CDC Laboratory Recommendations for Syphilis Testing, United States, 2024

Abstract

Summary This report provides new CDC recommendations for tests that can support a diagnosis of syphilis, including serologic testing and methods for the identification of the causative agent Treponema pallidum . These comprehensive recommendations are the first published by CDC on laboratory testing for syphilis, which has traditionally been based on serologic algorithms to detect a humoral immune response to T. pallidum . These tests can be divided into nontreponemal and treponemal tests depending on whether they detect antibodies that are broadly reactive to lipoidal antigens shared by both host and T. pallidum or antibodies specific to T. pallidum , respectively. Both types of tests must be used in conjunction to help distinguish between an untreated infection or a past infection that has been successfully treated. Newer serologic tests allow for laboratory automation but must be used in an algorithm, which also can involve older manual serologic tests. Direct detection of T. pallidum continues to evolve from microscopic examination of material from lesions for visualization of T. pallidum to molecular detection of the organism. Limited point-of-care tests for syphilis are available in the United States; increased availability of point-of-care tests that are sensitive and specific could facilitate expansion of screening programs and reduce the time from test result to treatment. These recommendations are intended for use by clinical laboratory directors, laboratory staff, clinicians, and disease control personnel who must choose among the multiple available testing methods, establish standard operating procedures for collecting and processing specimens, interpret test results for laboratory reporting, and counsel and treat patients. Future revisions to these recommendations will be based on new research or technologic advancements for syphilis clinical laboratory science.

A Unique Presentation of Secondary Syphilis With Painful Target Lesions

“…The reverse sequence syphilis screening (RSSS) algorithm begins with a treponemal assay as the initial screen, followed by confirmatory testing of reactive samples using a non-treponemal test. Additional confirmatory tests for RSSS include the TPPA test, FTA-ABS, multi-parameter line immunoassays, and Western blots [14]. In our patient, we followed the conventional detection method.…”

Prevalence and Treatment Outcomes of Syphilis among People with Human Immunodeficiency Virus (HIV) Engaging in High-Risk Sexual Behavior: Real World Data from Northern Greece, 2019–2022

“…We used the reverse syphilis screening algorithm, with the primary screening test performed using the CIA test. In case of positive CIA test, quantitative RPR test was used to determine serological activity of syphilis and monitor the effect of treatment in accordance with 2024 Centers for Disease Control and Prevention (CDC) laboratory recommendations for syphilis testing, 2021 CDC treatment guidelines on sexually transmitted infections, and 2020 European guideline on the management of syphilis [22][23][24].…”

Congenital Syphilis: A Re-Emerging but Preventable Infection

“…Various laboratory methods, such as darkfield microscopy, immunofluorescent antibody test staining, immunochemistry staining, silver stain, and nuclei acid amplification testing, can be used to evaluate lesions of early syphilis by directly detecting T. pallidum . However, these tests are not widely available, and direct fluorescent antibody testing is no longer available in the United States, while nucleic acid amplification tests (NAATs) are available and the results can be used for clinical diagnosis, but no assay has been approved by the Food and Drug Administration (FDA) for commercial use in the United States [ 30 , 38 ].…”

“…Therefore, serologic testing forms the basis of diagnosis, similar to nonpregnant individuals [ 38 ]. Serological tests for syphilis include treponemal and non-treponemal assays.…”