by A recent prospective study published in Lancet Microbe has shed light on the role of a cutting-edge metagenomic tool in enhancing the diagnosis of infections. The study focused on the use of non-targeted metagenomics, also known as global genetic characterization of samples, using next-generation sequencing (mNGS). Accurate identification of the microorganisms responsible for infections is crucial in ensuring that patients receive the most appropriate treatment. The emergence of recent epidemics has emphasized the need for a tool capable of detecting new or unexpected pathogens, particularly those with rapidly evolving genomes.
At present, the search for infectious agents primarily relies on “targeted” approaches that require prior knowledge of the potential causes of infection. However, in many cases, first-line testing fails to identify any microorganism, leading to suboptimal treatment due to the unknown cause of the infection.
mNGS, which utilizes next-generation sequencing, can detect a wide range of pathogens, including rare or novel microorganisms. This study aimed to improve the utilization of this innovative microbial identification technique, recognizing that its complexity and cost pose challenges for hospital laboratories, as it requires diverse expertise ranging from sample preparation to bioinformatics analysis.
Between October 29, 2019, and November 7, 2022, a total of 742 samples were collected from 523 patients for mNGS analysis. The samples were accompanied by a prescription form completed by physicians, which indicated the level of clinical suspicion of infection.
The results of the study focused on a panel of samples with either high (63%) or low (37%) initial suspicion of infection. In 117 patient samples where the infection was strongly suspected, causative or potentially causative pathogens were detected. This accounts for 25% of samples that had a high suspicion of infection based on preliminary assessments by physicians.
The diagnostic yield of mNGS was particularly high among immunocompromised patients and those with neurological disorders, especially when brain biopsies were available. Interestingly, mNGS demonstrated higher efficacy in detecting causative or potentially causative pathogenic viruses in brain biopsies compared to cerebrospinal fluid, which is the traditionally used sample type due to its ease of collection.
Furthermore, the study highlighted the potential of stool analyses in investigating not only digestive disorders but also hepatitis and various neurological symptoms.
In addition, the clinical performance of mNGS was found to be favorable compared to conventional microbiology. The results of this prospective observational study, along with future investigations, will help establish the role of mNGS in decision-making related to diagnosis and treatment.
The research team comprised scientists from Necker-Enfants Malades Hospital (AP-HP), the Institut Pasteur, Université Paris Cité, Inserm, Université Paris-Est Créteil, and the Alfort National Veterinary School. The coordination of the study was led by Professor Marc Eloit and Dr. Anne Jamet, in collaboration with Dr. Jacques Fourgeaud and Beatrice Regnault.
The Microbiology Laboratory, in conjunction with the Department of Infectious and Tropical Diseases and the Pediatric Immunohematology and Rheumatology Department at Necker-Enfants Malades Hospital, has extensive expertise in managing infections caused by unusual microorganisms, particularly among immunocompromised patients.
The Institut Pasteur’s Pathogen Discovery Laboratory, led by Professor Marc Eloit at the time of the study, has optimized high-throughput sequencing for pathogen discovery by developing techniques for both sample preparation and bioinformatics analysis.
This collaboration between Necker-Enfants Malades Hospital and the Institut Pasteur has provided valuable insights into identifying novel causes of infections when conventional techniques fail to make diagnoses. Dr. Anne Jamet, the study’s senior author and head of mNGS at Necker-Enfants Malades Hospital, emphasizes the practical impact of their work, which has resulted in reliable diagnoses and the discovery of a new virus responsible for hepatitis.
This sequencing-based tool has become essential in diagnosing patients suspected of having infections, with its use expanding to severe cases, particularly those involving the brain, as well as immunocompromised adults and children, explains Professor Olivier Lortholary, head of the Department of Infectious and Tropical Diseases at Necker-Enfants Malades Hospital and co-author of the study.
The study’s co-last author, Professor Marc Eloit, expresses satisfaction in contributing to improved medical care while expanding knowledge on infectious diseases. He also highlights the potential of this research to shape the future of infection diagnostics.
Further research on the microorganisms identified at the Necker microbiology laboratory will facilitate the development of faster and more accessible sequencing technologies for frontline microbiological analysis, thereby enhancing their potential in discovering new human pathogens, explains co-author Philippe Pérot, a research engineer at the Institut Pasteur’s Pathogen Discovery Laboratory.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
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