The Changing Epidemiology of Streptococcus pneumoniae Serotype 19A Clonal Complexes

Abstract

(See the article by Beall et al, on pages 1360-8.) Streptococcus pneumoniae is a leading cause of pneumonia throughout the world and a major cause of serious invasive disease, especially in the very young and the elderly. The major virulence factor of S. pneumoniae is its polysaccharide capsule, which can be expressed as 91 different capsular serotypes [1, 2].Seven serotypes (those of high prevalence in children prior to 2000; serotype [sero]4, sero6B, sero9V, sero14, sero18C, sero19F and sero23F) constitute a very effective protein conjugate vaccine, PCV7, which has been in use throughout the world, including the United States, since 2000. While the vaccine serotypes contained in PCV7 have declined in prevalence over the last decade, other serotypes, most notably sero19A, have become more prevalent throughout North America and Europe [3–8]. To add cause for concern, many of the sero19A strains circulating are also resistant to multiple antimicrobial agents, making them difficult to treat. Six years after the introduction of PCV7, sero19A is the most common invasive pneumococcal serotype in the United States, with a substantial proportion of its strains being antimicrobial resistant [9]. Although the serotype designation is important for understanding pneumococcal epidemiology, to gain a deeper perspective of the pneumococci circulating globally, a technique termed multilocus sequence typing (MLST) is used. MLST is a nucleotide sequence–based approach to characterizing bacterial strains [10]. It involves the DNA sequencing of internal fragments of 7 housekeeping genes from the pneumococcal genome. The sequences are compared with previously identified sequences (alleles) and assigned an allele number for each of the 7 loci. The 7 number combinations denote an allelic profile of the strain that is then assigned a sequence type (ST) designation. Sequence types are grouped into “clonal complexes.” To be part of clonal complex, members must have typically 5 or 6 loci that match. Interestingly and importantly, isolates with different serotypes can be members of the same clonal complex. Detailed information regarding S. pneumoniae MLST analysis is provided on the pneumococcal MLST website, hosted by Imperial College, London (http://spneumoniae.mlst.net/). The information provided by MLST is global in scope but more in-depth than the serotype designation. In this issue of the Journal, Beall and colleagues describe the recent epidemiology of S. pneumoniae sero19A in the United States from isolates collected through the Centers for Disease Control and Prevention (CDC) Active Bacterial Core (ABC) surveillance program. Their detailed MLST analysis of sero19A isolates has shown that while the prevalence of sero19A strains seems to have stabilized since 2005, the numbers of isolates within specific sero19A clonal complexes have fluctuated significantly. These changes have resulted in declines in clonal complex prevalence, increases in clonal complex prevalence, or appearance of new sero19A clonal complexes. Currently, 3 main clonal complexes dominate the invasive pneumococcal disease sero19A landscape in the United States. These have been designated clonal complex (CC)19919A, CC320/27119A, and CC69519A. These 3 clonal complexes collectively comprise approximately 87% of the sero19A isolates collected from 2005–2007 [11]. Brief descriptions of each of these clonal complexes with respect to prevalence over recent years is given below.