Assess the Performance of Metagenomic Sequencing in the Diagnosis of STI (NGS-IST)

Study Overview
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Brief Summary
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The main objective of the study will be to assess the performance of the Next-Generation-Sequencing (NGS) diagnostics of Chlamydia trachomatis and Neisseria gonorrhoeae compared to reference techniques.

Detailed Description
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Sexually Transmitted Infections (STIs) have become a major global public health problem and are among the most common infections. The increase antibiotic resistance, particularly in Neisseria gonorrhoeae and Mycoplasma genitalium, is of concern. Currently, the diagnosis of STIs is based on specific tests by pathogen, mainly by standard culture allowing an antibiotic susceptibility testing, gene amplification tests possibly allowing the search for resistance genes and serologies. Next-Generation-Sequencing (NGS) is based on the detection and analysis of any DNA and RNA present in the studied sample with a high degree of sensitivity, this method enables the precise identification of non-human sequences regardless its bacterial, viral or parasitologic origin, to detect resistance genes and to characterize the strains. The investigators propose to assess the performance of NGS for the diagnosis of STIs. A cohort of 332 PrEP users from Saint-Antoine and Tenon Hospitals will be followed for this purpose every 3 months during 1 year (including also the intermediate visits if needed in case of STIs symptoms). The main objective of the study will be to assess the performance of the NGS diagnostics of Chlamydia trachomatis and Neisseria gonorrhoeae compared to reference techniques. The secondary objectives will be (i) to evaluate the performance of the diagnosis by NGS of the other STIs compared to the reference techniques, (ii) to evaluate the interest and the sensitivity of a 3 sites pooled sample urine, throat and rectum and the swab sampling from the ulcer lesions in the case of the ulcerations presence for the diagnosis of STIs, (iii) to describe the natural history of colonization with Mycoplasma genitalium and the appearance of resistance or pressure of antibiotic selection and (iv) to evaluate the prevalence of agents not usually sought in screening for STI (HSV-1, HSV-2, Haemophilus ducreyi, Campylobacter sp, Shigella sp, Clostridioides difficile, Entamoeba histolytica). Improved diagnosis of STIs and resistance will allow a better patient management.

Official Title
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Assess the Performance of Metagenomic Sequencing in the Diagnosis of STI (NGS-IST)

Conditions
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Sexually Transmitted Infections (Not HIV or Hepatitis), Chlamydia Trachomatis Infection, Neisseria Gonorrhoeae Infection, Mycoplasma Genitalium Infection

Intervention / Treatment
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* Diagnostic Test: Assess the Performance of Metagenomic Sequencing in the Diagnosis of STI (NGS-IST)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old MSM PrEP users Acceptance of study constraints With or without Social Security scheme or State Medical Aid Signature of consent form to participate in the study Exclusion Criteria: Language barrier making questioning impossible.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: 12-months prospective multicenter longitudinal cohort with the biological samples collection.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 12-months prospective multicenter longitudinal cohort with the biological samples collection.<br>This is a single-arm interventional study. After acceptance of the study (signature of the informed consent form), patients are included in the single-arm interventional study for a period of 12 months with follow-up visits every 3 months and intermediate visits in the case of the symptoms presence or sexual contacts with partners having STIs (corresponding to standard care for the PrEP users). | Diagnostic Test: Assess the Performance of Metagenomic Sequencing in the Diagnosis of STI (NGS-IST)<br>* Proposal of the study to all eligible adult patients coming for pre-exposure prophylaxis (PrEP) consultations from the Infectious Diseases Department of Saint-Antoine and Tenon Hospitals (with delivery of a patient's information and signing an informed consent form). During each visit (D0, M3, M6, M9, M12 and intermediate visits), patients will be asked to: Respond to a questionnaire on their history of taking antibiotics, STIs, their foreign travels, their consumption of tobacco, drugs, alcohol and their sexual practices. Perform the following additional samples at each visit, including the intermediate: rectal and throat swabs, urine sample and swab from the lesions in the case of ulceration presence due to STIs. The diagnosis of STIs (NG and MG) will be carried out using 2 techniques: the reference technique and the Next-Generation-Sequencing (NGS) technique. A serum sample will be collected during routine care. All samples will be stored after the analysis under -80° C.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the performance of NGS metagenomic diagnosis of Chlamydia trachomatis (Ct) and Neisseria gonorrhoeae (Ng) compared to reference techniques. | Sensitivity, specificity, positive and negative predictive values of NGS compared to reference techniques for Ng and Ct. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the performance of the diagnosis by NGS of the other STIs compared to the reference techniques. | Sensitivity, specificity, positive and negative predictive values of NGS compared to reference techniques for other sexually transmitted infections (STIs). | 12 months | 
| Describe the epidemiology of circulating strains by molecular typing. | Total number of cases of Ct, Ng, agents not usually screened for in STI screening compared to the number of subjects at the time of their inclusion in the study cohort, with 95% confidence interval. | 12 months | 
| Estimate the incidence and describe the natural history of colonization by Mycoplasma genitalium (Mg). | Number of new cases Mycoplasma genitalium (Mg) compared to the number of subjects followed in the study cohort per month of follow-up. | 12 months | 
| Estimate the incidence of the appearance of Mycoplasma genitalium resistance under antibiotic selection pressure. | Number of new cases Mycoplasma genitalium (Mg) compared to the number of subjects followed in the study cohort per month of follow-up under antibiotic selection pressure. | 12 months | 
| Characterize circulating Neisseria gonorrhoeae (Ng) clones. | Total number of cases of circulating Neisseria gonorrhoeae (Ng) clones compared to the number of subjects at the time of their inclusion in the study cohort, with 95% confidence interval. | 12 months | 
| Characterize the circulating serotypes of Chlamydia trachomatis (Ct). | Total number of cases of circulating serotypes of Chlamydia trachomatis (Ct) compared to the number of subjects at the time of their inclusion in the study cohort, with 95% confidence interval. | 12 months | 
| Estimate the incidence of agents not usually screened for in STI screening (HSV-1, HSV-2, HPV, Mycoplasma hominis, Ureaplasma sp, Haemophilus ducreyi, Campylobacter sp, Shigella sp, Clostridium difficile, Entamoeba histolytica). | Number of new cases of agents not usually tested for in STI screening compared to the number of subjects followed in the study cohort per month of follow-up. | 12 months | 
| Determine the factors associated with STI events. | Hazard ratio of determinants (factors) associations with the STI cases incidence. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metagenomics Next-Generation-Sequencing (NGS), Sexually Transmitted Infections (STI), Pre-Exposure Prophylaxis (PrEP), Men who have Sex with Men (MSM)