Diagnosis

Syphilis has several clinical manifestations, making it difficult to diagnose based on clinical symptoms alone. Also, T. pallidum cannot be isolated in culture so confirmation must be performed either by ELISA-based serological assays or by direct visual inspection using microscopy. Serological tests are more commonly used however all syphilis diagnostic assays are unable to distinguish between the stages of the disease.

Categories of Serological Testing for Syphilis

1. Treponemal tests which are aimed at detecting an antigen or an antibody to T. pallidum. Examples include EIA assays that detect IgG and/or IgM and IgA antibodies to T. pallidum.
2. Non-treponemal tests which look for indirect indications of the infection such as the presence of cardiolipins (a mitochondrial membrane lipid), which are released when a treponeme bacteria damages cells. Since these tests do not detect the bacteria directly, they usually require confirmation testing. The T. pallidum genome is 1.14 Mb and encodes a putative 1,041 proteins (Genome Sequencing Project). Different strains of T. pallidum (Tp) may express different repertoires of Tp proteins as demonstrated by various immunologic studies (Leader, B. et al. (2003) Infect. Immun. 71:6054-6057). In the past few years, several highly immunogenic lipoproteins have been identified as diagnostic targets for the various stages of a syphilis infection, including Tp17, Tp15, Tp44.5 (TmpA), Tp47, Tp41, Tp35 (TmpC) and Tp0453. Several commercial tests have been developed using a combination of recombinant syphilis antigens and have proven to be highly sensitive and specific for the diagnosis of an active or latent syphilis infection. Other recent developments include rapid formats that can be performed at the point of care, such as lateral flow assays and agglutination tests using latex particles.