Background

We sought to measure trends in Streptococcus pneumoniae (SP) carriage and antibiotic resistance in young children in Massachusetts communities after widespread adoption of heptavalent pneumococcal conjugate vaccine (PCV7) and before the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13).

Methods

We conducted a cross-sectional study including collection of questionnaire data and nasopharyngeal specimens among children <7 years in primary care practices from 8 Massachusetts communities during the winter season of 2008–9 and compared with to similar studies performed in 2001, 2003–4, and 2006–7. Antimicrobial susceptibility testing and serotyping were performed on pneumococcal isolates, and risk factors for colonization in recent seasons (2006–07 and 2008–09) were evaluated.

Results

We collected nasopharyngeal specimens from 1,011 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 2008–09, newly-targeted PCV13 serotypes accounted for 20% of carriage isolates and 41% of penicillin non-susceptible S. pneumoniae (PNSP). 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 PNSP 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.

Defining the propensity of Streptoccocus pneumoniae (SP) serotypes to invade sterile body sites following nasopharyngeal (NP) acquisition has the potential to inform about how much invasive pneumococcal disease (IPD) may occur in a typical population with a given distribution of carriage serotypes. Data from enhanced surveillance for IPD in Massachusetts children ≤7 years in 2003/04, 2006/07 and 2008/09 seasons and surveillance of SP NP carriage during the corresponding respiratory seasons in 16 Massachusetts communities in 2003/04 and 8 of the 16 communities in both 2006/07 and 2008/09 were used to compute a serotype specific “invasive capacity (IC)” by dividing the incidence of IPD due to serotype x by the carriage prevalence of that same serotype in children of the same age. A total of 206 IPD and 806 NP isolates of SP were collected during the study period. An approximate 50-fold variation in the point estimates between the serotypes having the highest (18C, 33F, 7F, 19A, 3 and 22F) and lowest (6C, 23A, 35F, 11A, 35B, 19F, 15A, and 15BC) IC was observed. Point estimates of IC for most of the common serotypes currently colonizing children in Massachusetts were low and likely explain the continued reduction in IPD from the pre-PCV era in the absence of specific protection against these serotypes. Invasive capacity differs among serotypes and as new pneumococcal conjugate vaccines are introduced, ongoing surveillance will be essential to monitor whether serotypes with high invasive capacity emerge (e.g. 33F, 22F) as successful colonizers resulting in increased IPD incidence due to replacement serotypes.

Sensitive detection of Staphylococcus aureus colonization is important for epidemiologic studies, infection control, and decolonization measures. We examined the sensitivity of nasal and pharyngeal sampling for S. aureus colonization in 331 children admitted to intensive care units. Pharyngeal screening was more sensitive than nasal screening (92.6% versus 63.1%, P < 0.0001).

The emergence of pandemic H1N1 influenza in 2009 has prompted public health responses, including production and licensure of new influenza A (H1N1) 2009 monovalent vaccines. Safety monitoring is a critical component of vaccination programs. As proof-of-concept, the authors mimicked near real-time prospective surveillance for prespecified neurologic and allergic adverse events among enrollees in 8 medical care organizations (the Vaccine Safety Datalink Project) who received seasonal trivalent inactivated influenza vaccine during the 2005/06–2007/08 influenza seasons. In self-controlled case series analysis, the risk of adverse events in a prespecified exposure period following vaccination was compared with the risk in 1 control period for the same individual either before or after vaccination. In difference-in-difference analysis, the relative risk in exposed versus control periods each season was compared with the relative risk in previous seasons since 2000/01. The authors used Poisson-based analysis to compare the risk of Guillian-Barré syndrome following vaccination in each season with that in previous seasons. Maximized sequential probability ratio tests were used to adjust for repeated analyses on weekly data. With administration of 1,195,552 doses to children under age 18 years and 4,773,956 doses to adults, no elevated risk of adverse events was identified. Near real-time surveillance for selected adverse events can be implemented prospectively to rapidly assess seasonal and pandemic influenza vaccine safety.

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

A 26-valent Group A Streptococcus (GAS) vaccine candidate has been developed that may provide protection against pharyngitis, invasive disease and rheumatic fever. However, recommendations for the use of a new vaccine must be informed by a range of considerations, including parents' preferences for different relevant health outcomes. Our objectives were to: (1) describe parent preferences for GAS disease and vaccination using willingness-to-pay (WTP) and time trade-off (TTO) methods; and (2) understand how parents' implied WTP for a quality-adjusted life year (QALY) gained might vary depending on the particular health outcome considered (e.g. averted GAS disease vs. vaccine adverse events).

Methods

Telephone interviews were conducted with parents of children diagnosed with GAS pharyngitis at 2 pediatric practice sites in the Boston metropolitan area. WTP and TTO (trading parental longevity for child's health) questions for 2 vaccine and 4 disease-associated health states were asked using a randomly selected opening bid, followed by a 2nd bid and a final open-ended question about the amount willing to pay or trade. Descriptive analyses included medians and interquartile ranges for WTP and TTO estimates. The Wilcoxon signed-rank test was used to assess differences in WTP/QALY values for vaccine adverse events vs. disease states.

Results

Of 119 respondents, 100 (84%) and 96 (81%) provided a complete set of responses for WTP and TTO questions, respectively. The median WTP and discounted (at 3% per year) TTO values to avoid each health state were as follows: local reaction, $30, 0.12 days; systemic reaction, $50, 0.22 days; impetigo, $75, 1.25 days; strep throat, $75, 2.5 days; septic arthritis, $1,000, 6.6 days; and toxic shock syndrome, $3,000, 31.0 days. The median WTP/QALY was significantly higher for vaccine adverse events (~$60,000/QALY) compared to disease states ($18,000 to $36,000/QALY).

Conclusions

Parents strongly prefer to prevent GAS disease in children compared to vaccine adverse events. However, implied WTP/QALY ratios were higher for the prevention of vaccine adverse events. Regret for errors of commission vs. omission may differ and should be considered by vaccine policymakers.

Background

In February 2005, the US Advisory Committee on Immunization Practices recommended the new meningococcal conjugate vaccine (MCV4) for routine use among 11- to 12-year-olds (at the preadolescent health-care visit), 14- to 15-year-olds (before high-school entry), and groups at increased risk. Vaccine distribution started in March; however, in July, the manufacturer reported inability to meet demand and widespread MCV4 shortages were reported. Our objectives were to determine early uptake patterns among target (11-12 and 14-15 year olds) and non-target (13- plus 16-year-olds) age groups. A post hoc analysis was conducted to compare seasonal uptake patterns of MCV4 with polysaccharide meningococcal (MPSV4) and tetanus diphtheria (Td) vaccines.

Methods

We analyzed data for adolescents 11-16 years from five managed care organizations participating in the Vaccine Safety Datalink (VSD). For MCV4, we estimated monthly and cumulative coverage during 2005 and calculated risk ratios. For MPSV4 and Td, we combined 2003 and 2004 data and compared their seasonal uptake patterns with MCV4.

Results

Coverage for MCV4 during 2005 among the 623,889 11-16 years olds was 10%. Coverage for 11-12 and 14-15 year olds was 12% and 11%, respectively, compared with 8% for 13- plus 16-year-olds (p < 0.001). Of the 64,272 MCV4 doses administered from March-December 2005, 73% were administered June-August. Fifty-nine percent of all MPSV4 doses and 38% of all Td doses were administered during June-August.

Conclusion

A surge in vaccine uptake between June and August was observed among adolescents for MCV4, MPSV4 and Td vaccines. The increase in summer-time vaccinations and vaccination of non-targeted adolescents coupled with supply limitations likely contributed to the reported shortages of MCV4 in 2005.

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. ≥5 yrs, OR 0.39 [95% CI 0.24–0.64]; 1–1.99 yrs vs. ≥5 yrs, OR 0.35 [0.23–0.54]; 2–2.99 yrs vs. ≥5 yrs, OR 0.45 [0.28–0.73]; 3–3.99 yrs vs. ≥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.

Pertussis, an acute respiratory infection caused by Bordetella pertussis, classically manifests as a protracted cough illness. The incidence of pertussis in the United States has been increasing in recent years. Immunity wanes after childhood vaccination, leaving adolescents and adults susceptible to infection. The transmission of pertussis in health care settings has important medical and economic consequences. Acellular pertussis booster vaccines are now available for use and have been recommended for all adolescents and adults. These vaccines are safe, immunogenic, and effective. Health care workers are a priority group for vaccination because of their increased risk of acquiring infection and the potential to transmit pertussis to high-risk patients. Health care worker vaccination programs are likely to be cost-effective, but further research is needed to determine the acceptability of pertussis vaccines among health care workers, the duration of immunity after booster doses, and the impact of vaccination on the management of pertussis exposures in health care settings.

Background

The incidence of reported adolescent and adult pertussis continues to rise in the United States. Acellular pertussis vaccines for adolescents and adults have been developed and may be available soon for use in the U.S. Our objectives were: (1) to describe patient valuations of pertussis disease and vaccination; and (2) to compare valuations for short-term and long-term health states associated with pertussis.

Methods

We conducted telephone surveys with 515 adult patients and parents of adolescent patients with pertussis in Massachusetts to determine valuations of pertussis-related health states for disease and vaccination using time trade-off (TTO) and contingent valuation (CV) techniques. Respondents were randomized to complete either a short-term or long-term TTO exercise. Discrimination between health states for each valuation technique was assessed using Tukey's method, and valuations for short-term vs. long-term health states were compared using the Wilcoxon rank-sum test.

Results

Three hundred three (59%) and 309 (60%) respondents completed and understood the TTO and CV exercises, respectively. Overall, respondents gave lower valuations (lower TTO and higher CV values) to avoid a given state for adolescent/adult disease compared to vaccine adverse events. Infant complications due to pertussis were considered worse than adolescent/adult disease, regardless of the method of valuation. The short-term TTO resulted in lower mean valuations and larger mean differences between health states than the long-term TTO exercise.

Conclusion

Pertussis was considered worse than adverse events due to vaccination. Short-term health-state valuation is better able to discriminate among health states, which is useful for cost-utility analysis.