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Multicenter Study
. 2024 Jun 14;229(6):1628-1636.
doi: 10.1093/infdis/jiad582.

Prevalence and Predictors of Oral Treponema pallidum Detection by Quantitative Polymerase Chain Reaction in Early Syphilis

Jodie A Dionne  1 , Lorenzo Giacani  2   3 , Ashutosh Tamhane  1 , Kimberly Workowski  4 , Nicole A P Lieberman  5 , Alexander L Greninger  5   6 , Charlotte Perlowski  7 , Lori Newman  8 , Edward W Hook 3rd  1
Affiliations
Multicenter Study

Prevalence and Predictors of Oral Treponema pallidum Detection by Quantitative Polymerase Chain Reaction in Early Syphilis

Jodie A Dionne et al. J Infect Dis. .

Abstract

Background: Treponema pallidum prevalence and burden at oral and lesion sites in adults with early syphilis were assessed by quantitative polymerase chain reaction (qPCR). Factors associated with oral shedding were also examined.

Methods: Pretreatment oral and lesion swabs were collected from adults with early syphilis in a US multicenter syphilis treatment trial. Oral swabs were collected in the presence and absence of oral lesions. Following DNA extraction, qPCR and whole-genome sequencing (WGS) were performed to assess burden and strain variability.

Results: All 32 participants were male, mean age was 35 years, and 90.6% with human immunodeficiency virus (HIV). T. pallidum oral PCR positivity varied by stage: 16.7% primary, 44.4% secondary, and 62.5% in early latent syphilis. Median oral T. pallidum burden was highest in secondary syphilis at 63.2 copies/µL. Lesion PCR positivity was similar in primary (40.0%) and secondary syphilis (38.5%). Age 18-29 years was significantly associated with oral shedding (vs age 40+ years) in adjusted models. WGS identified 2 distinct strains.

Conclusions: T. pallidum DNA was directly detected at oral and lesion sites in a significant proportion of men with early syphilis. Younger age was associated with oral shedding. Ease of oral specimen collection and increased PCR availability suggest opportunities to improve syphilis diagnostic testing. Clinical Trials Registration. NCT03637660.

Keywords: Treponema pallidum; early syphilis; lesion swab; oral swab; quantitative PCR (qPCR); shedding; whole-genome sequencing (WGS).

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Conflict of interest statement

Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Proportion of swabs with Treponema pallidum qPCR positivity by stage and swab location (n = 32). Among all participants, 3 of 18 with secondary syphilis had visible oral lesions.
Figure 2.
Figure 2.
Treponema pallidum burden by syphilis stage and swab location (n = 32). Among all participants, 3 of 18 with secondary syphilis had visible oral lesions.
Figure 3.
Figure 3.
Phylogenetic tree of Treponema pallidum genomes showing the evolutionary relationships between the EM211ph (collected in Georgia, US) and UAB09TUH034 (collected in Birmingham, US) strains in participants and selected publicly available genomes from historical (eg, Nichols, Chicago, SS14, MexicoA) laboratory strains and modern global strains specified either by the strain name (eg, Italy, Japan, etc.) or indicated next to the strain name. The x axis units are the number of single nucleotide polymorphisms (SNPs) or mismatches that distinguish strains of T. pallidum.
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