Treponemal and Lipoidal Immunoglobulin M Tests in the Diagnosis and Management of Syphilis Among Nonpregnant Adults: A Systematic Review
Related Experiment Video
Updated: May 13, 2026

Procedures for In Vitro Cultivation of Treponema pallidum, the Syphilis Spirochete
Published on: January 24, 2025
Zachary W Lorenz1,2, Michael E McCarthy1,3, Susan Tuddenham1,2
1From the Department of Medicine.
Background:
There are many commercially available tests that isolate immunoglobulin M (IgM) antibodies to either treponemal-specific or lipoidal (non-treponemal) antigens. These IgM tests for syphilis are distinct from standard serologies that are routinely used (e.g., Treponema pallidum particle agglutination), most of which detect a combination of IgM and immunoglobulin G antibodies. There are several clinical scenarios where IgM tests for syphilis may be of clinical utility: in diagnosing early primary syphilis, in differentiating early from late latent syphilis, in detecting reinfections, and in identifying persons at increased risk for complications such as neurological syphilis.
Methods:
We performed a systematic review of IgM tests for syphilis among nonpregnant adults, focusing on these clinical scenarios.
Results:
Thirteen studies were included.
Conclusions:
The current data suffer from limited sample sizes and significant heterogeneity in syphilis staging, IgM assays, and serological comparators. Whether IgM serologies offer additional clinical benefits beyond standard serologies is unclear. These tests should not be routinely used in the absence of higher-quality data.
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