Clinical Metagenomic Next-Generation Sequencing for Diagnosis of Central Nervous System Infections: Advances and Challenges.

Autor: Su LD; British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.; The Consortium for Clinical Metagenomics in Infectious Diseases, Nashville, TN, USA., Chiu CY; The Consortium for Clinical Metagenomics in Infectious Diseases, Nashville, TN, USA.; Department of Laboratory Medicine and Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA., Gaston D; The Consortium for Clinical Metagenomics in Infectious Diseases, Nashville, TN, USA.; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Hogan CA; British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.; The Consortium for Clinical Metagenomics in Infectious Diseases, Nashville, TN, USA.; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada., Miller S; The Consortium for Clinical Metagenomics in Infectious Diseases, Nashville, TN, USA.; Delve Bio, Inc., San Francisco, CA, USA.; Department of Laboratory Medicine, University of California, San Francisco, CA, USA., Simon DW; The Consortium for Clinical Metagenomics in Infectious Diseases, Nashville, TN, USA.; Department of Pediatric Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Thakur KT; The Consortium for Clinical Metagenomics in Infectious Diseases, Nashville, TN, USA.; Department of Neurology, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, NY, USA., Yang S; The Consortium for Clinical Metagenomics in Infectious Diseases, Nashville, TN, USA.; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA., Piantadosi A; The Consortium for Clinical Metagenomics in Infectious Diseases, Nashville, TN, USA. anne.piantadosi@emory.edu.; Department of Pathology and Laboratory Medicine, and Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, 101 Woodruff Circle, Atlanta, GA, USA. anne.piantadosi@emory.edu.
Jazyk: angličtina
Zdroj: Molecular diagnosis & therapy [Mol Diagn Ther] 2024 Sep; Vol. 28 (5), pp. 513-523. Date of Electronic Publication: 2024 Jul 11.
DOI: 10.1007/s40291-024-00727-9
Abstrakt: Central nervous system (CNS) infections carry a substantial burden of morbidity and mortality worldwide, and accurate and timely diagnosis is required to optimize management. Metagenomic next-generation sequencing (mNGS) has proven to be a valuable tool in detecting pathogens in patients with suspected CNS infection. By sequencing microbial nucleic acids present in a patient's cerebrospinal fluid, brain tissue, or samples collected outside of the CNS, such as plasma, mNGS can detect a wide range of pathogens, including rare, unexpected, and/or fastidious organisms. Furthermore, its target-agnostic approach allows for the identification of both known and novel pathogens. This is particularly useful in cases where conventional diagnostic methods fail to provide an answer. In addition, mNGS can detect multiple microorganisms simultaneously, which is crucial in cases of mixed infections without a clear predominant pathogen. Overall, clinical mNGS testing can help expedite the diagnostic process for CNS infections, guide appropriate management decisions, and ultimately improve clinical outcomes. However, there are key challenges surrounding its use that need to be considered to fully leverage its clinical impact. For example, only a few specialized laboratories offer clinical mNGS due to the complexity of both the laboratory methods and analysis pipelines. Clinicians interpreting mNGS results must be aware of both false negatives-as mNGS is a direct detection modality and requires a sufficient amount of microbial nucleic acid to be present in the sample tested-and false positives-as mNGS detects environmental microbes and their nucleic acids, despite best practices to minimize contamination. Additionally, current costs and turnaround times limit broader implementation of clinical mNGS. Finally, there is uncertainty regarding the best practices for clinical utilization of mNGS, and further work is needed to define the optimal patient population(s), syndrome(s), and time of testing to implement clinical mNGS.
(© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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