Clinical trial NCT06152393: Value of an Intrathecal Synthesis Index of Specific Antitreponema IgG for Neurosyphilis Diagnosis
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Neurosyphilis
Keywords: Neurosyphilis
Treponema pallidum
Intrathecal synthesis
Specific anti-Treponema IgG
Otosyphilis
Ocular syphilis
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
Collaborators: name: Swiss HIV Cohort Study
name: Swiss National Science Foundation
First posted: 2023-11-30
Enrollment: 181
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: OTHER
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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 2020-2022 with retrospective samples from 2007 to 2019 and prospective samples from 2019 to 2022.
Secondary outcomes:
measure: Intrathecal oligoclonal IgG production analysis
timeFrame: 2020-2022 with retrospective samples from 2007 to 2019 and prospective samples from 2019 to 2022.
Other outcomes:
Locations:
city: Geneva
country: Switzerland
facility: Laurence Toutous Trellu
Study officials:
References:
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.
citation: 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.