Molecular and Direct Detection Tests for Treponema pallidum Subspecies pallidum: A Review of the Literature, 1964-2017

Abstract

Direct detection methods for Treponema pallidum include dark-field microscopy (DFM), direct fluorescence antibody (DFA) testing, immunohistochemistry (IHC), and nucleic acid amplification tests (NAATs). Here, we reviewed the relevant syphilis diagnostic literature to address 2 main questions with respect to T. pallidum direct detection techniques: "What are the performance characteristics for each direct detection test for T. pallidum and what are the optimal specimen types for each test?" and "What options are available for T. pallidum molecular epidemiology?" To answer these questions, we searched 5 electronic databases (OVID Medline, OVID Embase, CINAHL, Cochrane Library, and Scopus) from 1964 to 2017 using relevant search terms and identified 1928 articles, of which 37 met our inclusion criteria. DFM and DFA sensitivities ranged from 73% to 100% in cases of primary syphilis; and while sensitivity using silver stain histopathology for T. pallidum was generally low (0%-41%), higher performance characteristics were observed for T. pallidum-specific IHC (49-92%). Different genes have been targeted by T. pallidum-specific NAATs, with the majority of studies indicating that sensitivity is primarily dependent on the type of collected biological sample, with highest sensitivity observed in primary lesion exudate (75-95%). Given the rising incidence of syphilis, the development of direct, Food and Drug Administration-cleared T. pallidum NAATs should be considered an immediate priority.

Keywords: Treponema pallidum; dark-field microscopy; immunohistochemistry; nucleic acid amplification testing; strain typing.

Figure 1.

Summary of literature review process to identify relevant studies to answer the 2 key questions related to direct detection of Treponema pallidum. The term “Other” includes excluded articles due to focus on animal and pathogenesis studies (n = 4), blood donor screening (n = 3), electron microscopy (n = 2), lack of direct detection methods (n = 2), non-syphilis studies (n = 2), and T. pallidum resistance studies (n = 1). Abbreviations: GUD, genital ulcer disease; NAAT, nucleic acid amplification test; TOE, tables of evidence.