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

Neurosyphilis Clinical Trial

Official title:

Retro-prospective Multicentric Study Aiming to Evaluate the Benefit of Measuring an Intrathecal Synthesis Index of Specific Antitreponema IgG for Patients Suspected of Neurosyphilis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06152393
• Other study ID #: Study 2019-00232
• Status: Completed
• Start date: March 1, 2019
• Est. completion date: December 31, 2022

Study information

• Verified date: November 2023
• Source: University Hospital, Geneva
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 181
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neurosyphilis

Intervention

Diagnostic Test:
• 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).

Locations

Country	Name	City	State
Switzerland	Laurence Toutous Trellu	Geneva

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Geneva	Swiss HIV Cohort Study, Swiss National Science Foundation

Country where clinical trial is conducted

Switzerland, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Intrathecal oligoclonal IgG production analysis	IgG oligoclonal bands were analysed in CSF and serum of NS and control patients by the gold standard isoelectric focusing method	2020-2022 with retrospective samples from 2007 to 2019 and prospective samples from 2019 to 2022.