UC Berkeley

Traditional serological syphilis testing in the US currently includes screening with a nontreponemal assay that detects antibodies to lipoidal material released into the blood from host cells damaged by Treponema pallidum as well as lipids on the surface of nonspecific treponemes itself. Reactive nontreponemal tests are subsequently confirmed with a test that detects antibody specific for T. pallidum (termed "treponemal"). It has been suggested that this traditional serological algorithm could be reversed so that screening begins with a treponemal test, such as an enzyme immunoassay (EIA), and if reactive, infection would be confirmed with a nontreponemal test. In cases of discordance between the screening treponemal test and the confirmatory non-treponemal test, the CDC suggests that a second treponemal test (such as a TPPA) could be utilized to serve as a supplemental test.

The reverse sequence testing algorithm offers several advantages over the traditional algorithm for laboratories. Screening with an immunoassay (IA) (1) allows for the use of automation, thus potentially increasing laboratory efficiency; (2) provides objective instead of subjective results; (3) reduces the amount of manual manipulation that is involved with nontreponemal assays. However, the algorithm is not without issues. Perhaps greatest amongst them is that such tests will be reactive in cases where the patient has previously been treated for syphilis. This may be particularly problematic in a setting with a high prevalence of syphilis where many patients being tested may have had a previous case of the disease.

This dissertation is formatted as three individual, self-contained reports of research investigations with an overall introduction and conclusion. Chapter 2 reports on the performance of a reverse sequence algorithm in San Francisco and shows that this algorithm would cause a large amount of additional work for the laboratory. Chapter 3 describes a reduction in the number of supplemental treponemal tests that needs to be run if EIA signal-to-cutoff ratios were considered as part of the algorithm. Chapter 4 describes how a rapid syphilis test could potentially replace the TPPA as the second supplemental test in the reverse sequence algorithm, thus decreasing the turnaround time to report positive syphilis results.