The (1,3)β- d -Glucan Test as an Aid to Early Diagnosis of Invasive Fungal Infections following Lung Transplantation

Abstract

The Fungitell assay for (1,3)␤-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.Lung transplant recipients are at relatively high risk for developing invasive fungal infections (IFIs). A recent national surveillance program reported the 1-year cumulative incidence of IFIs in lung transplant recipients to be 8.6%. The most common invasive fungal pathogen was Aspergillus species, responsible for 44% (109/248) of IFIs, followed by Candida (23%) and non-Aspergillus molds (20%) (11). Unfortunately, fungal infections are associated with high mortality, which is in part related to delayed or missed diagnoses owing to the lack of sensitive, noninvasive diagnostic tests.(1,3)␤-D-Glucan (BG) is a cell wall constituent of many pathogenic fungi, including Aspergillus, Candida, and Pneumocystis, and is detectable in patient serum during invasive disease caused by these fungi. It is also detectable in patients with infections caused by species of Fusarium, Trichosporon, Saccharomyces, and Acremonium (14). The BG assay (Fungitell; Associates of Cape Cod, Falmouth, MA) was approved by the U.S. Food and Drug Administration (FDA) for the qualitative detection of BG in the serum of patients with symptoms of or medical conditions predisposing to IFIs and as an aid in the diagnosis of deep-seated mycoses and fungemia. The assay has been evaluated in a multicenter study of patients with IFIs that included healthy controls (10) as well as for the early diagnosis of IFIs in patient...

Diagnostic Accuracy of Serum 1,3-β- d -Glucan for Pneumocystis jiroveci Pneumonia, Invasive Candidiasis, and Invasive Aspergillosis: Systematic Review and Meta-Analysis

“…In 17 cohort studies (1,2,4,16,19,20,24,29,30,34,45,47,50,51,54,61,62), the pooled sensitivity, specificity, DOR, and AUC-SROC were 72% (95% CI, 67% to 77%), 78% (95% CI, 76% to 80%), 12.3 (95% CI, 6.0 to 25.1), and 0.79 (95% CI, 0.73 to 0.85), respectively. In 14 case-control studies (3, 14, 26, 27, 33, 38, 40, 43-46, 48, 49, 60), the pooled sensitivity, specificity, DOR, and AUC-SROC for IFI were 83% (95% CI, 80% to 86%), 86% (95% CI, 84% to 88%), 68.3 (95% CI, 30.7 to 151.8), and 0.95 (95% CI, 0.92 to 0.98), respectively.…”

“…The 36 studies included six assays: 17 used Fungitell (1,3,4,12,16,17,27,29,34,(45)(46)(47)(48)(49)(50)(51), 9 used the Fungitec G test (2,20,26,33,43,44,57,59,60), 6 used the Wako ␤-glucan test (14,19,24,40,54,56), 3 used the GKT-25 M set (32,61,62), and 1 used the fungal index (38). All studies but one were based in 1 of 13 countries, with the majority of assays in Japan (n ϭ 13), as well as in the United States (n ϭ 7), China (n ϭ 4), Spain (n ϭ 2), Austria (n ϭ 1), Belgium (n ϭ 1), Czech Republic (n ϭ 1), France (n ϭ 1), Germany (n ϭ 1), Kuwait (n ϭ 1), The Netherlands (n ϭ 1), Sweden (n ϭ 1), and Switzerland (n ϭ 1); one study that performed assays in multiple countries (Spain, Argentina, and France) was also included.…”

Contribution of (1,3)-Beta- d -Glucan to Diagnosis of Invasive Candidiasis after Liver Transplantation

“…One study evaluated a preemptive strategy that involved the use of BG monitoring to enable the early detection of IFD in liver transplant recipients and found its sensitivity and specificity for fungal infections to be 58% and 83%, respectively (17). The same degree of sensitivity (64%) was observed in lung transplant patients using a cutoff point set at 60 pg/ml, but specificity was much lower (9%) (18). Today, experts are in agreement that the principal drawback of the BG assay is its lack of specificity in detecting candidiasis.…”

Diagnosis of Invasive Fungal Disease Using Serum (1.RAR.3)-.BETA.-D-Glucan: A Bivariate Meta-Analysis

“…Of these publications, we eventually pooled 13 articles. The process of selection of flow diagram is not shown (Table 1) (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). Four articles had data from two and more definitions for a simultaneous BG-positive result (Table 2); therefore, there were 17 BG-related studies.…”