Performance of Clinical Metagenomics in Stool and Urine Samples for Unexplained Diseases Diagnostic and Emerging Diseases Surveillance in Immunocompromised Patients
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Metagenomics.
- Who it may be relevant to
- Registry conditions: Primary or Secondary Immune Deficiency Including Immunosuppressive Therapy, Chemotherapy, HIV Infection. Basic parameters: No limits · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Overview
The study is based on the hypothesis that the concomitant use of mNGS in non-invasive samples (stool, urine) could improve the rate of detected pathogens in immunodeficient patients compared with mNGS performed in an invasive reference sample alone (blood, CSF, broncho-alveolar lavage fluid (BAL), tissue).
Detailed description
Emerging and re-emerging infectious diseases require broad-spectrum diagnostic approaches capable of identifying a wide range of microorganisms without prior assumptions. This challenge is particularly relevant in immunocompromised patients, who are at high risk for opportunistic, atypical, or previously unknown infections. Conventional microbiological methods rely on targeted assays and may fail to detect uncommon or novel pathogens.
Clinical metagenomics based on high-throughput sequencing (metagenomic Next-Generation Sequencing, mNGS) enables unbiased detection of viral, bacterial, fungal, and parasitic genomes directly from clinical samples. At Necker-Enfants Malades Hospital (Paris, France), implementation of a diagnostic mNGS platform between 2019 and 2022 demonstrated a higher diagnostic yield in immunocompromised patients compared with immunocompetent individuals, with particularly high positivity rates in stool samples. These findings support the evaluation of non-invasive samples as complementary diagnostic matrices.
The SENTINEL study aims to assess the diagnostic performance of mNGS performed on non-invasive samples (stool and urine) compared with invasive reference samples (blood, cerebrospinal fluid, bronchoalveolar lavage fluid, or tissue) in immunocompromised pediatric and adult patients with suspected infection. The underlying hypothesis is that adding stool and/or urine mNGS to invasive sample analysis will increase the detection rate of causative or possibly causative pathogens.
In this multicenter study, invasive samples collected as part of standard of care and study-specific stool and urine samples will undergo centralized mNGS analysis. Non-invasive samples will be collected preferably on the same day as the reference sample or within a maximum of five days.
Clinical and laboratory data generated during routine care will be collected at inclusion. Participants will be followed for three months to evaluate the clinical impact of mNGS findings. For pathogens classified as possibly causative, confirmatory analyses will be performed to support causal attribution.
Secondary analyses will examine the detection of emergent or re-emergent pathogens, including previously unknown pathogens, as well as diagnostic performance according to clinical presentation and type of immune deficiency. The impact of non-invasive mNGS results on patient management and the incremental laboratory cost associated with adding stool and urine analyses will also be evaluated.
The study is sponsored by Assistance Publique - Hôpitaux de Paris and funded by the French Ministry of Health and ANRS Emerging Infectious Diseases.
Interventions
- Diagnostic test Metagenomics
The intervention aims to increase pathogen detection of mNGS with the addition of non-invasive samples compared with invasive sampling alone
Primary outcome measures
- Detection of a "causative" or "possibly causative" pathogens by mNGS in Non-Invasive (stool and/or urine) and invasive samples (blood, CSF, BAL and/or tissue) [Time frame: 14 days]
Secondary outcome measures (5)
- Detection of emergent or re-emergent pathogens by mNGS in non-invasive samples (stool and/or urine) and invasive sample (blood and/or CSF and/or BAL and/or tissue) [Time frame: 14 days]
- Changes in patient management [Time frame: 3 months]
- Detection of the "possibly causative" pathogen genomes by specific PCR in all available invasive and non-invasive samples collected at inclusion and by in situ hybridization in available tissue sample collected at inclusion [Time frame: 14 days]
- Detection of "causative" or "possibly causative" Pathogens by mNGS in Non-Invasive Samples in different subgroups [Time frame: 14 days]
- Cost of performing mNGS in invasive, stool and urine samples [Time frame: 14 days]
Eligibility criteria
Inclusion criteria
- Pediatric or adult patient with a primary or secondary immune deficiency (including immunosuppressive therapy, chemotherapy, HIV infection).
- mNGS prescription on tissue, CSF, BAL and/or blood to identify the causative pathogen in patient with symptoms or biological signs compatible with an infection as per investigator's judgment (e.g., fever, leukocytosis, increased CRP level)
- Non opposition of the participant (or parent(s)/ legal guardian(s) of infant participant)
Exclusion criteria
- No healthcare insurance
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
France · 1 center
- Hôpital Necker - Enfants Malades — Paris
Identifiers
NCT: NCT07603453 · APHP241015