Estimating the sensitivity of non-treponemal and treponemal antibody tests in primary syphilis

Abstract Among patients with primary syphilis, sensitivity of TRUST was 55% (6/11) compared to darkfield microscopy (DFM) and 60% (9/15) compared to Treponema pallidum PCR. Sensitivity of RPR was 78% (38/49) and 93% (43/46), respectively. TPPA had a sensitivity of 95% (41/43) compared to DFM and 96% (43/45) compared to PCR. Short Summary Compared to direct detection methods for the diagnosis of primary syphilis, TRUST has low sensitivity, RPR has moderate to good sensitivity, and TPPA has high sensitivity. Competing Interest Statement ACS reports royalties from UptoDate; past honoraria from Innoviva Specialty Therapeutics and Hologic, Inc, for their scientific advisory board and conference travel, respectively; and support for meetings or travel from the American Sexually Transmitted Diseases Association as a member of the Executive Board outside the scope of the current work. JAG-L reports honoraria from the Universidad de Antioquia; support for meetings or travel from Carnott Laboratories, Cantabria Labs, Epidermique, Pharmaderm, and Janssen; receipt of writing materials from Epidermique, Cantabria labs, Isdin, Pharmaderm, Skindrugs, Loreal, Galderma, Cetaphil, Cerave, Isispharma, Carnott, Janssen, Pharmalab, Novartis, Pfizer, and Lilly outside of the scope of work. JDR receives royalties from Biokit, Chembio, and Span Diagnostics for syphilis serodiagnostic reagents. JBP reports non-financial support from Abbott Diagnostics and past research support from Gilead Sciences, all outside the scope of the current work. Some of the material in this manuscript was presented as an abstract at the STI & HIV 2025 World Congress. Funding Statement This study was funded by the National Institutes of Health, the Bill and Melinda Gates Foundation, and Connecticut Children's. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Institutional review boards (IRBs) at the University of North Carolina at Chapel Hill (IRB protocol number 19-0311), the Dermatology Hospital of Southern Medical University in Guangzhou (IRB protocol Guangdong Dermatology Hospital Lunli Shencha-20181202 [R3]), CIDEIM in Cali (IRB protocol 1289), and the National Health Sciences Research Committee Ministry of Health in Lilongwe (IRB approval 2252) gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes Conflicts of Interest and Sources of Funding ACS reports royalties from UptoDate; past honoraria from Innoviva Specialty Therapeutics and Hologic, Inc, for their scientific advisory board and conference travel, respectively; and support for meetings or travel from the American Sexually Transmitted Diseases Association as a member of the Executive Board outside the scope of the current work. JAG-L reports honoraria from the Universidad de Antioquia; support for meetings or travel from Carnott Laboratories, Cantabria Labs, Epidermique, Pharmaderm, and Janssen; receipt of writing materials from Epidermique, Cantabria labs, Isdin, Pharmaderm, Skindrugs, Loreal, Galderma, Cetaphil, Cerave, Isispharma, Carnott, Janssen, Pharmalab, Novartis, Pfizer, and Lilly outside of the scope of work. JDR receives royalties from Biokit, Chembio, and Span Diagnostics for syphilis serodiagnostic reagents. JBP reports non-financial support from Abbott Diagnostics and past research support from Gilead Sciences, all outside the scope of the current work. This project was funded in part by the National Institute for Allergy and Infectious Diseases (NIAID; U19AI144177 to JDR and MAM). This work also was supported, in part, by the Bill & Melinda Gates Foundation (INV-036560 to ACS) and strategic research dollars from Connecticut Children’s. SFS is supported by NIH NIAID grant #T32-AI007001. Data Availability Deidentified data produced in the present study are available upon reasonable request to the authors.