Quantitative Assessment of the DPP Syphilis TnT assay in infection and treatment response

Johns Hopkins University, Baltimore MD

Investigators

Abstract

Title: Quantitative Assessment of the DPP Syphilis TnT assay in infection and treatment response Abstract Summary The number of syphilis cases continues to rise in the United States. Current testing algorithms for syphilis, a sexually transmitted infection, are based on serological assays developed in the first half of the 20th century; two different serological tests for syphilis need to be positive to make a serological diagnosis. Serologic testing is used to diagnose most syphilis cases using a test algorithm of a lipoidal (non-treponemal) rapid plasma reagin (RPR) measured as a titer through serial dilution testing (e.g., 1:1, 1:2, 1:4, etc) which is time- consuming, labor-intensive, and requires moderate complexity lab testing, followed by a sensitive and specific anti-treponemal test for confirmation. RPR titers are also required to monitor treatment response and for evidence of reinfection. Lateral flow tests with excellent performance characteristics for anti-treponemal antibodies have been developed and can be useful in screening patients at risk of infection but never treated for syphilis. The lack of the RPR titer limits the use of lateral flow treponemal antibody tests in high-prevalence settings in the US where serial RPR titers and clinical history are needed for test interpretation in previously treated patients. The importance and need for syphilis diagnostic innovation is clear. The point-of-care (POC) Dual Path Platform (DPP) Syphilis TnT (treponemal and non-treponemal) assay is under FDA approval consideration for the full diagnosis of syphilis infection. The goal of this proposal is to assess the feasibility of using the assay for the longitudinal evaluation of treatment response and reinfection. We propose to use the quantitative results from the microreader (which are currently hidden from the user) and to correlate it with the concentration of antibody (IgM and IgG subtypes) using statistical models. The reader results might be exploited to allow clinicians to determine stage of infection and response to treatment at point-of-care in lieu of a centralized lab RPR titer. Because the DPP Syphilis TnT assay separates the antibody responses into IgM and IgG specific channels, it might also add specificity to the diagnosis of active syphilis infection. Because people living with HIV have different antibody responses than those without HIV, we will stratify our analyses by HIV status. Using de-identified, characterized, syphilis serum discards from the Johns Hopkins Immunology Lab, we will also assess the correlation of the reader values to the concentration of antibody measured in the centralized treponemal tests and the correlation of the non-treponemal results to the RPR titers. Simple, fast, inexpensive lateral flow assays combined with quantitative microreader results with the DPP TnT could revolutionize a move away from RPR titers and give clinicians actionable diagnostic information within a clinical encounter in the US and resource-limited settings.