Emergence of Invasive Pneumococcal Disease Caused by Nonvaccine Serotypes in the Era of 7-valent Conjugate Vaccine

Clin Infect Dis. 2008 Jan 15;46(2):174-82. doi: 10.1086/524660.


Background: Little is known about the epidemiology of invasive pneumococcal disease (IPD) after the introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in Spain and other European countries.

Methods: We performed a 10-year prospective study including all children with culture-proven IPD admitted to Sant Joan de Deu Hospital, a children's center in the southern area of Barcelona, Catalonia, Spain. PCV7 was introduced in June 2001, and the current estimate of PCV7 coverage is 45%-50%.

Results: Comparing the prevaccine period (1997-2001) with the vaccine period (2002-2006), among children aged <2 years, the rate of IPD increased from 32.4 episodes per 100,000 population to 51.3 episodes per 100,000 population (an increase of 58%; 95% confidence interval, 2%-145%), and among children aged 2-4 years, the rate increased from 11.3 episodes per 100,000 population to 26.5 episodes per 100,000 population (an increase of 135%; 95% confidence interval, 31%-320%). At clinical presentation, the rate of pneumonia and/or empyema among children aged <5 years increased from 3.6 episodes per 100,000 population to 15.1 episodes per 100,000 population (an increase of 320%; 95% confidence interval, 98%-790%). These increased rates of IPD were caused by non-PCV7 serotypes, which represented 38% and 72% of infecting serotypes in the prevaccine and vaccine periods, respectively (P=.001). Penicillin resistance decreased from 48% in the prevaccine period to 27% in the vaccine period (P=.005). In the vaccine period, there was an emergence of previously established virulent clones of non-PCV7 serotypes 1 and 5. There was also an increase in the prevalence of serotypes 19A and 6A expressed with different clonal types, including Spain(23F)-1 and Spain(6B)-2.

Conclusions: Since the introduction of PCV7 for children, there has been an emergence of IPD caused by virulent clones of non-PCV7 serotypes that has been associated with significant clinical changes and a decrease in antibiotic resistance.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Drug Resistance, Multiple, Bacterial
  • Female
  • Heptavalent Pneumococcal Conjugate Vaccine
  • Humans
  • Immunization Programs
  • Infant
  • Male
  • Meningococcal Vaccines / immunology
  • Meningococcal Vaccines / therapeutic use*
  • Pneumococcal Infections / epidemiology*
  • Pneumococcal Infections / microbiology*
  • Pneumococcal Infections / prevention & control
  • Pneumococcal Vaccines / immunology
  • Pneumococcal Vaccines / therapeutic use*
  • Prospective Studies
  • Serotyping
  • Spain / epidemiology
  • Streptococcus pneumoniae / genetics
  • Streptococcus pneumoniae / immunology*
  • Streptococcus pneumoniae / isolation & purification


  • Heptavalent Pneumococcal Conjugate Vaccine
  • Meningococcal Vaccines
  • Pneumococcal Vaccines