Christina M Marra1. 1. From the Department of Neurology, University of Washington School of Medicine, Seattle, WA.
Abstract
BACKGROUND: The diagnosis of neurosyphilis relies in large part on the cerebrospinal fluid (CSF) Venereal Disease Research Laboratory (VDRL) test, which is diagnostically specific but not sensitive. METHODS: We determined the sensitivity and specificity of 3 CSF tests in addition to the CSF-VDRL in participants with syphilis enrolled in a research study: detection of Treponema pallidum ribosomal RNA, T. pallidum particle agglutination titer, and chemokine (C-X-C motif) ligand 13 (CXCL13) concentration. Neurosyphilis was defined as asymptomatic or symptomatic meningitis: CSF white blood cells >10/μL without or with neurological symptoms, including new vision or hearing loss. RESULTS: Cerebrospinal fluid-VDRL, CSF T. pallidum ribosomal RNA detection, and CSF T. pallidum particle agglutination titer ≥1:640 were specific (89%-96%) but not sensitive (12%-48%). In contrast, diagnostic sensitivity of CSF-CXCL13 thresholds established from receiver operating characteristic curves using the Youden index was 78% to 83% and specificity was 76% to 81%. In individuals with nonreactive CSF-VDRL, neurosyphilis diagnosis could be confirmed by CSF-CXCL13 concentration in 69% to 75%. CONCLUSIONS: Further studies of CSF-CXCL13 should include CSF samples from multiple cohorts and countries and should use standard neurosyphilis definitions to establish uniform thresholds for diagnosis.
BACKGROUND: The diagnosis of neurosyphilis relies in large part on the cerebrospinal fluid (CSF) Venereal Disease Research Laboratory (VDRL) test, which is diagnostically specific but not sensitive. METHODS: We determined the sensitivity and specificity of 3 CSF tests in addition to the CSF-VDRL in participants with syphilis enrolled in a research study: detection of Treponema pallidum ribosomal RNA, T. pallidum particle agglutination titer, and chemokine (C-X-C motif) ligand 13 (CXCL13) concentration. Neurosyphilis was defined as asymptomatic or symptomatic meningitis: CSF white blood cells >10/μL without or with neurological symptoms, including new vision or hearing loss. RESULTS: Cerebrospinal fluid-VDRL, CSF T. pallidum ribosomal RNA detection, and CSF T. pallidum particle agglutination titer ≥1:640 were specific (89%-96%) but not sensitive (12%-48%). In contrast, diagnostic sensitivity of CSF-CXCL13 thresholds established from receiver operating characteristic curves using the Youden index was 78% to 83% and specificity was 76% to 81%. In individuals with nonreactive CSF-VDRL, neurosyphilis diagnosis could be confirmed by CSF-CXCL13 concentration in 69% to 75%. CONCLUSIONS: Further studies of CSF-CXCL13 should include CSF samples from multiple cohorts and countries and should use standard neurosyphilis definitions to establish uniform thresholds for diagnosis.
Authors: Khutso M Mothapo; Marcel M Verbeek; Lieven B van der Velden; C Wim Ang; Peter P Koopmans; Andre van der Ven; Foekje Stelma Journal: J Clin Microbiol Date: 2015-03-18 Impact factor: 5.948
Authors: Christina M Marra; Lauren C Tantalo; Sharon K Sahi; Clare L Maxwell; Sheila A Lukehart Journal: Sex Transm Dis Date: 2010-05 Impact factor: 2.830
Authors: Christina M Marra; Clare L Maxwell; Shelia B Dunaway; Sharon K Sahi; Lauren C Tantalo Journal: J Clin Microbiol Date: 2017-04-05 Impact factor: 5.948
Authors: Christina M Marra; Clare L Maxwell; Stacy L Smith; Sheila A Lukehart; Anne M Rompalo; Molly Eaton; Bradley P Stoner; Michael Augenbraun; David E Barker; James J Corbett; Mark Zajackowski; Charles Raines; Judith Nerad; Romina Kee; Scott H Barnett Journal: J Infect Dis Date: 2004-01-27 Impact factor: 5.226