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  • Enhancing Infection Diagnostics with Metagenomics

    A collaborative study by scientists from Necker-Enfants Malades Hospital (AP-HP), the Institut Pasteur, and several other French institutions, recently published in Lancet Microbe, has made significant strides in the field of infection diagnostics using metagenomic next-generation sequencing (mNGS). This approach, which involves global genetic characterization of samples (non-targeted metagenomics), is spearheading a new era in identifying infectious microorganisms.

    The Challenge of Infection Identification
    Traditionally, identifying microorganisms responsible for infections has been a significant challenge, often requiring prior knowledge of potential infectious agents. This targeted approach frequently results in unidentified microorganisms, leading to suboptimal patient treatment. However, recent epidemics have underscored the necessity for a tool capable of detecting new or rapidly evolving pathogens.

    mNGS: A Comprehensive Diagnostic Tool
    Metagenomics, specifically mNGS, has emerged as a powerful tool capable of identifying a broad spectrum of pathogens, including rare or novel organisms. This technique is a leap forward but remains complex and resource-intensive for hospital laboratories, necessitating cross-disciplinary expertise in sample preparation and bioinformatics.

    Between October 2019 and November 2022, the study analyzed 742 samples from 523 patients. These samples, accompanied by a detailed clinical suspicion form, underwent mNGS analysis. Notably, in 117 cases where infection was strongly suspected, mNGS successfully detected causative or potentially causative pathogens.

    High Diagnostic Yield in Specific Cases
    The study found mNGS to be particularly effective in diagnosing infections in immunocompromised patients and those with neurological disorders. For instance, mNGS more readily identified pathogenic viruses in brain biopsies compared to cerebrospinal fluid. Additionally, stool analyses extended beyond digestive disorders to hepatitis and neurological symptoms.

    Dr. Anne Jamet, head of mNGS at Necker-Enfants Malades Hospital (AP-HP) and a key researcher in the study, emphasized the collaboration's expertise in managing infections, particularly in immunocompromised patients. “Our instincts have translated into reliable diagnoses in everyday practice as well as several noteworthy discoveries, including the identification of a new virus responsible for hepatitis,” added Dr. Jacques Fourgeaud, the study's first author.

    Comparing to Conventional Methods
    When compared to traditional microbiology techniques, mNGS showed favorable clinical performance. Its ability to detect a wider range of pathogens can significantly influence decision-making in both diagnosis and treatment.

    Prof. Olivier Lortholary, an infectious diseases specialist at Necker-Enfants Malades Hospital, stressed that “This sequencing-based tool is now indispensable for diagnosing patients with a suspected infection. We are now using it earlier and earlier in severe cases, particularly those involving the brain, and in immunocompromised adults and children.”

    Conclusion
    “The microorganisms we identify with the Necker microbiology laboratory will enable us to develop new tools to make sequencing technology faster and more accessible for front-line microbiological analysis while enhancing its potential for the discovery of new human pathogens,” concluded Philippe Pérot, a research engineer at the Institut Pasteur's Pathogen Discovery Laboratory. This study not only demonstrates the efficacy of mNGS in infection diagnosis but also opens avenues for future research and development in this vital area of medical science.

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