Reverse syphilis screening algorithm in a high-volume laboratory: CLIA–RPR–TPHA concordance and determinants of RPR reactivity

Abdurrahman Gülmez; Selda Kömeç

doi:10.18614/dehm.1772212

Reverse syphilis screening algorithm in a high-volume laboratory: CLIA–RPR–TPHA concordance and determinants of RPR reactivity

Abstract

Objective: Syphilis remains a major global health concern, with an estimated 8 million new infections annually. The reverse syphilis screening algorithm, which starts with a treponemal assay followed by a non-treponemal test, has gained wide adoption in diagnostic laboratories. Despite its advantages, the interpretation of discordant results and the factors influencing RPR reactivity in real-world practice are not fully understood. This study aimed to evaluate the diagnostic concordance between CLIA, RPR, and TPHA assays and to identify demographic and clinical factors associated with RPR reactivity in a high-volume tertiary laboratory. Methods: A retrospective analysis was performed on 109,390 serum samples tested between January 2021 and January 2023. CLIA-reactive samples underwent RPR testing and, when indicated, TPHA confirmation. Logistic regression analysis was used to determine predictors of RPR positivity, and receiver operating characteristic (ROC) analysis evaluated the performance of CLIA signal-to-cutoff (S/CO) ratios in predicting TPHA positivity. Results: Among 995 (0.91%) CLIA-reactive samples, 278 (29.4%) were RPR-positive. TPHA testing confirmed 76 (64.4%) of 118 RPR-negative samples as true positives. Younger age and outpatient status were independent predictors of RPR reactivity (adjusted OR for 18–45 years: 3.39, 95% CI: 2.10–5.48, p<0.001; outpatient vs. inpatient: OR 2.17, 95% CI: 1.47–3.19, p<0.001). A strong correlation was observed between CLIA and TPHA (ρ=0.706, p<0.001), whereas the CLIA–RPR correlation was weak (ρ=0.084, p=0.161). ROC analysis yielded an AUC of 0.964, with an optimal CLIA S/CO threshold of 18.3 (100% sensitivity, 85.7% specificity). Conclusion: The reverse syphilis screening algorithm demonstrated excellent diagnostic performance and high concordance between CLIA and TPHA assays. RPR reactivity was largely influenced by age and clinical setting, emphasizing the importance of integrating demographic context into serologic interpretation. CLIA can serve as a robust primary screening tool in high-throughput laboratories, complemented by RPR and TPHA for accurate staging and confirmation.

Keywords

Project Number

1

Ethical Statement

This study was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval was obtained from the Non-Interventional Clinical Research Ethics Committee of Basaksehir Cam and Sakura City Hospital, with the approval number KAEK/2022.12.399. Since this was a retrospective study, the requirement for informed consent was waived.

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Details

Primary Language

English

Subjects

Infectious Diseases, Clinical Microbiology

Journal Section

Research Article

Authors

Abdurrahman Gülmez ^*
0000-0003-3953-5267
Türkiye

Selda Kömeç
0000-0002-6726-0048
Türkiye

Early Pub Date

April 29, 2026

Publication Date

April 29, 2026

Submission Date

August 26, 2025

Acceptance Date

December 2, 2025

Published in Issue

Year 2026 Volume: 40 Number: 2

DOI

https://doi.org/10.18614/dehm.1772212

IZ

https://izlik.org/JA42HG82ZH

Cite

RIS / Bibtex

APA

Gülmez, A., & Kömeç, S. (2026). Reverse syphilis screening algorithm in a high-volume laboratory: CLIA–RPR–TPHA concordance and determinants of RPR reactivity. Developments and Experiments in Health and Medicine, 40(2), 210-219. https://doi.org/10.18614/dehm.1772212

AMA

1.Gülmez A, Kömeç S. Reverse syphilis screening algorithm in a high-volume laboratory: CLIA–RPR–TPHA concordance and determinants of RPR reactivity. Dev Exp Health Med. 2026;40(2):210-219. doi:10.18614/dehm.1772212

Chicago

Gülmez, Abdurrahman, and Selda Kömeç. 2026. “Reverse Syphilis Screening Algorithm in a High-Volume Laboratory: CLIA–RPR–TPHA Concordance and Determinants of RPR Reactivity”. Developments and Experiments in Health and Medicine 40 (2): 210-19. https://doi.org/10.18614/dehm.1772212.

EndNote

Gülmez A, Kömeç S (April 1, 2026) Reverse syphilis screening algorithm in a high-volume laboratory: CLIA–RPR–TPHA concordance and determinants of RPR reactivity. Developments and Experiments in Health and Medicine 40 2 210–219.

IEEE

[1]A. Gülmez and S. Kömeç, “Reverse syphilis screening algorithm in a high-volume laboratory: CLIA–RPR–TPHA concordance and determinants of RPR reactivity”, Dev Exp Health Med, vol. 40, no. 2, pp. 210–219, Apr. 2026, doi: 10.18614/dehm.1772212.

ISNAD

Gülmez, Abdurrahman - Kömeç, Selda. “Reverse Syphilis Screening Algorithm in a High-Volume Laboratory: CLIA–RPR–TPHA Concordance and Determinants of RPR Reactivity”. Developments and Experiments in Health and Medicine 40/2 (April 1, 2026): 210-219. https://doi.org/10.18614/dehm.1772212.

JAMA

1.Gülmez A, Kömeç S. Reverse syphilis screening algorithm in a high-volume laboratory: CLIA–RPR–TPHA concordance and determinants of RPR reactivity. Dev Exp Health Med. 2026;40:210–219.

MLA

Gülmez, Abdurrahman, and Selda Kömeç. “Reverse Syphilis Screening Algorithm in a High-Volume Laboratory: CLIA–RPR–TPHA Concordance and Determinants of RPR Reactivity”. Developments and Experiments in Health and Medicine, vol. 40, no. 2, Apr. 2026, pp. 210-9, doi:10.18614/dehm.1772212.

Vancouver

1.Abdurrahman Gülmez, Selda Kömeç. Reverse syphilis screening algorithm in a high-volume laboratory: CLIA–RPR–TPHA concordance and determinants of RPR reactivity. Dev Exp Health Med. 2026 Apr. 1;40(2):210-9. doi:10.18614/dehm.1772212