Diagnostic Advances
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Immunol. Mar 27, 2016; 6(1): 1-8
Published online Mar 27, 2016. doi: 10.5411/wji.v6.i1.1
Syphilis testing algorithms: A review
Steven R Binder, Elitza S Theel
Steven R Binder, Clinical Diagnostic Group, Bio-Rad Laboratories, Hercules, CA 94547, United States
Elitza S Theel, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, United States
Author contributions: Binder SR and Theel ES contributed equally to this work.
Conflict-of-interest statement: Binder SR is an employee of Bio-Rad Laboratories; Theel ES is an employee of Mayo Clinic and Mayo Medical Laboratories.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Steven R Binder, Senior Director, Clinical Diagnostic Group, Bio-Rad Laboratories, Mailstop 4-225, 4000 Alfred Nobel Drive, Hercules, CA 94547, United States. steve_binder@bio-rad.com
Telephone: +1-510-7247000
Received: July 3, 2015
Peer-review started: July 9, 2015
First decision: September 22, 2015
Revised: October 2, 2015
Accepted: November 23, 2015
Article in press: November 23, 2015
Published online: March 27, 2016

The methods and strategies used to screen for syphilis and to confirm initially reactive results can vary significantly across clinical laboratories. While the performance characteristics of these different approaches have been evaluated by multiple studies, there is not, as of yet, a single, universally recommended algorithm for syphilis testing. To clarify the currently available options for syphilis testing, this update will summarize the clinical challenges to diagnosis, review the specific performance characteristics of treponemal and non-treponemal tests, and finally, summarize select studies published over the past decade which have evaluated these approaches. Specifically, this review will discuss the traditional and reverse sequence syphilis screening algorithms commonly used in the United States, alongside a discussion of the European Centre for Disease Prevention and Control syphilis algorithm. Ultimately, in the United States, the decision of which algorithm to use is largely dependent on laboratory resources, the local incidence of syphilis and patient demographics.

Keywords: Syphilis, Treponemal infection, Immunoassay, Reverse sequence screening, Rapid plasma regain, Treponema pallidum particle agglutination test, Automation, Algorithm, Primary infection, Late latent infection

Core tip: Many laboratories have adapted automated immunoassay methods for syphilis screening in the past decade. Since measurement of antibodies to Treponema pallidum (treponemal) antigens cannot readily distinguish current from past infection, additional tests, including traditional non-treponemal tests, are required to further clarify the disease state. As the incidence of syphilis and population demographics influence test performance, and due to local differences in the way clinical follow-up is offered, there is no single approach to syphilis testing that is universally applicable.