title: Diagnosis of invasive pneumococcal disease among children in Kenya with enzyme-linked immunosorbent assay for immunoglobulin G antibodies to pneumococcal surface adhesin A.
abstract: 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.
authors.affiliation: Wellcome Trust/KEMRI Centre for Geographic Medicine Research--Coast, P. O. Box 230, Kilifi, Kenya. ascott@ikilifi.net
authors.forename: J Anthony G
authors.initials: JA
authors.lastname: Scott
authors.forename: Zena
authors.initials: Z
authors.lastname: Mlacha
authors.forename: Joyce
authors.initials: J
authors.lastname: Nyiro
authors.forename: Salome
authors.initials: S
authors.lastname: Njenga
authors.forename: Pole
authors.initials: P
authors.lastname: Lewa
authors.forename: Jacktone
authors.initials: J
authors.lastname: Obiero
authors.forename: Hanningtone
authors.initials: H
authors.lastname: Otieno
authors.forename: Jacquelyn S
authors.initials: JS
authors.lastname: Sampson
authors.forename: George M
authors.initials: GM
authors.lastname: Carlone
mesh_terms: D000367:Age Factors; D000907:Antibodies, Bacterial / Q000097:blood*; D001426:Bacterial Proteins / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods / Q000592:standards; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D007630:Kenya; D008297:Male; D011008:Pneumococcal Infections / Q000175:diagnosis*; D012698:Serologic Tests / Q000379:methods / Q000592:standards; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000302:isolation & purification
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; C051592:pneumococcal surface protein A