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

NCT ID: NCT06152393

Last Updated: 2023-11-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

181 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-03-01

Study Completion Date

2022-12-31

Brief Summary

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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

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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.

Conditions

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Neurosyphilis

Keywords

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Neurosyphilis Treponema pallidum Intrathecal synthesis Specific anti-Treponema IgG Otosyphilis Ocular syphilis

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

OTHER

Study Groups

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Control patients

Controls were patients diagnosed with TPHA/TPPA serology ≥80 and neurological symptoms requiring a lumbar puncture.

Measure of an antibody index for intrathecal synthesis of specific anti-Treponema pallidum IgG by ELISA.

Intervention Type DIAGNOSTIC_TEST

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.

Measure of an antibody index for intrathecal synthesis of specific anti-Treponema pallidum IgG by ELISA.

Intervention Type DIAGNOSTIC_TEST

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.

Measure of an antibody index for intrathecal synthesis of specific anti-Treponema pallidum IgG by ELISA.

Intervention Type DIAGNOSTIC_TEST

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).

Interventions

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Measure 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).

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Swiss HIV Cohort Study

NETWORK

Sponsor Role collaborator

Swiss National Science Foundation

OTHER

Sponsor Role collaborator

University Hospital, Geneva

OTHER

Sponsor Role lead

Responsible Party

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Laurence Toutous Trellu

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Laurence Toutous Trellu

Geneva, , Switzerland

Site Status

Countries

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Switzerland

References

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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.

Reference Type BACKGROUND
PMID: 11239944 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35138118 (View on PubMed)

Other Identifiers

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Study 2019-00232

Identifier Type: -

Identifier Source: org_study_id