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

NCT06152393 | Completed

• 1 other identifier: Study 2019-00232
• Study Type: observational
• Target: 181
• Locations: 1 country
• Sites: 1

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.

Conditions

Neurosyphilis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  2020-2022 with retrospective samples from 2007 to 2019 and prospective samples from 2019 to 2022.

Secondary Outcomes (1)

• Intrathecal oligoclonal IgG production analysis

  2020-2022 with retrospective samples from 2007 to 2019 and prospective samples from 2019 to 2022.

Study Arms (3)

Control patients

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

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

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.

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

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.

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

Interventions

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

Control patients; NS1 patients; NS2 patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This is a bidirectional retrospective and prospective multicenter study, including all the patients presenting neurological and neuro-sensory signs (ophthalmic and auditory), for whom we have serum and cerebrospinal fluid samples, from the University Hospitals of Geneva, Zurich and Lausanne, at the ADMED Microbiology Laboratory of La Chaux-de-Fonds and in SHCS centers.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Geneva: lead
• Swiss HIV Cohort Study: collaborator
• Swiss National Science Foundation: collaborator

Study Sites (1)

Laurence Toutous Trellu

Geneva, 1204, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 11239944 BACKGROUND

• 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.

  PMID: 35138118 BACKGROUND

MeSH Terms

Conditions

Neurosyphilis; Treponemal Infections

Condition Hierarchy (Ancestors)

Central Nervous System Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Syphilis; Spirochaetales Infections; Gram-Negative Bacterial Infections; Central Nervous System Infections; Central Nervous System Diseases; Nervous System Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 12, 2023
• First Posted: November 30, 2023
• Study Start: March 1, 2019
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: November 30, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)