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Value of an Intrathecal Synthesis Index of Specific Antitreponema IgG for Neurosyphilis Diagnosis

Completed
Conditions
Neurosyphilis
Interventions
Diagnostic Test: Measure of an antibody index for intrathecal synthesis of specific anti-Treponema pallidum IgG by ELISA.
Registration Number
NCT06152393
Lead Sponsor
University Hospital, Geneva
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
181
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.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Control patientsMeasure of an antibody index for intrathecal synthesis of specific anti-Treponema pallidum IgG by ELISA.Controls were patients diagnosed with TPHA/TPPA serology ≥80 and neurological symptoms requiring a lumbar puncture.
NS1 patientsMeasure of an antibody index for intrathecal synthesis of specific anti-Treponema pallidum IgG by ELISA.NS1 includes: 1) neurological symptoms suggestive of central nervous system (CNS) involvement or acute ophthalmological or acute auditory signs consistent with neurosyhilis (NS), or syphilis with treatment serological failure (\< fourfold decrease in the antibody titer of RPR/VDRL 12 months after treatment), and 2) a TPHA/TPPA serology ≥ 80 and a CSF-TPHA/TPPA test ≥ 320, and 3) either CSF-WBC \> 5 cells/mm3, and/or CSF-protein \> 0,45g/l in the absence of other known causes of these abnormalities, and/or a reactive CSF-VDRL/RPR test, and 4) no differential diagnosis.
NS2 patientsMeasure of an antibody index for intrathecal synthesis of specific anti-Treponema pallidum IgG by ELISA.NS2 includes:1) acute ocular symptoms (recent and sudden decrease in visual acuity) and/or acute otologic dysfunctions (sudden hearing loss, acute tinnitus or vertigo) without other known diagnosis for these clinical abnormalities, 2) and a TPHA/TPPA serology ≥ 80, 3) and a response to NS treatment assessed by ophthalmologic or hearing tests and at least a fourfold reduction of RPR/VDRL titer in blood after 12 months following treatment.
Primary Outcome Measures
NameTimeMethod
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 Outcome Measures
NameTimeMethod
Intrathecal oligoclonal IgG production analysis2020-2022 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

Trial Locations

Locations (1)

Laurence Toutous Trellu

🇨🇭

Geneva, Switzerland

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