- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06152393
Value of an Intrathecal Synthesis Index of Specific Antitreponema IgG for Neurosyphilis Diagnosis
Retro-prospective Multicentric Study Aiming to Evaluate the Benefit of Measuring an Intrathecal Synthesis Index of Specific Antitreponema IgG for Patients Suspected of Neurosyphilis
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Geneva, Switzerland, 1204
- Laurence Toutous Trellu
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
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 Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
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Control patients
Controls were patients diagnosed with TPHA/TPPA serology ≥80 and neurological symptoms requiring a lumbar puncture.
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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). |
NS1 patients
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.
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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). |
NS2 patients
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.
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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). |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
Time Frame: 2020-2022 with retrospective samples from 2007 to 2019 and prospective samples from 2019 to 2022.
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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.
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2020-2022 with retrospective samples from 2007 to 2019 and prospective samples from 2019 to 2022.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Intrathecal oligoclonal IgG production analysis
Time Frame: 2020-2022 with retrospective samples from 2007 to 2019 and prospective samples from 2019 to 2022.
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IgG oligoclonal bands were analysed in CSF and serum of NS and control patients by the gold standard isoelectric focusing method
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2020-2022 with retrospective samples from 2007 to 2019 and prospective samples from 2019 to 2022.
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Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Reiber H, Peter JB. Cerebrospinal fluid analysis: disease-related data patterns and evaluation programs. J Neurol Sci. 2001 Mar 1;184(2):101-22. doi: 10.1016/s0022-510x(00)00501-3.
- Alberto C, Deffert C, Lambeng N, Breville G, Gayet-Ageron A, Lalive P, Toutous Trellu L, Fontao L. Intrathecal Synthesis Index of Specific Anti-Treponema IgG: a New Tool for the Diagnosis of Neurosyphilis. Microbiol Spectr. 2022 Feb 23;10(1):e0147721. doi: 10.1128/spectrum.01477-21. Epub 2022 Feb 9.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Central Nervous System Diseases
- Nervous System Diseases
- Infections
- Central Nervous System Infections
- Gram-Negative Bacterial Infections
- Bacterial Infections
- Bacterial Infections and Mycoses
- Central Nervous System Bacterial Infections
- Spirochaetales Infections
- Treponemal Infections
- Syphilis
- Neurosyphilis
- Physiological Effects of Drugs
- Immunologic Factors
- Antibodies
Other Study ID Numbers
- Study 2019-00232
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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