Sensitivity and Specificity of 7 Treponemal Tests for Syphilis Diagnosis

Treponema pallidum particle agglutination assay is a better test to adjudicate syphilis results given its high specificity and superior sensitivity.

Treponema pallidum particle agglutination assay (TP-PA) is a better test to adjudicate syphilis results given its high specificity and superior sensitivity, according to a study recently published in Clinical Infectious Diseases.

Syphilis is increasing at epidemic rates in the United States, especially among men who have sex with men, women of reproductive age, and newborns. Traditionally, syphilis diagnosis involves use of nontreponemal serology (eg, rapid plasma reagin, Venereal Disease Research Laboratory) directed against lipoidal antigens including lecithin, cardiolipin, and cholesterol. Confirmation of reactive results is performed with a treponemal test (eg, TP-PA). Although nontreponemal tests are inexpensive and useful for monitoring treatment response, they require significant hands-on time by laboratory personnel.

This study compared the sensitivity and specificity of newer automated treponemal tests (eg, enzyme immunoassay [EIA], chemiluminescence immunoassay [CIA], microbead immunoassay [MBIA)] and manual treponemal tests (eg, fluorescent treponemal antibody absorption test [FTA-ABS], TP-PA) in individuals with and without a clinical diagnosis of syphilis. The findings will help inform the most appropriate second treponemal test selection for patients with initially discordant treponemal and nontreponemal serology, and selection of an automated treponemal test when the reverse sequence algorithm is used for a laboratory diagnosis of syphilis.

A total of 959 participants were included. Cases were characterized as: 1) current clinical diagnosis of syphilis: primary, secondary, early latent, or late latent (n=262); 2) prior treated syphilis (n=294); 3) no evidence of current syphilis no prior history of syphilis and at least 4/7 treponemal tests negative (n=403). Sensitivity and specificity of 7 treponemal assays were calculated, including: 1) ADVIA Centaur (CIA); 2) Bioplex 2200 (MBIA); 3) FTA-ABS; 4) INNO-LIA (line immunoassay); 5) LIAISON CIA; 6) TP-PA; 7) Trep-Sure (EIA).

In examining sensitivity by stage of syphilis, FTA-ABS had the lowest sensitivity for primary syphilis (78.2%) compared to the other immunoassays or TP-PA (94.5%-96.4%) (all P ≤.01). FTA-ABS was also significantly less sensitive for secondary syphilis (P =.007), while all other assays were 100% sensitive for secondary syphilis. All 7 assays demonstrated high sensitivity (95%-100%) for early latent syphilis, and a lower sensitivity (86.8%-98.5%) for late latent disease. TP-PA was significantly less sensitive than TrepSure EIA for late latent disease (P =.009). Overall, the 4 immunoassays routinely used for screening (LIAISON CIA, ADVIA Centaur CIA, TrepSure EIA, Bioplex 2200 MBIA) demonstrated high sensitivity for primary secondary, and early latent syphilis, comparable to traditional manual tests like TP-PA.

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Results showed greater variability in specificity among the 7 assays. While TP-PA had 100% specificity, TrepSure EIA demonstrated significantly lower specificity than other assays (82.5%; P <.0001). Of the 41 individuals classified as not having syphilis who had 1, 2, or 3 of 7 reactive treponemal tests, TrepSure EIA was most likely to be reactive (85%), followed by Centaur CIA (61%), LIAISON CIA (37%), INNO-LIA (25%), and Bioplex (20%). TP-PA and FTA-ABS were least likely to be reactive (2%).

Overall, the investigators conclude that, “Given its high specificity and superior sensitivity, TP-PA is a better test to adjudicate discordance results with the reverse sequence algorithm than the FTA-ABS.”


Park IU, Fakile YF, Chow JM, et al. Performance of treponemal tests for the diagnosis of syphilis. [published online July 9, 2018]. J Clin Infect Dis. doi:10.1093/cid/ciy558