Evaluation of a Treponema IgG ELISA alone and in combination with an IgM ELISA as substitutes for Treponema pallidum particle agglutination (TPPA) as confirmatory tests in a two-tier diagnostic algorithm for diagnosis of syphilis infection

Abstract

Objectives The Treponema pallidum particle agglutination (TPPA) has been used for decades for serological diagnostics of syphilis but is no longer available. Therefore, we evaluated the Treponema IgG ELISA (TpG) alone and in combination with the Treponema IgM ELISA (TpG+M, both from Euroimmun) as possible substitutes for TPPA as a confirmatory test in a two-tier syphilis screening algorithm. Furthermore, we investigated whether a TPPA titer of 5,120 which is used as cut-off for therapeutic decision in pregnant women in Germany can be transferred to an appropriate cut-off value of the TpG. Methods All serum samples with reactive syphilis screening test (CLIA, Diasorin) within a 13-months period were included (n=739). In addition to TPPA and rapid plasma reagin test both ELISA tests were done in all samples. Results Sensitivity, specificity, positive and negative predictive values were 92.2, 100, 100, and 74.5 % for TpG, and 93.2, 85.4, 96.6, and 74.1 % for TpG+M. By ROC analysis the cut-off of TpG corresponding to a TPPA titer ≥5,120 was calculated to be 54 RU/mL with a sensitivity of 99.6 % and a resulting specificity of 58.6 %. Conclusions TpG appears suitable to substitute TPPA as a confirmatory test for syphilis diagnostics but TpG-negative samples have to be evaluated by further tests like FTA-Abs or immunoblot. Treponema IgM determined in addition to TpG did not improve the test performance compared to the TPPA as a reference standard. Valid prediction of a TPPA titer ≥5,120 from TpG result appears not reasonable.