Comparative Analysis of Molecular and Serologic Testing for Primary Syphilis: A Population-Based Cohort Study.

Rising rates of syphilis () requires rapid diagnosis and treatment to manage the growing epidemic. Syphilis serology is imperfect and requires interpretation of multiple tests while molecular diagnostics allows for potential yes-no identification of highly infective, primary anogenital lesions. Accuracy of this testing modality has thus far been limited to small, highly selective studies. Therefore, we retrospectively assessed a large, adult population of patients with anogenital lesions seen at Sexually Transmitted Infection (STI) clinics in Alberta, Canada who were screened for syphilis and herpes simplex (HSV) 1/2 using PCR to evaluate PCR versus serology to diagnose primary syphilis. 114 (3.1%) of the 3,600 adult patients had at least one -PCR+ anogenital lesion with 99 (2.8%) patients having newly positive syphilis serology (new INNO-LIA positive or 4-fold RPR increase). PCR had a sensitivity of 49.3% (95% CI 42.6-56.1) and specificity of 99.9% (99.7-100.0). Positive predictive values and negative predictive values in the study population or when corrected for provincial prevalence were 97.4% (92.5-99.5) or 0.4% (0.4-1.2) and 96.7% (96.1-97.3) or 100.0% (100.0-100.0), respectively. Positive and negative likelihood ratios were estimated at 555 (178-1733) and 0.5 (0.4-0.6), respectively. Review of all -PCR performed with or without exclusion of HSV-positive lesions resulted in no significant change in PCR characteristics. Interestingly, 12 of the PCR+ samples had negative serology at time of lesion sampling but became positive within our 28-day testing window. Overall, this study further supports the use of PCR as an accurate assay to rapidly identify, treat, and prevent the spread of primary syphilis.