Point-Counterpoint: It Is Time To Use Treponema-Specific Antibody Screening Tests for Diagnosis of Syphilis

Abstract

Assays that detect treponema-specific antibodies, which are either automated or can be done as point-of-care tests, have been developed, some of which are FDA approved. These assays have the advantage of being easily performed and demonstrate high sensitivity, both key features of an infectious disease screening test. As a result, many high-volume clinical laboratories have begun to offer a reverse syphilis testing algorithm where a treponema-specific test is used for screening, followed by a nontreponemal test (i.e., rapid plasma reagin [RPR]) to assess disease activity and treatment status. Concerns about physicians being able to understand and apply this new testing algorithm have been expressed (8). In this point-counterpoint, Michael Loeffelholz of the University of Texas Medical Branch at Galveston explains why his laboratory has adopted this reverse algorithmic approach. Matthew Binnicker of the Mayo Clinic, Rochester, MN, explains why the reverse algorithm may not be suitable for all clinical laboratories and every clinical situation. POINT Several expert committees and organizations now either recommend or include the option for the use of treponemaspecific assays to screen for syphilis. In this approach, a reactive treponemal screening assay is followed by a quantitative nontreponemal assay to diagnose active disease and to monitor response to treatment (i.e., the "reverse algorithm"). This algorithm also consists of a second and different treponemal assay that is used either to confirm all reactive screening results or only to resolve discordant screening and nontreponemal assay results (Fig. 1). The Association of Public Health Laboratories (http://www .aphl.org/aphlprograms/infectious/std/Documents/Laboratory GuidelinesTreponemapallidumMeetingReport.pdf, last accessed 11 September 2011), the United Kingdom Health Protection Agency (6), and the International Union Against Sexually Transmitted Infections (7) all endorse or encourage the use of a reverse algorithm that begins with a treponemal immunoassay. The United States Centers for Disease Control and Prevention (CDC) continues to recommend the traditional algorithm (3). However, in that report, the CDC acknowledges the use of treponemal immunoassays as screening assays and provides recommendations for laboratories that choose this reverse algorithm approach.The traditional approach to the diagnosis of syphilis begins with a nontreponemal assay, either the venereal disease research laboratory (VDRL) test or, more commonly, the RPR test that detect anticardiolipin antibodies (Fig. 1). Since these antibodies are not specific for syphilis, reactive nontreponemal assay results must be confirmed with an assay that detects antibodies produced against T. pallidum. Traditional treponemal assays used in this algorithm are fluorescent treponemal antibody absorption (FTA-ABS), microhemagglutination for T. pallidum, T. pallidum hemagglutination (TPHA), and TPPA. In 1975, Veldkamp and Visser described for the first time the use of a laboratory-developed enzyme ...

Evaluation of the HISCL Anti-Treponema pallidum Assay as a Screening Test for Syphilis

“…Even though many diagnostic tests are available for syphilis, there is still no gold standard, and diagnosis usually relies upon a combination of tests (12). The traditional approach to the diagnosis of syphilis begins with a nontreponemal assay, either the VDRL test or, more commonly, the RPR test, which detects anticardiolipin antibodies (13). Since these antibodies are not specific for syphilis, reactive nontreponemal assay results must be confirmed with an assay that detects antibodies produced against T. pallidum, such as the FTA-ABS test, TPHA, or TPPA (13).…”

“…The traditional approach to the diagnosis of syphilis begins with a nontreponemal assay, either the VDRL test or, more commonly, the RPR test, which detects anticardiolipin antibodies (13). Since these antibodies are not specific for syphilis, reactive nontreponemal assay results must be confirmed with an assay that detects antibodies produced against T. pallidum, such as the FTA-ABS test, TPHA, or TPPA (13). As the nontreponemal tests are unsuitable for automation, labor-intensive, and have a lack of sensitivity in primary syphilis and the late stages of infection, more and more clinical laboratories have shifted to screening patients with a treponemal assay such as EIA and CLIA, followed by a quantitative nontreponemal test to assess disease activity and monitor response to treatment (i.e., the "reverse algorithm") (5,10).…”

The importance of IgM positivity in laboratory diagnosis of gestational and congenital syphilis

“…EIA) [11]. Samples that are reactive by EIA are then tested by RPR to assess disease and treatment status and provide a supplemental marker of infection recommended that sera testing reactive by EIA but nonreactive by RPR be analyzed by the TP-PA assay [12]. Several antigens that elicit high antibody titers during T. pallidum infection and are not cross-reactive with serum from patients with other common spirochetal diseases have been identified [13], TPPA and EIA tests have explored the use of these recombinant antigens.…”

Evaluation of the Boson Chemiluminescence Immunoassay as a First-Line Screening Test in the ECDC Algorithm for Syphilis Serodiagnosis in a Population with a High Prevalence of Syphilis

“…In a previous study, we proved that the ECDC algorithm demonstrated good performance for serological syphilis testing (2). In addition, the implementation of automated treponemal assays (e.g., enzyme immunoassays [EIA] and chemiluminescence immunoassays [CIA]) (4) has allowed clinical laboratories to meet increased demands for syphilis testing, increase their efficiency, and provide objective results (5). Thus, an increasing number of clinical laboratories have begun to use the ECDC algorithm (2,6).…”