Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine

N Engl J Med. 2003 May 1;348(18):1737-46. doi: 10.1056/NEJMoa022823.


Background: In early 2000, a protein-polysaccharide conjugate vaccine targeting seven pneumococcal serotypes was licensed in the United States for use in young children.

Methods: We examined population-based data from the Active Bacterial Core Surveillance of the Centers for Disease Control and Prevention to evaluate changes in the burden of invasive disease, defined by isolation of Streptococcus pneumoniae from a normally sterile site. Serotyping and susceptibility testing of isolates were performed. We assessed trends using data from seven geographic areas with continuous participation from 1998 through 2001 (population, 16 million).

Results: The rate of invasive disease dropped from an average of 24.3 cases per 100,000 persons in 1998 and 1999 to 17.3 per 100,000 in 2001. The largest decline was in children under two years of age. In this group, the rate of disease was 69 percent lower in 2001 than the base-line rate (59.0 cases per 100,000 vs. 188.0 per 100,000, P<0.001); the rate of disease caused by vaccine and vaccine-related serotypes declined by 78 percent (P<0.001) and 50 percent (P<0.001), respectively. Disease rates also fell for adults; as compared with base line, the rate of disease in 2001 was 32 percent lower for adults 20 to 39 years of age (7.6 cases per 100,000 vs. 11.2 per 100,000, P<0.001), 8 percent lower for those 40 to 64 years of age (19.7 per 100,000 vs. 21.5 per 100,000, P=0.03), and 18 percent lower for those 65 years of age or more (49.5 per 100,000 vs. 60.1 per 100,000, P<0.001). The rate of disease caused by strains that were not susceptible to penicillin was 35 percent lower in 2001 than in 1999 (4.1 cases per 100,000 vs. 6.3 per 100,000, P<0.001).

Conclusions: The use of the pneumococcal conjugate vaccine is preventing disease in young children, for whom the vaccine is indicated, and may be reducing the rate of disease in adults. The vaccine provides an effective new tool for reducing disease caused by drug-resistant strains.

Publication types

  • Evaluation Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Heptavalent Pneumococcal Conjugate Vaccine
  • Humans
  • Incidence
  • Infant
  • Meningococcal Vaccines*
  • Middle Aged
  • Penicillin Resistance
  • Pneumococcal Infections / epidemiology*
  • Pneumococcal Infections / microbiology
  • Pneumococcal Infections / prevention & control*
  • Pneumococcal Vaccines*
  • Population Surveillance
  • Serotyping
  • Streptococcus pneumoniae / classification
  • Streptococcus pneumoniae / drug effects
  • Streptococcus pneumoniae / isolation & purification
  • United States / epidemiology
  • Vaccines, Conjugate


  • Heptavalent Pneumococcal Conjugate Vaccine
  • Meningococcal Vaccines
  • Pneumococcal Vaccines
  • Vaccines, Conjugate