Metagenomic next-generation sequencing in patients with fever of unknown origin: A comprehensive systematic literature review and meta-analysis

Diagn Microbiol Infect Dis. 2024 Oct;110(2):116465. doi: 10.1016/j.diagmicrobio.2024.116465. Epub 2024 Jul 23.

Abstract

Metagenomic Next-Generation Sequencing (mNGS) holds promise in diagnosing fever of unknown origin (FUO) by detecting diverse pathogens. We systematically reviewed the literature to evaluate mNGS's accuracy, clinical efficacy, and limitations in FUO diagnosis. Nine studies revealed mNGS's positivity rate ranging from 66.7% to 93.5% for bacterial bloodstream infections and systemic infections. Meta-analysis of three studies involving 857 patients, including 354 with FUO, showed a sensitivity of 0.91 (95% CI: 0.87-0.93) and specificity of 0.64 (95% CI: 0.58-0.70). Despite lower specificity, mNGS demonstrated a higher Diagnostic Odds Ratio (DOR) of 17.0 (95% CI: 4.5-63.4) compared to conventional microbiological tests (CMTs) at 4.7 (95% CI: 2.9-7.6). While mNGS offers high sensitivity but low specificity in identifying causative pathogens for FUO, its superior DOR suggests potential for more accurate diagnoses and targeted interventions. Further research is warranted to optimize its clinical application in FUO management.

Keywords: Diagnostic methods; Fever of unknown origin; Metagenomic NGS; Systematic literature review.

Publication types

  • Systematic Review
  • Meta-Analysis
  • Review

MeSH terms

  • Bacteria / classification
  • Bacteria / genetics
  • Bacteria / isolation & purification
  • Bacterial Infections / diagnosis
  • Bacterial Infections / microbiology
  • Fever of Unknown Origin* / diagnosis
  • Fever of Unknown Origin* / microbiology
  • High-Throughput Nucleotide Sequencing* / methods
  • Humans
  • Metagenomics* / methods
  • Sensitivity and Specificity*