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Meta-Analysis
. 2024 Jul 19;79(1):161-168.
doi: 10.1093/cid/ciae239.

Polymerase Chain Reaction on Respiratory Tract Specimens of Immunocompromised Patients to Diagnose Pneumocystis Pneumonia: A Systematic Review and Meta-analysis

Lottie Brown  1 , Riina Rautemaa-Richardson  2 , Carlo Mengoli  3 , Alexandre Alanio  4 , Rosemary A Barnes  5 , Stéphane Bretagne  6 , Sharon C A Chen  7 , Catherine Cordonnier  8 , J Peter Donnelly  9 , Werner J Heinz  10 , Brian Jones  11 , Lena Klingspor  12 , Juergen Loeffler  13 , Thomas R Rogers  14 , Eleanor Rowbotham  15 , P Lewis White  16 , Mario Cruciani  9
Affiliations
Meta-Analysis

Polymerase Chain Reaction on Respiratory Tract Specimens of Immunocompromised Patients to Diagnose Pneumocystis Pneumonia: A Systematic Review and Meta-analysis

Lottie Brown et al. Clin Infect Dis. .

Abstract

Background: This meta-analysis examines the comparative diagnostic performance of polymerase chain reaction (PCR) for the diagnosis of Pneumocystis pneumonia (PCP) on different respiratory tract samples, in both human immunodeficiency virus (HIV) and non-HIV populations.

Methods: A total of 55 articles met inclusion criteria, including 11 434 PCR assays on respiratory specimens from 7835 patients at risk of PCP. QUADAS-2 tool indicated low risk of bias across all studies. Using a bivariate and random-effects meta-regression analysis, the diagnostic performance of PCR against the European Organisation for Research and Treatment of Cancer-Mycoses Study Group definition of proven PCP was examined.

Results: Quantitative PCR (qPCR) on bronchoalveolar lavage fluid provided the highest pooled sensitivity of 98.7% (95% confidence interval [CI], 96.8%-99.5%), adequate specificity of 89.3% (95% CI, 84.4%-92.7%), negative likelihood ratio (LR-) of 0.014, and positive likelihood ratio (LR+) of 9.19. qPCR on induced sputum provided similarly high sensitivity of 99.0% (95% CI, 94.4%-99.3%) but a reduced specificity of 81.5% (95% CI, 72.1%-88.3%), LR- of 0.024, and LR+ of 5.30. qPCR on upper respiratory tract samples provided lower sensitivity of 89.2% (95% CI, 71.0%-96.5%), high specificity of 90.5% (95% CI, 80.9%-95.5%), LR- of 0.120, and LR+ of 9.34. There was no significant difference in sensitivity and specificity of PCR according to HIV status of patients.

Conclusions: On deeper respiratory tract specimens, PCR negativity can be used to confidently exclude PCP, but PCR positivity will likely require clinical interpretation to distinguish between colonization and active infection, partially dependent on the strength of the PCR signal (indicative of fungal burden), the specimen type, and patient population tested.

Keywords: PCP; meta-analysis; pneumocystis; polymerase chain reaction; systematic review.

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Conflict of interest statement

Potential conflicts of interest. A. A. has received honoraria from Gilead Sciences. S. C.-A. A. has received united educational grants from F2G Ltd and consulted for MSD Australia. T. R. R. has received grants from Pfizer and the Irish Department of Agriculture, Food and the Marine and honoraria from Gilead and Menarini Pharma. P. L. W. has performed diagnostic evaluations and received meeting sponsorship from Associates of Cape Cod, Bruker, Dynamiker, and Launch Diagnostics; speaker fees, expert advice fees, and meeting sponsorship from Gilead; and speaker and expert advice fees from F2G. J. P. D. has received personal fees from F2G, Gilead Sciences, and Pfizer. W. J. H. has received lecture honoraria from AbbVie, Amgen, AstraZeneca, Celgene/BMS, Gilead Sciences, Janssen, MSD, and Pfizer; has received support to attend meetings and travel support from AbbVie, Alexion, Astellas, Janssen, Lilly, MSD, Novartis, and Pfizer; and has participated on advisory boards for AbbVie, Amgen, AstraZeneca, Basilea, Celgene/BMS, Gilead Sciences, Janssen, and Sanofi-Aventis. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Graphical abstract
Graphical abstract
This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/pcr-on-respiratory-tract-specimens-of-immunocompromised-patients-to-diagnose-pneumocystosis-pcp-a-systematic-review-and-meta-analysis-89aa7a50-efbc-4ebb-8f20-c17d207e8d8e?utm_campaign=tidbitlinkshare&utm_source=ITP
Figure 1.
Figure 1.
Study selection. Abbreviations: FN, false negative; FP, false positive; PCP, Pneumocystis pneumonia; TN, true negative; TP, true positive.
Figure 2.
Figure 2.
Positive predictive values (PPVs) and negative predictive values (NPVs) presented as probability curves for quantitative polymerase chain reaction on each sample type. PPVs increase and NPVs decrease with prevalence. The vertical dash-dotted line indicates the overall prevalence of Pneumocystis pneumonia in the data set (20.7%). Abbreviations: BALF, bronchoalveolar lavage fluid; IS, induced sputum; NPV, negative predictive value; PPV, positive predictive value; qPCR, quantitative polymerase chain reaction.
Figure 3.
Figure 3.
Forest plots for sensitivity and specificity of polymerase chain reaction by sample type. Heterogeneity was assessed by visual inspection of forest plots of sensitivity and specificity and through visual examination of the receiver operating characteristic plot of the raw data. Heterogeneity was further investigated by exploring the effects of several study-level covariates by random-effects meta-regression analysis. Abbreviations: BALF, bronchoalveolar lavage fluid; CI, confidence interval; FN, false negative; FP, false positive; IS, induced sputum; PCR, polymerase chain reaction; TN, true negative; TP, true positive; URT, upper respiratory tract.
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