Molecular Epidemiology of Pediatric Pneumococcal Empyema from 2001 to 2007 in Utah

The prevalence of parapneumonic empyema (PPE), once a rare complication of pediatric pneumonia (17), has been increasing worldwide over the last decade (10, 11, 13, 14, 19, 23, 26, 28, 30, 34, 37, 46). In Utah, rates of pediatric empyema were increasing prior to the introduction of the seven-valent pneumococcal conjugate vaccine (PCV-7) in 2000 (2, 3). In 1993, we documented empyema in 1/100,000 Utah children, and this rate increased 5-fold to 5/100,000 by 1999 (13). Children with empyema and a positive bacterial culture from blood or pleural fluid were most likely to have Streptococcus pneumoniae serotype 1 infection (13). Furthermore, we documented that all serotype 1 strains isolated in our population between 1996 and 2002 were multilocus sequence type (MLST) 227 (12). Following the licensure of PCV-7, the Utah pediatric population demonstrated immunization rates similar to those demonstrated by other regions of the United States but lower than those in the Centers for Disease Control and Prevention (CDC) Active Bacterial Core surveillance (ABCs) sites (http://www.cdc.gov/abcs/index.htm). By 2003, 55% of Utah children had received three doses of PCV-7 by 35 months, compared to 59% nationally and 62% in states with ABCs sites (16). In 2007, 88% of Utah children had received three doses of PCV-7 by 35 months, compared to 90% nationally and 92% in states with ABCs sites (15). In spite of vaccine uptake that was similar to the rest of the United States, children in Utah did not realize the same degree of decrease in invasive pneumococcal disease (IPD) reported in other parts of the United States (27, 47). The limited effectiveness of the PCV-7 in Utah was in part a result of the rapid emergence of IPD, particularly empyema, due to nonvaccine serotypes (11, 12). Other investigators have identified nonvaccine serotypes, particularly 19A, as important causes of IPD following the licensure of PCV-7 (33, 39-41, 45). Some isolates of 19A from children younger than 5 years old from the ABCs sites demonstrated serotype switching within certain vaccine serotypes (7, 40). Capsular switching or transformation in pneumococci is a well-documented mechanism for the evasion of the host immune response (18). Strain replacement (in part facilitated by capsular switching) in response to the selective pressure exerted by a successful pneumococcal vaccine program that targets a limited number of serotypes could limit the utility of PCV-7. MLST is a nucleotide sequence-based typing system for bacteria and other organisms (32). MLST is based on sequence variation within seven conserved “housekeeping genes” with essential functions. Changes in these gene sequences occur slowly, reflect evolutionary phylogeny, and are not affected by selection pressure. Different sequences at each locus are assigned distinct allele numbers, and “sequence types” (ST) are defined by the combination of alleles at the seven loci interrogated. In the case of S. pneumoniae, genes involved in capsular biosynthesis are not closely linked to MLST targets on the pneumococcal chromosome, so ST are generally unaffected by recombinational replacements that affect serotype switch events. Therefore, screening for new capsular associations found within established ST is an effective method to detect serotype switch events (22). The objectives of this study were to (i) describe the incidence of empyema in Utah children after the licensure of PCV-7, (ii) describe the molecular epidemiology of PPE in Utah in the years following licensure of the PCV-7 vaccine, and (iii) determine, by examining the MLST of PPE isolates, whether serotype replacement or serotype switch was occurring.