While the assessment of ␤-D-glucan (BDG) levels in adults improves the early diagnosis of invasive fungal disease (IFD), data on BDG levels in children are limited. We therefore assessed in a prospective cohort study the value of serial BDG screening for early detection of IFD in children undergoing allogeneic hematopoietic stem cell transplantation (HSCT). IFD was defined according to the revised European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) criteria, with the necessary modification that BDG was not included as a microbiological criterion. For the analysis, a total of 702 serum samples were obtained in 34 pediatric HSCT recipients. Proven IFD occurred in two patients (fusariosis and Candida sepsis, respectively), and probable invasive aspergillosis was diagnosed in four patients. Analyses including different cutoff values for BDG levels and different definitions of the onset of IFD demonstrated that the BDG assay has a relatively high sensitivity and good negative predictive value, whereas the positive predictive value has major limitations (<30%). Receiver operating characteristic analyses suggested an optimal cutoff between 60 and 70 pg/ml for different definitions of the onset of IFD. Our data show that BDG screening in pediatric HSCT recipients has a low positive predictive value and is therefore of limited usefulness. Despite improved supportive care strategies, the morbidity and mortality caused by invasive fungal disease (IFD) are still unacceptably high in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) (1). Early diagnosis of IFD is usually difficult, in particular in patients suffering from mold infections, but, on the other hand, early initiation of therapy correlates with better outcome (2, 3). Significant advances in the early detection of IFD have been made with the development of serum tests for fungal antigens, such as galactomannan (GM) or (1¡3)-␤-D-glucan (BDG). Both biomarkers have been included as microbiological criteria in the revised definitions for IFD by the European Organization for Research and Treatment of Cancer/ Mycosis Study Group (EORTC/MSG) consensus group (4), and FDA-approved assays are commercially available for the detection of these fungal antigens. Whereas the cell wall polysaccharide component GM is released by all Aspergillus species and can be detected in patients with invasive aspergillosis (IA), BDG can be detected in patients with IFD due to Aspergillus and Candida spp., Fusarium, Trichosporon, or Saccharomyces, and Pneumocystis jirovecii but also in various bacterial infections and even in healthy individuals (5). A number of factors, such as the concomitant administration of various antibiotic compounds, may result in false positivity, whereas systemic mold-active prophylaxis may increase the number of false-negative results (6, 7).Since GM data in children favorably compare with the results of a meta-analysis for GM testing in adults (8), prospective monitoring of GM levels twice weekly in ...

There is growing evidence that Natural Killer (NK) cells exhibit in vitro activity against both Aspergillus and non-Aspergillus molds. Cytotoxic molecules such as NK cell-derived perforin seem to play an important role in the antifungal activity. In addition, NK cells release a number of cytokines upon stimulation by fungi, which modulate both innate and adaptive host immune responses. Whereas the in vitro data of the antifungal activity of NK cells are supported by animal studies, clinical data are scarce to date.