An Investigation into Diagnostic Strategies for Central Nervous System Infections Through the Integration of Metagenomic Next-Generation Sequencing and Conventional Diagnostic Methods.

Abstract

Purpose: The optimal strategy for detecting central nervous system infections (CNSI) in cerebrospinal fluid (CSF) samples remains unclear.

Methods: In a one-year, multicenter retrospective study, we examined the efficacy of metagenomic next-generation sequencing (mNGS) in comparison to conventional pathogen diagnostic techniques for CSF in diagnosing CNSI. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Youden index for each diagnostic approach. Additionally, receiver operating characteristic (ROC) curves were constructed, and the area under the curve (AUC) was determined to assess the diagnostic performance of each method.

Results: The study included 68 patients, comprising both adults and children, who were suspected of having CNSI. Through the application of comprehensive clinical interpretation (CCI), the sensitivity and specificity of mNGS were found to be 67.6% (95% confidence interval [CI]: 50.85-80.87%) and 45.8% (95% CI: 27.89-64.92%), respectively. In comparison, traditional pathogenic diagnostic methods indicated that the culture method demonstrated a sensitivity of 10.6% (95% CI: 4.63-22.6%) and a specificity of 100% (95% CI: 84.54-100%). Furthermore, the sensitivity and specificity of the peripheral blood nucleated cell count were determined to be 34.0% (95% confidence interval: 22.17-48.33%) and 57.1% (95% confidence interval: 36.54-75.53%), respectively. CSF nucleated cell count demonstrated a sensitivity of 66.0% (95% confidence interval [CI]: 51.67-77.83%) and a specificity of 61.9% (95% CI: 40.87-79.25%). In comparison, the CSF protein content exhibited a sensitivity of 63.8% (95% CI: 49.54-76.03%) and a specificity of 57.1% (95% CI: 36.54-75.53%). When combining mNGS with traditional methodologies, the overall sensitivity increased to 91.3% (95% CI: 79.67-96.56%), although the specificity was reduced to 18.2% (95% CI: 7.31-38.51%). The area under the ROC curve for culture, peripheral blood nucleated cell count, mNGS, CSF nucleated cell count, and CSF protein content were 0.8088, 0.6038, 0.6103, 0.5588, and 0.5588, respectively. The variation in CSF nucleated cell count did not significantly affect the diagnostic efficacy of mNGS.

Conclusion: Currently, both mNGS and traditional diagnostic methods encounter substantial challenges in diagnosing CNSI.