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Metagenomic Next-Generation Sequencing for Pathogen Detection and Transcriptomic Analysis in Pediatric Central

Nanda Ramchandar1,2, Nicole G Coufal1,2,3, Anna S Warden4

  • 1Rady Children's Institute for Genomic Medicine, San Diego, California, USA.

Open Forum Infectious Diseases
|June 9, 2021
PubMed
Summary

Metagenomic next-generation sequencing (mNGS) rapidly identified pathogens in pediatric cerebrospinal fluid (CSF) infections. This advanced technique shows promise for quicker diagnosis and improved management of central nervous system (CNS) infections in children.

Keywords:
encephalitismeningitismetagenomicsnext-generation sequencingpediatric

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Area of Science:

  • Pediatric Infectious Diseases
  • Neuroscience
  • Genomics

Background:

  • Pediatric central nervous system (CNS) infections pose significant life-threatening risks and morbidity.
  • Accurate pathogen identification is crucial for effective treatment and prognosis in pediatric CNS infections.
  • Conventional diagnostic methods like culture and PCR often fail to identify causative agents.

Purpose of the Study:

  • To evaluate the systematic application of metagenomic next-generation sequencing (mNGS) for pathogen detection in pediatric cerebrospinal fluid (CSF) infections.
  • To assess the utility of transcriptomic analysis alongside mNGS in diagnosing CNS infections.
  • To compare the diagnostic yield of mNGS with standard testing methods.

Main Methods:

  • A prospective, multisite study enrolled children with suspected CNS infections and CSF pleocytosis.
  • Cerebrospinal fluid (CSF) samples underwent standard testing followed by metagenomic next-generation sequencing (mNGS) and transcriptomic analysis.
  • Data were collected from 3 tertiary pediatric hospitals over a 12-month period.

Main Results:

  • Out of 70 enrolled subjects, a pathogen was identified in 25 (35.7%) cases by any method.
  • Metagenomic next-generation sequencing (mNGS) identified a pathogen in 20 (28.6%) subjects.
  • All pathogens detected by mNGS were also identified by standard diagnostic tests, with a median turnaround time of 38 hours.

Conclusions:

  • Metagenomic sequencing of CSF demonstrates significant potential for the rapid identification of pathogens in pediatric CNS infections.
  • mNGS offers a valuable tool to complement existing diagnostic approaches for CNS infections.
  • Further research may optimize mNGS protocols for even broader pathogen detection and faster results.