Comparison of molecular and serological assays on cerebrospinal fluid for the diagnosis of neurosyphilis

Abstract

Background Many assays are available on cerebrospinal fluid (CSF) for the diagnosis of neurosyphilis (NS) but there is no ‘gold standard’. Objectives The aim of this study was to evaluate different molecular and serological assays used in NS. Methods We evaluated two PCR assays and three serological techniques in parallel on CSF samples collected between 2019 and 2020 from patients suspected of NS. Results The study included 143 patients comprising 30 early NS, 7 late NS and 106 patients without a diagnosis of NS. All patients with NS were symptomatic and had either neurological (67.6%) or ophthalmological signs (54.1%). The qPCR and nPCR assays had overall sensitivities (Se) of 41% and 27%, respectively; with each an overall specificity (Sp) of 100%. VDRL had a Se of 51% and a Sp of 92%. Immunoblot had a Se of 62% and a Sp of 85%. Finally, treponemal tests (TT) had a Se of 96% and a Sp of 69%. Conclusions Our study confirms the excellent specificity of molecular techniques allowing to avoid overdiagnosis of NS, and thus, unjustified intensive antibiotic therapy protocols. CSF TT, although not very specific, has an excellent Se confirming that there is almost never NS with negative CSF TT. VDRL and immunoblot tests have better overall diagnostic performance. However, none of these techniques has sufficient diagnostic performance to represent a ‘gold standard’. Thus, the diagnosis of NS relies on a combination of clinical and biological parameters with the association of PCR with serology, associating VDRL and immunoblot, in CSF.

Analysis of Treponema pallidum DNA and CXCL13 in Cerebrospinal Fluid in HIV-Negative Syphilis Patients

“… 13 Other relevant reports showed that the sensitivity of nPCR for detecting CSF TP was 42.5% and 27%, and the specificity was 97% and 100%, respectively. 14 , 15 The lower sensitivity of our results may be due to the difference in the study population, whereas Vanhecke’s study included HIV-infected as well as severely immunodeficient syphilis patients, which can exacerbate NS infection. 14 The nPCR test may not be the most sensitive method to diagnose NS.…”

Performance of the nontreponemal tests and treponemal tests on cerebrospinal fluid for the diagnosis of neurosyphilis: A meta-analysis

“…A total of 1,140 full-text publications were evaluated for eligibility, 489 were deemed irrelevant to the objective, and 622 lacked sufficient data therefore they were excluded. Ultimately, our meta-analysis was limited to 29 publications ( 2 , 4 , 7 – 33 ) to perform the quantitative synthesis.…”

“…Nine articles reported whether the cases were co-infected with HIV ( 4 , 10 , 11 , 22 , 26 , 27 , 30 – 32 ). Information on the presence or absence of symptoms in patients with neurosyphilis can be found in 13 studies ( 2 , 4 , 7 , 8 , 11 , 13 , 20 – 22 , 27 , 28 , 30 , 32 ).…”

“…Numerous approaches for analyzing cerebrospinal fluid have been developed, with serological assays being the most commonly used diagnostic tests. There are two serologic tests for syphilis: nontreponemal and treponemal tests, the former measuring antibodies against cardiolipin and are not specific to Treponema pallidum , and the latter detecting specific antibodies to Treponema pallidum ( 2 , 3 ).…”