The (1,3){beta}-D-glucan test as an aid to early diagnosis of invasive fungal infections following lung transplantation

Abstract

The Fungitell assay for (1,3)β-D-glucan (BG) detection in serum has been evaluated in patients with invasive fungal infections (IFIs) and healthy controls and for the early diagnosis of IFI in cancer patients. We evaluated the BG assay for the detection of IFI in lung transplant recipients. Serial serum samples were prospectively collected from patients undergoing lung transplants at Duke Hospital. Fungal infections were classified according to revised European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. A receiver operator characteristic (ROC) curve was generated; possible causes for false-positive and false-negative tests were investigated by linear regression analysis. Seven hundred fifty-six serum specimens from 59 subjects without IFI and 41 specimens from 14 patients with proven or probable IFI were tested. The area under the ROC curve was 0.69. Based on a 60-pg/ml positive cutoff, per-patient sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 64%, 9%, 14%, and 50%, respectively; per-test estimates were 71%, 59%, 9%, and 97%, respectively. The majority (92%) of patients not diagnosed with an IFI had at least one BG level of ≥60 pg/ml, and 90% had at least one BG level of ≥80 pg/ml. Respiratory colonization with mold and hemodialysis significantly affected mean BG levels. In conclusion, the accuracy of the BG test is marginal and its utility as a tool for the early diagnosis of IFI is questionable in the lung transplant population. Although the NPV of the BG test is high, the low PPV limits its utility as a screening tool for early diagnosis of IFI.

FIG. 1.

Distribution of (1,3)β-d-glucan (BG) levels in patients with (n = 14 subjects, 41 samples) and without (n = 59 subjects, 756 samples) proven or probable invasive fungal infection (IFI). For the box-and-whiskers plot, a horizontal line in the middle of the box represents the median; the top and bottom of the box show the 75th and 25th percentiles, respectively; and the top and bottom of whiskers show the 5th and 95th percentiles, respectively.

FIG. 2.

Distribution of (1,3)β-d-glucan (BG) levels in patients based on the type of proven or probable invasive fungal infection (IFI) (n = 8 Candida and 7 Aspergillus infections and 59 subjects without IFI). For the box-and-whiskers plot, a horizontal line in the middle of the box represents the median; the top and bottom of the box show the 75th and 25th percentiles, respectively; and the top and bottom of the whiskers show the 5th and 95th percentiles, respectively.

FIG. 3.

Receiver operator characteristic (ROC) curve of (1,3)β-d-glucan cutoff values to define invasive fungal infection (IFI) (n = 797 specimen results from 59 subjects without IFI and 14 patients with IFI). (1,3)β-d-Glucan values are in pg/ml.