Overall, the galactomannan test seems to be a highly specific diagnostic tool (94% to 99%), even though sensitivity has ranged from 50% to 93% in patients with haematologic malignancy.^72,77,78 In order to improve these results, some authors have suggested that the recommended cut-off value of the test should be reduced from 1,500 to 1,000.^72,77 A further reduction to 0.700 was suggested for adults who have not undergone allogeneic transplantation,⁹² and recent research suggests that an index of 0.5 is a more definitive threshold.¹⁰⁴ These modifications may increase the sensitivity of the test, with only a low decrease in specificity. Discussion persists about the best cut-off for galactomannan assays.

Because galactomannan is a water-soluble carbohydrate, it can be detected in other fluids.⁶⁹ Although the antigen can be detected in the urine,^{73,74,105–107} little is known about its pharmacokinetics and clearance by the kidney. The effect of renal failure or dialysis on the clearance of galactomannan is also indefinite. Little is known regarding the correlation between galactomannan detection in urine and disease progression, and false-positive results may be an important drawback for this test.^69,73,74
Because galactomannan is predominantly released by Aspergillus hyphae during growth and to a much lesser extent by conidia, detection of galactomannan in BAL fluid provides better evidence for aspergillosis than culture ^108,109 or polymerase chain reactions (PCRs), which do not discriminate between contamination conidia and hyphae.^110–112 However, false positive results may occur in patients only colonised with Aspergillus when BAL is tested,⁶⁹ but this can be improved when one combines this method with the high-resolution computed tomography (CT) scan.^34,113

Diagnosis of CNS aspergillosis is very difficult and even brain biopsies do not always result in a clear diagnosis.⁶⁹ Culture of CSF infrequently yields positive results,^94,114 and both chemical findings in the CSF and the CT results are often non-specific.^115–117 Galactomannan may also be detected in the CSF, with a sensitivity and specificity of 80% and 100%, respectively, according to a study involving only five patients with proven CNS aspergillosis.¹¹⁷ Galactomannan has been detected in other clinical specimens as well.⁶⁹

1,3-beta-D-glucan

1,3-beta-D-glucan is a cell wall component of yeast and filamentous fungi, which is detectable in the blood during most invasive fungal infections. Factor G, a coagulation factor, is a sensitive natural detector of this antigen.¹¹⁸ The reported sensitivity and specificity for the assay have ranged from 67% to 100%, and 84% to 100%, respectively.^118–122 The test does not detect cryptococcosis, and it is also not positive in cases of oral candidosis or fungal colonisation.¹²¹ However, in addition to invasive aspergillosis and candidosis, it detects infections caused by species of Fusarium, Trichosporon, Saccharomyces and Acremonium, which are less common but equally important fungal pathogens, especially in immunocompromised hosts.¹²¹ False positive tests have been reported in patients undergoing haemodialysis, patients with cirrhosis, recipients of antitumour polysaccharides, and patients immediately following abdominal surgery.⁶⁴

PCRn

Although PCR is at lest 19 times more sensitive than culture for A. fumigatus,123 PCR-based molecular diagnostic tests for aspergillosis are not commercially available and remain largely unstandardised. A sensitivity of 79% to 100% and a specificity of 81% to 93% have been documented, depending on the methodology used.^124–126 Such assays, when performed on blood or BAL samples, have shown a negative predictive value for invasive aspergillosis ranging from 92% to 99%. However, PCR-based assays performed with BAL samples have shown low positive predictive values that are likely to reflect respiratory tract colonisation.¹²⁷

Markers for Invasive Candidosis

Mannan is a cell wall surface carbohydrate that circulates during infection with Candida spp.,¹²⁸ and studies have shown a correlation between detectable mannanemia and tissue invasive in patients with candidaemia.129 However, mannan is rapidly cleared from the blood and occurs in low levels, necessitating frequent sampling for detection.¹³⁰ In addition, this is a very expensive test. D-arabinitol is a metabolite of certain species of Candida that accumulates in the urine of patients with invasive candidosis. Assay sensitivity for D-arabinitol is only ~50%, and does not detect C. krusei and C. glabrata.^131,132 Enolase is perhaps the antigen with the greatest promise for the diagnosis of invasive candidosis.^133,134 The sensitivities of assays for enolase have ranged from 54% to 75%, and higher sensitivity may be achieved with serial testing. Furthermore, the enolase antigen is highly specific for Candida spp., and is not present in superficial Candida colonisation.¹³³