Diagnostic Test Accuracy of the Fungitell Serum (1→3)-β-D-Glucan Assay for the Diagnosis of Pneumocystis jirovecii Pneumonia: A Systematic Review and Meta-Analysis.

Background: The diagnosis of Pneumocystis jirovecii pneumonia (PCP) can be challenging because of diagnostic tests that are imperfect and/or invasive. The Fungitell serum (1→3)-β-D-glucan (BDG) assay is a non-invasive blood test studied for PCP; however, the manufacturer-recommended cut-off of 80pg/mL is not well validated for this disease.

Objectives: We conducted a systematic review and meta-analysis to determine the diagnostic test accuracy of the Fungitell BDG assay for the diagnosis of PCP.

Methods: Data Sources A search strategy of MEDLINE and Embase from a previous meta-analysis on BDG was updated to January 31, 2024. Test Fungitell BDG assay. Reference Standard One or more of: lung biopsy, bronchoalveolar lavage, induced sputum, or nasopharyngeal swab specimens tested for PCP by histopathology, microscopy using immunofluorescence or staining, or polymerase chain reaction. Assessment of Risk of Bias The QUADAS-2 tool. Methods of Data Synthesis Diagnostic test accuracy data of the Fungitell serum BDG assay across all reported cut-offs were pooled by meta-analysis. We then evaluated a categorical approach using <80pg/mL as a rule-out threshold and ≥400pg/mL as a rule-in threshold.

Results: 26 articles were included comprising 5111 patients and 1150 PCP cases. At the conventional cut-off of 80pg/mL, the overall pooled sensitivity and specificity were 83.5% (95% Confidence Interval [95%CI]=72.8-90.6) and 75.5% (95%CI=66.0-83.0), respectively. At a pre-test probability of <20% and a BDG <80pg/mL, the post-test probability would be <5% (negative predictive value >95%). At 400pg/mL, sensitivity was reduced to 63.5% (95%CI=45.8-78.1) with specificity increased to 93.6% (95%CI=88.6-96.5). At a pre-test probability of 47.5%, a BDG >400pg/mL would have a post-test probability of >90%.

Discussion: A categorical approach using <80pg/mL to rule-out and >400pg/mL to rule-in PCP may allow for a more nuanced interpretation based on pre-test probability. More accurate estimates of pre-test probability and further external validation is required.