The role of IgM testing in the diagnosis and post-treatment follow-up of syphilis: a prospective cohort study

Objectives: The diagnosis of repeat syphilis and its follow-up remains challenging. We aimed to investigate if IgM testing may assist in the diagnosis of syphilis reinfection/relapse and its treatment follow-up. Methods: Sera were collected from 120 individuals with a new diagnosis of syphilis (72 with repeat infections) and 30 syphilis negative controls during a cohort study investigating syphilis biomarkers conducted at a STI/HIV clinic in Antwerp, Belgium. Syphilis was diagnosed based on a simultaneous positive treponemal and non-treponemal assay result and/or positive serum PCR targeting polA. Specimens collected at visit of diagnosis, and 3 and 6 months post-treatment were tested by two enzyme immuno assays (EIAs), recomWell (Mikrogen; MI) and Euroimmun (EU), to detect anti-treponemal IgM. Baseline specimens were also tested for anti-treponemal IgM using a line immuno assay (LIA) recomLine (Mikrogen). Quantitative kinetic decay curves were constructed from the longitudinal quantitative EIA results. Results: An overall sensitivity for the diagnosis of syphilis of 59.8 % (95 % confidence interval (CI): 50.3-68.7), 75.0 % (95 %(CI): 66.1-82.3) and 64.2 % (95 %(CI): 54.8-72.6) was obtained for the EU, MI EIAs, and MI LIA, respectively. When only considering repeat syphilis, the diagnostic sensitivity decreased to 45.7 % (95 %(CI): 33.9-58.0), 63.9 % (95 %(CI): 51.7-74.6) and 47.2 % (95 %(CI): 35.5-59.3), respectively. IgM seroreverted in most cases 6 months after treatment. Post-treatment IgM concentrations decreased 30 % faster for initial syphilis compared to repeat infection. The IgM EIAs and IgM LIA agreed from fairly to moderately (Cohen9s kappa: 0.36 [EU EIA]; Cohen9s kappa: 0.53 [MI EIA]; Cohen9s kappa: 0.40 [MI LIA]) with the diagnosis of syphilis. Conclusions: IgM detection was not a sensitive method to diagnose syphilis and was even poorer in the diagnosis of syphilis repeat infections, but might play a role in treatment follow-up.