Diagnostic tests performance in detecting Pneumocystis jirovecii: A systematic review and meta-analysis

Pneumocystis jirovecii (Pj) pneumonia (PJP) is a life-threatening opportunistic infection primarily affecting immunocompromised individuals. Detecting Pj is challenging, particularly in distinguishing between Pj colonization (PJC) and infection. We aimed to systematically evaluate the diagnostic accuracy of various tests in differentiating Pj colonization from infection.

Systematic reviews and meta-analyses were performed. Searches were conducted in PubMed, Embase, and Web of Science. Original clinical studies reporting sensitivity and specificity data for diagnostic tests such as quantitative polymerase chain reaction (qPCR), nested PCR, (1,3)-Beta-D glucan (BDG), metagenomic next-generation sequencing (mNGS), and digital PCR (ddPCR) to differentiate PJC from PJP were included. Quality assessment was performed using QUADAS-2 tool, and data processing followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Diagnostic performance was evaluated using either a random-effects or fixed-effects model.

Twenty-eight studies (2,550 patients, 1,445 with PJP) were included, with moderate methodological quality. The pooled sensitivity of these diagnostic tests was 0.80 (95% CI 0.77-0.82) and specificity was 0.83 (95% CI 0.81-0.85), with a diagnostic odds ratio (DOR) of 23.12. Among the individual tests, BDG (5 studies) showed high pooled sensitivity (0.83, 95% CI 0.77-0.88) but lower specificity (0.78, 95% CI 0.69-0.85). mNGS (3 studies) had the highest performance, with pooled sensitivity and specificity both at 0.87 (95% CI 0.80-0.92 and 95% CI 0.77-0.94, respectively), and the highest DOR of 41.57. qPCR (19 studies) demonstrated adequate pooled sensitivity (0.78, 95% CI 0.76-0.81) and high specificity (0.83, 95% CI 0.81-0.86), with a DOR of 20.44.

While BDG has low specificity and mNGS is costly with no standardized interpretation, along with the limited number of relevant studies in BDG and mNGS, this meta-analysis concluded that qPCR remains valuable for distinguishing P. jirovecii infection from colonization. A well-designed randomized clinical trial that standardizes the technical aspects of the qPCR protocol is needed to assess its effectiveness and provide a solid basis for clinical diagnosis.