Clearance of cryptococcal polysaccharide (CP) from tissues and body fluids of nonimmune mice was studied. Mice were injected intravenously only with one mg of purified CP, and serum, urine and tissues were obtained from each animal at various intervals for a period of 84 days. Tissue extracts, serum and urine were tested for CP content by enzyme-linked immunosorbent assay (ELISA) and latex agglutination. High concentrations of CP were detected by both assays one-half hour after injection in blood (serum), liver, spleen, kidney and lung (extracts). The duration of ELISA detectable CP was longest (70 days) in liver and spleen and shortest (14 days) in lung extract. By 14 days after injection, concentration of CP in the blood fell below that found in the liver and spleen. CP remained detectable (titers 32-64) after all other extracts became negative. These results indicate that CP is stored in tissues (binding mechanism and site unknown), and that the liver and spleen possess greater storage capacity than other tissues. Antibody (IgM) to CP appeared in low titer on the 14th day and thereafter.
An enzyme immunoassay for the measurement of cryptococcal capsular polysaccharide in human body fluids is described. The enzyme immunoassay detects cryptococcal capsular polysaccharide at a concentration of 6 ng/ml, compared with 35 ng/ml detectable by the latex agglutination test. The enzyme immunoassay detects cryptococcal capsular polysaccharide in body-fluid specimens that are negative by the latex agglutination test. Titers by enzyme immunoassay are generally higher and persist longer into the treatment period than those determined by latex agglutination. No cryptococcal capsular polysaccharide is detected by the enzyme immunoassay procedure in fluids from subjects not known to have cryptococcosis. The enzyme immunoassay procedure presented here provides earlier detection of cryptococcal material in body fluids, and thereby diagnosis and treatment of cryptococcosis can be made earlier in the course of disease.
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