Metagenomic next-generation sequencing shows higher sensitivity than conventional tests for pediatric infectious disease diagnosis.

This systematic literature review and meta-analysis assessed the diagnostic accuracy of metagenomic next-generation sequencing (mNGS) versus conventional microbiological tests (CMTs) in pediatric patients aged 21 years or younger with suspected infectious diseases. The analysis pooled data from 33 identified studies, of which 9 were eligible for quantitative meta-analysis. The setting and specific study locations were not reported in the source data. The primary objective was to compare diagnostic performance against clinical diagnosis, while secondary outcomes included diagnostic odds ratios and changes in antimicrobial management.

The meta-analysis focused on diagnostic accuracy, specifically sensitivity and specificity. For mNGS compared to clinical diagnosis, the pooled sensitivity was 0.84 (95% CI: 0.82-0.86). In contrast, the pooled sensitivity for CMTs versus clinical diagnosis was lower at 0.40 (95% CI: 0.37-0.43). Regarding specificity, mNGS showed a pooled value of 0.71 (95% CI: 0.66-0.75), whereas CMTs demonstrated a higher pooled specificity of 0.82 (95% CI: 0.78-0.86). These findings indicate a trade-off between the ability to detect true infections and the rate of false positives between the two methods.

Diagnostic odds ratios (DOR) further characterized the discriminatory power of each method. The pooled DOR for mNGS was 18.6, significantly higher than the pooled DOR of 5.4 observed for CMTs. No p-values were reported for these specific effect sizes in the source data. The analysis did not report absolute numbers of patients or events for these specific outcomes, nor did it provide effect sizes beyond the point estimates and confidence intervals.

Safety and tolerability data were not reported for either mNGS or CMTs in this meta-analysis. Adverse events, serious adverse events, discontinuations, and general tolerability profiles were not available from the included studies. Consequently, no conclusions can be drawn regarding the safety profile of mNGS relative to standard testing based on this evidence alone.

The study highlights several methodological limitations that must be considered. Key constraints included the high cost of mNGS testing and the lack of methodological standardization across the included studies. Additionally, the complex interpretation of mNGS data, which may detect genetic material from commensal organisms or environmental sources, poses challenges for clinical integration. The review notes that results are derived from a meta-analysis of 33 studies, with only 9 eligible for meta-analysis, which may limit the generalizability of the pooled estimates.

In comparison to prior landmark studies in pediatric infectious disease diagnostics, this meta-analysis reinforces the potential utility of mNGS as a complementary tool rather than a replacement for conventional methods. The higher sensitivity of mNGS suggests it may be particularly useful in cases where conventional tests yield negative results but clinical suspicion remains high. However, the lower specificity of mNGS compared to CMTs indicates a need for careful clinical correlation to avoid unnecessary treatment based on false-positive findings.

Clinical implications suggest that mNGS represents a promising complement to conventional diagnostics in pediatric infectious disease management. Physicians should consider mNGS as an adjunctive test, particularly when CMTs are negative or inconclusive, while remaining aware of the higher cost and the necessity for specialized expertise in result interpretation. It is not recommended to view mNGS as a universal replacement for CMTs, especially given the superior specificity of conventional methods in this dataset.

Several questions remain unanswered by this evidence. The long-term impact of mNGS on patient outcomes, such as mortality or length of stay, was not reported. Furthermore, the optimal clinical scenarios for deploying mNGS in pediatric populations require further investigation. The lack of reported funding sources or conflicts of interest limits the ability to assess potential biases in the included studies or the meta-analysis itself. Future research should aim to standardize mNGS protocols and evaluate cost-effectiveness in real-world pediatric settings.