Skip to main content
Log in

Pneumococcal serology in children’s respiratory infections

  • Review
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

The role of Streptococcus pneumoniae in the etiology of respiratory tract infections has been studied serologically using microbe-specific antibody and immune complex assays. Serological methods are sensitive in the bacteremic pneumococcal pneumonia of adults. In children, however, pneumococcal pneumonia is seldom bacteremic, and, thus, in the absence of a gold standard for the detection of pneumococcal infection, serological methods are still insufficiently validated. We report here indirect evidence for the sensitivity and specificity of pneumococcal serology in children. Serological evidence of pneumococcal infection has been found in 27% to 38% of children with radiologically confirmed pneumonia, in 7% to 8% of children with viral wheezy bronchitis, and in <1% to 5% of children and young adults with viral upper respiratory infection. Serological findings for pneumococcal infection have been dependent on the study venue, whether in hospital or ambulatory subjects, and on the test panel used. Where both antibody and immune complex assays have been available, the proportion of children with pneumococcal infection has been 32% to 37% in inpatients and 27% to 28% in outpatients. The respective rates have been 10% to 18% by antibody assays alone. Pneumococcal acute otitis media, when present with pneumonia, may confound findings in pneumococcal serology, but pure nasopharyngeal carriage of S. pneumoniae has little effect. In contrast, carriage acquisition of a new serotype may induce significant antibody production. Thus, understandably, significant rises between paired sera in antibodies to pneumococcal capsular polysaccharides and pneumococcal pneumolysin have been found in <1% to 3% of non-symptomatic children and young adults. Findings from the last 20 years indirectly suggest that pneumococcal antibody and immune complex assays are sensitive and specific enough for the detection of pneumococcal infection in children. However, the methods are too complex for routine clinical practice, and, so far, serological methods for S. pneumoniae infections have only been used for research purposes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. McIntosh K (2002) Community-acquired pneumonia in children. N Engl J Med 346:429–437

    Article  PubMed  Google Scholar 

  2. Korppi M (2003) Community-acquired pneumonia in children: issues in optimizing antibacterial treatment. Paediatr Drugs 5:821–832

    Article  PubMed  Google Scholar 

  3. Byington CL, Spencer LY, Johnson TA et al (2002) An epidemiological investigation of a sustained high rate of pediatric parapneumonic empyema: risk factors and microbiological associations. Clin Infect Dis 34:434–440

    Article  PubMed  Google Scholar 

  4. Toikka P, Virkki R, Mertsola J et al (1999) Bacteremic pneumococcal pneumonia in children. Clin Infect Dis 29:568–572

    Article  PubMed  CAS  Google Scholar 

  5. Korppi M (2002) Mixed microbial aetiology of community-acquired pneumonia in children. APMIS 110:515–522

    Article  PubMed  Google Scholar 

  6. Korppi M, Katila M-L, Kalliokoski R et al (1992) Pneumococcal finding in a sample from upper airways does not indicate pneumococcal infection of lower airways. Scand J Infect Dis 24:445–451

    Article  PubMed  CAS  Google Scholar 

  7. Claesson B, Trollfors B, Brolin I et al (1989) Etiology of community-acquired pneumonia in children based on antibody responses to bacterial and viral antigens. Pediatr Infect Dis J 8:856–862

    PubMed  CAS  Google Scholar 

  8. Nohynek H, Eskola J, Laine E et al (1991) The causes of hospital-treated acute lower respiratory tract infection in children. Am J Dis Child 145:618–622

    PubMed  CAS  Google Scholar 

  9. Ruuskanen O, Nohynek H, Ziegler T et al (1992) Pneumonia in childhood: etiology and response to antimicrobial therapy. Eur J Clin Microbiol Infect Dis 11:217–223

    Article  PubMed  CAS  Google Scholar 

  10. Korppi M, Heiskanen-Kosma T, Jalonen E et al (1993) Aetiology of community-acquired pneumonia in children treated in hospital. Eur J Pediatr 152:24–30

    Article  PubMed  CAS  Google Scholar 

  11. Juvén T, Mertsola J, Waris M et al (2000) Etiology of community-acquired pneumonia in 254 hospitalized children. Pediatr Infect Dis J 19:293–298

    Article  PubMed  Google Scholar 

  12. Heiskanen-Kosma T, Korppi M, Jokinen C et al (1998) Etiology of childhood pneumonia: serologic results of a prospective, population-based study. Pediatr Infect Dis J 17:986–991

    Article  PubMed  CAS  Google Scholar 

  13. Wubbel L, Muniz L, Ahmed A et al (1999) Etiology and treatment of community-acquired pneumonia in ambulatory children. Pediatr Infect Dis J 18:98–104

    Article  PubMed  CAS  Google Scholar 

  14. Michelow IC, Olsen K, Lozano J et al (2004) Epidemiology and clinical characteristics of community-acquired pneumonia in hospitalized children. Pediatrics 113:701–707

    Article  PubMed  Google Scholar 

  15. Don M, Fasoli L, Paldanius M et al (2005) Aetiology of community-acquired pneumonia: serological results of a paediatric survey. Scand J Infect Dis 37:806–812

    Article  PubMed  Google Scholar 

  16. Korppi M, Leinonen M (1998) Pneumococcal immune complexes in the diagnosis of lower respiratory tract infections in children. Pediatr Infect Dis J 17:992–995

    Article  PubMed  CAS  Google Scholar 

  17. Mäkelä M, Puhakka T, Ruuskanen O et al (1998) Viruses and bacteria in the etiology of the common cold. J Clin Microbiol 36:539–542

    PubMed  Google Scholar 

  18. Korppi M, Launiala K, Leinonen M et al (1990) Bacterial involvement in laryngeal infections in children. Acta Paediatr Scand 79:564–565

    Article  PubMed  CAS  Google Scholar 

  19. Korppi M, Leinonen M, Mäkelä PH et al (1990) Bacterial involvement in parainfluenza virus infection in children. Scand J Infect Dis 22:307–312

    Article  PubMed  CAS  Google Scholar 

  20. Korppi M, Leinonen M, Koskela M et al (1991) Bacterial infection in under school age children with expiratory difficulty. Pediatr Pulmon 10:254–259

    Article  CAS  Google Scholar 

  21. Lehtinen P, Jartti T, Virkki R et al (2006) Bacterial coinfections in children with viral wheezing. Eur J Clin Microbiol Infect Dis 25:463–469

    Article  PubMed  CAS  Google Scholar 

  22. Leinonen M (1994) Serological diagnosis of pneumococcal pneumonia—will it ever become a clinical reality? Semin Respir Infect 9:189–191

    PubMed  CAS  Google Scholar 

  23. Nohynek H, Eskola J, Kleemola M et al (1995) Bacterial antibody assays in the diagnosis of acute lower respiratory tract infection in children. Pediatr Infect Dis J 14:478–484

    PubMed  CAS  Google Scholar 

  24. Koskela M (1986) Antibody response of young children to parenteral vaccination with pneumococcal capsular polysaccharides: a comparison between antibody levels in serum and middle ear effusion. Pediatr Infect Dis 5:431–434

    PubMed  CAS  Google Scholar 

  25. Koskela M (1987) Serum antibodies to pneumococcal C polysaccharide in children: response to acute pneumococcal otitis media or to vaccination. Pediatr Infect Dis J 6:519–526

    PubMed  CAS  Google Scholar 

  26. Jalonen E, Paton J, Koskela M et al (1989) Measurement of antibody responses to pneumolysin—a promising method for the presumptive aetiological diagnosis of pneumococcal pneumonia. J Infect 19:127–134

    Article  PubMed  CAS  Google Scholar 

  27. Korppi M, Koskela M, Jalonen E et al (1992) Serologically indicated pneumococcal respiratory infection in children. Scand J Infect Dis 24:437–443

    Article  PubMed  CAS  Google Scholar 

  28. Freymyth F, Vabret A, Brouard J et al (1999) Detection of viral, Chlamydia pneumoniae and Mycoplasma pneumoniae infections in exacerbations of asthma in children. J Clin Virol 13:131–139

    Article  Google Scholar 

  29. Esposito S, Blasi F, Arosio C et al (2000) Importance of acute Mycoplasma pneumoniae and Chlamydia pneumoniae infections in children with wheezing. Eur Respir J 16:1142–1146

    Article  PubMed  CAS  Google Scholar 

  30. Biscardi S, Lorrot M, Marc E et al (2004) Mycoplasma pneumoniae and asthma in children. Clin Infect Dis 38:1341–1346

    Article  PubMed  Google Scholar 

  31. Hall CB, Powell KR, Schnabel KC et al (1988) Risk of secondary bacterial infection in infants hospitalized with respiratory syncytial viral infection. J Pediatr 113:266–271

    Article  PubMed  CAS  Google Scholar 

  32. Korppi M, Leinonen M, Koskela M et al (1989) Bacterial coinfection in children hospitalized with respiratory syncytial virus infections. Pediatr Infect Dis J 8:687–692

    PubMed  CAS  Google Scholar 

  33. Korppi M, Leinonen M (1997) Pneumococcal pneumonia in children; new data from circulating immune complexes. Eur J Pediatr 156:341–342

    PubMed  CAS  Google Scholar 

  34. Michelow IC, Lozano J, Olsen K et al (2002) Diagnosis of Streptococcus pneumoniae lower respiratory infection in hospitalized children by culture, polymerase chain reaction, serological testing, and urinary antigen detection. Clin Infect Dis 34:E1–E11

    Article  PubMed  Google Scholar 

  35. Heiskanen-Kosma T, Korppi M, Leinonen M (2003) Serologically indicated pneumococcal pneumonia in children: a population-based study in primary care settings. APMIS 111:945–950

    Article  PubMed  Google Scholar 

  36. Scott JA, Hall AJ, Leinonen M (2000) Validation of immune-complex enzyme immunoassays for diagnosis of pneumococcal pneumonia among adults in Kenya. Clin Diagn Labor Immunol 7:64–67

    CAS  Google Scholar 

  37. Scott JA, Obiero J, Hall AJ et al (2002) 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. J Infect Dis 186:220–226

    Article  PubMed  CAS  Google Scholar 

  38. Gutiérrez F, Masiá M, Rodríguez J et al (2003) Evaluation of the immunochromatographic Binax NOW assay for detection of Streptococcus pneumoniae urinary antigen in a prospective study of community-acquired pneumonia in Spain. Clin Infect Dis 36:286–292

    Article  PubMed  Google Scholar 

  39. Marcos MA, Jiménez de Anta MT, de la Bellecasa JP et al (2003) Rapid urinary antigen test for diagnosis of pneumococcal community-acquired pneumonia in adults. Eur Respir J 21:209–214

    Article  PubMed  CAS  Google Scholar 

  40. Smith MD, Derrington P, Evans R et al (2003) Rapid diagnosis of bacteremic pneumococcal infections in adults by using the Binax NOW Streptococcus pneumoniae urinary antigen test: a prospective, controlled clinical evaluation. J Clin Microbiol 41:2810–2813

    Article  PubMed  CAS  Google Scholar 

  41. Rosón B, Fernández-Sabé N, Carratalà J et al (2004) Contribution of a urinary antigen assay (Binax NOW) to the early diagnosis of pneumococcal pneumonia. Clin Infect Dis 38:222–226

    Article  PubMed  Google Scholar 

  42. Strålin K, Kaltoft M, Konradsen H et al (2004) Comparison of two urinary antigen tests for establishment of pneumococcal etiology of adult community-acquired pneumonia. J Clin Mirobiol 42:3620–3625

    Article  CAS  Google Scholar 

  43. Dowell S, Garman R, Liu G et al (2001) Evaluation of Binax NOW, an assay for the detection of pneumococcal antigen in urine samples, performed among pediatric patients. Clin Infect Dis 32:824–825

    Article  PubMed  CAS  Google Scholar 

  44. Hamer DH, Egas J, Estrella B et al (2002) Assessment of the Binax NOW Streptococcus pneumoniae urinary antigen test in children with nasopharyngeal pneumococcal carriage. Clin Infect Dis 34:1025–1028

    Article  PubMed  Google Scholar 

  45. Neuman MI, Harper MB (2003) Evaluation of a rapid urine antigen assay for the detection of invasive pneumococcal disease in children. Pediatrics 112:1279–1282

    Article  PubMed  Google Scholar 

  46. Domínguez J, Blanco S, Rodrigo C et al (2003) Usefulness of urinary antigen detection by an immunochromatographic test for diagnosis of pneumococcal pneumonia in children. J Clin Microbiol 41:2161–2163

    Article  PubMed  Google Scholar 

  47. Esposito S, Bosis S, Colombo R et al (2004) Evaluation of rapid assay for detection of Streptococcus pneumoniae urinary antigen among infants and young children with possible invasive pneumococcal disease. Pediatr Infect Dis J 23:365–367

    Article  PubMed  Google Scholar 

  48. Vuori E, Peltola H, Kallio M et al (1998) Etiology of pneumonia and other common childhood infections requiring hospitalization and parenteral antimicrobial therapy. Clin Infect Dis 27:566–572

    Article  PubMed  CAS  Google Scholar 

  49. Esposito S, Bosis S, Cavagna R et al (2002) Characteristics of Streptococcus pneumoniae and atypical bacterial infections in children 2–5 years of age with community-acquired pneumonia. Clin Infect Dis 35:1345–1352

    Article  PubMed  Google Scholar 

  50. Juvén T, Mertsola J, Toikka P et al (2001) Clinical profile of serologically diagnosed pneumococcal pneumonia. Pediatr Infect Dis J 20:1028–1033

    Article  PubMed  Google Scholar 

  51. Korppi M, Heiskanen-Kosma T, Kleemola M (2004) Incidence of community-acquired pneumonia in children caused by Mycoplasma pneumoniae: serological results of a prospective, population-based study in primary health care. Respirology 9:109–114

    Article  PubMed  Google Scholar 

  52. Jartti T, Lehtinen P, Vuorinen T et al (2004) Respiratory picornaviruses and respiratory syncytial virus as causative agents of acute expiratory wheezing in children. Emerg Infect Dis 10:1095–1101

    PubMed  Google Scholar 

  53. Koskela M, Leinonen M, Luotonen J (1982) Serum antibody response to pneumococcal otitis media. Pediatr Infect Dis 1:245–252

    PubMed  CAS  Google Scholar 

  54. Virolainen A, Jero J, Chattopadhyay P et al (1996) Comparison of serum antibodies to pneumolysin with those to pneumococcal capsular polysaccharides in children with acute otitis media. Pediatr Infect Dis J 15:128–133

    Article  PubMed  CAS  Google Scholar 

  55. Soininen A, Pursiainen H, Kilpi T et al (2001) Natural development of antibodies to pneumococcal capsular polysaccharides depends on the serotype: association with pneumococcal carriage and acute otitis media in young children. J Infect Dis 184:569–576

    Article  PubMed  CAS  Google Scholar 

  56. Soininen A, Lahdenkari M, Kilpi T et al (2002) Antibody response to pneumococcal capsular polysaccharides in children with acute otitis media. Pediatr Infect Dis J 21:186–192

    Article  PubMed  Google Scholar 

  57. Rapola S, Jäntti V, Haikala R et al (2000) Natural development of antibodies to pneumococcal surface protein A, pneumococcal surface adhesin A, and pneumolysin in relation to pneumococcal carriage and acute otitis media. J Infect Dis 182:146–152

    Article  Google Scholar 

  58. Rapola S, Kilpi T, Lahdenkari M et al (2001) Antibody response to the pneumococcal proteins pneumococcal surface adhesin A and pneumolysin in children with acute otitis media. Pediatr Infect Dis J 20:482–487

    PubMed  CAS  Google Scholar 

  59. Kalin M, Kanclerski K, Granström M et al (1987) Diagnosis of pneumococcal pneumonia by enzyme-linked immunosorbent assay of antibodies to pneumococcal hemolysin (pneumolysin). J Clin Microbiol 25:226–229

    PubMed  CAS  Google Scholar 

  60. Kanclerski K, Blomquist S, Granström M et al (1988) Serum antibodies to pneumolysin in patients with pneumonia. J Clin Microbiol 26:96–100

    PubMed  CAS  Google Scholar 

  61. Porath A, Schlaeffer F, Pick N et al (1997) Pneumococcal community-acquired pneumonia in 148 hospitalized adult patients. Eur J Clin Microbiol Infect Dis 16:863–870

    Article  PubMed  CAS  Google Scholar 

  62. Forgie I, O’Neill K, Lloyd-Evans N et al (1991) Etiology of acute lower respiratory tract infections in Gambian children. II: acute lower respiratory tract infection in children ages one to nine years presenting at the hospital. Pediatr Infect Dis J 10:42–47

    Article  PubMed  CAS  Google Scholar 

  63. Torzillo P, Dixon J, Manning K et al (1999) Etiology of acute lower respiratory tract infection in Central Australian Aboriginal children. Pediatr Infect Dis J 18:714–721

    Article  PubMed  CAS  Google Scholar 

  64. Musher DM, Phan HM, Watson DA et al (2000) Antibody to capsular polysaccharide of Streptococcus pneumoniae at the time of hospital admission for pneumococcal pneumonia. J Infect Dis 182:156–167

    Article  Google Scholar 

  65. Musher DM, Mediwala R, Phan HM et al (2001) Nonspecificity of assaying for IgG antibody to pneumolysin in circulating immune complexes as a means to diagnose pneumococcal pneumonia. Clin Infect Dis 32:534–538

    Article  PubMed  CAS  Google Scholar 

  66. Holloway Y, Snijder JA, Boersma WG (1993) Demonstration of circulating pneumococcal immunoglobulin G immune complexes in patients with community-acquired pneumonia by means of an enzyme-linked immunosorbent assay. J Clin Microbiol 31:3247–3254

    PubMed  CAS  Google Scholar 

  67. Scott JA, Mlacha Z, Nyiro J et al (2005) Diagnosis of invasive pneumococcal disease among children in Kenya with enzyme-linked immunosorbent assay for immunoglobulin G antibodies to pneumococcal surface adhesin A. Clin Diagn Labor Immunol 12:1195–1201

    Article  CAS  Google Scholar 

  68. Lankinen KS, Ruutu P, Nohynek H et al (1999) Pneumococcal pneumonia diagnosis by demonstration of pneumolysin antibodies in precipitated immune complexes: a study in 350 Philippine children with acute lower respiratory infection. Scand J infect Dis 31:155–161

    Article  PubMed  CAS  Google Scholar 

  69. Musher DM, Groover JE, Reichler MR et al (1997) Emergence of antibody to capsular polysaccharides of Streptococcus pneumoniae during outbreaks of pneumonia: association with nasopharyngeal colonization. Clin Infect Dis 24:441–446

    PubMed  CAS  Google Scholar 

  70. Musher DM, Groover JE, Watson DA et al (1997) Genetic regulation of the capacity to make immunoglobulin G to pneumococcal capsular polysaccharides. J Investig Med 45:57–68

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. Korppi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Korppi, M., Leinonen, M. & Ruuskanen, O. Pneumococcal serology in children’s respiratory infections. Eur J Clin Microbiol Infect Dis 27, 167–175 (2008). https://doi.org/10.1007/s10096-007-0436-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-007-0436-8

Keywords

Navigation