May 01, 2007
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Invasive pneumococcal disease finds way around vaccine

Ninety-six percent of the 2005 IPD cases in Dallas were caused by serotypes not contained in PCV7.

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The evolution and changing epidemiology of Streptococcus pneumoniae isolates have caused the continued occurrence of invasive pneumococcal disease in children, despite immunization.

According to findings presented at Miami Children’s Hospital 42nd Annual Pediatric Postgraduate Course: “Perspectives in Pediatrics” by George H. McCracken Jr., MD, the incidence of invasive pneumococcal disease (IPD) significantly decreased in Dallas between 1999 (94 cases/100,000 patients) and 2003 (41 cases/100,000 patients); however, in 2005 the incidence increased (64 cases/100,000 patients). Ninety-six percent of the 2005 IPD cases in Dallas were caused by serotypes not contained in the heptavalent pneumococcal conjugate vaccine (PCV7; Prevnar, Wyeth), with 40% of the disease caused by 19A strains.

“It is likely that PCV7 immunization exerted selective pressure in the nasopharynx of immunized children favorable to colonization by NVT [non-vaccine type] strains, especially serotype 19A, that could subsequently cause IPD in some children,” said McCracken, who is a professor of pediatrics, Glaxo-SmithKline Distinguished Professor of Pediatric Infectious Disease and the Sarah M. and Charles E. Seay Chair in Pediatric Infectious Disease at University of Texas Southwestern Medical Center, Dallas.

Dallas study

Researchers determined the effect of PCV7 on the epidemiology of pneumococcal isolates from children with IPD at the Children’s Medical Center in Dallas from 1999 to 2005. They also identified any new pneumococcal strains causing disease and attempted to determine their genetic characteristics and molecular origins.

IPD isolates were obtained between January 2001 and December 2005 from sterile sites and patients were identified by hospital censuses and culture reports from the Children’s Medical Center microbiology laboratory. All serotype 19A isolates were subjected to additional testing to evaluate genetic relatedness and the strains’ origins.

The analysis of the 19A isolates showed that 67% belonged to a single clonal group, ST-199, which shares origin with vaccine serotype 6. This finding suggests that serotype 6 switched capsules and was replaced by 19A sometime before the start of the Dallas study.

“The capsule can be switched among pneumococci. It’s like taking your sports coat off and putting it on another organism,” said McCracken, who is also the chief editor of the Pediatric Infectious Disease Journal. “It’s just changing its coat to avoid detection and consequent elimination by the immune system.”

Invasive Pneumococcal Diseases at CMC from 1999-2005
Source: George H. McCracken Jr., MD

Future vaccines

According to the CDC, 60,000 cases of IPD occurred each year in the United States before 2000, 17,000 of which were in patients younger than 5 years. S. pneumoniae causes 1.2 million pneumonia deaths every year worldwide, with nearly 40% of those cases in children younger than 5 years.

McCracken said that “future pneumococcal conjugate vaccines will include additional serotypes, and vaccines targeting novel pneumococcal antigens or incorporating different peptide-conjugates are being evaluated.” – by Leanor A. Pigliacelli

For more information:
  • Black S, Shinefield H, Fireman B, et al. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Northern California Kaiser Permanente Vaccine Study Center Group. Pediatr Infect Dis J. 2000;19:187-195.
  • CDC. Preventing pneumococcal disease among infants and young children. MMWR. 2000;49(RR09): 1-38.
  • Klein JO, McCracken GH. Summary: role of a new oral cephalosporin, cefdinir, for therapy of infections of infants and children. Pediatr Infect Dis J. 2000;19:S181-183.
  • Feil EJ, Li BC, Aanensen DM, Hanage WP, Spratt BG. eBURST: inferring patterns of evolutionary descent among clusters of related bacterial genotypes from multilocus sequence typing data. J Bacteriol. 2004;186:1518-1530.
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  • McCracken GH. Impact of the pneumococcal vaccine on invasive disease at a large Children’s Hospital. Grand Session. Presented at: Miami Children’s Hospital 42nd Annual Pediatric Postgraduate Course: “Perspectives in Pediatrics;” March 19-22, 2007; Miami.
  • Messina A, Katz-Gaynor K, Barton T, et al. Impact of the pneumococcal conjugate vaccine on serotype distribution and antimicrobial resistance of invasive Streptococcus pneumoniae isolates in Dallas, TX from 1999 through 2005. Pediatr Infect Dis J. 2007;26:in press.
  • Obaro S, Adegbola R. The pneumococcus: carriage, disease and conjugate vaccines. J Med Microbiol. 2002;51:98-104.
  • Prymula R, Peeters P, Chrobok V, et al. Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typable Haemophilus influenzae: a randomised double-blind efficacy study. Lancet. 2006;367:740-748.
  • Whitney CG, Farle MM, Hadler J. Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med. 2003;348:1737-1746.