NONCULTURE METHODS FOR DIAGNOSIS OF DISSEMINATED CANDIDIASIS

Nonculture methods to diagnose disseminated candidiasis (DC) are needed because blood cultures are nonproductive for 27% or more of patients with DC. Recent reports indicate the emergence of Candida (Torulopsis) glabrata, Candida parapsilosis, and Candida krusie as agents of DC in addition to Candida albicans and Candida tropicalis. The Candida species metabolite D-arabinitol, expressed as serum D-arabinitol/creatinine, is an indicator of DC in as many as two-thirds of patients studied. Detection is expedited by an enzymatic-fluorometric assay kit as an alternative to gas-liquid chromatography, but interference from mannitol may detract from test specificity. Polymerase chain reaction (PCR)-amplified Candida species DNA has been recovered from blood and urine samples from a small number of human subjects. PCR-based tests are promising but cumbersome prototypes. The sensitivity to detect 1 to 10 CFU/ml of blood has not been reliably achieved. Immunoassay detection of marker antigens for DC has proceeded on several fronts. A liposomal immunoassay kit for the 48-kDa enolase received a successful prospective clinical evaluation. Secreted aspartyl proteinase was detected in urine from immunosuppressed rabbits with DC, but data on human subjects are unavailable. Western blot (immunoblot) was used to detect antigenuria, and this method appears promising. The cell wall mannoprotein (mannan) of Candida species circulates in the low nanogram-per-milliliter range in DC, but frequent sampling is needed for detection during granulocytopenia. The incorporation in the sandwich enzyme immunoassay of antibodies of broad specificity, reflecting the epitopes of C. albicans and the mannan of emerging Candida species, is necessary for maximal sensitivity.