The Performance of Cerebrospinal Fluid Treponemal-Specific Antibody Tests in Neurosyphilis: A Systematic Review

Background: No single laboratory test is both sensitive and specific to diagnose neurosyphilis. Several major clinical guidelines suggest that negative cerebrospinal fluid (CSF) treponemal-specific antibody tests rule out the diagnosis of neurosyphilis. Our aim was to systematically review the literature and describe the performance of treponemal-specific CSF antibody tests when diagnosing neurosyphilis. Methods: Two reviewers independently assessed studies published in electronic databases, trial registries, and bibliographies for content and quality. Entry criteria included the assessment of treponemal-specific CSF tests currently used in clinical practice, and the use of standard criteria for both diagnosis and exclusion of neurosyphilis. The primary outcomes were sensitivity, specificity, and negative predictive values of treponemal-specific CSF antibody tests. Results: Of 141 unique citations, 18 studies were included in the systematic review. Due to significant heterogeneity among studies, we were unable to generate pooled summary statistics. Seven different treponemal-specific tests were assessed. Of those, 13 studies evaluated the CSF FTA-ABS (fluorescent treponemal antibody-absorbed) and 9 evaluated the CSF fluorescent treponemal antibody. The performance estimates of these tests were highly variable and depended on the choice of negative and positive controls. No single test had perfect sensitivity, thus the negative predictive value was dependant on the specificity of the test and the prevalence (i.e., pretest probability) of neurosyphilis: the higher the prevalence, the lower the negative predictive value. Few studies included HIV-infected persons. Conclusions: A negative CSF-treponemal-specific antibody test may not exclude the diagnosis of neurosyphilis when the clinical suspicion for neurosyphilis is high.