| Title: |
Performance of clinical metagenomics in France: a prospective observational study |
| Authors: |
Fourgeaud, Jacques; Regnault, Béatrice; Ok, Vichita; da Rocha, Nicolas; Sitterlé, Émilie; Mekouar, Meryem; Faury, Hélène; Milliancourt-Seels, Catherine; Jagorel, Florence; Chrétien, Delphine; Bigot, Thomas; Troadec, Éric; Marques, Isabelle; Serris, Alexandra; Seilhean, Danielle; Neven, Bénédicte; Frange, Pierre; Ferroni, Agnès; Lecuit, Marc; Nassif, Xavier; Lortholary, Olivier; Leruez-Ville, Marianne; Pérot, Philippe; Eloit, Marc; Jamet, Anne |
| Contributors: |
Fédération pour la recherche en explorations et thérapeutiques innovantes in utéro (FETUS (URP 7328)); Université Paris Cité (UPCité); Hôpital Necker - Enfants Malades AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Découverte de pathogènes – Pathogen discovery; Institut Pasteur Paris (IP)-Université Paris Cité (UPCité); Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB; Centre d'infectiologie Necker-Pasteur CHU Necker; Institut Pasteur Paris (IP)-Hôpital Necker - Enfants Malades AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité); Institut du Cerveau = Paris Brain Institute (ICM); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS); Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163); Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Biologie des Infections - Biology of Infection; Institut Pasteur Paris (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC); Institut Pasteur Paris (IP)-Organisation Mondiale de la Santé / World Health Organization Office Genève, Suisse (OMS / WHO)-Université Paris Cité (UPCité); Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA); Centre Collaborateur de l'OIE de Détection et identification chez l’homme des pathogènes animaux émergents et développement d’outils pour leur diagnostic / Collaborating Center for the Detection and identification in humans of emerging animal pathogens and development of tools for their diagnoses (CCOIE-OIECC); Institut Pasteur Paris (IP)-Organisation Mondiale de la Santé Animale / World Organisation for Animal Health Paris (OIE)-Université Paris Cité (UPCité); École nationale vétérinaire d'Alfort (ENVA); Necker-Enfants Malades Hospital and Institut Pasteur; ME is part of the STROBE-metagenomics working group. We thank the sequencing platform of Necker-Enfants Malades Hospital and Biomics platform of Institut Pasteur for providing access to the sequencers. We thank Fanny Lanternier and Claire Rouzaud for providing clinical material from immunocompromised patients. We thank the technicians, biologists, and administrative staff of the microbiology department at Necker-Enfants Malades Hospital. |
| Source: |
ISSN: 2666-5247 ; The Lancet Microbe ; https://pasteur.hal.science/pasteur-04320314 ; The Lancet Microbe, 2023, ⟨10.1016/s2666-5247(23)00244-6⟩. |
| Publisher Information: |
CCSD; Elsevier |
| Publication Year: |
2023 |
| Subject Terms: |
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases; [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry; Molecular Biology/Genomics [q-bio.GN] |
| Description: |
International audience ; Background Metagenomic next-generation sequencing (mNGS) allows untargeted identification of a broad range of pathogens, including rare or novel microorganisms. Despite the recognition of mNGS as a valuable diagnostic tool for infections, the most relevant indications for this innovative strategy remain poorly defined. We aimed to assess the determinants of positivity and clinical utility of mNGS. Methods In this observational study, we prospectively performed short-read shotgun metagenomics analysis as a second-line test (in cases of negative first-line test or when the symptoms were not fully explained by initial positive results) or as a first-line test in life-threatening situations requiring urgent non-targeted pathogen identification at the Necker-Enfants Malades Hospital (Paris, France). All sample types, clinical indications, and patient populations were included. Samples were accompanied by a mandatory form completed by the senior clinician or pathologist, on which the clinical level of suspected infection (defined as high or low) was indicated. We assessed the variables (gender, age, immune status, initial suspicion of infection, indication, and sample type) associated with mNGS pathogen detection using odds ratios (ORs) from multivariate logistic regression. Additional investigations were carried out using specific PCR or culture techniques, to confirm positive mNGS results, or when infectious suspicion was particularly high despite a negative mNGS result. Findings Between Oct 29, 2019, and Nov 7, 2022, we analysed 742 samples collected from 523 patients. The initial suspicion of infection was either high (n=470, 63%) or low (n=272, 37%). Causative or possibly causative pathogens were detected in 117 (25%) samples from patients with high initial suspicion of infection, versus nine (3%) samples analysed to rule out infection (OR 9•1, 95% CI 4•6-20•4; p |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1016/s2666-5247(23)00244-6 |
| Availability: |
https://pasteur.hal.science/pasteur-04320314; https://pasteur.hal.science/pasteur-04320314v1/document; https://pasteur.hal.science/pasteur-04320314v1/file/PIIS2666524723002446.pdf; https://doi.org/10.1016/s2666-5247(23)00244-6 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.77642414 |
| Database: |
BASE |