Diagnosis of Invasive Pneumococcal Infection by Serotype-Specific Urinary Antigen Detection

Abstract

Widespread use of conjugate pneumococcal polysaccharide-protein vaccines may alter the spectrum of pneumococci producing invasive disease. Novel sensitive diagnostic methods would be valuable for monitoring the epidemiology of pneumococcal disease within populations and vaccine recipients. Ideally, these methods should allow determination of the serotype of the infecting clone. Serotype-specific enzyme-linked immunosorbent assays (ELISA) for 13 capsular polysaccharides (types 1, 3, 4, 5, 6A, 6B, 7A, 9V, 14, 18C, 19A, 19F, and 23F) were developed. Experiments with pure capsular polysaccharide demonstrated that the assays were sensitive (0.01 to 1.0 ng/ml) and specific. These assays were used to detect capsular polysaccharide in urine from 263 adult patients with proven (blood culture-positive) invasive pneumococcal disease and pneumonia of unknown etiology and from patients with positive blood cultures yielding bacteria other than pneumococci (control group). Among 76 patients with invasive pneumococcal disease from whom blood culture isolates had been serotyped, 62 (82%) had infections with pneumococci of serotypes represented in the ELISA panel. Capsular antigen matching the serotype of the blood culture isolate was detected in the urine of 52 of these patients, giving a sensitivity of 83.9% for the target serotypes. The tests were significantly more sensitive for urine from patients with pneumococcal pneumonia (89.8%) than for urine from patients with nonpneumonic invasive infection (61.5%; P < 0.05). Data from the control group indicated a specificity of 98.8%. These assays should prove valuable in epidemiological investigation of invasive pneumococcal infection in adults, particularly if combined with a sensitive C-polysaccharide detection assay to screen for positive samples.

Diagnostic accuracy of a serotype-specific antigen test in community-acquired pneumonia

“…Serotype-specific antigen detection in urine has been attempted before, with excellent specificity (98-99%), but disappointing sensitivity (55-84%), when compared with S. pneumoniae isolates detected in sterile sites [19][20][21][22]. The sensitivity of the ICA test in the present study was 63%.…”

“…However, at this point, there is no other reference standard to better test accuracy of serotype specific diagnostic tools. Secondly, pneumococcal antigens can persist in urine samples after infection for periods as long as from 7 days [19,29] to 3 months [30]. Although we did not have detailed information about disease history in the weeks before the clinical episode of CAP, we could determine that only eight (0.7%) patients had been hospitalised in the weeks before the CAP episode.…”

Competitive Inhibition Flow Analysis Assay for the Non-Culture-Based Detection and Serotyping of Pneumococcal Capsular Polysaccharide

“…Serotype-specific identification assays have previously been reported and include assays based on latex agglutination (28) and enzyme-linked immunosorbent assay (ELISA) (17). Leeming et al (17) reported on an ELISA capable of detecting serotype-specific polysaccharide in urine, but this assay is dependent upon the availability of MAbs with high degrees of specificity for pneumococcal capsular polysaccharides which are not commercially available.…”

Validation of an Immunodiagnostic Assay for Detection of 13 Streptococcus pneumoniae Serotype-Specific Polysaccharides in Human Urine

“…While this assay is rapid (15-min performance time), the BinaxNOW S. pneumoniae urine antigen test measures the presence only of the C-PS antigen, which is present on all S. pneumoniae strains, and does not distinguish between the different serotypes of this organism. In addition, the sensitivity of this method has also been called into question by users in the field (27,43).…”