Diagnostic performance of PCR assays for the diagnosis of neurosyphilis: a systematic review.

INTRODUCTION: Syphilis continues to be a major public health problem and the recent resurgence in syphilis in high-income settings has seen an accompanying increase in cases of neurosyphilis. While the introduction of PCR has had a significant impact on the diagnosis of early syphilis, cerebrospinal fluid (CSF) serological assays remain the most commonly used tests to diagnosis neurosyphilis. We reviewed data on the performance of CSF-PCR for the diagnosis of neurosyphilis. METHODS: We searched Pubmed, Medline, EMBASE and the grey literature for references on PCR in neurosyphilis. We calculated the sensitivity and specificity of PCR compared with reference testing for the diagnosis of neurosyphilis. RESULTS: We identified 66 articles of which seven met the study inclusion criteria. The sensitivity of PCR for definite neurosyphilis varied between 40% and 70% and specificity between 60% and 100% across the studies. The most commonly used PCR assay targeted Tp47 which had an overall sensitivity of 68% and a specificity of 91.9%. DISCUSSION: The sensitivity of PCR was low compared with CSF-serological assays but the challenges of evaluating a diagnostic test in the absence of a clear gold standard make definitive interpretation challenging. Most studies were small and not adequately powered highlighting the need for multicentre, multicountry trials to provide adequate statistical power in evaluations of new tests the diagnosis of neurosyphilis.