title: Measurement of serum antigen concentration by ultrasound-enhanced immunoassay and correlation with clinical outcome in meningococcal disease.
abstract: 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 microparticles. Specimens (169 sera/plasma from 145 patients with confirmed meningococcal disease) were tested retrospectively. The ultrasonic immunoassay detected serum antigen in 136 samples from 112 patients. Titration of antigen-positive specimens allowed estimation of blood antigen concentration. The modal blood antigen titre was 1/16, corresponding to an estimated polysaccharide concentration of 0.85 microg/ml. The lowest mean blood antigen concentration found ultrasonically was 0.05 microg/ml; compared to the 1.98 microg/ml found by conventional latex agglutination, this represents an approximately 30-fold improvement in sensitivity. Three grades of outcome were correlated with the presenting antigen titre in 83 patients: (i) <2 weeks hospitalisation, (ii) > or =2 weeks hospitalisation and (iii) mortality. High polysaccharide concentrations correlated with mortality. Nine of 15 patients with a serum antigen titre of 1/64 or greater (> or =3.4 microg/ml polysaccharide) died, whereas no patient with titres equal to or less than 1/4 (< or = 0.21 microg/ml) died, including those patients in whom antigen was undetectable by ultrasonic immunoassay. Increasing antigen concentration significantly correlated with severity of outcome (P<0.001). Ultrasound-enhanced agglutination provides a rapid prognostic indicator by sensitive measurement of serum antigen level.
authors.affiliation: School of Biosciences, Cardiff University, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Sobanski
authors.forename: R A
authors.initials: RA
authors.lastname: Barnes
authors.forename: S J
authors.initials: SJ
authors.lastname: Gray
authors.forename: A D
authors.initials: AD
authors.lastname: Carr
authors.forename: E B
authors.initials: EB
authors.lastname: Kaczmarski
authors.forename: A
authors.initials: A
authors.lastname: O'Rourke
authors.forename: K
authors.initials: K
authors.lastname: Murphy
authors.forename: M
authors.initials: M
authors.lastname: Cafferkey
authors.forename: R W
authors.initials: RW
authors.lastname: Ellis
authors.forename: K
authors.initials: K
authors.lastname: Pidcock
authors.forename: P
authors.initials: P
authors.lastname: Hawtin
authors.forename: W T
authors.initials: WT
authors.lastname: Coakley
mesh_terms: D006801:Humans; D007841:Latex Fixation Tests / Q000379:methods*; D008589:Meningococcal Infections / Q000175:diagnosis / Q000382:microbiology* / Q000401:mortality; D009345:Neisseria meningitidis / Q000276:immunology / Q000302:isolation & purification*; D011135:Polysaccharides, Bacterial / Q000097:blood*; D011379:Prognosis; D011933:Reagent Kits, Diagnostic; D012189:Retrospective Studies; D014465:Ultrasonics
chemical_list: D011135:Polysaccharides, Bacterial; D011933:Reagent Kits, Diagnostic