Pneumococcal Serotypes before and after Introduction of Conjugate Vaccines, United States, 1999–2011¹

Sandra S. Richter

, Kristopher P. Heilmann, Cassie L. Dohrn, Fathollah Riahi, Daniel J. Diekema, and Gary V. Doern

Author affiliations: Cleveland Clinic, Cleveland, Ohio, USA (S.S. Richter); University of Iowa Carver College of Medicine, Iowa City, Iowa, USA (K.P. Heilmann, C.L. Dohrn, F. Riahi, D.J. Diekema, G.V. Doern)

Abstract

Serotyping data for pneumococci causing invasive and noninvasive disease in 2008–2009 and 2010–2011 from >43 US centers were compared with data from preconjugate vaccine (1999–2000) and postconjugate vaccine (2004–2005) periods. Prevalence of 7-valent pneumococcal conjugate vaccine serotypes decreased from 64% of invasive and 50% of noninvasive isolates in 1999–2000 to 3.8% and 4.2%, respectively, in 2010–2011. Increases in serotype 19A stopped after introduction of 13-valent pneumococcal vaccine (PCV13) in 2010. Prevalences of other predominant serotypes included in or related to PCV13 (3, 6C, 7F) also remained similar for 2008–2009 and 2010–2011. The only major serotype that increased from 2008–2009 to 2010–2011 was nonvaccine serotype 35B. These data show that introduction of the 7-valent vaccine has dramatically decreased prevalence of its serotypes and that addition of serotypes in PCV13 could provide coverage of 39% of isolates that continue to cause disease.

Infections caused by Streptococcus pneumoniae include meningitis, pneumonia, bacteremia, bronchitis, sinusitis, and otitis media. The World Health Organization estimated that 50%–60% of the 1.6 million deaths caused by pneumococcal infections in 2005 were in children <5 years of age (1). In the United States, ≈39,750 cases of invasive pneumococcal disease and 4,000 deaths occur annually (2). Since 1977, immunization with a 14-valent (now 23-valent) polysaccharide vaccine has been available in the United States for persons >2 years of age who have an increased risk for serious pneumococcal disease (3). Increasing antimicrobial drug resistance in S. pneumoniae during the 1990s highlighted the need for a vaccine with effectiveness in young children (4,5). In 2000, a 7-valent pneumococcal polysaccharide protein conjugate vaccine (PCV7, Prevnar; Wyeth, New York, NY, USA) for serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F became available in the United States for routine use in all children 2–23 months of age and for children 24–59 months of age who are at increased risk for pneumococcal disease (6).
A 30% decrease in the incidence of pneumococcal meningitis in the United States from 1998–1999 through 2004–2005 was attributed to direct vaccine effect and herd immunity, but the percentage of cases caused by non-PCV7 serotype strains, particularly 19A, increased (7,8). In 2007, the World Health Organization recommended use of PCV7 in all countries as part of routine childhood immunization (1), and Centers for Disease Control and Prevention (CDC) (Atlanta, GA, USA) guidance for routine use was revised to include healthy children 24–59 months of age who had not yet completed any recommended PCV7 vaccination schedule (9). A second pneumococcal conjugate 13-valent vaccine (PCV13) with 6 additional serotypes (1, 3, 5, 6A, 7F, and 19A) was licensed for use in the United States in March 2010 (10).
The large number of pneumococcal serotypes and ability of this organism to switch capsules has made prevention of disease through vaccination challenging. The recognition of new serotypes, 6C and 6D, in 2007 and 2009 brought the total number of known pneumococcal serotypes to 93 (11,12). A large portion of isolates identified as serotype 6A in the past were likely 6C or 6D. Monitoring of pneumococcal serotypes causing disease provides insight into pathogenesis and guidance for vaccine composition.
Although the effect of pneumococcal vaccine on invasive disease has been documented (7,8,13,14), the effect on noninvasive disease is unclear. CDC has conducted longitudinal surveillance for invasive pneumococcal disease by using 10 selected sites since the 1990s, but noninvasive disease has been excluded (2). Collection of diagnostic specimens that confirm the etiologic agent causing pneumonia, bronchitis, sinusitis, and otitis media can be difficult. Although isolation of S. pneumoniae from a normally sterile site is always considered a pathogen, recovery from a respiratory site may represent colonization. Despite these limitations, the role of surveillance that is not limited to isolates causing invasive disease is shown by recent studies reporting high case-fatality rates for noninvasive serotypes (15–17).
The purpose of this study was to examine changes in pneumococcal serotypes causing invasive and noninvasive disease in all age groups in the United State from 1999–2000 through 2010–2011. The data examined reflect longitudinal surveillance from 4 periods before and after conjugate vaccine use was implemented.