title: Serological diagnosis of pneumococcal infection in children with pneumonia using protein antigens: A study of cut-offs with positive and negative controls.
abstract: The etiological diagnosis of infection by Streptococcus pneumoniae in children is difficult, and the use of indirect techniques is frequently warranted. We aimed to study the use of pneumococcal proteins for the serological diagnosis of pneumococcal infection in children with pneumonia. We analyzed paired serum samples from 13 Brazilian children with invasive pneumococcal pneumonia (positive control group) and 23 Finnish children with viral pharyngitis (negative control group), all aged <5years-old. Children with pharyngitis were evaluated for oropharyngeal colonization, and none of them carried S. pneumoniae. We used a multiplex bead-based assay with eight proteins: Ply, CbpA, PspA1 and 2, PcpA, PhtD, StkP and PcsB. The optimal cut-off for increase in antibody level for the diagnosis of pneumococcal infection was determined for each antigen by ROC curve analysis. The positive control group had a significantly higher rate of ≥2-fold rise in antibody levels against all pneumococcal proteins, except Ply, compared to the negative controls. The cut-off of ≥2-fold increase in antibody levels was accurate for pneumococcal infection diagnosis for all investigated antigens. However, there was a substantial increase in the accuracy of the test with a cut-off of ≥1.52-fold rise in antibody levels for PcpA. When using the investigated protein antigens for the diagnosis of pneumococcal infection, the detection of response against at least one antigen was highly sensitive (92.31%) and specific (91.30%). The use of serology with pneumococcal proteins is a promising method for the diagnosis of pneumococcal infection in children with pneumonia. The use of a ≥2-fold increase cut-off is adequate for most pneumococcal proteins.
authors.affiliation: Postgraduate Programme in Health Sciences, Federal University of Bahia School of Medicine, Salvador, Bahia, Brazil. Electronic address: andradedafne@yahoo.com.br.
authors.forename: Dafne Carvalho
authors.initials: DC
authors.lastname: Andrade
authors.affiliation: Postgraduate Programme in Health Sciences, Federal University of Bahia School of Medicine, Salvador, Bahia, Brazil.
authors.forename: Igor Carmo
authors.initials: IC
authors.lastname: Borges
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland.
authors.forename: Lauri
authors.initials: L
authors.lastname: Ivaska
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Peltola
authors.affiliation: Valneva Austria GmbH, Campus Vienna Biocenter 3, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinke
authors.affiliation: Postgraduate Programme in Health Sciences, Federal University of Bahia School of Medicine, Salvador, Bahia, Brazil; Department of Pathology, Federal University of Bahia School of Medicine and Centro de Pesquisa Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Bahia, Brazil.
authors.forename: Aldina
authors.initials: A
authors.lastname: Barral
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Helena
authors.initials: H
authors.lastname: Käyhty
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Ruuskanen
authors.affiliation: Postgraduate Programme in Health Sciences, Federal University of Bahia School of Medicine, Salvador, Bahia, Brazil; Department of Pediatrics, Federal University of Bahia School of Medicine, Salvador, Bahia, Brazil.
authors.forename: Cristiana Maria
authors.initials: CM
authors.lastname: Nascimento-Carvalho
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D001938:Brazil; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007223:Infant; D008297:Male; D008863:Microspheres; D011018:Pneumonia, Pneumococcal / Q000175:diagnosis*; D011446:Prospective Studies; D012372:ROC Curve; D012680:Sensitivity and Specificity; D012698:Serologic Tests; D013296:Streptococcus pneumoniae / Q000302:isolation & purification
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins
keywords: Bacteremia; Fluorescent multiplex microsphere immunoassay (FMIA); Immune response; Invasive pneumococcal disease; Luminex; Respiratory infection