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BackgroundIn April 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 for use in the United States. We evaluated rates of pneumococcal colonization, by serotype and antibiotic resistance, in Massachusetts communities where serial cross-sectional surveillance has been conducted for the past decade.MethodsNasopharyngeal swabs were obtained from children 0 to

BackgroundWe 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).MethodsWe conducted a cross-sectional study including collection of questionnaire data and nasopharyngeal specimens among children aged

BackgroundVaccination 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 In carriage, vaccine serotypes have been replaced by nonvaccine serotypes.MethodsWe used multilocus sequence typing to analyze a sample of 294 isolates of S. pneumoniae carried by Massachusetts children (aged, 3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.ResultsEighty-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.ConclusionsSome 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.

Pneumococcal type 1 pilus proteins have been proposed as potential vaccine candidates. Following conjugate pneumococcal vaccination, the prevalence of the pneumococcal type 1 pilus declined dramatically, a decline associated with the elimination of vaccine-type (VT) strains. Here we show that between 2004 and 2007, there has been a significant increase in pilus prevalence, now exceeding rates from the pre-conjugate vaccine era. This increase is primarily due to non-VT strains. These emerging piliated non-VT strains are mostly novel clones, with some exceptions. The rise in pilus type 1 frequency across multiple distinct genetic backgrounds suggests that the pilus may confer an intrinsic advantage.

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.

BackgroundThe 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.MethodsSwabs 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

ObjectivesThe 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).MethodsNasopharyngeal specimens and questionnaire/medical record data were obtained from children 3 months to

BackgroundThe long-term effects of selective pressure from conjugate pneumococcal vaccine on the serotype distribution and antimicrobial resistance of carriage and invasive isolates of Streptococcus pneumoniae are unknown. Early changes demonstrate a reduction in vaccine serotypes and an increase in nonvaccine serotypes (NVT) among both carriage and invasive isolates. Ongoing surveillance is necessary to identify emerging invasive serotypes and antimicrobial susceptibilities.MethodsEnhanced surveillance of invasive pneumococcal disease in Massachusetts began in October 2001 and remains ongoing. Isolates from children less than 5 are sent to the Massachusetts Department of Public Health and subsequently to the Maxwell Finland laboratory for serotyping and determination of antimicrobial susceptibility. Annual incidence rates for vaccine serotype and NVT disease are calculated using 2000 census data.ResultsNVT caused 72%-91% of invasive pneumococcal disease annually in children less than 5 years of age between 2002 and 2005. Serotype 19A has emerged as the most frequent cause of IPD in Massachusetts. A multidrug-resistant clone (ceftriaxone, amoxicillin, azithromycin and trimethoprim-sulfamethoxazole) (MLST 320) was first identified in Massachusetts in 2005.ConclusionsThree years after the introduction of pneumococcal conjugate vaccine for universal administration to children less than 2 in Massachusetts, a significant increase in invasive disease due to serotype 19A was observed. Although MLST 199 remains the most frequent sequence type among invasive isolates (of 19A), a multidrug-resistant sequence type, not previously identified in Massachusetts, has become an important cause of invasive disease. Further surveillance of the changing ecology of S. pneumoniae is necessary as a 4-year time period is not sufficient to fully evaluate the impact of PCV of pneumococcal infections.

BackgroundIn 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.MethodsTo 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

ObjectiveThe introduction of heptavalent conjugate pneumococcal vaccine (PCV7) has raised concerns for replacement with nonvaccine serotypes in both invasive disease and asymptomatic carriage. Analysis of colonizing serotypes among healthy children in the community provides critical data on such changes.MethodsNasopharyngeal specimens were obtained from children who were younger than 7 years during well-child or sick visits in primary care practices in 16 Massachusetts communities during 2001 and 2004. Susceptibility testing and serotyping were performed on isolated Streptococcus pneumoniae strains. Vaccination history with PCV7 was abstracted from the medical record.ResultsAmong colonizing pneumococcal isolates, PCV7 serotypes decreased from 36% to 14%, and non-PCV7 serotypes increased from 34% to 55%. Overall carriage did not change (26% to 23%); neither did carriage of potentially cross-reactive serotypes (30% to 31%). The most common non-PCV7 serotypes were serotypes 11, 15, and 29. There was a substantial increase in penicillin nonsusceptibility from 8% to 25% in non-PCV7 serotypes; 35% were highly resistant to penicillin. Penicillin nonsusceptibility increased from 45% to 56% among PCV7 serotypes while remaining stable among PCV7 potentially cross-reactive strains (51% vs 54%).ConclusionsPneumococcal colonization has changed after the introduction of PCV7, both in serotype distribution and in patterns of antibiotic resistance. The frequency of nonvaccine strains has increased, and the proportion of nonvaccine isolates that are not susceptible to penicillin has tripled. This shift toward increased carriage of nonvaccine serotypes warrants vigilance for changes in the epidemiology of invasive pneumococcal disease.

ObjectiveDespite 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.MethodsChildren who were 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.ConclusionsIn 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.

Background: Cell-based quadrivalent influenza vaccines (QIVc) can increase effectiveness against seasonal influenza by avoiding mismatch from egg adaption of vaccine viruses. This study evaluates the population-level cost-effectiveness and impacts on health outcomes of QIVc versus an egg-based vaccine (QIVe) in children aged 6 months to 17 years in the US. Research Design and Methods: A dynamic age-structured susceptible-exposed-infected-recovered model was used to simulate influenza transmission in low and high incidence seasons for two scenarios: 1. QIVe for 6 months–17 year-olds, QIVc for 18–64 year-olds, and adjuvanted QIV (aQIV) for ≥ 65 year-olds, and 2. QIVc for 6 months–64 year-olds, and aQIV for ≥ 65 year-olds. Probabilistic sensitivity analysis was performed to account for uncertainty in parameter estimates. Cost-effectiveness was evaluated as incremental cost-effectiveness ratios (ICERs). Results: Extension of QIVc to children resulted in 3–4% reductions in cases (1,656,271), hospitalizations (16,688), and deaths (2,126) at a population level in a high incidence season, and 65% reductions (cases: 2,856,384; hospitalizations: 31667; deaths: 4,163) in a low incidence season. Use of QIVc would be cost-saving, with ICERs of -$16,427/QALY and -$8,100/QALY from a payer perspective and -$22,669/QALY and -$15,015/QALY from a societal perspective, for low and high incidence seasons respectively. Cost savings were estimated at approximately $468 million and $1.366 billion for high and low incidence seasons, respectively. Conclusion: Use of QIVc instead of QIVe in children > 6 months of age in the US would reduce the disease burden and be cost-saving from both a payer and societal perspective. [ABSTRACT FROM AUTHOR]

Background: Clinical evidence supports use of enhanced influenza vaccines in older adults. Few economic outcome studies have compared adjuvanted trivalent inactivated (aIIV3) and standard egg-derived quadrivalent inactivated influenza vaccines (IIV4e). Research Design and Methods: A retrospective cohort study was conducted leveraging deidentified US hospital data linked to claims data during the 2018–19 and 2019–20 influenza seasons. Relative vaccine effectiveness (rVE) was compared in adults aged ≥ 65 years receiving aIIV3 or IIV4e using inverse probability of treatment weighting (IPTW) and Poisson regression. An economic assessment quantified potential real-world cost savings. Results: The study included 715,807 aIIV3 and 320,991 IIV4e recipients in the 2018–19 and 844,169 aIIV3 and 306,270 IIV4e recipients in the 2019–20 influenza seasons. aIIV3 was significantly more effective than IIV4e in preventing cardiorespiratory disease (2018–19 rVE = 6.2%; and 2019–20 rVE = 6.0%) and respiratory disease (2018–19 rVE = 8.9%; and 2019–20 rVE = 10.1%). During the 2018–19 influenza season cardiorespiratory hospitalization cost savings for the aIIV3 population were $392 M, and $221 M for the 2019–20 season. Respiratory hospitalization cost savings for the aIIV3 population were $145 M and $97 M, respectively. Conclusions: Our findings suggest that aIIV3 provides clinical and economic advantages versus IIV4e in the elderly. Plain Language Summary: Flu vaccines do not work as well in older adults due to the aging of their immune system. One approach to improving vaccine efficacy is the addition of a substance, or adjuvant, to the vaccine in order to boost an individual's immune response. This study evaluated an adjuvanted vaccine compared to an unadjuvanted vaccine for preventing cardiorespiratory hospitalizations and hospitalization costs. The findings demonstrated that the adjuvanted flu vaccine, compared to the unadjuvanted vaccine, prevented more hospitalizations and greatly reduced associated hospital costs. [ABSTRACT FROM AUTHOR]