Performance of 1,3‐β‐D‐glucan for diagnosing invasive fungal diseases in children

Abstract

Plasma 1,3-β-D-glucan (BDG) is indicated as a tool for early diagnosis of invasive fungal diseases (IFD). However, data on its diagnostic value are scarce in children. Therefore, definition of BDG test performance in paediatrics is needed. BDG was evaluated in children admitted to "Istituto Giannina Gaslini," Genoa, Italy, who developed clinical conditions at risk for IFD. Results were analysed for sensitivity, specificity, predictive values, likelihood ratios, accuracy, informedness and probability of missing one case by a negative test. A total of 1577 BDG determinations were performed on 255 patients (49% males, median age 5.4 years). Overall 46 IFD were diagnosed, 72% proven/probable. The test performance was evaluated for 80 pg/mL, 120 pg/mL, 200 pg/mL, 350 pg/mL, 400 pg/mL cut offs. Sensitivity was always <0.80 and specificity > 0.90 only for cut offs ≥200 pg/mL. Negative predictive value was ≥0.90 for all the cut offs evaluated, while positive predictive value resulted barely 0.50 (8% IFD prevalence). Accuracy was never >0.90, and informedness was at best 0.50. The risk of missing one IFD by a negative result was < 10%. Analyses in haemato-oncological or newborn patients did not show major differences. Detection of serum BDG does not appear a valuable adjunctive diagnostic tool for IFD in paediatrics.

Serum (1 → 3)‐β‐D‐glucan could be useful to rule out invasive candidiasis in neonates with an adapted cut‐off

“…Moreover, some studies suggested that the cut‐off value used in adults was too low for children 21,22 because many factors in neonates could increase the BDG values. Indeed, the different cut‐off values suggested in neonate infants in previous studies ranged from 106 to 305 pg/mL 11,12,23 . Otherwise, the diagnostic performance may vary depending on the BDG assay kit used such as Fungitell, Dynamiker Fungus or GKT‐5M and the studied population 13,24 .…”

“…Indeed, the different cut-off values suggested in neonate infants in previous studies ranged from 106 to 305 pg/mL. 11,12,23 Otherwise, the diagnostic performance may vary depending on the BDG assay kit used such as Fungitell, Dynamiker Fungus or GKT-5M and the studied population. 13,24 Indeed, some studied populations in false-positive BDG results as observed in previous studies.…”

Diagnosis by metagenomic next-generation sequencing of invasive pulmonary aspergillosis in an infant with chronic granulomatous disease

“…The traditional ‘gold standard’ is microbial culture, but Aspergillus culture requires an extended time period and has a low detection sensitivity. Calitri et al [ 8 ] suggested the G test as a screening tool for early diagnosis of invasive fungal disease in children, but this suggestion has not been widely accepted because of many false-positives including piperacillin treatment, hemodialysis, blood product transfusion, and bacteremia [ 9 ]. In immunosuppressed and critically ill patients, the G test has a sensitivity of 88% and a specificity of 82% for probable IPA [ 10 ].…”

Advances in the Treatment of Mycoses in Pediatric Patients

“…Non-culture assays have been studied for the early diagnosis of IC in neonates and thus initiation of preemptive therapy with the goal to improve the outcome. (1,3)-β- d -glucan (BDG), a reliable biomarker of most clinically relevant fungi in adults, has been studied very little in neonates with variable results [79,80]. In a more recently published study of premature neonates comparing those with proven or probable invasive yeast infections with controls, BDG was shown to have promising results [81].…”