Triacetylfusarinine C: A urine biomarker for diagnosis of invasive aspergillosis

Abstract

s u m m a r yObjectives: Early diagnosis of invasive aspergillosis (IA) remains challenging, with available diagnostics being limited by inadequate sensitivities and specificities. Triacetylfusarinine C, a fungal siderophore that has been shown to accumulate in urine in animal models, is a potential new biomarker for diagnosis of IA. Methods: We developed a method allowing absolute and matrix-independent mass spectrometric quantification of TAFC. Urine TAFC, normalized to creatinine, was determined in 44 samples from 24 patients with underlying hematologic malignancies and probable, possible or no IA according to current EORTC/MSG criteria and compared to other established biomarkers measured in urine and same-day blood samples. Results: TAFC/creatinine sensitivity, specificity, positive and negative likelihood ratio for probable versus no IA (cut-off ≥ 3) were 0.86, 0.88, 6.86, 0.16 per patient. Conclusion:For the first time, we provide proof for the occurrence of TAFC in human urine. TAFC/creatinine index determination in urine showed promising results for diagnosis of IA offering the advantages of non-invasive sampling. Sensitivity and specificity were similar as reported for GM determination in serum and bronchoalveolar lavage, the gold standard mycological criterion for IA diagnosis.

Baseline predictors influencing the prognosis of invasive aspergillosis in adults

“…High GM levels represent increased Aspergillus burden, thus increasing the risk for dissemination due to invasion of blood vessels by the fungus. In case of GM negative IA, other biomarkers such as triacetylfusarinine C in urine has shown potential for outcome and treatment response assessment …”

Point‐of‐care diagnosis of invasive aspergillosis in non‐neutropenic patients: Aspergillus Galactomannan Lateral Flow Assay versus Aspergillus‐specific Lateral Flow Device test in bronchoalveolar lavage

“…Given the absence of widely accepted criteria for defining IPA in non‐neutropenic patients, studies on new diagnostic tests for IPA focus mostly on patients with underlying haematological malignancies, where broadly accepted classification criteria exist, while diagnostic studies in non‐neutropenic patients are scarce. Importantly, two novel point‐of‐care diagnostic tests, both European conformity (CE) marked for diagnosis of IPA in BALF, have recently become commercially available, but to date have been only validated in patients with underlying haematological malignancies .…”

“…17 While an alternative clinical algorithm for diagnosing IPA in the ICU setting seems to overcome some of those limitations including attempting to distinguish colonisation from true infection/ disease, 22 that algorithm relies on clinical signs that typically occur during later stages of IPA in non-neutropenic patients, 8 and is applicable only to those with a positive BALF culture for Aspergillus spp., which is an entry criteria in this algorithm. 20,24 Given the absence of widely accepted criteria for defining IPA in non-neutropenic patients, studies on new diagnostic tests for IPA focus mostly on patients with underlying haematological malignancies, 21,[25][26][27] where broadly accepted classification criteria exist, while diagnostic studies in non-neutropenic patients are scarce. Importantly, two novel point-of-care diagnostic tests, both European conformity (CE) marked for diagnosis of IPA in BALF, have recently become commercially available, but to date have been only validated in patients with underlying haematological malignancies.…”

Immune Parameters for Diagnosis and Treatment Monitoring in Invasive Mold Infection

“…Mycological diagnosis of IMI is challenging, with many molds not growing in blood cultures and cultures of bronchoalveolar lavage fluid (BALF) having a low sensitivity [10][11][12]. Consequently, fungal biomarkers such as galactomannan (GM), (1,3)-β-d-glucan (BDG), and extracellular glycoprotein, as well as molecular diagnostic tests (polymerase chain reaction (PCR)) applied to blood or bronchoalveolar lavage fluid (BALF), have emerged [7,11,[13][14][15][16]. However, performance of these biomarkers and diagnostic tests has been shown to be less than optimal for invasive aspergillosis (IA) in patients receiving mold-active prophylaxis or treatment, which has been shown to reduce sensitivity of diagnostic tests [13,[17][18][19][20][21][22].…”