Some replacement in pneumococcal carriage with nonvaccine serotypes has been reported since the release of PCV7.9–11,22
This was associated with initial sharp decreases in rates of IPD attributable to vaccine serotypes,1–5,7,8
followed by increases in rates of IPD attributable to nonvaccine strains.1,12–17
Some of these effects on colonization and IPD rates were demonstrated in Massachusetts.10,22,34,35
Through the continued sampling of young children in Massachusetts communities, we now show that nonvaccine serotypes have virtually completely replaced colonizing vaccine serotypes within the 7 years since the release of PCV7. Replacement was correlated temporally with vaccine penetration and was rapid and relatively complete, compared with expectations based on incomplete effects on colonization during vaccine trials.36–38
These results suggest that the risk of pneumococcal disease, although clearly lower than in the prevaccine era, may continue to change in the absence of immunization against noncovered serotypes.
As vaccine serotypes disappear, nonvaccine serotypes have been increasing rapidly in all age groups. Common nonvaccine serotypes found in 2004 have become even more prevalent, with the proportions of infrequent serotypes decreasing. We report significant increases in 19A, 35B, 23A, and 7F prevalence, as well as trends toward increased prevalence of 23B and 16F. Although 19A has already been shown to be responsible for an increasing proportion of IPD, it remains to be seen whether these other serotypes will have similar invasive potential.
We suggest that the selective advantage of penicillin nonsusceptibility may explain in part the increase in specific serotypes. High rates of antibiotic use for common conditions such as acute otitis media may provide pressure in favor of resistant strains among colonized children.39–41
Previous genetic typing work suggested that clonal expansion of serotypes 19A, 35B, and 15A has favored strains that are resistant to penicillin, such as sequence type 199 among 19A serotypes, sequence type 558 among serogroup 35B isolates, and sequence type 63 among 15A serotypes.22,42
The revised national breakpoints for penicillin susceptibility are intended to reflect more closely the likelihood of clinical failure in response to antibiotic therapy. However, attention to the expansion of clones associated with resistance genes and incremental increases in MICs for common antibiotics can warn of impending loss of therapeutic efficacy before detection with these higher laboratory thresholds. Continued evaluation of the changing epidemiological features of pneumococcal serotypes, strain types, and phenotypic resistance is important during a time when the population dynamics of S pneumoniae are changing rapidly and invasive potential remains to be seen.
Despite the nearly complete replacement of vaccine serotypes by nonvaccine serotypes, we found that predictors of carriage remained quite similar between 2001 and 2007, with the exception of age and RTI. This change in age as a risk factor came as a surprise and seemed to be associated with higher colonization rates in young infants. Because we had no previous hypothesis in this direction, additional work will be required to determine whether this apparent trend is real. In later sampling periods, we found that RTI was less strongly associated with S pneumoniae carriage, a finding that seemed to be mediated by a loss of effect on PNSP carriage. Whether this is related to the changing serotype representation of PNSP isolates is not known. Child care persisted as the strongest predictor of pneumococcal carriage, with young siblings and RTI continuing to confer added independent risk. Together, these risk factors conferred a 2.5- to 3-fold increased risk of carriage in all age groups examined.
The persistence of pneumococcal carriage in 30% of young children through the post-PCV7 era and the continued influence of these common characteristics on carriage suggest that reductions in IPD rates will be influenced by the capacity of specific serotypes to produce IPD when carried, rather than by a vaccine-induced reduction in overall carriage rates. Knowledge of the dynamic changes in carried serotypes will be invaluable for understanding invasive potential. For example, we observed minimal evidence of serotype 3 colonization (<1%) in this large multi-community study of young children. Recent reports of increased rates of serotype 3 IPD in some areas of the United States might be better understood in the context of whether increases in serotype 3 carriage prevalence occurred previously.43,44
There are several limitations to this study. We sampled serially during winter respiratory virus seasons to assess changes in the S pneumoniae reservoir during peak times of annual carriage and transmission risk. We cannot know whether changes in carriage or the distributions of S pneumoniae serotypes are similar throughout the year or whether we adjusted completely for differences in respiratory illness rates between sampling periods. In addition, sampling in physician offices may bias our data toward serotypes that are cultured more easily during respiratory illnesses. The frequency of well-child visits and our adjustment for respiratory illness should have mitigated these effects, and the inclusion of children with respiratory illnesses allows assessment of pneumococcal carriage related to a common illness state in this age group. Finally, we did not examine the possibility that children carried multiple strains simultaneously. If this was common, this might have altered perceptions of antibiotic resistance and the relative proportions of nonvaccine serotypes.