Neurosyphilis
Conditions
Keywords
Neurosyphilis, Treponema pallidum, Intrathecal synthesis, Specific anti-Treponema IgG, Otosyphilis, Ocular syphilis
Brief summary
A retro-prospective case-control Swiss study was conducted to evaluate the diagnostic performance of measuring an antibody index (AI) for intrathecal synthesis of specific anti-Treponema pallidum (T. pallidum) IgG for the diagnosis of neurosyphilis.
Detailed description
The diagnosis of neurosyphilis (NS) lacks a true gold standard which makes the diagnosis challenging while consequences of a misdiagnosis are potentially severe. The aim of this study was to evaluate the diagnostic performance of measuring an antibody index (AI) for intrathecal synthesis of specific anti-Treponema pallidum (T. pallidum) IgG for the diagnosis of NS. CSF parameters were analysed and specific anti-T. pallidum IgG were measured simultaneously on paired cerebrospinal fluid (CSF)-serum samples collected between 2007 and 2022 from patients suspected of NS, in Switzerland. An AI was calculated to consider blood-brain barrier integrity. Two NS definitions were used: NS1 included patients with suspicion of NS presenting neurological symptoms and/or acute neuro-sensory signs and positive TPHA/TPPA serology and CSF-TPHA/TPPA≥320, and either CSF-leucocytes \>5cells/mm3 and/or CSF-protein \>0,45g/l and/or a reactive CSF-VDRL/RPR test. NS2 included patients with NS suspicion presenting acute ocular and/or otologic symptoms, and positive TPHA/TPPA serology, and a favourable response to NS treatment. Controls were patients diagnosed with any other CNS pathologies and with positive TPHA/TPPA serology.
Interventions
DIAGNOSTIC_TESTMeasure of an antibody index for intrathecal synthesis of specific anti-Treponema pallidum IgG by ELISA.
Paired CSF/serum samples from all patients were blind tested for anti-T. pallidum IgG with an ELISA containing recombinant T. pallidum proteins (Euroimmun). The AI was calculated conforming to Reiber's method (PMID 11239944) and as previously described in Alberto et al. (PMID 35138118).
Sponsors
Swiss HIV Cohort Study
Swiss National Science Foundation
University Hospital, Geneva
Study design
Observational model
CASE_CONTROL
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* All patients who have serum / CSF sample pairs collected concomitantly (3 days maximum interval between blood test and lumbar puncture). * Age \> or = 18 years old.
Exclusion criteria
* All patients for whom the stored samples do not meet the needs of the diagnostic study, or whose serum and CSF collection date is more than 3 consecutive days. * Age \< 18 years old. * No written consent form for the prospective part.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the diagnostic performance of measuring an antibody index (AI) for intrathecal synthesis of specific anti-Treponema pallidum IgG for the diagnosis of neurosyphilis. | 2020-2022 with retrospective samples from 2007 to 2019 and prospective samples from 2019 to 2022. | AI testing measured with an Elisa specific for anti-Treponema pallidum IgG for all patients : number of patients with positive AI, sensitivity/specificity of the test, and positive/negative predictive values of AI test were estimated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intrathecal oligoclonal IgG production analysis | 2020-2022 with retrospective samples from 2007 to 2019 and prospective samples from 2019 to 2022. | IgG oligoclonal bands were analysed in CSF and serum of NS and control patients by the gold standard isoelectric focusing method |
Countries
Switzerland
Outcome results
None listed