Diagnostic accuracy of (1→3)-β-D-glucan to predict Pneumocystis jirovecii pneumonia in non-HIV-infected patients

Abstract

BackgroundPneumocystis jirovecii pneumonia (PCP) is a common and potentially fatal opportunistic infection in immunocompromised non-HIV individuals. There are problems with clinical and diagnostic protocols for PCP that lack sensitivity and specificity. We designed a retrospective study to compared several methods that were used in diagnostics of PCP.Patients and methodsOne hundred and eight immunocompromised individuals with typical clinical picture for PCP and suspicious radiological findings were included in the study. Serum samples were taken to measure the values of (1→3)-β-D-glucan (Fungitell, Associates of Cape Cod, USA). Lower respiratory tract samples were obtained to perform direct immunofluorescence (DIF, MERIFLUOR® Pneumocystis, Meridian, USA) stain and real-time PCR (qPCR).ResultsFifty-four (50%) of the 108 patients in our study had (1→3)-β-D-glucan > 500 pg/ml. Patients that had (1→3)-β-D-glucan concentrations < 400 pg/ml in serum, had mean threshold cycles (Ct) 35.43 ± 3.32 versus those that had (1→3)-β-D-glucan concentrations >400 pg/mL and mean Ct of 28.97 ± 5.27 (P < 0.001). If we detected P. jirovecii with DIF and qPCR than PCP was proven. If the concentration of (1→3)-β-D-glucan was higher than 400 pg/ml and Ct of qPCR was below 28.97 ± 5.27 than we have been able be certain that P. jirovecii caused pneumonia (odds ratio [OR] 2.31, 95% confidence interval [CI] 1.62–3.27, P < 0.001).ConclusionsMeasurement of (1→3)-β-D-glucan or qPCR alone could not be used to diagnose PCP. Diagnostic cut-off value for (1→3)-β-D-glucan > 400pg/ml and qPCR below 30 Ct, allow us to conclude that patient has PCP. If the values of (1→3)-β-D-glucan are < 400 pg/ml and qPCR is above 35 Ct than colonization with P. jirovecii is more possible than PCP.

Performance of a Real Time PCR for Pneumocystis jirovecii Identification in Induced Sputum of AIDS Patients: Differentiation between Pneumonia and Colonization

“…The role of the BDG assay in the diagnosis of PcP has been intensely discussed: its major asset is its high negative predictive value, but its high sensitivity and lack of specificity due to factors that interfere with the tests [ 66 , 74 , 75 , 76 , 77 ] can lead to false-positive results. Based on this, it was recommended as a screening test and that higher cutoff values should be used for the diagnosis of PcP, up to 400 pg/mL in AIDS or non-HIV infected patients [ 57 , 78 , 79 ]. Indeed, in our study, the group of patients having PcP presented mean BDG values of 441 pg/mL ( Table 1 ).…”

Use of β-D-glucan in diagnosis of suspected Pneumocystis jirovecii pneumonia in adults with HIV infection

“…[7] We determined sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of BDG (above or below 80 and 400 pg/mL (five-times diagnostic threshold) for diagnosis of PCP. [8]…”

A Negative (1,3)-β-D-Glucan Result Alone Is Not Sufficient to Rule Out a Diagnosis of Pneumocystis Pneumonia in Patients With Hematological Malignancies

“…In this context, it was suggested that a negative BG result could accurately exclude a PCP diagnosis (Held et al, 2011;Onishi et al, 2012;Alanio et al, 2016;Lahmer et al, 2017;Morjaria et al, 2019;Ideguchi et al, 2020;Szvalb et al, 2020). In contrast, other reports describe a suboptimal sensitivity of this assay, especially in HIV-negative patients (Nakamura et al, 2009;Li et al, 2015;Engsbro et al, 2019;Kato et al, 2019;Del Corpo et al, 2020;Mercier et al, 2020;Rogina and Skvarc, 2020). These discrepant results regarding the usefulness of serum BG assay in HIV-negative PCP patients could be related to the underlying condition that exposes to PCP risk.…”