Laboratory Diagnostic Tools for Syphilis: Current Status and Future Prospects

Abstract

With the increasing number of patients infected with syphilis in the past 20 years, early diagnosis and early treatment are essential to decline syphilis prevalence. Owing to its diverse manifestations, which may occur in other infections, the disease often makes clinicians confused. Therefore, a sensitive method for detecting T. pallidum is fundamental for the prompt diagnosis of syphilis. Morphological observation, immunohistochemical assay, rabbit infectivity test, serologic tests, and nucleic acid amplification assays have been applied to the diagnosis of syphilis. Morphological observation, including dark-field microscopy, silver-staining, and direct fluorescent antibody staining for T. pallidum, can be used as a direct detection method for chancre specimens in primary syphilis. Immunohistochemistry is a highly sensitive and specific assay, especially in the lesion biopsies from secondary syphilis. Rabbit infectivity test is considered as a sensitive and reliable method for detecting T. pallidum in clinical samples and used as a historical standard for the diagnosis of syphilis. Serologic tests for syphilis are widely adopted using non-treponemal or treponemal tests by either the traditional or reverse algorithm and remain the gold standard in the diagnosis of syphilis patients. In addition, nucleic acid amplification assay is capable of detecting T. pallidum DNA in the samples from patients with syphilis. Notably, PCR is probably a promising method but remains to be further improved. All of the methods mentioned above play important roles in various stages of syphilis. This review aims to provide a summary of the performance characteristics of detection methods for syphilis.

Direct fluorescence antibody testing augments syphilis diagnosis, compared to serology alone

“…9,[11][12][13] Considering this, clinicians must interpret a negative DFA result with caution and prioritize use of NAAT for syphilis diagnosis when available. 12,13 In instances where patients' risk factors and STI history are suspicious for primary infection at the point of care, 4,6,19 prescribers should consider offering empiric treatment for syphilis knowing that such treatment may halt seroconversion of treponemal antibodies (IgG and IgM), 9 which could yield negative serology results, but not mean the patient did not have syphilis. When syphilis is less likely, clinicians could alternatively consider completing syphilis serology at the visit and, if negative, repeating testing in 4 weeks to rule out infection.…”

“…These tests include (1) nucleic acid amplification testing (NAAT), which has a sensitivity of 93.1-100% in primary syphilis and specificity of 100% [11][12][13] and can be used on genital, oral, and rectal lesions; (2) dark-field microscopy, which has a sensitivity of 86-97% and specificity of 100% 9 and examines the morphology and movement of live spirochetes in genital lesions; and (3) DFA, which has a sensitivity of 73-100% and specificity of 100% 9 and can be used on lesions of all sites, but is limited by potential cross-reactivity with non-pathogenic treponemal organisms in the oral and rectal mucosa. 4,9 While NAAT is considered to be a superior non-serologic testing approach due to its increased sensitivity to detect primary syphilis, [12][13][14] in Ontario, where this review occurred, this test is not available. 8 For this reason, DFA was used for this study, despite reduced sensitivity on exudate from primary or secondary genital lesions 9,11 and limited validation and approval for use outside of select Canadian provinces.…”

Laboratory Evaluation of the DPP Syphilis Screen & Confirm Assay

“…Laboratory diagnosis of syphilis is mainly through serological assays that detect nontreponemal and treponemal antibodies. Both types of tests are needed to identify active syphilis cases and are performed as consecutive steps or in testing algorithms ( 5 ). For years, syphilis screening was done using a nontreponemal antibody test like the rapid plasma reagin (RPR) test or the Venereal Disease Research Laboratory (VDRL) test, and Treponema pallidum particle agglutination (TPPA) assay or fluorescent treponemal antibody absorption (FTA-ABS) tests were used as confirmatory tests; this was called the traditional algorithm.…”

Syphilis in Brazil: time of COVID-19

“…Despite the existence of inexpensive and effective antibiotic treatment regimens, syphilis continues to have a profound impact on the reproductive, sexual and psychological health of the population (Kidd et al, 2018;Luo et al, 2021).…”