Stephen I Pelton

Boston Medical Center, Boston, Massachusetts, United States

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Publications (184)1053.59 Total impact

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    ABSTRACT: Background: The impact of the 7-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal disease in children and adults has been substantial. In 2010, PCV13, a second generation pneumococcal conjugate vaccine was introduced for infants with catch up dosing. A decline in IPD and specifically vaccine serotypes in children < 5 years of age has already been reported. We present data on the incidence and serotype distribution of IPD in adults over 18 years of age for the 6 years before and after introduction of PCV13. Methods: Kaiser Permanente Northern California (KPNC) is an integrated health care plan serving approximately 3.3 million members. IPD cases were identified from the KPNC Lab system, and defined as S.pneumoniae from a normally sterile body site, from May 2008 through April 2014, in members age 18 and over. Serotyping was done at the Boston University Schools of Medicine. Age and race were derived from KPNC membership databases. Rates were calculated as Annual Incidence of IPD = (IPD cases / (Membership / 105). Study years begin in May and end in April of the following year, to coincide with the introduction of PCV13. Results: The rate of IPD in the adult population declined coinciding with the introduction of PCV13 (5.10-4.11 per 100,000) and continued through the year ending April 2013 (table 1). In 2014 an increase in incidence, mainly in non-PCV13 serotypes, was observed. The greatest increase from 2013 to 2014 was in individuals of Black race (10.38 per 100,000 in 2012 to 20.64 per 100,000 in 2013). In this group, the increase was observed in PCV7, PCV13, and non-PCV13 serotypes. Conclusion: We observed increased IPD in adults in 2013-2014 after 2 consecutive years of decline following PCV13 introduction. Much of this increase was seen in individuals of Black race. Racial differences should be considered in policy decisions regarding use of the conjugated vaccine in adults. Table. Rates of IPD in KPNC, 2008-2014, per 100,000. Serotype categories contain serotypes specific to the vaccines. Serotype Category 5/08-4/09 5/09-4/10 Year of PCV13 Introduction 5/10-4/11 5/11-4/12 5/12-4/13 5/13-4/14 All Cases 9.91 11.72 10.83 10.26 7.97 8.61 PCV13 4.90 5.78 5.42 4.51 2.96 2.59 PCV7 0.37 0.27 0.30 0.33 0.29 0.28 Non- PCV13 3.81 4.37 4.41 5.13 4.26 4.73
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
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    ABSTRACT: Background: Despite widespread vaccination, Streptococcus pneumoniae (SPN) continues to cause invasive pneumococcal disease (IPD), particularly in the immunocompromised. Current recommendations in the United States target the immunocompromised for use of the 13-valent conjugate vaccine. We examined the impact of chronic kidney disease on the development of invasive pneumococcal disease (IPD). Methods: Kaiser Permanente Northern California (KPNC) is an integrated health care plan serving approximately 3.3 million members. IPD cases (defined as cultured from a normally sterile body site) were identified from the KPNC Lab system from May 2005 - April 2013. We used diagnostic codes from the electronic medical record to identify chronic kidney disease(CKD) as CKD3 (Glomerular filtration rate [GFR]30-59 ml/min), CKD4 (GFR 15-29 ml/min) and CKD5,6 (GFR <15 or on dialysis). We estimated rates of IPD in KPNC members with CKD and compared to rates of IPD in the general membership. We used KPNC registries to identify members with asthma, coronary artery disease (CAD), diabetes (DM), stroke, heart failure (HF), and HIV infection for the analysis. We ran a single multivariate poisson regression model to estimate the incidence of IPD, and included age, race and each condition as predictor variables. Results: The unadjusted relative risk of IPD in members of all ages with CKD compared to the general membership was 4.1 for CKD3; 5.7 for CKD4; and 15.1 for CKD5,6. After controlling for multiple underlying factors in the multivariate analysis, CKD3 was associated with a 2.29 (95% CI 1.63-3.19) RR for IPD; and CKD 4,5 with a 7.10 RR (3.95-12.23) (preliminary analysis). Conclusion: In adults, chronic kidney disease is strongly associated with an increased risk of IPD. This has important implications for recommendations on who should receive conjugated pneumococcal vaccines.
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
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    ABSTRACT: Background: The identification of site specific genes and functions essential for virulence may provide further understanding of the pathogenesis of pneumococcal disease and potentially reveal novel targets for treatment and prevention. Methods: We screened more than 10 selected serotypes of Streptococus pneumoniae in our chinchilla model of experimental otitis media (EOM), initially using nasopharyngeal inoculation followed by barotrauma and subsequently with direct intrabullar challenge. Genomic DNA of these isolates was extracted by standard methods and sequenced using the HiSeq Illumina platform. De novo assembled sequences were annotated with RAST (Rapid Annotation by Subsystem Technology). Functional comparative genomic analysis was performed in SEED viewer; genes of subsystems identified as uniquely absent in 33F strains underwent detailed analysis in SEED, BRIG and BLAST. Results: The serotype 33F isolates colonized the nasopharynx comparable to all other serotypes but failed to produce either clinically apparent or culture-positive middle ear disease. The lack of virulence was confirmed by the failure to develop middle ear disease following direct intrabullar challenge as well as with 2 additional 33F isolates. Functional genomic comparison against OM producing strains as well as ~50 invasive strains revealed that all three 33F strains lack the pneumococcal serine-rich repeat protein (PsrP) pathogenicity island. The PsrP island appeared to be present in the sequenced IPD strains. Conclusion: Serotype 33F failed to produce EOM using either NP colonization and barotrauma or direct inoculation. Comparative genomic analysis revealed the absence of the PsrP pathogenicity island in these strains. PsrP is a representative of serine-rich repeat proteins found in many pathogenic streptococci and Staphylococcus aureus. Although non-essential for survival, it plays an important role in the formation of biofilms and adhesion to host cells. Further characterization of the function of this island in S. pneumoniae is necessary to define its role in virulence both for middle ear infection as well as invasive disease and pneumonia.
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
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    ABSTRACT: In the current era of universal immunization of young children with pneumococcal conjugate vaccine, it is unclear whether the high risk ratios for pneumococcal disease previously attributed to specified chronic conditions have persisted. In addition, further analysis of pneumococcal disease risk may clarify whether certain chronic conditions that currently are not specified as significantly increasing the risk of pneumococcal disease, should be so considered. We conducted a retrospective cohort analysis utilizing healthcare claims data from 2007 - 2010 to compare rates of pneumococcal disease among children <5 and 5-17 years of age with high-risk and at-risk conditions to rates among children without these conditions in the same age group. Risk profiles and manifestations of pneumococcal infection were ascertained from diagnosis, procedure, and drug codes. Among at-risk children, rate ratios for invasive pneumococcal disease (vs. children without at/high-risk conditions) were 1·8 (95% CI 1·4-2·3) in children <5 years of age and 3·3 (2·4-4·4) in children 5-17 years of age. Corresponding rate ratios for high-risk children were 11·2 (7·0-17·9) and 40·1 (28·8-56·0). Rate ratios increased in asthmatic children with increasing disease severity and in all at-risk children by the number of concurrent at-risk conditions. Rate ratios for pneumococcal pneumonia and all-cause pneumonia demonstrated similar patterns. Children with high-risk and at-risk conditions continue to demonstrate an increased burden of pneumococcal disease. Pneumococcal disease rates are high among asthmatic children with moderate and severe disease and children with multiple at-risk conditions.
    Clinical Infectious Diseases 05/2014; · 9.37 Impact Factor
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    ABSTRACT: The direct impact of PCV13 on colonization with unique PCV13 serotypes and the uptake of vaccine necessary to create indirect protection in non-immunized children was assessed. Carriage surveillance among children < 60 months began in July 2010 at a pediatric practice in Boston, MA. Children had NP cultures and parents completed questionnaires detailing demographics and health status. Concurrently, we monitored uptake of PCV13 in children in the community. Children were classified as 'presumed immune' or 'presumed non-immune' based on age and PCV13 immunizations received. We assessed trends using adjusted prevalence rates calculated within rolling, 25-week, consecutive intervals. Between July 2010 and June 2012, 1050 SP were recovered from 1042 children. Eighty-nine isolates (8.5%) were one of 6 unique PCV13 serotypes. The expected fall/winter peak in PCV13 carriage was observed in non-immune children, but was blunted in immune children. There was a 74% reduction in PCV13 colonization in immune compared with non-immune children. We document a 50% or more decline in the PCV13 carriage in non-immune children, at the time when the approximately 75% or more of the community children had received PCV13 and were considered immune. During the study, the difference in PCV13 serotype colonization prevalence in non-immune and immune children disappeared. No evidence of replacement has been observed to date. The direct impact of PCV13 on colonization was demonstrated. Evidence of indirect protection in unimmunized (non-immune) children was observed as vaccine uptake reached 75% in the target community.
    The Pediatric Infectious Disease Journal 03/2014; · 3.57 Impact Factor
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    ABSTRACT: In 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. Nasopharyngeal swabs were obtained from children 0 to <7 years of age and seen by primary care providers for well child or acute illness visits in 2001, 2004, 2007, 2009, and 2011. Pneumococcal isolates were serotyped by Quellung reaction and classified as PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F), additional PCV13 serotypes (1, 3, 5, 6A, 7F, 19A), or non-PCV13 serotypes. Changes in colonization and impact of PCV13 were assessed using generalized linear mixed models, adjusting for known risk factors and accounting for clustering by community. Introduction of PCV13 did not affect the rate of overall pneumococcal colonization (31% in 2011). Colonization with non-PCV13 serotypes increased between 2001 and 2011 for all children (odds ratio [OR] per year, 1.12; 95% confidence interval [CI], 1.10, 1.15; P < .0001). 19A remained the second most common serotype in 2011, although a decline from 2009 was observed. Penicillin (7%), erythromycin (28%), ceftriaxone (10%), and clindamycin (10%) nonsusceptibility were commonly identified, concentrated among a small number of serotypes (including 19A, 35B, 15B/C, and 15A). Among healthy children 6-23 months old, colonization with PCV13 serotypes was lower among recipients of PCV13 vaccine (adjusted OR, 0.30; 95% CI, 0.11, 0.78). This effect was not observed in 6- to 23-month-old children with a concomitant respiratory tract infection (adjusted OR 1.36; 95% CI, 0.66, 2.77) or children 2 to <7 years old (adjusted OR, 1.17; 95% CI, 0.58, 2.34). 13-Valent pneumococcal conjugate vaccine reduced the prevalence of colonization with PCV13 serotypes among children 6-23 months old, but its efficacy was not shown among older children.
    Journal of the Pediatric Infectious Diseases Society. 03/2014; 3(1):23-32.
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    ABSTRACT: The pneumococcal Pilus-1 enhances attachment to epithelial cells in the respiratory tract and subsequent invasion. Pilus-1 expression is bi-stable and positively regulated by the RlrA transcriptional regulator. To delineate the role of pilus-1 in Experimental Otitis Media (EOM), we evaluated colonization and disease due to a Streptococcus pneumoniae (SP) wild type strain (Taiwan19F-14 wt) and its otherwise isogenic pilus-1 and pilus-2 deficient mutant (Taiwan19F-14 ΔPI-1/PI-2-) as well as potential for a chimeric protein (RrgB321) vaccine candidate for prevention of middle ear (ME) disease. Chinchillas were challenged intranasally with either Taiwan19F-14 wt or Taiwan19F-14PI-1/PI-2 deficient mutant. ME status was assessed and direct cultures performed. New cohorts of animals were immunized with RrgB321 or alum. Intranasal challenge with Taiwan19F-14 wt [erythromycin susceptible E(S)] was performed. Subsequently, a second cohort of animals was immunized and challenged with either Taiwan19F-14 wt or a Pilus-1 over-expressing mutant [Taiwan19F-14+pMU1328_Pc-rlrA mutant; E resistant (R)] strain. Pilus-1 expression was analyzed in SP isolated from nasopharynx (NP) and ME fluids by flow cytometry. Culture positive EOM developed following challenge with either wild type SP (Taiwan19F-14) or its pilus-1 deficient mutant. Culture positive EOM developed following challenge with wild type in both RrgB321 immunized and control animals. Pilus-1 expression in ME fluids was significantly higher in controls compared to immunized chinchillas. In second cohort of immunized and control animals challenged with the over-expressing Pilus-1 mutant, delayed development of EOM in the immunized animals was observed. Pneumococci recovered from ME fluid of immunized animals were no longer E(R) signifying the loss of the pMU1328_Pc-rlrA plasmid. Pneumococcal pilus-1 was not essential for EOM. Regulation of Pilus-1 expression in ME fluids in the presence of anti RrgB321 antibody was essential for survival of S. pneumoniae. Pneumococci have evolved mechanisms of regulation of non-essential surface proteins to evade host defenses.
    PLoS ONE 01/2014; 9(1):e83798. · 3.53 Impact Factor
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    ABSTRACT: In February 2012, the Advisory Committee on Immunization Practices (ACIP) advised that all adults aged ≥65 years receive a single dose of reduced-antigen-content tetanus, diphtheria, and acellular pertussis (Tdap), expanding on a 2010 recommendation for adults >65 that was limited to those with close contact with infants. We evaluated clinical and economic outcomes of adding Tdap booster of adults aged ≥65 to "baseline" practice [full-strength DTaP administered from 2 months to 4-6 years, and one dose of Tdap at 11-64 years replacing decennial Td booster], using a dynamic model. We constructed a population-level disease transmission model to evaluate the cost-effectiveness of supplementing baseline practice by vaccinating 10% of eligible adults aged ≥65 with Tdap replacing the decennial Td booster. US population effects, including indirect benefits accrued by unvaccinated persons, were estimated during a 1-year period after disease incidence reached a new steady state, with consequences of deaths and long-term pertussis sequelae projected over remaining lifetimes. Model outputs include: cases by severity, encephalopathy, deaths, costs (of vaccination and pertussis care) and quality-adjusted life-years (QALYs) associated with each strategy. Results in terms of incremental cost/QALY gained are presented from payer and societal perspectives. Sensitivity analyses vary key parameters within plausible ranges. For the US population, the intervention is expected to prevent >97,000 cases (>4,000 severe and >5,000 among infants) of pertussis annually at steady state. Additional vaccination costs are $4.7 million. Net cost savings, including vaccination costs, are $47.7 million (societal perspective) and $44.8 million (payer perspective). From both perspectives, the intervention strategy is dominant (less costly, and more effective by >3,000 QALYs) versus baseline. Results are robust to sensitivity analyses and alternative scenarios. Immunization of eligible adults aged ≥65, consistent with the current ACIP recommendation, is cost saving from both payer and societal perspectives.
    PLoS ONE 01/2014; 9(1):e72723. · 3.53 Impact Factor
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    ABSTRACT: We hypothesized that capsular switch event, in which pneumococcus acquires a new capsule operon by horizontal gene transfer, may result in emergence of strains with increased virulence in acute otitis media. Using serotype 6A strain from a patient with invasive pneumococcal disease and clonally distant serotype 6C strain isolated from asymptomatic carrier we created 6A:6C (6A background with 6C capsule) capsular transformants and applied whole genome macro-restriction analysis to assess conservation of the 6A chassis. Next, we assessed complement (C3) and antibodies deposition on surface of peumococcal cells and tested capsule recipient, capsule donor and two 6A:6C transformants for virulence in chinchilla experimental otitis media model. Both 6A:6C(1or2) transformants bound less C3 compared to 6C capsule-donor strain but more compared to serotype 6A capsule-recipient strain. Pneumococci were present in significantly higher proportion of ears among animals challenged with either of two 6A:6C(1 or 2) transformants compared to chinchillas infected with 6C capsule-donor strain [p<0.001] whereas a significantly decreased proportion of ears were infected with 6A:6C(1or 2) transformants as compared to 6A capsule-recipient strain. Our observations though limited to two serotypes demonstrate that capsular switch events can result in S. pneumoniae strains of enhanced virulence for respiratory tract infection.
    Microbes and Infection 12/2013; · 2.92 Impact Factor
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    ABSTRACT: Background: In the United States, conjugated pneumococcal vaccines are recommended for all infants, and for immunocompromised individuals of older ages. Polysaccharide pneumococcal vaccines are recommended for older adults and others with underlying medical conditions, including asthma. We examined the impact of underlying medical conditions on the development of invasive pneumococcal disease (IPD). Methods: Kaiser Permanente Northern California (KPNC) is an integrated health care plan serving approximately 3.3 million members. IPD cases were identified by the KPNC Lab as S.pneumoniae from a normally sterile body site, from May 2005 through April 2011, in members age 18 and over. Age and race were derived from KPNC membership databases. We used KPNC registries to identify members with asthma, coronary artery disease (CAD), diabetes (DM), stroke, heart failure (HF), HIV infection, and hypertension (HTN). Rates were calculated as Annual Incidence of IPD = (IPD cases / (Members / 105). We used Poisson regression to estimate the incidence of IPD in relation to these conditions and demographic groups. Results: The adjusted incidence rate ratio of IPD for persons with asthma versus without asthma was 5.68 (95%CI 4.90-6.56); for CAD 1.93 (1.57-2.36); DM: 2.41 (2.08-2.78); stroke: 5.02 (3.72-6.66); HF: 4.24 (3.42-5.25); HIV: 57.89 (42.27-77.46), and HTN: 1.13 (0.98-1.31). The adjusted RR by race for Black (compared with White) was 3.52 (2.97-4.16), Asian: 1.68 (1.40-1.99), and Hispanic: 1.78 (1.52-2.08). Conclusion: In adults, HIV, asthma, HF, stroke, DM and CAD were associated with increased risk of IPD. This has important implications for recommendations on who should receive pneumococcal vaccines.
    IDWeek 2013 Meeting of the Infectious Diseases Society of America; 10/2013
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    ABSTRACT: Pneumococcal conjugate vaccines (PCVs) have been introduced worldwide. However, few developing countries have high-quality surveillance systems available for monitoring vaccine impact. We evaluated whether data from nasopharyngeal carriage studies can be used to accurately monitor post-PCV changes in the incidence of invasive pneumococcal disease (IPD) among children under 5 years of age. For various dates during 1991-2010, data on nasopharyngeal pneumococcal carriage and on IPD before and after administration of 7-valent PCV (PCV7) were available from England and Wales, the Netherlands, the Navajo and White Mountain Apache American Indian populations, and the US states of Massachusetts and Alaska. We estimated the change in carriage prevalence for each serotype in each study and then either calculated the average change (inverse variance-weighted) among vaccine and nonvaccine serotypes (model 1) or used mixed-effects models to estimate the change for each serotype individually, pooling serotype data within or between studies (models 2 and 3). We then multiplied these values by the proportion of IPD caused by each serotype during the pre-PCV7 period to obtain an estimate of post-PCV7 disease incidence. Model 1 accurately captured overall changes in IPD incidence following PCV7 introduction for most studies, while the more detailed models, models 2 and 3, were less accurate. Carriage data can be used in this simple model to estimate post-PCV changes in IPD incidence.
    American journal of epidemiology 09/2013; · 5.59 Impact Factor
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    ABSTRACT: The capacity of pneumococcal vaccination to confer memory in HIV-infected children is critical for durable protection. HIV-infected children 2-<19 years administered two doses of pneumococcal conjugate vaccine (PCV7) and one dose of polysaccharide vaccine (PPV) on HAART were randomized 4-5 years later to receive a PCV7 or PPV booster. Total and high avidity antibodies to serotypes 1 (PPV) and 6B and 14 (PCV7 and PPV) were determined by ELISA. Memory was defined as persistence of ≥0.5mcg/mL of serotype-specific antibody on day 0 or change from <0.5mcg/mL to ≥0.5mcg/mL between day 0 and week 1, or, ≥4-fold antibody rise between day 0 and week 1. Prior to boosting, 4-5 years after the previous PCV7-PCV7-PPV series, geometric mean concentrations (GMCs) were 0.46mcg/mL (serotype 1), 1.31mcg/mL (serotype 6B), and 1.47mcg/mL (serotype 14), with concentrations ≥0.5mcg/mL in 41% (serotype 1) to 82% (serotypes 6B and 14). Memory based on antibody concentration ≥0.5mcg/mL before or 1 week after boosting with PCV7 or PPV was demonstrated in 42-61% for serotype 1 and 87-94% for serotypes 6B and 14, with lower rates based on day 0 to week 1 ≥4-fold antibody rise (serotype 1, 3-13%; serotype 6B, 13-31%; serotype 14, 29-53%). Antibody concentrations post-boosting were greater following PCV7 than PPV for serotypes 6B and 14. Ratios of highly avid to total antibody pre- and post-boosting were 0.5-0.8. Predictors of memory included higher CD4% (nadir before HAART and at P1024 and P1061s entry), CD19% (at P1024 and P1061s entry), and antibody response after the PCV7-PCV7-PPV primary series and lower viral load (at P1024 and P1061s entry) and age. Protective antibody concentrations, high avidity, and booster responses to PCV7 or PPV indicative of memory were present 4-5 years after PCV7-PCV7-PPV in HIV-infected children on HAART. Clinical Trials Registration: NCT00257127 (
    Vaccine 08/2013; · 3.77 Impact Factor
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    ABSTRACT: Microbial capsular antigens are effective vaccines but are chemically and immunologically diverse, resulting in a major barrier to their use against multiple pathogens. A β-(1→6)-linked poly-N-acetyl-d-glucosamine (PNAG) surface capsule is synthesized by four proteins encoded in genetic loci designated intercellular adhesion in Staphylococcus aureus or polyglucosamine in selected Gram-negative bacterial pathogens. We report that many microbial pathogens lacking an identifiable intercellular adhesion or polyglucosamine locus produce PNAG, including Gram-positive, Gram-negative, and fungal pathogens, as well as protozoa, e.g., Trichomonas vaginalis, Plasmodium berghei, and sporozoites and blood-stage forms of Plasmodium falciparum. Natural antibody to PNAG is common in humans and animals and binds primarily to the highly acetylated glycoform of PNAG but is not protective against infection due to lack of deposition of complement opsonins. Polyclonal animal antibody raised to deacetylated glycoforms of PNAG and a fully human IgG1 monoclonal antibody that both bind to native and deacetylated glycoforms of PNAG mediated complement-dependent opsonic or bactericidal killing and protected mice against local and/or systemic infections by Streptococcus pyogenes, Streptococcus pneumoniae, Listeria monocytogenes, Neisseria meningitidis serogroup B, Candida albicans, and P. berghei ANKA, and against colonic pathology in a model of infectious colitis. PNAG is also a capsular polysaccharide for Neisseria gonorrhoeae and nontypable Hemophilus influenzae, and protects cells from environmental stress. Vaccination targeting PNAG could contribute to immunity against serious and diverse prokaryotic and eukaryotic pathogens, and the conserved production of PNAG suggests that it is a critical factor in microbial biology.
    Proceedings of the National Academy of Sciences 05/2013; · 9.81 Impact Factor
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    ABSTRACT: Whole-genome sequencing of 616 asymptomatically carried Streptococcus pneumoniae isolates was used to study the impact of the 7-valent pneumococcal conjugate vaccine. Comparison of closely related isolates showed the role of transformation in facilitating capsule switching to non-vaccine serotypes and the emergence of drug resistance. However, such recombination was found to occur at significantly different rates across the species, and the evolution of the population was primarily driven by changes in the frequency of distinct genotypes extant before the introduction of the vaccine. These alterations resulted in little overall effect on accessory genome composition at the population level, contrasting with the decrease in pneumococcal disease rates after the vaccine's introduction.
    Nature Genetics 05/2013; · 35.21 Impact Factor
  • Value in Health 05/2013; 16(3):A232. · 2.19 Impact Factor
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    ABSTRACT: SUMMARY 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.
    Epidemiology and Infection 04/2013; · 2.87 Impact Factor
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    ABSTRACT: Objective To update progress on the effectiveness of vaccine for prevention of acute otitis media (AOM) and identification of promising candidate antigens against Streptococcus pneumoniae, nontypeable Haemophilus influenzae, and Moraxella catarrhalis. Review Methods Literature searches were performed in OvidSP and PubMed restricted to articles published between June 2007 and September 2011. Search terms included otitis media, vaccines, vaccine antigens, and each of the otitis pathogens and candidate antigens identified in the ninth conference report. Conclusions The current report provides further evidence for the effectiveness of pneumococcal conjugate vaccines (PCVs) in the prevention of otitis media. Observational studies demonstrate a greater decline in AOM episodes than reported in clinical efficacy trials. Unmet challenges include extending protection to additional serotypes and additional pathogens, the need to prevent early episodes, the development of correlates of protection for protein antigens, and the need to define where an otitis media vaccine strategy fits with priorities for child health. Implications for Practice Acute otitis media continues to be a burden on children and families, especially those who suffer from frequent recurrences. The 7-valent PCV (PCV7) has reduced the burden of disease as well as shifted the pneumococcal serotypes and the distribution of otopathogens currently reported in children with AOM. Antibiotic resistance remains an ongoing challenge. Multiple candidate antigens have demonstrated the necessary requirements of conservation, surface exposure, immunogenicity, and protection in animal models. Further research on the role of each antigen in pathogenesis, in the development of correlates of protection in animal models, and in new adjuvants to elicit responses in the youngest infants is likely to be productive and permit more antigens to move into human clinical trials.
    Otolaryngology Head and Neck Surgery 04/2013; 148(4 Suppl):E90-E101. · 1.73 Impact Factor
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    ABSTRACT: Health benefits and costs of combined reduced-antigen-content tetanus, diphtheria, and pertussis (Tdap) immunization among adults ≥65 years have not been evaluated. In February 2012, the Advisory Committee on Immunization Practices (ACIP) recommended expanding Tdap vaccination (one single dose) to include adults ≥65 years not previously vaccinated with Tdap. Our study estimated the health and economic outcomes of one-time replacement of the decennial tetanus and diphtheria (Td) booster with Tdap in the 10% of individuals aged 65 years assumed eligible each year compared with a baseline scenario of continued Td vaccination. We constructed a model evaluating the cost-effectiveness of vaccinating a cohort of adults aged 65 with Tdap, by calculating pertussis cases averted due to direct vaccine effects only. Results are presented from societal and payer perspectives for a range of pertussis incidences (25-200 cases per 100,000), due to the uncertainty in estimating true annual incidence. Cases averted were accrued throughout the patient 's lifetime, and a probability tree used to estimate the clinical outcomes and costs (US$ 2010) for each case. Quality-adjusted life-years (QALYs) lost to acute disease were calculated by multiplying cases of mild/moderate/severe pertussis by the associated health-state disutility; QALY losses due to death and long-term sequelae were also considered. Incremental costs and QALYs were summed over the cohort to derive incremental cost-effectiveness ratios. Scenario analyses evaluated the effect of alternative plausible parameter estimates on results. At incidence levels of 25, 100, 200 cases/100,000, vaccinating adults aged 65 years costs an additional $336,000, $63,000 and $17,000/QALY gained, respectively. Vaccination has a cost-effectiveness ratio less than $50,000/QALY if pertussis incidence is >116 cases/100,000 from societal and payer perspectives. Results were robust to scenario analyses. Tdap immunization of adults aged 65 years according to current ACIP recommendations is a cost-effective health-care intervention at plausible incidence assumptions.
    PLoS ONE 01/2013; 8(9):e67260. · 3.53 Impact Factor
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    ABSTRACT: We have developed a drug delivery system for prolonged trans-tympanic antibiotic delivery from a single dose administration. Increased permeability to ciprofloxacin of the intact tympanic membrane (TM) was achieved by chemical permeation enhancers (CPEs - bupivacaine, limonene, sodium dodecyl sulfate); this was also seen by CPEs contained within a hydrogel (poloxamer 407) to maintain the formulation at the TM. The CPE-hydrogel formulation had minimal effects on auditory thresholds and tissue response in vivo. CPE-hydrogel formulations have potential for ototopical delivery of ciprofloxacin for the treatment of acute otitis media (AOM) and other middle ear diseases.
    Biomaterials 11/2012; · 8.31 Impact Factor

Publication Stats

4k Citations
1,053.59 Total Impact Points


  • 1981–2014
    • Boston Medical Center
      Boston, Massachusetts, United States
  • 2013
    • Children's Hospital Colorado
      Aurora, Colorado, United States
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States
  • 2006–2013
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
    • Bronx-Lebanon Hospital
      Bronxville, New York, United States
  • 2009–2012
    • Policy Analysis Inc.
      Brookline, Massachusetts, United States
    • State University of New York
      New York City, New York, United States
    • Riley Hospital for Children
      Indianapolis, Indiana, United States
    • University of California, Irvine
      • Department of Medicine
      Irvine, CA, United States
    • University of Alabama at Birmingham
      • Department of Pathology
      Birmingham, AL, United States
    • Harvard Pilgrim Health Care
      Quincy, Massachusetts, United States
    • University of Massachusetts Amherst
      Amherst Center, Massachusetts, United States
  • 1996–2012
    • Boston University
      • • Department of Epidemiology
      • • Department of Medicine
      • • Department of Pediatrics
      • • Section of Infectious Diseases
      Boston, Massachusetts, United States
  • 2011
    • Vanderbilt University
      • Department of Preventive Medicine
      Nashville, MI, United States
  • 2010
    • Université Libre de Bruxelles
      Bruxelles, Brussels Capital Region, Belgium
    • Yale University
      • Department of Epidemiology of Microbial Diseases
      New Haven, CT, United States
    • University of Medical Sciences
      San José, San José, Costa Rica
    • Children's Memorial Hospital
      Chicago, Illinois, United States
  • 1991–2010
    • Beverly Hospital, Boston MA
      Beverly, Massachusetts, United States
  • 2008
    • King Saud University
      Ar Riyāḑ, Ar Riyāḑ, Saudi Arabia
  • 2007
    • Imperial College London
      • Department of Infectious Disease Epidemiology
      London, ENG, United Kingdom
  • 2005
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, MA, United States
  • 2004
    • University of Miami Miller School of Medicine
      • Department of Pediatrics
      Miami, FL, United States
  • 2001–2004
    • Boston Children's Hospital
      • Division of Infectious Diseases
      Boston, MA, United States
  • 2000
    • Harvard University
      • Center for AIDS Research
      Cambridge, MA, United States
    • Massachusetts General Hospital
      • Division of Infectious Diseases
      Boston, Massachusetts, United States
  • 1998
    • Hospital Universitari Mutua de Terrassa
      Terrassa, Catalonia, Spain
  • 1993
    • Stanford Medicine
      • Department of Pediatrics
      Stanford, California, United States
    • University of Massachusetts Medical School
      • Department of Pediatrics
      Worcester, MA, United States
  • 1984
    • Washington University in St. Louis
      San Luis, Missouri, United States
  • 1975–1980
    • Harvard Medical School
      Boston, Massachusetts, United States