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Diagnostic performance of PCR assays for the diagnosis of neurosyphilis: a systematic review
  1. Michael Marks1,2,
  2. David Lawrence1,
  3. Christian Kositz1,
  4. David Mabey1,2
  1. 1 Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK
  2. 2 Hospital for Tropical Diseases, Mortimer Market Centre, London, UK
  1. Correspondence to Dr Michael Marks, Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK; michael.marks{at}


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.

  • PCR
  • syphilis
  • serology
  • neurology

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  • Handling editor Catherine A Ison

  • Contributors MM and DL conceived of the study. MM, CK, DL reviewed the papers. MM wrote the first draft of the manuscript. All authors revised the manuscript.

  • Funding MM is supported by the National Institute of Health Research. DL is supported by a grant from EDCTP and the Wellcome Trust.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.