Cross‐sectional study of <i>Treponema pallidum</i> PCR in diagnosis of primary and secondary syphilis

Costa‐Silva, Miguel; Coutinho, Daniel; Sobrinho‐Simões, Joana; Azevedo, Filomena; Lisboa, Cármen

doi:10.1111/ijd.13823

Cited by 22 publications

(24 citation statements)

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“…Among 545 men with at least one TMA test result, the addition of rectal and pharyngeal TMA testing to standard procedures identified 2 extra cases of syphilis, although 1 of those persons would have been treated in the absence of a definitive diagnosis because he presented following known exposure to syphilis. Although we are not aware of prior studies that used T. pallidum NAATs to screen high-risk patients for syphilis, our findings are largely consistent with prior studies showing that 5% to 20% of persons with primary syphilis have negative syphilis serological results but test positive using NAATs of genital lesions (6,13,22,27,28). Similarly, PCR results for blood samples from patients with negative serological results who are evaluated as known syphilis contacts are sometimes positive (23).…”

Section: Discussionsupporting

confidence: 86%

“…The incubation period from the initial Treponema pallidum infection to the development of a chancre, the lesion associated with primary syphilis, is usually said to vary from 10 to 90 days (8), with experimental studies of T. pallidum inoculation suggesting a mean incubation period of 3 to 4 weeks (9,10). The sensitivity of serological testing in primary infections varies widely, i.e., from 50 to 90%, depending on the test used and the population studied (6,7,(11)(12)(13)(14). Thus, in many cases, there is a substantial period between the time of infection and the time at which infections are detectable using available laboratory tests.…”

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confidence: 99%

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Treponema pallidum Nucleic Acid Amplification Testing To Augment Syphilis Screening among Men Who Have Sex with Men

et al. 2019

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Syphilis rates in much of the world are now at their highest levels in almost three decades, and new approaches to controlling syphilis, including diagnostic tests with shorter window periods, are urgently needed. We compared the sensitivity of syphilis serological testing using the rapid plasma reagin (RPR) test with that of the combination of serological testing and an experimental 23S rRNA Treponema pallidum real-time transcription-mediated amplification (TMA) assay performed on rectal and pharyngeal mucosal swabs. T. pallidum PCR assays for the tpp47 gene were performed on all TMA-positive specimens, as well as specimens from 20 randomly selected TMA-negative men. A total of 545 men who have sex with men (MSM) who were seen in a sexually transmitted disease clinic provided 506 pharyngeal specimens and 410 rectal specimens with valid TMA results. Twenty-two men (4%) were diagnosed with syphilis on the basis of positive RPR test results and clinical diagnoses, including 3 men with primary infections, 8 with secondary syphilis, 9 with early latent syphilis, 1 with late latent syphilis, and 1 with an unstaged infection. Two additional men were diagnosed based on positive rectal mucosal TMA assay results alone, and both also tested positive by PCR assay. At least 1 specimen was TMA positive for 12 of 24 men with syphilis (sensitivity, 50% [95% confidence interval [CI], 29 to 71%]). RPR testing and clinical diagnosis were 92% sensitive (95% CI, 73 to 99%) in identifying infected men. Combining mucosal TMA testing and serological testing may increase the sensitivity of syphilis screening in high-risk populations.

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Section: Discussionsupporting

confidence: 86%

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confidence: 99%

Treponema pallidum Nucleic Acid Amplification Testing To Augment Syphilis Screening among Men Who Have Sex with Men

et al. 2019

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“…Matt Shields’ study showed that the sensitivity of routine PCR ranged from 84.6% to 89.1%, and the specificity ranged from 93.1% to 100% for primary syphilis, while in the secondary stage of disease, the sensitivity declined to 50%. This result implied that routine PCR should be used only for early‐stage syphilis, which was supported by Gayet‐Ageron et al However, an other research showed that routine PCR could also be used effectively for secondary syphilis, obtaining a sensitivity and specificity that reached 81.1% and 100%, respectively. Additionally, routine PCR has been reported to detect atypical cases in tonsillar, vertebral, and ocular syphilis.…”

Section: Introductionmentioning

confidence: 99%

PCR detection for syphilis diagnosis: Status and prospects

Zhou

Zhang

et al. 2019

Clinical Laboratory Analysis

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Syphilis, a re‐emerging public health problem worldwide caused by Treponema pallidum subsp pallidum (T. pallidum), usually induces systemic and chronic inflammation in hosts who do not receive timely therapy after exposing to high‐risk factors such as leprous sexual contact. Before the treatment, rapid and accurate detection of syphilis is essential. However, the existing detection methods, which focus on the treponemal or non‐treponemal antibody test, both have inherent limitations. For instance, both of them cannot distinguish the stage and severity of syphilis. Non‐treponemal test such as RPR, which is generally deemed to be used for assessing treatment response, is influenced by biological false positives. Therefore, it is imperative to seek out a new and effective diagnostic test. With recent advancements in molecular biology and whole‐genome sequencing, the molecular diagnosis has increased in popularity, especially the use of polymerase chain reaction (PCR). Here, we firstly present a mini‐review on the research of PCR detection methods used for syphilis diagnosis over the past decade, and we then compare these methodologies to assess their potential and the challenges faced. This information can provide a fresh perspective to help researchers address the current challenges.

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“…Specific tests like PCR and IHC are useful supplementary diagnostic tools, PCR test increases the sensitivity of the diagnosis of primary syphilis during the window period, 10 and IHC has shown to be a test with high sensitivity. 35,36 The strength of the present case lies in the clinical, histopathological, and serological findings, which evidence the overlap between the primary stage and secondary stage of oral syphilis in PLWH.…”

Section: Case Descriptionmentioning

confidence: 99%

“…7,8 The VDRL test is cheap and simple to perform but requires confirmation by a treponemal test such as FTA-ABS. 7 False-negative results may be caused by (a) the failure of dysfunctional B-cells to develop an appropriate antibody response against T. pallidum antigens, 9 or (b) the Hook effect or prozone phenomena, a condition present in 0.2% to 2% of PLWH with syphilis, [10][11][12] a consequence of abnormal B-cell activation leading to excess antibody production. 11 In these challenging cases, the confirmation of syphilis diagnosis should be complemented by the direct detection of T. pallidum in tissue specimens using immunohistochemistry (IHC), which has shown a sensitivity of 91%, 13 or by the amplification of the polA gene by polymerase chain reaction (PCR), 10,14,15 an assay with a sensitivity of 95.8% and specificity of 95.7% 16 that has been shown its effectiveness for diagnosing early-stage syphilis.…”

Section: Introductionmentioning

confidence: 99%

The challenging diagnosis of overlapping oral primary/secondary syphilis with nonreactive serology

2020

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The prevalence of oral syphilis, known as "the great imitator" because of its diagnostic complexity and varied clinical manifestations, is increasing worldwide, particularly in people living with HIV (PLWH), who could present false-negative serological results. Although some studies have described the variable presentation of oral syphilis in the context of HIV infection, the difficulty in distinguishing between the primary and secondary stages, clinically and histopathologically, underscores the need to describe atypical cases. We report the case of a 28-year-old HIV-positive man presenting with a 3-month history of painless white/red ulcerated lesion on the soft palate. Physical examination revealed an ulcerated lesion with local signs of inflammation. Initial biopsy revealed a nonspecific inflammatory process and immunohistochemistry (IHC) using anti-Treponema pallidum antibodies showed negative results. The results of serological tests for syphilis (Venereal Disease Research Laboratory and fluorescent treponemal antibody-absorption test) were negative on repeated occasions. Nonetheless, polymerase chain reaction (PCR) assay and subsequent IHC for T. pallidum showed positive results, confirming the diagnosis of oral syphilis. This case illustrates that the diagnosis of oral syphilis is challenging in the absence of serological evidence, and specific tests such as PCR and IHC are useful complementary diagnostic tools.

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Cross‐sectional study of Treponema pallidum PCR in diagnosis of primary and secondary syphilis

Abstract: Background Syphilis remains a major challenge and a complex diagnosis. We aim to

Cited by 22 publications

References 11 publications

Treponema pallidum Nucleic Acid Amplification Testing To Augment Syphilis Screening among Men Who Have Sex with Men

Treponema pallidum Nucleic Acid Amplification Testing To Augment Syphilis Screening among Men Who Have Sex with Men

PCR detection for syphilis diagnosis: Status and prospects

The challenging diagnosis of overlapping oral primary/secondary syphilis with nonreactive serology

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