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Updated: Aug 23, 2026

Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid for the Detection of Central Nervous System Pathogens
Published on: April 17, 2026
Alternative cerebrospinal fluid tests to diagnose neurosyphilis in HIV-infected individuals
C M Marra1, L C Tantalo, C L Maxwell
1Department of Neurology, University of Washington School of Medicine, Seattle, USA. cmarra@u.washington.edu
Objective:
To identify alternatives to the CSF-Venereal Disease Research Laboratory (VDRL) test for the diagnosis of neurosyphilis in HIV-infected individuals.
Methods:
CSF fluorescent treponemal antibody (FTA) reactivity and % CSF lymphocytes that were B cells in fresh and frozen samples were determined for 47 HIV-infected cases with syphilis and 26 HIV-infected controls. As for serum, CSF fluorescent treponemal antibody reactivity > or =2+ was considered positive. Based on the results in controls and cases with normal CSF measures, cut-offs for elevated CSF B cells were proposed to be > or =9% in fresh and > or =20% in frozen samples. Neurosyphilis was defined as a reactive CSF-VDRL.
Results:
CSF-FTA-ABS (absorbed) and CSF-FTA (unabsorbed and undiluted) were 100% sensitive for the diagnosis of neurosyphilis. Elevated % CSF B cells in fresh and cryopreserved samples was specific (100%) but not sensitive (40 and 43%) in post hoc analyses. The results of CSF-FTA and assessment of % CSF B cells together allowed 16% of cases with pleocytosis but nonreactive CSF-VDRL to be diagnosed with neurosyphilis and 26% to be diagnosed as not having neurosyphilis.
Conclusion:
When the CSF-VDRL is nonreactive, CSF-FTA and % CSF B cells may help exclude or establish the diagnosis of neurosyphilis.
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