Increased sensitivity of mannanemia detection tests by joint detection of alpha- and beta-linked oligomannosides during experimental and human systemic candidiasis.

Abstract

An enzyme immunoassay (EIA)-the commercially available Platelia Candida antigen test-developed for the diagnosis of systemic candidiasis is based on the detection of alpha-linked oligomannose residues (alpha-Man) released from Candida cells into the serum. This test has good specificity but has to be repeated frequently because of the rapid clearance of detectable mannanemia. We have developed a second EIA based on detection of beta-linked oligomannoses (beta-Man), since beta-Man are linked to different Candida molecules and interact differently with the host immune system and endogenous lectins and should therefore present different kinetics of serum clearance. In a guinea pig model of Candida albicans systemic infection, the relative amounts of detectable alpha- and beta-Man differed considerably according to the virulence of the strain, the infecting dose, and the time after challenge that serum samples were drawn. Detection of alpha-Man was more sensitive per serum sample than that of beta-Man, and the sensitivity for the combination reached 90%. The same tests were applied to 90 sera from 26 patients selected retrospectively for having been infected with the most-pathogenic Candida species: C. albicans (19), C. tropicalis (4), and C. glabrata (3). A total of 22 patients had positive antigenemia, 4 had alpha-mannanemia, 4 had beta-mannanemia, and 14 showed the presence of both. For the patients showing the presence of both forms of mannanemia, the use of both tests enhanced the duration of the detection of mannanemia. Mannanemia was correlated with early clinical symptoms and isolation of Candida in culture, which occurred in 55% of the patients at an average of 4.7 days after the first positive mannanemia test result. A combination of the two tests had a cumulated specificity of 95%, and positive and negative predictive values were 79 and 97%, respectively. These findings provide evidence for different kinetics of beta- and alpha-Man circulation during experimental and human candidiasis and suggest the joint detection of both types of epitopes as a rational approach contributing to increases in the sensitivity and earliness of diagnosis.