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This paper examined whether previously identified community-level factors (high proportion of crowded households and/or persons below the poverty level) remained associated with childhood pneumococcal carriage in the heptavalent pneumococcal conjugate vaccine (PCV7) era. Using logistic regression, individual factors were used to develop base models to which community-level factors were added to evaluate impact on pneumococcal carriage within two paediatric study cohorts from Massachusetts (urban Boston, outside Boston). Six years after introduction of universal childhood PCV7 vaccination, we found no consistent evidence that census tract characteristics (e.g. population size and density, age and race distribution, percent participating in group childcare, parental education, percent lacking in-unit plumbing, poverty, and community stability) affected odds of pneumococcal carriage when added to individual predictors (e.g. younger age, current respiratory tract infections, and attendance in group childcare). How community-level factors influence pneumococcal carriage continues to change in the era of increasing immunization coverage.

Background: We sought to measure trends in Streptococcus pneumoniae carriage and antibiotic resistance in young children in Massachusetts communities after widespread adoption of heptavalent 7-valent pneumococcal conjugate vaccine (PCV7) and before the introduction of the 13-valent PCV (PCV13)., Methods: We conducted a cross-sectional study including collection of questionnaire data and nasopharyngeal specimens among children aged <7 years in primary care practices from 8 Massachusetts communities during the winter season of 2008-2009 and compared with similar studies performed in 2001, 2003-2004, and 2006-2007. Antimicrobial susceptibility testing and serotyping were performed on pneumococcal isolates, and risk factors for colonization in recent seasons (2006-2007 and 2008-2009) were evaluated., Results: We collected nasopharyngeal specimens from 1011 children, 290 (29%) of whom were colonized with pneumococcus. Non-PCV7 serotypes accounted for 98% of pneumococcal isolates, most commonly 19A (14%), 6C (11%), and 15B/C (11%). In 2008-2009, newly targeted PCV13 serotypes accounted for 20% of carriage isolates and 41% of penicillin-nonsusceptible S. pneumoniae. In multivariate models, younger age, child care, young siblings, and upper respiratory illness remained predictors of pneumococcal carriage, despite near-complete serotype replacement. Only young age and child care were significantly associated with penicillin-nonsusceptible S. pneumoniae carriage., Conclusions: Serotype replacement post-PCV7 is essentially complete and has been sustained in young children, with the relatively virulent 19A being the most common serotype. Predictors of carriage remained similar despite serotype replacement. PCV13 may reduce 19A and decrease antibiotic-resistant strains, but monitoring for new serotype replacement is warranted.

Background: Vaccination against 7 serotypes of Streptococcus pneumoniae has led to the near extinction of vaccine serotypes in both disease and asymptomatic carriage. In carriage, vaccine serotypes have been replaced by nonvaccine serotypes., Methods: We used multilocus sequence typing to analyze a sample of 294 isolates of S. pneumoniae carried by Massachusetts children (aged, 3 months-7 years) and examine the results for serotype switching and association with antimicrobial resistance., Results: Eighty-six distinct sequence types (STs) were found, 10 of which exhibited a serotype other than that which would be expected from previous carriage samples. We interpret this as evidence of past or recent serotype switching. Switched variants include ST 320, which is a common and increasing source of multidrug resistance in this community. Switching events within serogroups were more common than expected by chance (P = 0.043 by a Monte Carlo approach). Using multilocus sequence typing data and eBURST analysis, we also describe clonal dynamics within the important replacement serotypes 19A, 15B/C, 35B, and the recently described 6C., Conclusions: Some strains generated by serotype switching are increasingly important parts of the carriage population. In the case of 19A, it appears that the majority of increase is due to ST 320, a recently reported switched variant. This may have consequences for the STs causing invasive pneumococcal disease.

Background: The incidence of community-associated methicillin-resistant Staphylococcus aureus (MRSA) has risen dramatically in the U.S., particularly among children. Although Streptococcus pneumoniae colonization has been inversely associated with S. aureus colonization in unvaccinated children, this and other risk factors for S. aureus carriage have not been assessed following widespread use of the heptavalent pneumococcal conjugate vaccine (PCV7). Our objectives were to (1) determine the prevalence of S. aureus and MRSA colonization in young children in the context of widespread use of PCV7; and (2) examine risk factors for S. aureus colonization in the post-PCV7 era, including the absence of vaccine-type S. pneumoniae colonization., Methods: Swabs of the anterior nares (S. aureus) were obtained from children enrolled in an ongoing study of nasopharyngeal pneumococcal colonization of healthy children in 8 Massachusetts communities. Children 3 months to <7 years of age seen for well child or sick visits in primary care offices from 11/03-4/04 and 10/06-4/07 were enrolled. S. aureus was identified and antibiotic susceptibility testing was performed. Epidemiologic risk factors for S. aureus colonization were collected from parent surveys and chart reviews, along with data on pneumococcal colonization. Multivariate mixed model analyses were performed to identify factors associated with S. aureus colonization., Results: Among 1,968 children, the mean age (SD) was 2.7 (1.8) years, 32% received an antibiotic in the past 2 months, 2% were colonized with PCV7 strains and 24% were colonized with non-PCV7 strains. The prevalence of S. aureus colonization remained stable between 2003-04 and 2006-07 (14.6% vs. 14.1%), while MRSA colonization remained low (0.2% vs. 0.9%, p = 0.09). Although absence of pneumococcal colonization was not significantly associated with S. aureus colonization, age (6-11 mo vs. > or =5 yrs, OR 0.39 [95% CI 0.24-0.64]; 1-1.99 yrs vs. > or =5 yrs, OR 0.35 [0.23-0.54]; 2-2.99 yrs vs. > or =5 yrs, OR 0.45 [0.28-0.73]; 3-3.99 yrs vs. > or =5 yrs, OR 0.53 [0.33-0.86]) and recent antibiotic use were significant predictors in multivariate models., Conclusion: In Massachusetts, S. aureus and MRSA colonization remained stable from 2003-04 to 2006-07 among children <7 years despite widespread use of pneumococcal conjugate vaccine. S. aureus nasal colonization varies by age and is inversely correlated with recent antibiotic use.

Objectives: The goals were to assess serial changes in Streptococcus pneumoniae serotypes and antibiotic resistance in young children and to evaluate whether risk factors for carriage have been altered by heptavalent pneumococcal conjugate vaccine (PCV7)., Methods: Nasopharyngeal specimens and questionnaire/medical record data were obtained from children 3 months to <7 years of age in primary care practices in 16 Massachusetts communities during the winter seasons of 2000-2001 and 2003-2004 and in 8 communities in 2006-2007. Antimicrobial susceptibility testing and serotyping were performed with S pneumoniae isolates., Results: We collected 678, 988, and 972 specimens during the sampling periods in 2000-2001, 2003-2004, and 2006-2007, respectively. Carriage of non-PCV7 serotypes increased from 15% to 19% and 29% (P < .001), with vaccine serotypes decreasing to 3% of carried serotypes in 2006-2007. The relative contribution of several non-PCV7 serotypes, including 19A, 35B, and 23A, increased across sampling periods. By 2007, commonly carried serotypes included 19A (16%), 6A (12%), 15B/C (11%), 35B (9%), and 11A (8%), and high-prevalence serotypes seemed to have greater proportions of penicillin nonsusceptibility. In multivariate models, common predictors of pneumococcal carriage, such as child care attendance, upper respiratory tract infection, and the presence of young siblings, persisted., Conclusions: The virtual disappearance of vaccine serotypes in S pneumoniae carriage has occurred in young children, with rapid replacement with penicillin-nonsusceptible nonvaccine serotypes, particularly 19A and 35B. Except for the age group at highest risk, previous predictors of carriage, such as child care attendance and the presence of young siblings, have not been changed by the vaccine.

Background: Because pneumococcal serotype 6C was previously not distinguished from serotype 6A, the impact of the 7-valent pneumococcal conjugate vaccine (PCV7) on the carriage of serotype 6C is unknown., Methods: The nasopharyngeal (NP) prevalence of the 6C serotype was determined using 1326 pneumococcal isolates collected from 7 cohorts of Massachusetts children between 1994 and 2007. Initially, the isolates were serotyped using the quellung reaction; subsequently, stored specimens of all putative 6A isolates were tested for 6C using monoclonal antibodies. The opsonophagocytic and antibiotic susceptibilities of the isolates were determined., Results: The prevalence of 6A was 9.6% (33/343) before 2001, 8.0% (18/226) in 2004, and 2.9% (12/416) in 2007. In contrast, the prevalence of 6C was 0.6% (2/343) before 2001, 2.2% (5/226) in 2004, and 8.7% (36/416) in 2007 (P<.001 for 2/343 vs. 36/416). 6C isolates from 2007 were more susceptible to antibiotics than were 6A isolates. PCV7 induced a low ability to opsonize different isolates of 6C., Conclusions: Among NP isolates, the prevalence of 6C isolates has increased and the prevalence of 6A isolates has decreased since the introduction of PCV7 in Massachusetts in 2000. The observed increase in serotype 6C prevalence may be explained by the induction by PCV7 of low amounts of functional anti-6C antibody, compared with anti-6A and anti-6B antibodies.

Background: In response to the selective pressure of pneumococcal conjugate vaccine, increased asymptomatic carriage of antibiotic-nonsusceptible nonvaccine serotypes (NVTs) has been observed. Possible mechanisms include de novo acquisition of resistance, serotype switching, introduction of new clones, and expansion of existing clones., Methods: To investigate the process of increased antibiotic nonsusceptibility among replacing serotypes, we applied multilocus sequence typing to samples of 126 and 222 pneumococci collected in 2001 and 2004, respectively, from the nasopharynges of children <7 years of age in 16 Massachusetts communities., Results: We found no evidence of penicillin resistance due to either serotype switching or de novo acquisition. Nonetheless, resistance increased through the expansion of previously recognized clones of NVTs, particularly in serotypes 19A, 15A, and 35B. In 19A, several unrelated clones increased in frequency, whereas, in the other 2 serotypes, single resistant lineages were responsible for the increased prevalence of resistant strains., Conclusions: The decreased prevalence of antibiotic resistance with the introduction of heptavalent pneumococcal conjugate vaccine is likely to be partially eroded over time as vaccine-included serotypes are replaced by resistant clones of NVTs. The clinical significance of this will depend on the pathogenic potential of replacing clones to cause local (e.g., otitis media) or invasive disease.

Background: The prevalence of pneumococcal carriage varies widely across communities. This variation is not fully explained by risk factors at the individual level but may be explained by factors producing effects at both the individual and community levels, such as child-care center (CCC) attendance., Methods: We developed a transmission model to evaluate whether the combined risks of attending CCCs and associating with playmates who attend CCCs account for a large proportion of the variability in the prevalence of pneumococcal carriage across communities. We based parameters for the model on data from a multicommunity study., Results: According to our model, differences in the proportion of children who attend CCCs can account for a range of 4%-56% in the prevalence of pneumococcal carriage across communities. Our model, which was based on data collected from 16 Massachusetts communities, predicts that the odds of carriage associated with CCC attendance are 2-3 times the odds associated with no CCC attendance (individual-level effect). The model also predicts that the odds of carriage for nonattendees in a community with CCCs are up to 6 times the odds for children in a community without CCCs (community-level effect). In addition, the mean number of hours spent at CCCs by a single attendee appears to exert effects on pneumococcal carriage that are independent of either the proportion of CCC attendance in the community or the mean number of hours these attendees spend in child care., Conclusions: We used data from multiple communities to develop a transmission model that explains marked differences in pneumococcal carriage across communities by variations in CCC attendance. This model only accounts for CCC attendance among young children and does not include other known risk factors for pneumococcal carriage.

Pneumococcal carriage and resistance vary markedly among communities and are not fully explained by individual predictors. Community risk factors may explain this variation. The authors geocoded addresses from a multicommunity sample of 710 Massachusetts children previously swabbed for pneumococcal carriage in 2001. Using regression models, the authors evaluated associations between census tract measures and pneumococcal carriage or resistance. Living in census tracts with an average household size of more than 2.9 predicted carriage (odds ratio = 3.0, 95% confidence interval: 1.7, 5.5), and living in socioeconomically disadvantaged census tracts conferred an additional two- to threefold odds of carriage equal to attending child care. Living in a census tract with a median household income of less than $35,000 predicted carriage among nonattendees (odds ratio = 2.7, 95% confidence interval: 1.7, 4.3). The predictive value of a low-income census tract was interchangeable with any of several socioeconomic measures, including poverty, unemployment, low educational attainment, and low owner occupancy, in addition to high density of children and limited household plumbing facilities. Furthermore, living in census tracts with low educational attainment significantly predicted resistance (odds ratio = 4.0, 95% confidence interval: 1.3, 12.7) and was interchangeable with a high density of children (odds ratio = 3.5, 95% confidence interval: 1.0, 11.7). The two- to threefold odds of pneumococcal carriage conferred by certain community characteristics suggest that these measures may target communities for interventions to decrease transmission.

Objective: Despite immunization with heptavalent pneumococcal conjugate vaccine (PCV7), the rising prevalence of antibiotic resistance makes Streptococcus pneumoniae a continuing threat to child health. Data on carriage of resistant organisms by healthy children in communities in which immunization with PCV7 has been implemented will help to define and decrease these risks further., Methods: Children who were <7 years old, resided in a study community, and presented for routine well care or a "sick" visit between March 13 and May 11, 2001, at 31 primary care practices in 16 geographically distinct Massachusetts communities were studied. Consenting parents provided demographic information and data on potential risk factors for carriage of S pneumoniae and of penicillin-nonsusceptible S pneumoniae (PNSP). S pneumoniae isolates from nasopharyngeal specimens were tested for resistance to commonly used antibiotics including penicillin, ceftriaxone, erythromycin, and trimethoprim/sulfamethoxazole. Isolates were serotyped and grouped into PCV7-included serotypes, potentially cross-reactive serotypes (ie, an organism of a serogroup included in the vaccine), or non-PCV7 serotypes. Diagnosis on the day of collection, history of recent antibiotic use, and history of PCV7 immunization were obtained by chart review. Separate bivariate and multivariate analyses were performed to identify correlates of colonization with S pneumoniae and colonization with PNSP, accounting for clustering within communities., Results: S pneumoniae was isolated from the nasopharynx of 190 (26%) of the 742 children studied. Of the 166 tested, 33% were nonsusceptible to penicillin, with 14% showing intermediate susceptibility (minimum inhibitory concentration [MIC] 0.12-1.0) and 19% fully resistant (MIC > or =2). Nonsusceptibility to other antibiotics was common, including ceftriaxone (14%), erythromycin (22%), and trimethoprim/sulfa (31%); 20% of S pneumoniae isolates were not susceptible to > or =3 antibiotics. Thirty-six percent of isolates were of serotypes covered by PCV7; 30% were of PCV7 serogroups and potentially cross-reactive, but not 1 of the 7 included serotypes; and 34% were unrelated to PCV7 serogroups. Nonsusceptibility to penicillin was more common in PCV7-included strains (45%) and potentially cross-reactive strains (51%) than in non-PCV7 serotypes (8%). Risk factors for PNSP colonization included child care attendance (odds ratio [OR]: 3.9; 95% confidence interval [CI]: 2.3-6.5), current respiratory tract infection (OR: 4.7; 95% CI: 2.5-8.6), and recent antibiotic use (OR: 1.7; 95% CI: 1.0-2.8). PCV7 immunization was associated with decreased carriage of PCV7-included serotypes but not with an overall decrease in S pneumoniae colonization or with a decline in PNSP colonization., Conclusions: In this multicommunity sample, pneumococcal antibiotic resistance was common and was most frequently found in PCV7-included and PCV7 serogroup strains. The long-term impact of PCV7 immunization will be partially determined by the protection that it affords against invasive infection with potentially cross-reactive serotypes, as well as the virulence and future resistance patterns of unrelated serotypes.

As part of an ongoing study of the response of the Streptococcus pneumoniae population to conjugate vaccination, we applied multi-locus sequence typing (MLST) to 291 isolates sampled from nasopharyngeal carriage in Massachusetts children. We found 94 distinct sequence types (STs), including 19 that had not been previously recorded, and a xpt allele containing a large insertion. Comparison with a similar sample collected in 2007 revealed no significant overall difference in the ST composition (p=0.51) suggesting that the population has reached a new equilibrium following the introduction of 7 valent vaccination in 2000. Within serotypes, a large and statistically significant increase (p=0.014 Fisher's Exact test) was noted in the prevalence of the major multiresistant clone ST 320, which is apparently outcompeting ST 199 among serotype 19A strains. This sample will be used as a baseline to study the future evolution of the pneumococcal population in Massachusetts following introduction of vaccines with higher valency.