Toimprove diagnostic options for pneumococcal pneumonia, an ELISA systemwas developed that can detect~6 ng/mI capsular polysaccharide in serum. The test was limited to 39 serotypes causing >95% of pneumococcal infections. In clinical evaluation the test identified 14of 15cases (missing one serotype not included). No false-positivereaction occurred. However, the duration and level of antigenemia were variable (~500-2.5 ng/mI) and seemed not to depend solely on the severityof infection. Therefore, the question of whether the extent of antigenemia was determined by a serotype-dependent variation in the elimination rates of polysaccharides was investigated. Clearance rates for 12 serotypes varied in rabbits and rats by a factor of >250. This remarkable variability appeared to affect the extent of clinical antigenemia. Thus, only very sensitive systemscan detect circulating antigen from rapidly cleared polysaccharide serotypes. Furthermore, the question arises whether slowpolysaccharide clearance contributes to the virulence of some pneumococcal serotypes.Streptococcus pneumoniae still is one of the most important respiratory pathogens. Despite extensive research [1][2][3][4][5][6][7][8], diagnosis of nonbacteremic pneumococcal pneumonia remains an enigma [9,10]. It is estimated that nonbacteremic cases account for 70%-80% ofpneumonias caused by S. pneumoniae. Results of sputum cultures or of sputum inoculation into mice are hampered mainly by a lack of specificity [2, 9-11], particularly in populations with a high incidence of chronic obstructive lung disease in which bronchial colonization with S. pneumoniae is common [12]. Furthermore, an appreciable number of patients with pneumonia do not produce sputum at the time they need antibiotic therapy [7,9]. Percutaneous lung aspiration has an impressive diagnostic yield with an acceptable complication rate when done by an experienced practitioner but has not gained wide popularity for fear of serious complications [3,10,13].Detection of pneumococcal antigens in body fluids for the diagnosis ofpneumococcal pneumonia has a tradition of>70 years [14]. The method for detection of specific capsular polysaccharide (SCP) in blood and urine by counterimmunoe1ec-trophoresis has been well characterized [1,4] and is used in many centers despite its limited and serotype-dependent sensitivity [1,7,9]. The more convenient agglutination tests have provided a somewhat higher sensitivity in serum but not urine [5,7,8]. By using ELISA techniques and commercial sera, the test sensitivity can be significantly improved for many but not all important SCP types [7,15,16]. In a small study, 12 of 17 cases ofbacteremic pneumococcal pneumonia were detected by an ELISA technique based on IgG prepared from serum containing antibodies to all 84 known capsular polysaccharide types (Omniserum; Statens Serum Institute, Copenhagen), but for some SCP types this test system was relatively blind [7,16].Commercial sera are not specifically raised to react uniformly in ELISA systems but to produce uniform ...