locations, in conjunction with the particular sociocultural characteristics of the population, pose unique challenges to the traditional diagnostic and treatment paradigms for syphilis. As a consequence of this increased incidence of syphilis, there has been interest in the utility of point-of-care tests (POCTs), nucleic acid amplification tests (NAATs), the role of IgM testing in suspected congenital syphilis, and the laboratory investigation of possible neurosyphilis. This review looks at the current status of traditional serological assays and provides an update on more recent methods. It assesses the published literature in this area and makes recommendations for the rational use of pathology testing to aid in the diagnosis of the many facets of syphilis.

Keywords: diagnostics; syphilis.

Publication types

  • Review

MeSH terms

  • Antibodies, Bacterial
  • Humans
  • Neurosyphilis*
  • Syphilis Serodiagnosis
  • Syphilis* / diagnosis
  • Treponema pallidum / genetics


  • Antibodies, Bacterial