Stopping Syphilis Transmission in Arctic Communities Through Rapid Diagnostic Testing (STAR Study): A Multisite Prospective Field Diagnostic Accuracy Study in an Intended-Use Setting

Abstract

Background: Isolated Canadian Arctic communities face numerous barriers to timely syphilis diagnostics. Deployment of rapid dual diagnostic tests (RDT) may reduce long laboratory delays, yet performance in intended-use settings is poorly defined. We evaluated the field diagnostic accuracy of a syphilis RDT, using whole blood and serum in two Arctic communities.

Methods: In this multisite prospective field evaluation, patients were screened by an RDT containing both treponemal and non-treponemal components (Chembio DPP® Syphilis Screen & Confirm) at or near the point-of-care in Nunavik and Nunavut between January 2020–December 2021. Venous whole blood and serum were collected for rapid testing and compared to laboratory-based serology reference testing using a standard reverse sequence algorithm of treponemal and rapid plasma reagin (RPR) testing.

Findings: A total of 303 specimens were collected (150 whole blood and 153 serum) from 161 participants (median age 29 years [IQR: 23–38] and 61% female) during 176 encounters. Treponemal-RDT sensitivity compared to a treponemal-reference standard (45/176 confirmed cases) was similar for serum (76% [95%CI 60–88%]) and whole blood (79% [95%CI 63–90%]). In those with RPR titres >1:8 (i.e., suggestive of recent/active infection), sensitivity increased to 93% [95%CI 79–99%] for serum and 93% [95%CI 76–99%] for whole blood. Treponemal-RDT specificity was excellent (99% [95%CI 95–100%]) for both specimen types. Non-treponemal-RDT sensitivity relative to RPR was 95% [95%CI 83–99%] for serum and 80% [95%CI 63–91%] for whole blood. Sensitivity increased to 100% [95%CI 89–100%] for serum and 93% [95%CI 76–99%] for whole blood when RPR titres >1:8.

Interpretation: Compared to standard laboratory testing, the RDT accurately identified individuals with infectious syphilis requiring prompt treatment when performed under real-world conditions in an intended-use setting. Whole blood and serum yielded similar performance, demonstrating the RDT can be successfully implemented at the point-of-care.

Funding Statement: Supported by the Canadian Institutes of Health Research PJT-162262 and the Fonds de recherche du Québec-Santé (CPY)

Declaration of Interests: CPY reports being on an Independent Data Monitoring Committee (IDMC) for Medicago Inc. MM-G reports and investigator-sponsored research grant from Gilead Sciences Inc., and contractual arrangements from the Institut national de santé publique du Québec (INSPQ), the Institut d’excellence en santé et services sociaux (INESS), the World Health Organization, and the Joint United National Programme on HIV/AIDS (UNAIDS), all outside of the submitted work. All other authors declare no competing interests.

Ethics Approval Statement: This study was approved by the research ethics board of the Research Institute of the MUHC (# 2020-5834) and the Nunavut Research Institute (Nunavut Research License: 0300520N-M). The conduct of this study also adhered to the Tri-Council policy statement on the ethical conduct of research involving First Nations, Inuit and Métis peoples of Canada. Verbal informed consent was obtained from all participants providing serum specimens for rapid testing. At the request of the participating communities, written informed consent was obtained from those providing an additional whole blood specimen in Nunavut whereas verbal informed consent was obtained in Nunavik.

Keywords: syphilis, sexually transmitted infection, point-of-care, rapid diagnostic test, diagnostic accuracy, specimen type, circumpolar health