Longitudinal analysis of pneumococcal antibodies during community-acquired pneumonia reveals a much higher involvement of Streptococcus pneumoniae than estimated by conventional methods alone

Abstract

In up to half of all cases of community-acquired pneumonia (CAP), no pathogen can be identified with conventional diagnostic methods. The most common identified causative agent is Streptococcus pneumoniae. In this study, pneumococcal antibody responses during CAP were analyzed to estimate the contribution of the pneumococcus to all cases of CAP for epidemiological purposes. Pneumococcal antibodies against 14 different serotypes were measured in serum of hospitalized CAP patients. Patients participated in one of two consecutive clinical trials in a general 600-bed teaching hospital in the Netherlands (between October 2004 and June 2009). A significant pneumococcal immune response was defined as at least a 2-fold increase in antibody concentrations against a single serotype between an early (day 1) and a late (day 30) serum sample of each patient with an end concentration above 0.35 μg/ml. A total of 349 adult CAP patients participated in two consecutive clinical trials. For 200 patients, sufficient serum samples were available to determine antibody responses: 62 pneumococcal pneumonia patients, 57 nonpneumococcal pneumonia patients, and 81 patients with an unidentified causative agent. A significant immune response was detected in 45% (28/62 patients) of pneumococcal pneumonia patients, in 5% (3/57) of nonpneumococcal pneumonia patients, and in 28% (23/81) of patients with an unidentified causative agent. The estimated contribution of pneumococci in patients with an unidentified causative agent was calculated to be 57% (95% confidence interval, 36 to 86%). A substantial fraction of pneumococcal pneumonia patients do not elicit a serotype-specific immune response.

Figures

Fig. 1.

Flowchart of study design. A total of 349 CAP patients participated in two clinical trials. In 94 patients (27%) Streptococcus pneumoniae was found to be the causative agent by conventional microbiological techniques, in 86 patients (25%) a pathogen other than S. pneumoniae was identified, and in 169 patients (48%) no pathogen was identified. Sufficient samples for pneumococcal antibody measurements were available for 200 patients. A pneumococcal polysaccharide (PPS) antibody response was defined as at least a 2-fold increase in antibody concentrations with an end concentration above 0.35 μg/ml. The fold increase against a single pneumococcal serotype had to be at least two times greater than the fold increase against any other serotype.