Skip to main content

Advertisement

SpringerLink
Log in

Serotype 3 is a common serotype causing invasive pneumococcal disease in children less than 5 years old, as identified by real-time PCR

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

Abstract

Serotype 3 is one of the most often detected pneumococcal serotypes in adults and it is associated with serious disease. In contrast, the isolation of serotype 3 by bacterial culture is unusual in children with invasive pneumococcal disease (IPD). The purpose of this study was to learn the serotype distribution of IPD, including culture-negative episodes, by using molecular methods in normal sterile samples. We studied all children <5 years of age with IPD admitted to two paediatric hospitals in Catalonia, Spain, from 2007 to 2009. A sequential real-time polymerase chain reaction (PCR) approach was added to routine methods for the detection and serotyping of pneumococcal infection. Among 257 episodes (219 pneumonia, 27 meningitis, six bacteraemia and five others), 33.5% were identified by culture and the rest, 66.5%, were detected exclusively by real-time PCR. The most common serotypes detected by culture were serotypes 1 (26.7%) and 19A (25.6%), and by real-time PCR, serotypes 1 (19.8%) and 3 (18.1%). Theoretical coverage rates by the PCV7, PCV10 and PCV13 vaccines were 10.5, 52.3 and 87.2%, respectively, for those episodes identified by culture, compared to 5.3, 31.6 and 60.2% for those identified only by real-time PCR. Multiplex real-time PCR has been shown to be useful for surveillance studies of IPD. Serotype 3 is underdiagnosed by culture and is important in paediatric IPD.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. O’Brien KL, Wolfson LJ, Watt JP, Henkle E, Deloria-Knoll M, McCall N et al (2009) Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet 374:893–902

    Article  PubMed  Google Scholar 

  2. Zhang Y, Isaacman DJ, Wadowsky RM, Rydquist-White J, Post JC, Ehrlich GD (1995) Detection of Streptococcus pneumoniae in whole blood by PCR. J Clin Microbiol 33:596–601

    PubMed  CAS  Google Scholar 

  3. Muñoz-Almagro C, Gala S, Selva L, Jordan I, Tarragó D, Pallares R (2011) DNA bacterial load in children and adolescents with pneumococcal pneumonia and empyema. Eur J Clin Microbiol Infect Dis 30:327–335

    Article  PubMed  Google Scholar 

  4. Azzari C, Moriondo M, Indolfi G, Massai C, Becciolini L, de Martino M et al (2008) Molecular detection methods and serotyping performed directly on clinical samples improve diagnostic sensitivity and reveal increased incidence of invasive disease by Streptococcus pneumoniae in Italian children. J Med Microbiol 57:1205–1212

    Article  PubMed  CAS  Google Scholar 

  5. Corless CE, Guiver M, Borrow R, Edwards-Jones V, Fox AJ, Kaczmarski EB (2001) Simultaneous detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae in suspected cases of meningitis and septicemia using real-time PCR. J Clin Microbiol 39:1553–1558

    Article  PubMed  CAS  Google Scholar 

  6. Van Gastel E, Bruynseels P, Verstrepen W, Mertens A (2007) Evaluation of a real-time polymerase chain reaction assay for the diagnosis of pneumococcal and meningococcal meningitis in a tertiary care hospital. Eur J Clin Microbiol Infect Dis 26:651–653

    Article  PubMed  Google Scholar 

  7. Lahti E, Mertsola J, Kontiokari T, Eerola E, Ruuskanen O, Jalava J (2006) Pneumolysin polymerase chain reaction for diagnosis of pneumococcal pneumonia and empyema in children. Eur J Clin Microbiol Infect Dis 25:783–789

    Article  PubMed  CAS  Google Scholar 

  8. Picazo J, Ruiz-Contreras J, Casado-Flores J, Giangaspro E, Del Castillo F, Hernández-Sampelayo T et al (2011) Relationship between serotypes, age, and clinical presentation of invasive pneumococcal disease in Madrid, Spain, after introduction of the 7-valent pneumococcal conjugate vaccine into the vaccination calendar. Clin Vaccine Immunol 18:89–94

    Article  PubMed  CAS  Google Scholar 

  9. Muñoz-Almagro C, Jordan I, Gene A, Latorre C, García-García JJ, Pallares R (2008) Emergence of invasive pneumococcal disease caused by nonvaccine serotypes in the era of 7-valent conjugate vaccine. Clin Infect Dis 46:174–182

    Article  PubMed  Google Scholar 

  10. Clinical and Laboratory Standards Institute (CLSI) (2010) Performance Standards for Antimicrobial Susceptibility Testing; Twentieth Informational Supplement. M100-S20. CLSI, Wayne, PA, USA

  11. Tarragó D, Fenoll A, Sánchez-Tatay D, Arroyo LA, Muñoz-Almagro C, Esteva C et al (2008) Identification of pneumococcal serotypes from culture-negative clinical specimens by novel real-time PCR. Clin Microbiol Infect 14:828–834

    Article  PubMed  Google Scholar 

  12. Singleton RJ, Hennessy TW, Bulkow LR, Hammitt LL, Zulz T, Hurlburt DA et al (2007) Invasive pneumococcal disease caused by nonvaccine serotypes among Alaska native children with high levels of 7-valent pneumococcal conjugate vaccine coverage. JAMA 297:1784–1792

    Article  PubMed  CAS  Google Scholar 

  13. Lehmann D, Willis J, Moore HC, Giele C, Murphy D, Keil AD et al (2010) The changing epidemiology of invasive pneumococcal disease in aboriginal and non-aboriginal western Australians from 1997 through 2007 and emergence of nonvaccine serotypes. Clin Infect Dis 50:1477–1486

    Article  PubMed  Google Scholar 

  14. Fenoll A, Granizo JJ, Aguilar L, Giménez MJ, Aragoneses-Fenoll L, Hanquet G et al (2009) Temporal trends of invasive Streptococcus pneumoniae serotypes and antimicrobial resistance patterns in Spain from 1979 to 2007. J Clin Microbiol 47:1012–1020

    Article  PubMed  CAS  Google Scholar 

  15. Siira L, Rantala M, Jalava J, Hakanen AJ, Huovinen P, Kaijalainen T et al (2009) Temporal trends of antimicrobial resistance and clonality of invasive Streptococcus pneumoniae isolates in Finland, 2002 to 2006. Antimicrob Agents Chemother 53:2066–2073

    Article  PubMed  CAS  Google Scholar 

  16. Harboe ZB, Benfield TL, Valentiner-Branth P, Hjuler T, Lambertsen L, Kaltoft M et al (2010) Temporal trends in invasive pneumococcal disease and pneumococcal serotypes over 7 decades. Clin Infect Dis 50:329–337

    Article  PubMed  Google Scholar 

  17. Byington CL, Hulten KG, Ampofo K, Sheng X, Pavia AT, Blaschke AJ et al (2010) Molecular epidemiology of pediatric pneumococcal empyema from 2001 to 2007 in Utah. J Clin Microbiol 48:520–525

    Article  PubMed  CAS  Google Scholar 

  18. Weatherholtz R, Millar EV, Moulton LH, Reid R, Rudolph K, Santosham M et al (2010) Invasive pneumococcal disease a decade after pneumococcal conjugate vaccine use in an American Indian population at high risk for disease. Clin Infect Dis 50:1238–1246

    Article  PubMed  Google Scholar 

  19. Marimon JM, Ercibengoa M, Alonso M, Zubizarreta M, Pérez-Trallero E (2009) Clonal structure and 21-year evolution of Streptococcus pneumoniae serotype 1 isolates in Northern Spain. Clin Microbiol Infect 15:875–877

    Article  PubMed  CAS  Google Scholar 

  20. Nunes S, Sá-Leão R, Pereira LC, Lencastre H (2008) Emergence of a serotype 1 Streptococcus pneumoniae lineage colonising healthy children in Portugal in the seven-valent conjugate vaccination era. Clin Microbiol Infect 14:82–84

    Article  PubMed  CAS  Google Scholar 

  21. Kaplan SL, Barson WJ, Lin PL, Stovall SH, Bradley JS, Tan TQ et al (2010) Serotype 19A is the most common serotype causing invasive pneumococcal infections in children. Pediatrics 125:429–436

    Article  PubMed  Google Scholar 

  22. Muñoz-Almagro C, Esteva C, de Sevilla MF, Selva L, Gene A, Pallares R (2009) Emergence of invasive pneumococcal disease caused by multidrug-resistant serotype 19A among children in Barcelona. J Infect 59:75–82

    Article  PubMed  Google Scholar 

  23. Moore MR, Gertz RE Jr, Woodbury RL, Barkocy-Gallagher GA, Schaffner W, Lexau C et al (2008) Population snapshot of emergent Streptococcus pneumoniae serotype 19A in the United States, 2005. J Infect Dis 197:1016–1027

    Article  PubMed  Google Scholar 

  24. Reinert RR, Reinert S, van der Linden M, Cil MY, Al-Lahham A, Appelbaum P (2005) Antimicrobial susceptibility of Streptococcus pneumoniae in eight European countries from 2001 to 2003. Antimicrob Agents Chemother 49:2903–2913

    Article  PubMed  CAS  Google Scholar 

  25. Imöhl M, Reinert RR, Ocklenburg C, van der Linden M (2010) Association of serotypes of Streptococcus pneumoniae with age in invasive pneumococcal disease. J Clin Microbiol 48:1291–1296

    Article  PubMed  Google Scholar 

  26. Hausdorff WP, Bryant J, Paradiso PR, Siber GR (2000) Which pneumococcal serogroups cause the most invasive disease: implications for conjugate vaccine formulation and use, part I. Clin Infect Dis 30:100–121

    Article  PubMed  CAS  Google Scholar 

  27. Rückinger S, von Kries R, Siedler A, van der Linden M (2009) Association of serotype of Streptococcus pneumoniae with risk of severe and fatal outcome. Pediatr Infect Dis J 28:118–122

    Article  PubMed  Google Scholar 

  28. Obando I, Muñoz-Almagro C, Arroyo LA, Tarrago D, Sanchez-Tatay D, Moreno-Perez D et al (2008) Pediatric parapneumonic empyema, Spain. Emerg Infect Dis 14:1390–1397

    Article  PubMed  Google Scholar 

  29. Bender JM, Ampofo K, Byington CL, Grinsell M, Korgenski K, Daly JA et al (2010) Epidemiology of Streptococcus pneumoniae-induced hemolytic uremic syndrome in Utah children. Pediatr Infect Dis J 29:712–716

    Article  PubMed  Google Scholar 

  30. Ogami M, Hotomi M, Togawa A, Yamanaka N (2010) A comparison of conventional and molecular microbiology in detecting differences in pneumococcal colonization in healthy children and children with upper respiratory illness. Eur J Pediatr 169:1221–1225

    Article  PubMed  Google Scholar 

  31. Arbique JC, Poyart C, Trieu-Cuot P, Quesne G, Carvalho Mda G, Steigerwalt AG et al (2004) Accuracy of phenotypic and genotypic testing for identification of Streptococcus pneumoniae and description of Streptococcus pseudopneumoniae sp. nov. J Clin Microbiol 42:4686–4696

    Article  PubMed  CAS  Google Scholar 

  32. Keith ER, Podmore RG, Anderson TP, Murdoch DR (2006) Characteristics of Streptococcus pseudopneumoniae isolated from purulent sputum samples. J Clin Microbiol 44:923–927

    Article  PubMed  Google Scholar 

  33. Simões AS, Sá-Leão R, Eleveld MJ, Tavares DA, Carriço JA, Bootsma HJ et al (2010) Highly penicillin-resistant multidrug-resistant pneumococcus-like strains colonizing children in Oeiras, Portugal: genomic characteristics and implications for surveillance. J Clin Microbiol 48:238–246

    Article  PubMed  Google Scholar 

  34. Muñoz-Almagro C, Selva L, Sanchez CJ, Esteva C, de Sevilla MF, Pallares R et al (2010) PsrP, a protective pneumococcal antigen, is highly prevalent in children with pneumonia and is strongly associated with clonal type. Clin Vaccine Immunol 17:1672–1678

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by Fondo de Investigación Sanitaria (FIS, project number 06/1597), Caja Navarra Foundation and AGAUR 2009/SGR00136.

We are very appreciative of Dr. Fenoll (National Center of Microbiology, Majadahonda, Madrid, Spain) for the conventional serotyping of isolates.

This paper was published in part at the 7th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD-7), Tel Aviv, Israel, March 14–18, 2010 (abstract P-134).

Transparency declaration

P. Ciruela., M.F. de Sevilla, S. Hernandez and J.J. García-García have received a travel grant from Pfizer. F. Moraga has received honoraria for consultancy and speaking at scientific meetings from Pfizer and GSK. L. Salleras has received travel grants and honoraria for speaking at scientific meetings organised by Sanofi Pasteur MSD, GSK, Novartis Vaccines, Pfizer, Crucell Berna and Esteve.

Author information

Authors and Affiliations

  1. Molecular Microbiology Department, Hospital Universitari Sant Joan de Déu, Passeig Sant Joan de Déu, 2, 08950, Esplugues de Llobregat, Barcelona, Spain

    L. Selva, C. Esteva, M. F. de Sevilla, S. Hernandez, J. J. García-García, I. Jordan & C. Muñoz-Almagro

  2. General Directorate of Public Health, Generalitat de Catalunya, C. Roc Boronat, 81–95, 08005, Barcelona, Spain

    P. Ciruela, N. Cardeñosa & J. Batalla

  3. Hospital Universitari Vall d’Hebron, Passeig Vall d’Hebron, 08038, Barcelona, Spain

    G. Codina, F. Moraga, A. Planes & F. Coll

  4. Public Health Department, University of Barcelona, C. Casanova 143, 08036, Barcelona, Spain

    N. Cardeñosa, L. Salleras & A. Dominguez

  5. CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain

    L. Salleras & A. Dominguez

Authors
  1. L. Selva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Ciruela
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Esteva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. F. de Sevilla
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Codina
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. Hernandez
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. F. Moraga
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J. J. García-García
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A. Planes
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. F. Coll
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. I. Jordan
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. N. Cardeñosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. J. Batalla
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. L. Salleras
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. A. Dominguez
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. C. Muñoz-Almagro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. Muñoz-Almagro.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Selva, L., Ciruela, P., Esteva, C. et al. Serotype 3 is a common serotype causing invasive pneumococcal disease in children less than 5 years old, as identified by real-time PCR. Eur J Clin Microbiol Infect Dis 31, 1487–1495 (2012). https://doi.org/10.1007/s10096-011-1468-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-011-1468-7

Keywords

Search

Navigation