Ann. N.Y. Acad. Sci. ISSN 0077-8923 ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Issue: Advances Against Aspergillosis Application of diagnostic markers to invasive aspergillosis in children Emmanuel Roilides and Zoi-Dorothea Pana Third Pediatric Department, Aristotle University School of Medicine, Hippokration General Hospital, Thessaloniki, Greece Address for correspondence: Emmanuel Roilides, Third Department of Pediatrics, Hippokration General Hospital, Konstantinoupoleos 49, 54642, Thessaloniki, Greece. roilides@med.auth.gr Early mycological detection of Aspergillus species is the cornerstone for a prompt diagnosis, appropriate treatment strategies, and improved survival of patients with invasive aspergillosis (IA), irrespective of age. However, the currently available laboratory tests for the diagnosis of IA include culture with direct microscopy, histology, and antigenic markers, such as galactomannan and -1, 3-d-glucan, Aspergillus spp. DNA detection by PCR, and imaging studies, such as high-resolution CT scan. However, all need further validation, especially in children. In this review we focus on the diagnosis of IA emphasizing the current perspectives, difficulties in interpretation, and the need of further evaluation from a pediatric point of view. Keywords: invasive aspergillosis; -1, 3-d-glucan; galactomannan; children Introduction Invasive aspergillosis (IA) is an increasing problem in children and is associated with high attributable morbidity and mortality rates, as well as early and late onset complications. 1 There are significant differences reported in the epidemiology patterns of IA among different pe- diatric populations and adults. 2 Children with ei- ther congenital or acquired immunodeficiency may suffer from IA. Previous studies have emphasized the increased risk for IA in children with ac- quired immunodeficiencies after immunosuppres- sive therapy for cancer (especially for hemato- logical malignancies), in children with advanced human immunodeficiency virus infection, bone marrow failure syndromes or allogeneic hematopoi- etic stem cell or solid organ transplantation. 3–5 Furthermore, children with inherited defects of phagocytic host defenses, including chronic gran- ulomatous disease and those with cystic fibrosis are at increased risk of presenting IA. 6,7 Addi- tionally, low-birth weight and premature infants are susceptible to IA due to reduced chemotactic, phagocytic, and microbicidal activity, skin break- down, prior antibiotic therapy, or prolonged use of steroids. 8 Early mycological detection of Aspergillus species is the cornerstone for a prompt diagnosis, appro- priate treatment strategy, and improved survival of patients with IA, irrespective of age. On the other hand, current laboratory examinations for IA detec- tion need further validation, especially in children. Routine methods for rapid specific identification of Aspergillus species are generally not available. The current diagnostic markers for IA include conven- tional and more recent methods under evaluation. Conventional methods of diagnosis include direct microscopy and histology, and culture of respiratory and various fluids and tissues. Recently, more rapid and sensitive methods have been developed, for ex- ample, the detection of antigenic markers, such as galactomannan and -1, 3-d-glucan, the detection of molecular markers of Aspergillus DNA by poly- merase chain reaction, and improved imaging stud- ies such as high-resolution CT scans. Various problems characterize the older and the more recently introduced diagnostic markers, especially in pediatric patients. A few examples of these problems include in vitro culture lacks sensitivity, histological diagnosis requires invasive methods that are often difficult in children and are nonspecific to speciation, galactomannan lacks sensitivity in children compared with adults, doi: 10.1111/j.1749-6632.2012.06828.x Ann. N.Y. Acad. Sci. 1272 (2012) 1–8 c  2012 New York Academy of Sciences. 1