Discussion on objective inclusion criteria for sending cerebrospinal fluid pathogen metagenomic next⁃generation sequencing

Abstract

Objective By comparing consistency of cerebrospinal fluid (CSF) pathogen metagenomic next⁃generation sequencing (mNGS) results and final clinical diagnoses of central nervous system infection, we discuss the objective inclusion criteria for suspected central nervous system infection patients sending CSF pathogen mNGS. Methods From March 2017 to April 2020, Department of Neurology, Beijing Tongren Hospital, Capital Medical University sent CSF of 35 patients for pathogen mNGS and conventional pathogen testing to exclude central nervous system infection. Sensitivities, specificities and Youden's index of mNGS as well as conventional pathogen testing were calculated and compared. We also drew receiver operating characteristic (ROC) curves and calculated areas under the curve (AUC) to compared diagnostic efficacies of two methods. All patients were then scored according to objective inclusion criteria for sending samples (one score for one item). Positive coincidence rates of CSF pathogen mNGS and final clinical diagnoses of central nervous system infection of each score were also calculated. Results Nineteen of 35 patients enrolled were finally clinical diagnosed as central nervous system infection. Eighteen cases were positive by CSF pathogen mNGS, with positive rate 51.43% (18/35). Seventeen cases were positive by conventional pathogen testing with positive rate 48.57% (17/35). Seventeen cases of clinical diagnosed central nervous system infection were CSF pathogen mNGS positive, with diagnostic sensitivity 17/19, specificity 15/16 and Youden index 0.832. Fourteen cases of clinical diagnosed central nervous system infection were conventional pathogen testing positive, with diagnostic sensitivity 14/19, specificity 13/16 and Youden index 0.612. ROC curve showed the AUC of CSF pathogen mNGS was 0.916 (95%CI: 0.822-1.000, P=0.000), and AUC of conventional pathogen testing was 0.806 (95%CI: 0.674-0.938, P=0.000). There was no difference in diagnostic efficacies between CSF pathogen mNGS and conventional pathogen testing (Z=1.245, P=0.213). According to objective inclusion criteria for sending pathogen mNGS of CBF, the positive coincidence rates of mNGS were 0 score (0/4), 1 score (0/2), 2 scores (1/8), 3 scores (3/4), 4 scores (4/6), 5 scores (3/4), 6 scores (6/7). The positive coincidenc rates of mNGS showed an overall trend of increase with scores, and notably cases≥3 scores had higher positive coincidence rates than cases<3 scores (Fisher exact probability: P=0.000). Conclusions CSF pathogen mNGS can assist in accurate diagnosis of central nervous system infection. Sending CSF according to objective inclusion criteria based on clinical and routine auxiliary examination results can improve positive coincidence rate of pathogen mNGS.

doi：10.3969/j.issn.1672⁃6731.2021.05.004