Metagenomic Next-generation Sequencing in Patients With Infectious Meningoencephalitis: A Comprehensive Systematic Literature Review and Meta-analysis

Background We aimed to assess the accuracy, clinical efficacy, and limitations of metagenomic next-generation sequencing (mNGS) for diagnosing infectious meningoencephalitis. Methods We performed a systematic literature review and meta-analysis of studies that evaluated the performance of mNGS to determine the cause of infectious meningoencephalitis. We explored PubMed, Cumulative Index to Nursing and Allied Health, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Web of Science up to 12 November 2024. To perform a meta-analysis, we calculated the pooled diagnostic odds ratio (DOR) for mNGS and for conventional microbiological tests (CMTs) compared to the clinical diagnosis. Results Thirty-four studies met the inclusion criteria, with mNGS-positive rates ranging from 43.5% to 93.5% for infectious meningoencephalitis. The meta-analysis included 23 studies with 1660 patients. The pooled sensitivity was 0.70 (95% confidence interval [CI], .67-.72), and its specificity was 0.93 (95% CI, .92-.94). The DOR for mNGS was 26.7 (95% CI, 10.4-68.8), compared to 12.2 (95% CI, 3.2-47.0) for CMTs. For tuberculosis meningoencephalitis, mNGS demonstrated a pooled sensitivity of 0.67 (95% CI, .61-.72) and specificity of 0.97 (95% CI, .95-.99), with a DOR of 43.5 (95% CI, 7.4-256.6). Conclusions Our review indicates that mNGS can be a valuable diagnostic tool for infectious meningoencephalitis, offering high sensitivity and specificity. mNGS's superior DOR compared to that of CMTs highlights its potential for more accurate diagnoses and targeted interventions. Further research is needed to optimize which patients and at what point in the diagnostic process mNGS should be used.