Stage-Specific Associations of Automated RPR With Treponema pallidum qPCR Positivity and Cycle Threshold in Early Symptomatic Syphilis: A Multicenter Study Using Specimens Collected During Routine Care

@misc{kasamatsu2026stagespecific,
  title = {{Stage-Specific Associations of Automated RPR With Treponema pallidum qPCR Positivity and Cycle Threshold in Early Symptomatic Syphilis: A Multicenter Study Using Specimens Collected During Routine Care}},
  author = {A. Kasamatsu and Y. Ohama and Y. Tomo and K. Imai and S.-i. Nakayama and R. Omori and T. Yamagishi and M. Yasuda and Y. Akeda},
  howpublished = {medRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.14.26365521},
  url = {https://www.medrxiv.org/content/10.64898/2026.10.14.26365521v1},
  note = {CC BY-NC},
}

TY  - UNPB
TI  - Stage-Specific Associations of Automated RPR With Treponema pallidum qPCR Positivity and Cycle Threshold in Early Symptomatic Syphilis: A Multicenter Study Using Specimens Collected During Routine Care
AU  - A. Kasamatsu
AU  - Y. Ohama
AU  - Y. Tomo
AU  - K. Imai
AU  - S.-i. Nakayama
AU  - R. Omori
AU  - T. Yamagishi
AU  - M. Yasuda
AU  - Y. Akeda
PY  - 2026
DA  - 2026/10/14
PB  - medRxiv
DO  - 10.64898/2026.10.14.26365521
UR  - https://www.medrxiv.org/content/10.64898/2026.10.14.26365521v1
AB  - BackgroundTreponema pallidum quantitative polymerase chain reaction (qPCR) positivity and cycle threshold (Ct) by rapid plasma reagin (RPR), disease stage, and other characteristics are poorly characterized in routine-care specimens, leaving it unclear when qPCR of such specimens is informative for diagnosis.  MethodsThis Japanese multicenter cross-sectional study explored qPCR positivity and Ct by these characteristics. Nonblood specimens collected during routine care underwent qPCR at a central laboratory for this study. Bayesian logistic and normal regressions modeled positivity and mean Ct of TP0574 and polA with stage-specific continuous automated RPR terms, patient characteristics, collection site, and facility random intercepts. Estimates were standardized over the analyzed specimens. Population-group predictions were instead averaged within each group.  ResultsAmong 154 nonblood specimens from 145 patients (71.7% non-MSM men and women) at 14 facilities, 109 (70.8%) were qPCR positive. At RPR 1, adjusted positivity was 72.2% (95% credible interval, 60.9%-82.9%) in primary and 43.8% (16.7%-69.9%) in secondary syphilis. Positivity showed a modest downward trend with RPR in primary but increased in secondary syphilis, reflecting a stage-by-RPR interaction (secondary-to-primary ratio of odds ratios, 1.78; 1.25-2.65). Predicted positivity showed an upward trend with RPR values among MSM; adjusted positivity was relatively high for genital/urethral/urinary and anal/perianal/rectal specimens. Adjusted mean Ct increased with RPR in primary and followed an inverted-U pattern in secondary syphilis.  ConclusionsIn primary syphilis, nonblood qPCR positivity was high even at low RPR. When serologic findings remain inconclusive in this stage, qPCR is highly recommended for securing an early diagnosis.  SummaryIn nonblood specimens collected during routine care, Treponema pallidum qPCR positivity was high even at low automated RPR values in primary syphilis, potentially supporting earlier diagnostic confirmation when serology is inconclusive. In secondary syphilis, positivity increased with RPR.
ER  -