Comparison of (1→3)-β- d -Glucan, Mannan/Anti-Mannan Antibodies, and Cand-Tec Candida Antigen as Serum Biomarkers for Candidemia

Abstract

bWe conducted a case-control study using the Fungitell assay, the novel Platelia Candida Antigen (Ag) Plus and Candida Antibody (Ab) Plus assays, and the Cand-Tec latex agglutination test to evaluate the usefulness of (1¡3)-␤-D-glucan (BDG), mannan antigen with/without anti-mannan antibody, and Cand-Tec Candida antigen measurement for the diagnosis of candidemia. A total of 56 patients fulfilled the inclusion criteria and were enrolled. One hundred patients with bacteremia and 100 patients with sterile blood cultures served as negative controls. In the candidemia group, median (1¡3)-␤-D-glucan, mannan antigen, and anti-mannan antibody levels were 427 pg/ml, 190 pg/ml, and 18.6 antibody units (AU)/ml, respectively. All three parameters were significantly elevated in patients with candidemia. The sensitivity and specificity were, respectively, 87.5% and 85.5% for (1¡3)-␤-D-glucan, 58.9% and 97.5% for mannan antigen, 62.5% and 65.0% for anti-mannan antibody, 89.3% and 63.0% for mannan antigen plus anti-mannan antibody, 89.3% and 85.0% for BDG plus mannan antigen, and 13.0% and 93.9% for CandTec Candida antigen. The low mannan antigen sensitivity was in part caused by Candida parapsilosis and Candida guilliermondii fungemias, which were not detected by the Platelia Candida Ag Plus assay. When the cutoff was lowered from 125 pg/ml to 50 pg/ml, mannan antigen sensitivity increased to 69.6% without severely affecting the specificity (93.5%). Contrary to recently published data, superficial candidiasis was not associated with elevated mannan antigen levels, not even after the cutoff was lowered. Combining procalcitonin (PCT) with (1¡3)-␤-D-glucan to increase specificity provided a limited advantage because the benefit of the combination did not outweigh the loss of sensitivity. Our results demonstrate that the Cand-Tec Candida antigen and the mannan antigen plus anti-mannan antibody measurements have unacceptably low sensitivity or specificity. Of the four tests compared, (1¡3)-␤-D-glucan and mannan antigen are the superior biomarkers, depending on whether a sensitivity-driven or specificity-driven approach is used.

Presence of Candida cell wall derived polysaccharides in the sera of intensive care unit patients: relation with candidaemia and Candida colonisation

“…In contrast to the other more pathogenic Candida species, the mannan epitope detected by the Platelia test is poorly expressed on C. parapsilosis [11]. As in a recent study [31], exclusion of C. parapsilosis resulted in a moderate gain in sensitivity (from 38% to 45%). Surprisingly, the specificity of BDG detection was also affected by the exclusion of C. parapsilosis cases (from 30% to 45%).…”

Diagnostic Immunology

“…Both Platelia Candida tests have been recently refined and are now marketed as Candida Ag Plus and Candida Ab Plus. In one initial evaluation of their performance using a case-control design, their sensitivity and specificity were, respectively, [24]. Further evaluation of the newer test is warranted before widespread clinical application.…”

Preliminary evidence for a serum disaccharide signature of invasive Candida albicans infection detected by MALDI Mass Spectrometry

“…These glycans can be detected using immunological and biochemical tests, respectively. Both methods now detect molecules in the range of pg/mL with high reliability [4] and may be complementary [12].…”