Measurement of serum antigen concentration by ultrasound-enhanced immunoassay and correlation with clinical outcome in meningococcal disease

The distribution of Neisseria meningitidis serogroup B and C polysaccharide antigen in blood and the prognostic significance of antigen concentration was examined by ultrasound-enhanced immunoagglutination of coated micropart icles. Specimens (169 sera/plasma from 145 patients with confirmed meningoc occal disease) were tested retrospectively. The ultrasonic immunoassay dete cted serum antigen in 136 samples from 112 patients. Titration of antigen-p ositive specimens allowed estimation of blood antigen concentration. The mo dal blood antigen titre was 1/16, corresponding to an estimated polysacchar ide; concentration of 0.85 mu g/ml. The lowest mean blood antigen concentra tion found ultrasonically was 0.05 mu g/ml; compared to the 1.98 mu g/ml fo und by conventional latex agglutination, This represents an approximately 3 0-fold improvement in sensitivity. Three grades of outcome were correlated with the presenting antigen titre in 83 patients: (i) <2 weeks hospitalisat ion, (ii) greater than or equal to 2 weeks hospitalisation and (iii) mortal ity. High polysaccharide concentrations correlated with mortality. Nine of 15 patients with a serum antigen titre of 1/64 or greater (greater than or equal to 3.4 mu g/ml polysaccharide) died, whereas no patient with titres e qual to or less than 1/4(less than or equal to 0.21 mu g/ml) died, includin g those patients in whom antigen was undetectable by ultrasonic immunoassay . Increasing antigen concentration significantly correlated with severity o f outcome (P<0.001). Ultrasound-enhanced agglutination provides a rapid pro gnostic indicator by sensitive measurement of serum antigen level.