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Background: Rates of invasive pneumococcal disease have declined since widespread introduction of pneumococcal conjugate vaccines (PCVs) in the United States. We evaluated the impact of immunization status and recent antibiotic use on an individual child's risk of colonization., Methods: This study extends previously reported data from children <7 years of age seen for well child or acute care visits in Massachusetts communities. Nasopharyngeal swabs were collected during 6 surveillance seasons from 2000 to 2014. Parent surveys and medical record reviews confirmed immunization status and recent antibiotic use. We estimated the proportions of children colonized with PCV7-included, additional PCV13-included, and non-PCV13 serotypes. Risk factors for colonization with additional PCV13-included and non-PCV13 serotypes were assessed by using generalized linear mixed models adjusted for clustering by community., Results: Among 6537 children, 19A emerged as the predominant serotype in 2004, with substantial reductions in 2014. Among non-PCV serotypes, 15B/C, 35B, 23B, 11A, and 23A were most common in 2014. We observed greater odds for both additional PCV13 and non-PCV13 colonization in younger children, those with more child care exposure, and those with a concomitant respiratory tract infection. Adjusted odds for additional PCV13 colonization was lower (odds ratio 0.48 [95% confidence interval 0.31-0.75]) among children up-to-date for PCV13 vaccines. Recent antibiotic use was associated with higher odds of additional PCV13 colonization but substantially lower odds of non-PCV13 colonization., Conclusions: Despite the success of pneumococcal vaccines in reducing colonization and disease due to targeted serotypes, ongoing community-based surveillance will be critical to evaluate the impact of interventions on pneumococcal colonization and disease., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Lipsitch has received consulting fees from Pfizer, Antigen Discovery, and Affinivax and has received research funding through his institution from Pfizer and PATH Vaccine Solutions. Dr Hanage has received consulting fees from Antigen Discovery. Ms Huang conducts clinical studies in which participating hospitals and nursing homes receive contributed products from Sage Products, Molnlycke, 3M, Clorox, and Xttrium. Dr Kleinman conducts trials in which participating hospitals and nursing homes receive contributed products from Sage Products and Clorox. Dr Pelton received honorarium for participation in scientific advisory boards from Pfizer, GlaxoSmithKline, Sequiris, and Merck as well as research funding to Boston University Medical Campus from Pfizer and Merck; the other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2017 by the American Academy of Pediatrics.)

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.

Invasive pneumococcal disease (IPD) has been reduced in the US following conjugate vaccination (PCV7) targeting seven pneumococcal serotypes in 2000. However, increases in IPD due to other serotypes have been observed, in particular 19A. How much this "serotype replacement" will erode the benefits of vaccination and over what timescale is unknown. We used a population genetic approach to test first whether the selective impact of vaccination could be detected in a longitudinal carriage sample, and secondly how long it persisted for following introduction of vaccine in 2000. To detect the selective impact of the vaccine we compared the serotype diversity of samples from pneumococcal carriage in Massachusetts children collected in 2001, 2004 and 2007 with others collected in the pre-vaccine era in Massachusetts, the UK and Finland. The 2004 sample was significantly (p >0.0001) more diverse than pre-vaccine samples, indicating the selective pressure of vaccination. The 2007 sample showed no significant difference in diversity from the pre-vaccine period, and exhibited similar population structure, but with different serotypes. In 2007 the carriage frequency of 19A was similar to that of the most common serotype in pre-vaccine samples. We suggest that serotype replacement involving 19A may be complete in Massachusetts due to similarities in population structure to pre-vaccine samples. These results suggest that the replacement phenomenon occurs rapidly with high vaccine coverage, and may allay concerns about future increases in disease due to 19A. For other serotypes, the future course of replacement disease remains to be determined.

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.

Background: The introduction of pneumococcal conjugate vaccine (PCV) to the U.S. recommended childhood immunization schedule in the year 2000 added three injections to the number of vaccinations a child is expected to receive during the first year of life. Surveys have suggested that the addition of PCV has led some immunization providers to move other routine childhood vaccinations to later ages, which could increase the possibility of missing these vaccines. The purpose of this study was to evaluate whether introduction of PCV affected immunization coverage for recommended childhood vaccinations among 13-month olds in four large provider groups., Methods: In this retrospective cohort study, we analyzed computerized data on vaccinations for 33,319 children in four large provider groups before and after the introduction of PCV. The primary outcome was whether the child was up to date for all non-PCV recommended vaccinations at 13 months of age. Logistic regression was used to evaluate the association between PCV introduction and the primary outcome. The secondary outcome was the number of days spent underimmunized by 13 months. The association between PCV introduction and the secondary outcome was evaluated using a two-part modelling approach using logistic and negative binomial regression., Results: Overall, 93% of children were up-to-date at 13 months, and 70% received all non-PCV vaccinations without any delay. Among the entire study population, immunization coverage was maintained or slightly increased from the pre-PCV to post-PCV periods. After multivariate adjustment, children born after PCV entered routine use were less likely to be up-to-date at 13 months in one provider group (Group C: OR = 0.5; 95% CI: 0.3-0.8) and were less likely to have received all vaccine doses without any delay in two Groups (Group B: OR = 0.4, 95% CI: 0.3 - 0.6; Group C: OR = 0.5, 95% CI: 0.4-0.7). This represented 3% fewer children in Group C who were up-to-date and 14% (Group C) to 16% (Group B) fewer children who spent no time underimmunized at 13 months after PCV entered routine use compared to the pre-PCV baseline. Some disruptions in immunization delivery were also observed concurrent with temporary recommendations to suspend the birth dose of hepatitis B vaccine, preceding the introduction of PCV., Conclusion: These findings suggest that the introduction of PCV did not harm overall immunization coverage rates in populations with good access to primary care. However, we did observe some disruptions in the timely delivery of other vaccines coincident with the introduction of PCV and the suspension of the birth dose of hepatitis B vaccine. This study highlights the need for continued vigilance in coming years as the U.S. introduces new childhood vaccines and policies that may change the timing of existing vaccines.

Objective: To measure parents' and other adults' values for preventing disease associated with pneumococcal infection and to evaluate how including these values changes the economic appraisal of pneumococcal conjugate vaccine., Methods: Data on preferences and willingness to pay to reduce risk of illness were collected for 6 illnesses that are preventable by pneumococcal conjugate vaccine (simple otitis media, complex otitis media, moderate pneumonia, severe pneumonia, bacteremia, and meningitis) and 1 vaccine-related adverse event (fever and fussiness after vaccine). Interviews were conducted with 2 groups of respondents: 1) parents of children who had experienced 1 or more of the outcomes described in the survey (n = 101) and 2) a US community sample (n = 109). The 30-minute telephone interview used modified time trade-off questions and willingness-to-pay questions. Values from the interview were incorporated in an existing decision-analytic model that simulated the cost-effectiveness and cost-benefit of pneumococcal conjugate vaccine in a hypothetical cohort of newborns., Results: Among parents, the median amount of time that respondents said that they would be willing to trade to avoid diseases ranged from 0 days for otitis media to 1 year for severe pneumonia and 2 years for meningitis. Among the US community sample, the median amounts of time traded were higher, ranging from 7 days for otitis media to 3 years for meningitis. Median willingness-to-pay amounts varied from 100 dollars to prevent 1 episode of otitis media and 500 dollars to reduce the risk of meningitis from 21 in 100 000 to 6 in 100 000 and were similar between parents and community members. Incorporating time trade-off amounts into the existing economic model for pneumococcal conjugate vaccine resulted in cost-effectiveness ratios <10 000 dollars per quality-adjusted life year at a vaccine cost of 58 dollars per dose., Conclusions: Both parents and community members assign relatively high values to preventing meningitis, pneumonia, and complex otitis media. When the value of preventing pneumococcal diseases is incorporated into economic analyses, pneumococcal conjugate vaccine has a cost-effectiveness ratio in the range of other widely used health interventions.

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.

Objectives: To 1) describe barriers to pneumococcal conjugate vaccine adoption and 2) estimate the value of the vaccine based on pediatricians' responses to willingness-to-pay questions., Methods: In June 2000, we mailed a random sample of pediatricians in Massachusetts a questionnaire about barriers to adoption of the vaccine and willingness to pay for the vaccine and associated outcomes. Respondents were assigned at random to 1 of 2 survey versions: the Personal Perspective version, for which they imagined spending their own money for their own child, or the Public Perspective version, for which they imagined spending the government's money for the average child., Results: Of the 546 pediatricians who responded (estimated completion rate, 80%), only 9% were using the vaccine routinely at the time of the survey. Most said that if the state did not provide the vaccine, financial barriers including inadequate insurance reimbursement would limit their use of the vaccine either a great deal (61%) or a moderate amount (25%). Pediatricians who were asked how much they would pay for the vaccine for their own child (personal perspective) gave a mean of $56 per dose, whereas those who were asked how much the government should pay on behalf of an average child (public perspective) gave a mean of $36 per dose. Alternatively, when we used a decision analysis model and incorporated pediatricians' values for preventing pneumococcal infections to estimate the vaccine's value, the value per dose was $38 from the personal perspective and $34 from the public perspective., Conclusions: Pediatricians in Massachusetts identified significant financial barriers to the adoption of pneumococcal conjugate vaccine related to insurance arrangements. Based on willingness-to-pay questions, the value of the vaccine is lower than the current list price. The methods used to estimate the value of a vaccine, including the perspective used to frame questions, may substantially influence the results.