Diagnosis of syphilis

Diagnostic procedures include: (1)

Dark ground microscopy - detection of spirochete in primary and secondary syphilis

Serology. Serology testing requires the use of both treponemal (specific) and non-treponemal (non-specific) tests with the usual approach being a treponemal test as the initial serological test, followed by a non-treponemal test if the treponemal test is positive.

Treponemal tests include:

• Treponemal enzyme immunoassay (EIA) - can be for immunoglobulin M (IgM) for early infection or immunoglobulin G (IgG) (the latter becomes positive at five weeks) or both
• T pallidum haemagglutination assay (TPHA)
• Fluorescent antibody absorption (FTA-ABS)
• Immunocapture assay (ICA).

The Treponema pallidum particle agglutination (TPPA) assay was withdrawn from the UK in 2022 due to regulatory requirements.

Following a positive treponemal test, a non-treponemal test should always be undertaken to confirm the diagnosis, and to provide evidence of active disease or re-infection. Non-treponemal tests include:

• RPR test
• VDRL test

Note (1)

• Treponemal-specific tests remain reactive lifelong and so are unable to differentiate between active and past infections, or monitor response to treatment. This means that patients should be informed that any future treponemal-specific testing will reveal previously treated syphilis infection.
• Investigations should also include a screen for all sexually transmitted infections (including HIV) as well as investigation for other possible diagnoses. All patients with neurological signs or symptoms and those who fail treatment should have a lumbar puncture and neurological imaging if appropriate.

Reference

1. Kingston M et al. BASHHUK. Guidelines for the management of syphilis 2024. International Journal of STD & AIDS 2024, Vol. 0(0) 1–19