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. 2024 Dec 16;230(6):e1322-e1333.
doi: 10.1093/infdis/jiae322.

Clinical Presentation of Early Syphilis and Genomic Sequences of Treponema pallidum Strains in Patient Specimens and Isolates Obtained by Rabbit Inoculation

Ligang Yang  1 , Xiaohui Zhang  1 , Wentao Chen  1   2 , Arlene C Seña  3 , Heping Zheng  1   2 , Yinbo Jiang  1   2 , Peizhen Zhao  1 , Rongyi Chen  1 , Liuyuan Wang  1 , Wujian Ke  1   2 , Juan C Salazar  4   5 , Jonathan B Parr  3 , Joseph D Tucker  3 , Kelly L Hawley  4   5   6 , Melissa J Caimano  4   5   6 , Christopher M Hennelly  3 , Farhang Aghakanian  3 , Everton B Bettin  4 , Feifei Zhang  1 , Jane S Chen  3 , M Anthony Moody  7 , Justin D Radolf  4   5   6 , Bin Yang  1
Affiliations

Clinical Presentation of Early Syphilis and Genomic Sequences of Treponema pallidum Strains in Patient Specimens and Isolates Obtained by Rabbit Inoculation

Ligang Yang et al. J Infect Dis. .

Abstract

Background: The global resurgence of syphilis necessitates vaccine development.

Methods: We collected ulcer exudates and blood from 17 participants with primary syphilis (PS) and skin biopsies and blood from 51 patients with secondary syphilis (SS) in Guangzhou, China, for Treponema pallidum subsp pallidum (TPA) quantitative polymerase chain reaction, whole genome sequencing (WGS), and isolation of TPA in rabbits.

Results: TPA DNA was detected in 15 of 17 ulcer exudates and 3 of 17 blood PS specimens. TPA DNA was detected in 50 of 51 SS skin biopsies and 27 of 51 blood specimens. TPA was isolated from 47 rabbits with success rates of 71% (12/17) and 69% (35/51), respectively, from ulcer exudates and SS bloods. We obtained paired genomic sequences from 24 clinical samples and corresponding rabbit isolates. Six SS14- and 2 Nichols-clade genome pairs contained rare discordances. Forty-one of the 51 unique TPA genomes clustered within SS14 subgroups largely from East Asia, while 10 fell into Nichols C and E subgroups.

Conclusions: Our TPA detection rate was high from PS ulcer exudates and SS skin biopsies and over 50% from SS blood, with TPA isolation in more than two-thirds of samples. Our results support the use of WGS from rabbit isolates to inform vaccine development.

Keywords: Treponema pallidum; polA qPCR; chancre; early syphilis; genomic sequences; primary syphilis; rabbit inoculation; secondary syphilis.

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Conflict of interest statement

Potential conflicts of interest. J. B. P. reports research support from Gilead Sciences, nonfinancial support from Abbott Laboratories, and consulting for Zymeron Corporation outside the scope of the current manuscript. J. D. R. has licensing agreements for recombinant TPA proteins as syphilis serodiagnostic reagents with Biokit SA, Chembio, and Span Diagnostics. All other authors report no potential conflicts. 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

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
Workflow of the study for patient enrollment, specimen acquisition, and genomic sequencing. Abbreviations: DFM, darkfield microscopy; qPCR, quantitative polymerase chain reaction; RIT, rabbit infectivity testing; WGS, whole genome sequencing.
Figure 2.
Figure 2.
Representative clinical manifestations in study participants. A, Penile chancre. B, Perianal condyloma lata. C, Alopecia of secondary syphilis. D, Psoriasiform rash of secondary syphilis on the feet.
Figure 3.
Figure 3.
Phylogenomic diversity of Guangzhou Treponema pallidum strains. The recombination-masked phylogenetic tree was constructed using whole genome sequences from 51 newly identified Chinese strains, 109 previously published strains [3, 8, 9, 26–28], and 2 outgroup strains (T pallidum subsp pertenue and T pallidum subsp endemicum) for comparison. The Guangzhou strains are highlighted on the tree, featuring direct clinical samples in green, rabbit-passaged isolates derived from bloods in red, and rabbit-passaged isolates originating from ulcer exudates in purple.
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Comment in

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Supplementary concepts