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.

Highlights

  • Syphilis is a multi-stage disease caused by Treponema pallidum subsp. pallidum (T. pallidum)

  • polymerase chain reaction (PCR)-based test and IHC may be useful for the diagnosis of secondary syphilis

  • Researchers found that the sensitivity of nPCR ranged from 53.6 to 62.9% in blood (Wang et al, 2018), while the sensitivity of routine PCR ranged from 36.1 to 50.2%, suggesting that nPCR may be a worthy method for detecting T. pallidum DNA (Tp-DNA) in the blood (Gayet-Ageron et al, 2013). Another investigation demonstrated that the positive rate of nPCR was 42% in cerebrospinal fluid (CSF), whereas the positive rate of CSF Venereal Disease Research Laboratory (VDRL) was merely 30%. These findings suggest that nPCR has potential value in the diagnosis of neurosyphilis as well (Vanhaecke et al, 2016)

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Summary

Introduction

Syphilis is a multi-stage disease caused by Treponema pallidum subsp. pallidum (T. pallidum). Syphilis is a multi-stage disease caused by Treponema pallidum subsp. In the absence of treatment, the natural history of syphilis is divided into primary, secondary, latent, and tertiary stages. Some untreated infected patients develop tertiary syphilis, characterized by destructive visceral, cardiovascular, or neurological disorders as well as severe skin lesions. Symptoms of tertiary syphilis occur 10 to 20 years after the initial infection. In primary syphilis the diagnostic criteria are based on positive darkfield result or polymerase chain reaction (PCR) of material from chancres, or a combination of a clinical diagnosis and positive serologic tests. Secondary syphilis is diagnosed using positive darkfield examination and reactive treponemal or alternative nontreponemal tests. In some stages, the disease may be asymptomatic, generating difficulty in diagnosing very early syphilis, neurosyphilis, and tertiary syphilis (Table 1) (Tuddenham et al, 2020)

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