Role of Molecular Biomarkers in the Diagnosis of Invasive Fungal Diseases in Children

Abstract

Invasive fungal diseases are important clinical problems that are often complicated by severe illness and therefore the inability to use invasive measures to definitively diagnose the disease. Tests for a range of fungal biomarkers that do not require an invasive sample-collection procedure have been incorporated into adult clinical practice, but pediatric data and pediatric-specific recommendations for some of these diagnostic tools are lacking. In this review, we summarize the published literature and contemporary strategies for using the biomarkers galactomannan, (1→3)-β-d-glucan, Candida mannan antigen and anti-mannan antibody, and fungal polymerase chain reaction for diagnosing invasive fungal disease in children. Data on biomarker use in neonates and children with cancer, history of hematopoietic stem cell transplant, or primary immunodeficiency are included. Fungal biomarker tests performed on blood, other body fluids, or tissue specimens represent promising adjuncts to the diagnostic armamentarium in populations with a high prevalence of invasive fungal disease, but substantial gaps exist in the correct use and interpretation of these diagnostic tools in pediatric patients.

Diagnostic value of Candida mannan antigen and anti‐mannan IgG and IgM antibodies for Candida infection

“…This is consistent with the difference in sensitivity for antigenic detection by EB‐CA1 monoclonal antibody of the different Candida species Mannose epitopes and is less likely to detect C . parapsilosis mannan . The difference in the Candida MN serum concentrations in different Candida species infections was statistically significant ( P = .001), and the difference was also statistically significant ( P < .001) when compared with the Candida MN level of healthy controls, which was 14.45 (P25‐P75, 7.41‐31.45 AU/mL).…”

“…22 In this study, the serum Candida MN concentration of patients with Candida-positive venous blood, tracheal aspirate and urine cultures was significantly higher than that of the healthy con- and is less likely to detect C. parapsilosis mannan. 23 The difference in Because the serum samples were collected on the same day as a Candida-positive culture was observed (or on the day after), there was a concern that the window for antibody production might be…”

Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised Children

“…However, as only 10% of samples originated from patients with suspected IPA, patient-specific factors such as antifungal pretreatment, immune reconstitution, alloreactive inflammation, and impaired mucociliary clearance remain crucial in determining which child might develop IPA [16]. While this study was not powered to assess performance characteristics of this assay for IPA, pan-fungal and Aspergillus-specific PCR have demonstrated 76%-79% sensitivity and 93%-95% specificity for probable/proven IPA [14,[40][41][42][43][44][45][46][47]. Combining nucleic acid tests with galactomannan can hasten diagnosis and improve clinical outcomes in some populations [48][49][50][51]; further, incorporation of immune function may also improve discrimination of colonization and invasive mycosis [52][53][54][55][56].…”

Biomarkers of Infection and Inflammation

“…74 For more than two decades research has been ongoing for two fungal biomarkers, galactomannan (GM) and 1,3-β-D-glucan (BDG). 75,76 Galactomannan is a cell-wall polysaccharide that is released from hyphae of Aspergillus spp. and other fungi in body fluids.…”

“…There are FDA-approved immunoassays for the detection of GM in serum and bronchoalveolar on August 31 2020 http://hwmaint.clsjournal.ascls.org/ Downloaded from lavage. [74][75][76] Another circulating biomarker of fungal infection is BDG, a cell wall glucose polysaccharide found the majority of fungi. [74][75][76] The BDG assay can detect a variety of clinically important fungi except for Cryptococcus spp., Blastomyces dermatitidis, and the Mucorales group as they either lack BDG entirely or produce it at minimal levels.…”