The Utility of Biomarkers in the Clinical Management of Syphilis: A Systematic Review

Abstract

Background: Routinely available laboratory tests for Treponema pallidum remain suboptimal for diagnostic, prognostic, predictive, and monitoring purposes. Biomarkers with enhanced performance characteristics can improve diagnostic confidence and facilitate management. We conducted a systematic review to examine the utility of biomarkers in the diagnosis and management of syphilis.

Methods: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses to identify articles for inclusion and independently reviewed them for eligibility and study quality using a 3-stage procedure. The search, conducted by a senior library informationist, used PubMed, Embase, Cochrane Library, and Scopus and included any study published before May 2022.

Results: Of the 111 studies identified, 31 (27.9%) were included in our review. Most studies were cross-sectional or prospective. The data were strikingly heterogeneous examining a variety of biomarkers across different syphilis stages, using different methodologies and definitions of treatment success. Available publications chiefly focused on diagnosing various syphilis stages, neurosyphilis and congenital syphilis, serological cure, the serofast state, and reinfection.

Conclusions: Despite increasing attempts to identify novel biomarkers, we found limited evidence to support the use of any biomarker in clinical decision making at this time; the syphilis biomarker literature is heterogenous and lacks measurement of clinically meaningful end points. We recommend the formation of a working group to set priorities for syphilis biomarker research and to guide future study of clinically meaningful biomarkers.