Diagnostic performance of metagenomic next-generation sequencing for Pneumocystis jirovecii pneumonia

Abstract

Objective: Pneumocystis jirovecii pneumonia (PJP) can be a life-threatening opportunistic infection. We aimed to evaluate the diagnostic accuracy of metagenomic next-generation sequencing (mNGS) for PJP.

Methods: A comprehensive electronic literature search of Web of Knowledge, PubMed, Cochrane Library, CNKI and Wanfang data was performed. Bivariate analysis was conducted to calculate the pooled sensitivity, specificity, diagnostic odds ratio (DOR), the area under the summary receiver operator characteristic (SROC) curve and the Q-point value (Q*).

Results: The literature search resulted in 9 studies with a total of 1343 patients, including 418 cases diagnosed with PJP and 925 controls. The pooled sensitivity of mNGS for diagnosis of PJP was 0.974 [95% confidence interval (CI), 0.953-0.987]. The pooled specificity was 0.943 (95% CI, 0.926-0.957), the DOR was 431.58 (95% CI, 186.77-997.27), the area under the SROC curve was 0.987, and the Q* was 0.951. The I² test indicated no heterogeneity between studies. The Deek funnel test suggested no potential publication bias. Subgroup analyses showed that the area under the SROC curve of mNGS for diagnosis of PJP in immunocompromised and non-HIV patients was 0.9852 and 0.979, respectively.

Conclusions: Current evidence indicates that mNGS exhibits excellent accuracy for the diagnosis of PJP. The mNGS is a promising tool for assessment of PJP in both immunocompromised and non-HIV patients.

Keywords: Bronchoalveolar lavage fluid; Diagnosis; Metagenomic next-generation sequencing; Pneumocystis jirovecii pneumonia; meta-analysis.

Fig. 1

Flow diagram of the study selection process

Fig. 2

Forest plot of sensitivity and specificity for metagenomic next-generation sequencing in diagnosis of Pneumocystis jirovecii pneumonia. The pooled sensitivity was 0.974 (95% CI, 0.953–0.987) and the pooled specificity was 0.943 (95% CI, 0.926–0.957)

Fig. 3

Summary receiver operating characteristic (SROC) curve of metagenomic next-generation sequencing in diagnosis of Pneumocystis jirovecii pneumonia. The area under the SROC curve was 0.987, and the Q* was 0.951

Fig. 4

I² test for the pooled diagnostic odds ratio (DOR). The value of I² test for the pooled DOR indicated no heterogeneity between studies

Fig. 5

The Deek’s funnel plot for assessment of publication bias. No publication bias was found among the included studies

Fig. 6

Forest plot of sensitivity and specificity for bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing in diagnosis of Pneumocystis jirovecii pneumonia. The pooled sensitivity was 0.957 (95% CI, 0.917–0.981) and the pooled specificity was 0.939 (95% CI, 0.918–0.956)

Fig. 7

Forest plot of sensitivity and specificity for metagenomic next-generation sequencing in diagnosis of immunocompromised patients with Pneumocystis jirovecii pneumonia. The pooled sensitivity was 0.967 (95% CI, 0.925–0.989) and the pooled specificity 0.880 (95% CI, 0.827–0.922)

Fig. 8

Forest plot of sensitivity and specificity for metagenomic next-generation sequencing in diagnosis of non-HIV patients with Pneumocystis jirovecii pneumonia. The pooled sensitivity was 0.992 (95% CI, 0.972–0.999) and the pooled specificity was 0.910 (95% CI, 0.873–0.939)