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

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Abstract

Background

Treponema 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.

Methods

This 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.

Results

Among 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.

Conclusions

In 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.

Summary

In 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.

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