Measurement of Serum Antigen Concentration by Ultrasound-Enhanced Immunoassay and Correlation with Clinical Outcome in Meningococcal Disease |
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Authors: | M A Sobanski R A Barnes S J Gray A D Carr E B Kaczmarski A O'Rourke K Murphy M Cafferkey R W Ellis K Pidcock P Hawtin W T Coakley |
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Institution: | (1) School of Biosciences, Cardiff University, PO Box 915, Cardiff CF1 3TL, UK, GB;(2) Department of Medical Microbiology and Public Health Laboratory Service, University of Wales College of Medicine, Cardiff CF4 4XN, UK, GB;(3) Meningococcal Reference Unit, Public Health Laboratory Service, Withington Hospital, Manchester M20 2LR, UK, GB;(4) Meningococcal Reference Laboratory, The Childrens Hospital, Temple Street, Dublin 1, Ireland, IE;(5) Department of Medical Microbiology, City Hospital National Health Service Trust, Dudley Road, Birmingham B18 7QH, UK, GB;(6) Public Health Laboratory Service, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK, GB |
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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 μg/ml. The lowest mean blood antigen concentration
found ultrasonically was 0.05 μg/ml; compared to the 1.98 μg/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) ≥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 (≥3.4 μg/ml polysaccharide) died,
whereas no patient with titres equal to or less than 1/4 (≤0.21 μg/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. |
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