Validation of immunoglobulin G enzyme-linked immunosorbent assay for antibodies to pneumococcal surface adhesin A in the diagnosis of pneumococcal pneumonia among adults in Kenya.

Epidemiologic studies of pneumococcal pneumonia, including vaccine efficacy trials, are hampered by a lack of sensitive and specific diagnostic tests. Pneumococcal surface adhesin A (PsaA) is a genetically conserved, surface-expressed protein common to all serotypes of Streptococcus pneumoniae and is highly immunogenic. Detection of anti-PsaA immunoglobulin G by recombinant PsaA enzyme-linked immunosorbent assay was evaluated for diagnosis of pneumococcal pneumonia in paired serum samples from 4 adult populations: 47 healthy control subjects, 56 clinic control subjects without pneumococcal disease syndromes, 109 patients with pneumococcal pneumonia, and 93 pneumonia patients with no evidence of pneumococcal etiology. By considering a 2-fold increase in antibody concentration as positive, sensitivity was 0.70, and specificity was 0.98. With a 1.3-fold increase, these were 0.89 and 0.98, respectively. The test's performance was not affected by the patients' human immunodeficiency virus status or by the pneumococcal serotype. The combination of high sensitivity and high specificity makes this an ideal assay for epidemiologic studies of pneumococcal pneumonia

Age-Specific Immunoglobulin G (IgG) and IgA to Pneumococcal Protein Antigens in a Population in Coastal Kenya

Streptococcus pneumoniae is the primary etiological agent of community-acquired pneumonia and a major cause of meningitis and bacteremia. Three conserved pneumococcal proteins—pneumolysin, pneumococcal surface adhesin A (PsaA), and pneumococcal surface protein A (PspA)—are currently being investigated as vaccine candidates. Such protein-based vaccines, if proven effective, could provide a cheaper alternative to conjugate vaccine formulae. Few data from sub-Saharan Africa exist concerning the development of natural antibody to these antigens, however. To investigate the age-specific development of antiprotein immunoglobulin G (IgG) and IgA antibody responses, the sera of 220 persons 2 weeks to 84 years of age from coastal Kenya were assayed using enzyme-linked immunosorbent assays. IgG and IgA antibody responses to each antigen were observed in all age groups. Serum concentrations of IgG and IgA antibody responses to PspA and PdB (a recombinant toxoid derivative of pneumolysin), but not to PsaA, increased significantly with age (P < 0.001). No decline was observed in the sera of the elderly. Anti-protein IgG concentrations were only weakly correlated (0.30 < r < 0.56; P < 0.0001), as were IgA concentrations (0.24 < r < 0.54; P < 0.0001)

Diagnosis of Invasive Pneumococcal Disease among Children in Kenya with Enzyme-Linked Immunosorbent Assay for Immunoglobulin G Antibodies to Pneumococcal Surface Adhesin A

Diagnostic techniques for invasive pneumococcal disease (IPD) in children are insensitive and underestimate both the burden of disease and the cost-effectiveness of pneumococcal conjugate vaccination (PCV). Consequently, there is little demand for the highly effective PCV outside the United States and Europe. In Kenya, diagnosis of pneumococcal pneumonia in adults was achieved with a sensitivity of 0.70 and a specificity of 0.98 using enzyme-linked immunosorbent assays (ELISAs) of paired plasma samples for immunoglobulin G (IgG) to pneumococcal surface adhesin A (PsaA). We aimed to validate the same technique in children. We assayed paired blood samples from 98 children with IPD, 95 age-matched children with malaria/anemia, and 97 age-matched healthy controls by using an ELISA for anti-PsaA IgG. Sensitivity and specificity were determined in IPD patients and healthy controls. Specificity (0.97; 95% confidence interval [CI], 0.91 to 0.99) and sensitivity (0.42; 95% CI, 0.32 to 0.52) were optimized at a 2.7-fold rise in anti-PsaA antibody concentration. Sensitivity was improved to a maximum of 0.50 by restricting testing to children of <2 years old, by excluding IPD patients who were not sampled on the first day of presentation, and by incorporating high existing antibody concentrations in the analysis. Assay performance was independent of nasopharyngeal carriage of pneumococci at recruitment. This assay improves on existing diagnostic tools for IPD in children but would still leave over half of all cases undetected in epidemiological studies. Effective diagnosis of pneumococcal disease in children is urgently required but poorly served by existing technology