Seroconversion in syphilis screening without positive confirmatory tests points at early infection

Introduction The chemiluminescence immunoassay (CLIA) is a widely used screening test for syphilis. A CLIA seroconversion in the absence of a positive line immunoassay (LIA) or rapid plasma reagin (RPR) could indicate either an early incubating syphilis or a false positive result. We aimed to evaluate the diagnostic value of such seroconversions. Methods We retrospectively analysed data of clients visiting the Centre for Sexual Health Amsterdam between July 2013 and August 2021 with a positive CLIA and a negative RPR and negative or indeterminate LIA (at time T_o), and a preceding visit (T_-1) with a negative CLIA <6 months of T_o ('unconfirmed CLIA seroconversion'). If available, data of follow-up visits (T₁) <2 months of T_o were also included. A syphilis diagnosis was confirmed if darkfield microscopy or PCR for Treponema pallidum was positive at T₀ or T₁, or if RPR and/or LIA were positive at T₁. Results We included data of 107 clients with unconfirmed CLIA seroconversion. The value of CLIA seroconversion could not be established in 13 (12.1%) clients. In the remaining 94 clients, the unconfirmed CLIA seroconversion was confirmed as early syphilis in 72 (76.6%) clients and probable syphilis in 6 (6.4%) clients. In 16 (17.0%) clients, the unconfirmed CLIA seroconversion was regarded as a false positive reaction of whom 4 (5.3%) clients had a seroreversion of the CLIA at T₁. Conclusion The majority of unconfirmed CLIA seroconversions represented early syphilis infections. Therefore, additional T. pallidum PCR, a follow-up consultation or early treatment is recommended.