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Objectives: This study assesses the impact of expanding pneumococcal vaccination to all 50-year-olds to decrease racial disparities by estimating from the societal perspective, the cost-effectiveness of 20-valent pneumococcal conjugate vaccine (PCV20) and 15-valent conjugate vaccine followed by 23-valent polysaccharide vaccine (PCV15/PPSV23) for 50-year-olds., Methods: A Markov model compared the cost-effectiveness of PCV20 or PCV15/PPSV23 in all general population 50- and 65-years-olds compared with current US recommendations and with no vaccination in US Black and non-Black cohorts. US data informed model parameters. Pneumococcal disease societal costs were estimated using direct and indirect costs of acute illness and of pneumococcal-related long-term disability and mortality. Hypothetical 50-year-old cohorts were followed over their lifetimes with costs and effectiveness discounted 3% per year. Deterministic and probabilistic sensitivity analyses assessed model uncertainty., Results: In Black cohorts, PCV20 for all at ages 50 and 65 was the least costly strategy and had greater effectiveness than no vaccination and current recommendation strategies, whereas PCV15/PPSV23 at 50 and 65 cost more than $1 million per quality-adjusted life year (QALY) gained compared with PCV20 at 50 and 65. In non-Black cohorts, PCV20 at 50 and 65 cost $62 083/QALY and PCV15/PPSV23 at 50 and 65 cost more than $1 million/QALY with current recommendations, again being more costly and less effective. In probabilistic sensitivity analyses, PCV20 at 50 and 65 was favored in 85.7% (Black) and 61.8% (non-Black) of model iterations at a $100 000/QALY gained willingness-to-pay threshold., Conclusions: When considering the societal costs of pneumococcal disease, PCV20 at ages 50 and 65 years in the general US population is a potentially economically viable strategy, particularly in Black cohorts., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Background: Streptococcus pneumoniae is a significant global pathogen that colonises the nasopharynx of healthy children. Pneumococcal conjugate vaccines, which reduce nasopharyngeal colonisation of vaccine-type S. pneumoniae, may have broader effects on the nasopharyngeal microbiota; however, data are limited. In Fiji, nasopharyngeal carriage prevalence of S. pneumoniae and other colonising species differ between the two main ethnic groups. Here, we examined the association between the 7-valent pneumococcal conjugate vaccine (PCV7) and the nasopharyngeal microbiota of children in Fiji, including for each of the two main ethnic groups-indigenous Fijians (iTaukei) and Fijians of Indian descent (FID)., Method: The nasopharyngeal microbiota of 132 Fijian children was examined using nasopharyngeal swabs collected from 12-month-old iTaukei and FID children who were vaccinated (3 doses PCV7) or unvaccinated in infancy as part of a phase II randomised controlled trial. Microbiota composition was determined by sequencing the V4 region of the 16S rRNA gene. Species-specific carriage of S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus was determined using real-time quantitative PCR. Associations between microbiota composition and other host and environmental factors were considered in the analysis., Results: PCV7 had no overall impact on microbial diversity or composition. However, ethnic differences were observed in both diversity and composition with iTaukei children having higher relative abundance of Moraxella (p = 0.004) and Haemophilus (p = 0.004) and lower relative abundance of Staphylococcus (p = 0.026), Dolosigranulum (p = 0.004) and Corynebacterium (p = 0.003) compared with FID children. Further, when we stratified by ethnicity, associations with PCV7 could be detected: vaccinated iTaukei children had a lower relative abundance of Streptococcus and Haemophilus compared with unvaccinated iTaukei children (p = 0.022 and p = 0.043, respectively); and vaccinated FID children had a higher relative abundance of Dolosigranulum compared with unvaccinated FID children (p = 0.037). Children with symptoms of an upper respiratory tract infection (URTI) had a significantly different microbiota composition to children without symptoms. The microbiota composition of iTaukei children without URTI symptoms was most similar to the microbiota composition of FID children with URTI symptoms., Conclusions: Associations between PCV7 and nasopharyngeal microbiota differed within each ethnic group. This study highlights the influence that ethnicity and URTIs have on nasopharyngeal microbiota.

INTRODUCTION There is a deficit of knowledge in New Zealand as the epidemiology of invasive pneumococcal disease varies significantly between countries. AIM Time trends and sociodemographic characteristics of cases of invasive pneumococcal disease (IPD) in the Auckland region are reviewed after the introduction of a conjugate vaccination, to provide evidence for future vaccine policy and to ensure Auckland region analysis is representative of national trends for subsequent IPD analysis. METHODS Data on all cases of IPD occurring in Waitemata, Auckland and Counties Manukau District Health Boards between 2009 and 2016 were extracted from EpiSurv. Denominator data were drawn from mid-year estimates supplied by Statistics New Zealand. Descriptive epidemiology and time-series regression was performed to analyse trends. RESULTS Rates of IPD have fallen in the Auckland region over the past 8 years by 32%. While absolute rates in the elderly have reduced by 12%, they have the highest disease burden at 32/100,000. The ethnic disparity continues with Pacific people (33/100,000) and Māori (14/100,000) over represented compared to European (10/100,000). In the elderly, the 19A serotype has increased from an incidence of 0 in 2008 to 8.2/100,000. DISCUSSION Large ethnic and age-related disparities are observed in the Auckland region, consistent with the rest of the country, since the start of the pneumococcal vaccination era. Extending immunisation to the elderly may help close these gaps. As with other countries, there is 19A serotype replacement occurring following conjugate vaccine introduction.

Background: Despite the use of pneumococcal vaccines, indigenous populations are consistently disproportionately affected by invasive pneumococcal disease (IPD). With recent changes in Ontario's provincial pneumococcal vaccination program, we sought to evaluate the epidemiology and burden of IPD in northwestern Ontario (NWO) Canada - a region that contains a substantial (19.2%) indigenous population., Methods: We retrospectively reviewed all adult cases of IPD that were reported to the Thunder Bay District Health Unit, in Thunder Bay, Ontario, Canada, over a 10-year period (2006-2015). Patients admitted to the Thunder Bay Regional Health Sciences Centre with IPD had their charts reviewed to abstract clinical data. Statistical analysis, including incidence rates of IPD, was performed., Results: Two hundred sixty-two cases of IPD occurred over the 10-year observation period and clinical data was available for 182 cases. Fifty-three of 182 (29.1%) patients were indigenous. 73 of 182 (40.1%) of patients were immunocompromised. Indigenous patients with IPD were more likely to be immunocompromised than non-indigenous patients (p < 0.001). Serotype data was available for 159 cases of IPD; PCV7, PCV13, and PPV23 covered 5.7%, 28.3%, and 79.2% of isolates, respectively, while 29 (20.8%) were non-vaccine serotypes. The annual incidence rate of IPD ranged from 8.9 to 25.9 per 100,000 among adults 18-64 years old; among adults 65 years of age and older the annual incidence of IPD ranged from 18.5 to 60.7 per 100,000., Conclusion: Among adults in NWO, Canada, there is a high incidence of IPD. Immunocompromised indigenous adults in NWO may benefit from pneumococcal vaccination coverage. Emerging non-vaccine serotypes of Streptococcus pneumoniae warrant the consideration of the provincial pneumococcal vaccination program.

This systematic review analyzes research examining racial/ethnic disparities in influenza and pneumococcal vaccination coverage between White and racial/ethnic minority (Black and Hispanic) nursing home residents. A review of the literature for years 1966-2014 using Medline, Web of Science, and PubMed was conducted. The Epidemiological Appraisal Instrument was used to appraise the quality of the 13 included studies. Overall, articles were strong in reporting and data analysis, but weak in sample selection and measurement quality. Disparities between vaccination coverage among racial/ethnic minorities versus Whites ranged from 2% to 20% for influenza and 6% to 15% for pneumococcal vaccination. Researchers reported racial/ethnic minorities were more likely to refuse vaccinations and less likely to have vaccinations offered and their vaccination status tracked compared to Whites. Policies/strategies that focus on ensuring racial/ethnic minorities are offered influenza and pneumococcal vaccinations and their vaccination status are tracked in nursing homes are warranted. Updated evaluation on vaccination disparities is also needed.

Background: Indigenous adults residing in the Northern Territory of Australia experience elevated rates of invasive pneumococcal disease despite the routine use of 23-valent pneumococcal polysaccharide vaccine (23vPPV). We hypothesised that the limited protection from 23vPPV may be due to hyporesponsiveness as a result of vaccine failure from repeated vaccination. To explore this possibility, we evaluated the immune response to a first and second dose of 23vPPV in Indigenous adults and a first dose of 23vPPV in non-Indigenous adults., Methods: Serotype-specific IgG was measured by ELISA for all 23 vaccine serotypes at baseline and at one month post-vaccination. Individuals were considered to have an adequate immune response if paired sera demonstrated either: a four-fold rise in antibody concentration; a two-fold rise if the post vaccination antibody was >1.3μg/ml but <4.0μg/ml; or a post-vaccination antibody concentration >4.0μg/ml for at least half of the serotypes tested (12/23). Our per-protocol analysis included the comparison of outcomes for three groups: Indigenous adults receiving a second 23vPPV dose (N=20) and Indigenous (N=60) and non-Indigenous adults (N=25) receiving their first 23vPPV dose., Results: All non-Indigenous adults receiving a first dose of 23vPPV mounted an adequate immune response (25/25). There was no significant difference in the proportion of individuals with an adequate response using our definition (primary endpoint), with 88% of Indigenous adults mounted an adequate response following first dose 23vPPV (53/60) compared to 70% having an adequate response following a second dose of 23vPPV (14/20; p=0.05). The risk difference between Indigenous participants receiving first dose compared to non-Indigenous participants receiving first dose was significant when comparing a response threshold of at least 70% (-27%, 95% CI: -43% to -11%; p=0.01) and 90% (-38%, 95% CI: -60% to -16%; p=0.006) of serotypes with a positive response., Conclusion: Indigenous participants demonstrated a poorer response to a first dose 23vPPV compared to their non-Indigenous counterparts, with lower IgG following a second 23vPPV dose. These findings highlight the critical need to evaluate the efficacy of future pneumococcal vaccine programs in the Australian Indigenous populations that recommend repeated doses of 23vPPV., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Racial disparities in rates of pneumococcal vaccine (PPSV23) exist. In one practice, 3.1 % of white patients refused PPSV23 following doctor recommendation, whereas 11.2 % of black patients refused vaccination. Our objective was to understand reasons black patients refused PPSV23., Methods: Mixed-method telephone survey in 2012 of black patients aged ≥65 with a documented refusal of PPSV23. The survey assessed beliefs about PPSV23; reasons for non-receipt of PPSV23; receipt of other vaccinations; and comparative perceptions of adult vs. childhood vaccines. Participants responded to items on a Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree)., Results: Participants' (N = 40) mean age was 73 years; 95 % were female. Participants recognized pneumonia could be deadly (M = 4.3, SD = 1.0), but reported low levels of personal susceptibility (M = 2.8, SD = 1.4). Participants perceived childhood vaccines to be safer (M = 4.2, SD = 1.2) than adult vaccines (M = 3.4, SD = 1.4; p < 0.01). Qualitative analyses to understand reasons for refusal of vaccine both reinforced identified low perceptions of personal susceptibility as well as identified numerous additional barriers to receipt of PPSV23 (e.g., fear, side effects, and mistrust)., Conclusions: Black patients in our sample who refused PPSV23 may not perceive themselves susceptible to the disease, suggesting that strategies to improve PPSV23 rates among these patients may need to emphasize susceptibility to pneumonia. Further, given the discrepancies in perceptions toward childhood versus adult vaccinations, focusing on vaccination across the lifespan may be a promising vaccine promotion strategy.

Pneumococcal conjugate vaccines (PCVs) have substantially reduced the burden of pneumococcal disease, including the incidence of otitis media (OM). However, in most countries, no surveillance exists to monitor the change in pneumococcal OM incidence after the introduction of PCVs. We explored whether measuring pneumococcal carriage was a useful surrogate for monitoring postvaccination changes in the incidence of pneumococcal OM. The 7-valent PCV was introduced to Israel's national immunization program in July 2009 and gradually replaced by the 13-valent PCV starting in November 2010. Each day since 2009, nasopharyngeal swabs have been obtained from the first 4 Bedouin children and the first 4 Jewish children who were younger than 5 years old and attended a pediatric emergency room in southern Israel. During the same time, OM surveillance in southern Israel included all children younger than 2 years of age who were diagnosed with OM and had undergone a middle-ear fluid culture. The relative change in the prevalence of vaccine-serotype (VT) pneumococcal carriage was predictive of the relative change in incidence of OM due to VT pneumococcus. However, the serotype replacement observed in non-VT carriage is not paralleled in the incidence of OM due to non-VT pneumococcus. This could indicate that there are more complex mechanisms of the immune response involved in preventing initial and consecutive episodes of OM, which has been changed through declining prevalence of the most virulent serotypes as a result of vaccination., (© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Invasive pneumococcal disease (IPD) and pneumonia are major causes of morbidity, especially in developing countries. While pneumococcal disease rates differences between various populations are well known, data are scarce regarding disparities in PCV impact on pneumococcal disease rates between populations living in the same country., Objective: The aim of this systematic literature review was to describe disparities in PCV impact between different populations., Methods: A systematic literature search was performed using the PubMed database. Studies evaluating pneumococcal disease rates at any age were included. The search was limited to articles written in English and published between 2000 and 2015. Independent extraction of articles was performed by two authors (NS, SB-S). Search terms included: pneumococcus, pneumococcal disease, IPD, pneumonia, PCV, pneumococcal vaccine, population, race, ethnicity, differences, and disparity. We defined resource-poor populations as African-Americans, Aboriginal, Alaska natives and Navajo native-Americans populations compared with the respective resource-rich populations, including White, non-Aboriginal, non-Alaska natives and general US population., Results: Eighteen articles meeting the selection criteria were identified; 17 regarding IPD and one regarding pneumonia. Nine articles compared IPD rates in African-Americans and Whites in the US, six compared Aboriginal and non-Aboriginal populations; two compared Alaska natives vs. non-native Alaskans in the US and one article compared Navajo native-Americans and general population in the US. Only minor difference where usually noted in the incidence rate ratios (IRRs) comparing pre- and post-PCV rates of IPD and pneumonia between resource rich and resource poor populations. In contrast, absolute rate reductions were higher in resource-poor compared with resource-rich populations., Conclusion: While differences in IPD and pneumonia rates between resource-poor and resource-rich populations were decreased following PCV introduction, disparity is still apparent and is not fully eliminated in any of the studies. Younger (<2years) populations in resource-poor populations seem to benefit the most from PCV introduction., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: A prior 7- and 13-valent pneumococcal conjugate vaccine (PCV7 and PCV13) study provided sufficient data (N=1754; Jewish, n=1154; Bedouin, n=595; other, n=5) to investigate the association between nasopharyngeal (NP) acquisition of common PCV7 serotypes and cross-reacting 6A (PCV7+6A) and IgG concentrations., Methods: Using a logistic regression model, serotype specific association between postinfant series IgG concentration (age 7months) and new NP acquisition between ages 7 and 24months was assessed and adjusted for ethnicity. From a subset of subjects with new NP acquisition (n=9-152 across serotypes studied), new acquisition percentiles and associated IgG concentrations were calculated., Results: For the serotypes studied, new NP acquisition rates decreased as IgG concentrations increased. Ethnicity did not influence these associations despite differences in carriage rates. From the subset with new acquisitions, 50% of the events occurred at IgG concentrations >0.61-5.58μg/mL; and 10% of the acquisitions occurred at IgG concentrations >2.48-17.69μg/mL., Conclusion: Remarkably high IgG concentrations are required to reduce NP acquisition. These IgG concentrations differ between serotypes. Ethnicity did not influence the association between high IgG concentrations and prevention of carriage despite differences in carriage rates. Since carriage determines transmission, these results may have important implications for herd protection., Trial Registration: ClinicalTrials.gov number, NCT00508742; http://clinicaltrials.gov/ct2/show/NCT00508742., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: Pneumococcal illnesses affect over one million Americans annually, making invasive pneumococcal disease (pneumonia) the most prevalent vaccine-preventable illness. Despite well-documented vaccine safety and efficacy, pneumococcal vaccine (PPSV23) uptake remains low, particularly among minorities. This study sought to define variables predicting PPSV23 uptake in eligible African-American (AA) adults., Design and Sample: This was a cross-sectional study using a combined version of the Health Belief (HBM) and Precaution Adoption Process Models (PAPM). A convenience sample of 295 AA adults self-administered the Vaccine Uptake Questionnaire (VUQ)., Measures: Bivariate chi-square analyses were conducted and significant variables evaluated using backward stepwise logistic regression., Results: PPSV23 uptake was 32.2% (n = 95). Older age, female gender, vaccine awareness, increased knowledge, higher trust scores, perceived susceptibility, and presence of provider recommendation for PPSV23 predicted vaccine uptake. In regression modeling, age, awareness, and provider recommendation remained significant predictors with younger age, unawareness, and lack of provider recommendation decreasing the likelihood of vaccination., Conclusion: Three dimensions of the HBM (barriers, cues, and susceptibility) predicted PPSV23 uptake. With 147 (47.8%) unaware of PPSV23 existence prior to this study, adding the dimension "unaware" from the PAPM may strengthen the model and assist efforts to increase PPSV23 uptake among AA adults., (© 2016 Wiley Periodicals, Inc.)

Background: In Japan, the seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2010. PCV13 has replaced PCV7 since November 2013., Methods: The effectiveness of PCV7 in protecting against invasive pneumococcal disease (IPD) in children aged <5 years was evaluated in a nationwide active population-based surveillance of IPD in 2008-2013 in 10 prefectures in Japan., Results: 1181 cases were identified; 711 pneumococcal strains were analyzed for serotyping and antimicrobial resistance. Compared with the baseline IPD incidence (25.0 per 100,000), a 98% decline in IPD caused by PCV7 serotypes was found after the introduction of PCV7. This was partially offset by an increased incidence of IPD caused by PCV13 minus PCV7 and non-PCV13 serotypes, resulting in a 57% decline in overall IPD incidence. Absolute increases in the incidence rates of IPD caused by PCV13 minus PCV7 and non-PCV13 serotypes were 2.1 and 2.8 per 100,000 during the study period, respectively. The proportion of meropenem-nonsusceptible strains, especially with serotypes 19A and 15A, increased significantly after PCV7 introduction., Conclusions: Our data confirmed a 98% decline in IPD incidence caused by PCV7 serotypes in children aged <5 years and serotype replacement after PCV7 introduction. This shows the importance of continuing surveillance of serotypes responsible for IPD and their antimicrobial resistance in Japan., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background and Objectives: Invasive pneumococcal disease (IPD) remains an important cause of illness in US children. We assessed the impact of introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) on pediatric IPD rates, as well as changes in racial and regional differences in IPD, in Tennessee., Methods: Data from active laboratory and population-based surveillance of IPD were used to compare IPD rates in the early-PCV7 (2001-2004), late-PCV7 (2005-2009), and post-PCV13 (2011-2012) eras. IPD rates were further stratified according to age, race, and region (east and middle-west TN)., Results: Among children aged <2 years, IPD rates declined by 70% from 67 to 19 per 100 000 person-years in the early-PCV7 era and post-PCV13 era, respectively. Similar decreasing trends in IPD rates were observed in older children aged 2 to 4 years and 5 to 17 years. In the late-PCV7 era, IPD rates in children aged <2 years were higher in black children compared with white children (70 vs 43 per 100 000 person-years); however, these racial differences in IPD rates were no longer significant after PCV13 introduction. Before PCV13, IPD rates in children aged <2 years were also higher in east Tennessee compared with middle-west Tennessee (91 vs 45 per 100 000 person-years), but these differences were no longer significant in the post-PCV13 era., Conclusions: PCV13 introduction led to substantial declines in childhood IPD rates and was associated with reduced regional and racial differences in IPD rates in Tennessee., (Copyright © 2015 by the American Academy of Pediatrics.)

Background: There are disparities in influenza and pneumococcal vaccination rates among elderly minority groups and little guidance as to which intervention or combination of interventions to eliminate these disparities is likely to be most cost-effective. Here, we evaluate the cost-effectiveness of four hypothetical vaccination programs designed to eliminate disparities in elderly vaccination rates and differing in the number of interventions., Methods: We developed a Markov model in which we assumed a healthcare system perspective, 10-year vaccination program and lifetime time horizon. The cohort was the combined African-American and Hispanic 65 year-old birth cohort in the United States in 2009. We evaluated five different vaccination strategies: no vaccination program and four vaccination programs that varied from "low intensity" to "very high intensity" based on the number of interventions deployed in each program, their cumulative cost and their cumulative impact on elderly minority influenza and pneumococcal vaccination rates., Results: The very high intensity vaccination program ($24,479/quality-adjusted life year; QALY) was preferred at willingness-to-pay-thresholds of $50,000 and $100,000/QALY and prevented 37,178 influenza cases, 342 influenza deaths, 1,158 invasive pneumococcal disease (IPD) cases and 174 IPD deaths over the birth cohort's lifetime. In one-way sensitivity analyses, the very high intensity program only became cost-prohibitive (>$100,000/QALY) at less likely values for the influenza vaccination rates achieved in year 10 of the high intensity (>73.5%) or very high intensity (<76.8%) vaccination programs., Conclusions: A practice-based vaccination program designed to eliminate disparities in elderly minority vaccination rates and including four interventions would be cost-effective.

Background: Before the introduction of 7-valent pneumococcal conjugate vaccine (PCV7), invasive pneumococcal disease (IPD) rates among blacks were twice the rates in whites. We measured the effects of trends in PCV7-type and non-PCV7-type IPD rates on racial disparities in overall IPD and estimated the proportion of IPD caused by serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13)., Methods: We analyzed data from the Active Bacterial Core surveillance system, which performs active, laboratory- and population-based surveillance for IPD for 29.2 million people in the United States, for the period 1998-2009. For patients with unknown race, we multiplied imputed race to calculate age-, race-, and serotype-specific IPD incidence rates., Results: During 1998-2009, 47 449 IPD cases were identified; race was unknown for 5419 (11%). After multiple imputation, 31 981 (67%) patients were considered white and 13 750 (29%) black. PCV7-type IPD rates in all ages in both races decreased to <1 case per 100 000, whereas there were no decreases in overall IPD rates after 2002. By 2009, PCV13 serotypes caused 71% of cases among whites aged <5 years compared with 58% among blacks (P < .01). PCV13 serotypes caused 50% of IPD cases in whites aged ≥5 years compared with 43% among blacks (P < .01)., Conclusions: Despite near elimination of PCV7-type IPD in both races, overall disparities in IPD rates persisted because non-PCV7-type IPD rates are higher among blacks. Whereas PCV13 introduction may reduce racial disparities in IPD, higher valency conjugate vaccines and strategies to directly address underlying causes are needed to eliminate IPD disparities.

Background: Racial differences have been well described for invasive pneumococcal disease (IPD), but little information exists on how race interacts with community socioeconomic factors., Methods: The Active Bacterial Core surveillance/Emerging Infections Program performed active surveillance for IPD in the 20-county Metropolitan Atlanta area. All IPD cases among children younger than 5 years from 2001 to 2009 were geocoded and linked to census tract-level socioeconomic measures from the 2000 US Census. Race- and socioeconomic-specific average annual incidence rates per 100,000 population were calculated. Trends in IPD incidence were determined by χ² tests for trend. Rate ratios (RRs) and 95% confidence intervals (CIs) were estimated using Poisson regression., Results: IPD incidence among the total population of children increased as percentage of household poverty increased (P = 0.002), as median household income decreased (P < 0.001), as wealth decreased (P = 0.018) and as percentage of individuals with less than a high school education increased (P = 0.023). After stratifying by race, there was no significant linear trend between socioeconomic characteristics and IPD incidence among white children; among black children, however, IPD incidence decreased as socioeconomic conditions worsened. Despite adjusting for sex and socioeconomic factors, the IPD rate remained higher among black children compared with white children (RR = 1.60; 95% CI: 1.39-1.84). Differences in RR of IPD associated with highest poverty and lowest wealth noted in 2001 [RR = 2.71 (95% CI: 2.17-3.39) and 1.80 (95% CI: 1.09-2.96), respectively] declined in 2009 [RR = 1.33 (95% CI: 0.90-1.96) and 0.76 (95% CI: 0.48-1.19), respectively]., Conclusions: Although socioeconomic disparities in IPD incidence exist among children, the association between socioeconomic characteristics and IPD rates may differ by race and may change over time. Community-level socioeconomic factors did not account for racial differences in IPD incidence.

Background: American Indian/Alaska Native (AI/AN) people suffer substantially higher rates of invasive pneumococcal disease (IPD) than the general US population. We evaluated antimicrobial prescribing data and their association with non-susceptibility in Streptococcus pneumoniae causing IPD in AI/AN people between 1992 and 2009., Methods: Antimicrobial use data were gathered from the electronic patient management system and included all prescriptions dispensed to Alaska Native patients aged 5 years and older from outpatient pharmacies at the Alaska Native Medical Center (ANMC). Antimicrobial susceptibility data were gathered from pneumococcal isolates causing IPD among Anchorage Service Unit AI/AN residents aged 5 years and older. Data were restricted to serotypes not contained in the pneumococcal vaccine (PCV7)., Results: Over the study period, overall antimicrobial prescribing increased 59% (285/1,000 persons/year in 1992 to 454/1,000 persons per year in 2009, p<0.001). Trimethoprim/sulfamethoxazole prescribing increased (43/1,000 persons/year in 1992 to 108/1,000 persons/year in 2009, p<0.001) and non-susceptibility to trimethoprim/sulfamethoxazole in AI/AN patients ≥5 years of age increased in non-PCV7 serotypes (0-12%, p<0.05). Similarly, prescribing rates increased for macrolide antibiotics (46/1,000 persons/year in 1992 to 84/1,000 persons/year in 2009, p<0.05). We observed no statistically significant change over time in erythromycin non-susceptibility among non-PCV7 serotypes in AI/AN patients aged 5 years or greater (0-7%, p=0.087)., Conclusion: Antimicrobial prescribing patterns of some antibiotics in the AI/AN population corresponded to increased antimicrobial resistance in clinical isolates. This study highlights the on-going threat of antimicrobial resistance, the critical importance of judicious prescribing of antibiotics and the potential utility of prescribing data for addressing this issue.

Introduction: The International Circumpolar Surveillance network is a population-based surveillance system that collects data on invasive pneumococcal disease (IPD) in Northern Canada. A 7-valent pneumococcal conjugate vaccine was first introduced in some regions of Northern Canada in 2002, followed by 10-valent (2009) and 13-valent (PCV-13) vaccines (2010). A 23-valent polysaccharide (PPV-23) vaccine was first introduced in 1988 for special populations and adults aged 65 years and older. To describe the epidemiology in the context of pneumococcal vaccination programs, we analysed surveillance data from Northern Canada from 1999 to 2010., Methods: A standardized case report form capturing demographic and clinical information was completed for all IPD cases in Northern Canada meeting the national case definition. Isolates were sent to a reference laboratory for confirmation, serotyping and antimicrobial resistance testing. Both laboratory and epidemiological data were sent to the Public Health Agency of Canada for analysis. Population denominators were obtained from Statistics Canada., Results: From 1999 to 2010, 433 IPD cases were reported (average 36 cases per year). Incidence was greatest among infants aged < 2 years and among those aged 65 years and older, with an average annual incidence of 133 and 67 cases per 100,000 population, respectively. After a peak in incidence in 2008, rates among infants have declined. Incidence rates varied from 2 to 16 times greater, depending on the year, among Aboriginals compared to non-Aboriginals. Hospitalization was reported in 89% of all cases and the case fatality ratio was 6.0%. Clinical manifestations varied, with some patients reporting > 1 manifestation. Pneumonia was the most common (70%), followed by bacteremia/septicaemia (30%) and meningitis (8%). Approximately, 42% of cases aged < 2 years in 2009 and 2010 had serotypes covered by the PCV-13. In addition, the majority (89%) of serotypes isolated in cases aged 65 years and older were included in the PPV-23 vaccine., Conclusion: IPD continues to be a major cause of disease in Northern Canadian populations, with particularly high rates among infants and Aboriginals. Continued surveillance is needed to determine the impact of conjugate pneumococcal vaccine programs. Additional studies investigating factors that predispose infants and Aboriginal peoples would also be beneficial.

Objective: Invasive pneumococcal disease is a major cause of preventable morbidity and mortality in the United States, particularly among the elderly (>65 years). There are large racial disparities in pneumococcal vaccination rates in this population. Here, we estimate the cost-effectiveness of a hypothetical national vaccination intervention program designed to eliminate racial disparities in pneumococcal vaccination in the elderly., Methods: In an exploratory analysis, a Markov decision-analysis model was developed, taking a societal perspective and assuming a 1-year cycle length, 10-year vaccination program duration, and lifetime time horizon. In the base-case analysis, it was conservatively assumed that vaccination program promotion costs were $10 per targeted minority elder per year, regardless of prior vaccination status and resulted in the elderly African American and Hispanic pneumococcal vaccination rate matching the elderly Caucasian vaccination rate (65%) in year 10 of the program., Results: The incremental cost-effectiveness of the vaccination program relative to no program was $45,161 per quality-adjusted life-year gained in the base-case analysis. In probabilistic sensitivity analyses, the likelihood of the vaccination program being cost-effective at willingness-to-pay thresholds of $50,000 and $100,000 per quality-adjusted life-year gained was 64% and 100%, respectively., Conclusions: In a conservative analysis biased against the vaccination program, a national vaccination intervention program to ameliorate racial disparities in pneumococcal vaccination would be cost-effective., (Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: Pneumococci could evade pneumococcal conjugate vaccines (PCV) by modifying, mutating, or deleting vaccine-serotype capsule genes or by downregulating capsule production. We sought to assess whether pneumococci that are nontypeable (NT) by the Quellung reaction truly lack capsule genes or are failing to produce capsule in vitro., Methods: We applied multilocus sequence typing and a microarray for detection of pneumococcal polysaccharide capsule biosynthesis genes to NT carriage (children aged <5 years; years 1997-2000, 2006-2008) and NT invasive disease (IPD) (all ages; years 1994-2007) isolates from Native American communities., Results: Twenty-seven of 28 (96.4%) NT IPD isolates had sequence types (STs) typically found among typeable IPD isolates and contained whole or fragments of capsule genes that matched known serotypes; 1 NT-IPD isolate had a profile resembling NT carriage isolates. Forty-nine of 76 (64.5%) NT carriage isolates had STs that typically lack capsule genes and were similar to NT carriage isolates found globally., Conclusions: This is the first documentation of IPD from an NT strain confirmed to lack all known capsule genes. Most NT IPD isolates have or had the capacity to produce capsule, whereas a majority of NT carriage isolates lack this capacity. We found no evidence of pneumococcal adaptation to PCV7 via downregulation or deletion of vaccine-serotype capsule genes.

Background: Although invasive pneumococcal disease (IPD) has significantly decreased in children since the introduction of the pneumococcal conjugate vaccine, instances of IPD from non-PCV7 serotypes have increased. Concerns remain regarding the risk for IPD during the neonatal period. Our objective was to measure quantitative antibody levels to 16 serotypes of Streptococcus pneumoniae in pregnant non-Hispanic black, non-Hispanic white, and Hispanic mothers, and in cord blood samples., Methods: Antibody levels were evaluated by Luminex assay., Results: Forty-two percent of all mothers had protective (-0.35 microg/mL) antibody levels to 16 serotypes. Hispanic mothers were most likely to possess protective antibody levels for 12 serotypes but were less likely to possess protective antibody levels for serotypes 9V, 12F, and 18C, compared to non-Hispanic white or black mothers. Thirty-three percent of cord blood samples demonstrated protective antibody levels. Hispanic infants had a higher prevalence of protective antibodies to all serotypes except 11A, 14, 18C, and 23F. Non-Hispanic black infants had a higher prevalence of protective immunity to serotypes 11A, 14, and 18C, and non-Hispanic white infants to only serotype 23F., Conclusions: Hispanic mothers and their infants have a higher prevalence of protective immunity to most serotypes of S pneumoniae, compared to white or black mothers/infants. We found no evidence of a lower prevalence of protective immunity to specific serotypes in non-Hispanic black vs. non-Hispanic white infants that might account for the reported higher incidence of IPDs in blacks. Environmental factors in Hispanic mothers may be responsible for their enhanced level of immunity. A significant number of cord blood samples had inadequate levels of protective immunity to a variety of S pneumoniae serotypes.

Background: Multi-locus sequence typing (MLST) of pneumococcal isolates collected during an efficacy trial of the 7-valent pneumococcal conjugate vaccine (PCV7) among Navajo and White Mountain Apache children from 1998 to 2000 showed a non-differential expansion of pre-existing sequence types (STs) and only one capsule-switching event in the PCV7-randomized communities. PCV7 was introduced as a routine infant vaccine in October 2000. We assessed variability in PCV7 effectiveness and mechanisms of ST replacement after prolonged routine PCV7 use., Methods: We applied MLST to 267 non-vaccine type pneumococcal carriage and invasive disease isolates from Navajo and White Mountain Apache children from 2006 to 2008, and compared them to those from 1998 to 2000. Microarray was used to confirm capsule switching events., Results: The primary mechanism of ST replacement among Navajo and White Mountain Apache children was expansion of existing STs, although introduction of new STs was an important secondary mechanism. ST199, a majority being serotype 19A, was the most common ST in both eras. Only ST193 (serotype 21) was preferentially expanding in the PCV7 era. Three examples of capsule switching were identified. No variability in vaccine effectiveness by ST was observed., Conclusion: We did not observe an influence of ST on PCV7 serotype-specific effectiveness, although some STs may be favored in replacement., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objectives: We compared invasive pneumococcal disease (IPD) incidence by race/ethnicity and neighborhood poverty level and assessed their relative utility to describe disparities in IPD in 1998-1999 and again in 2007-2008, after introduction of the 7-valent pneumococcal conjugate vaccine (PCV7)., Methods: We conducted laboratory surveillance for pneumococcal isolates from sterile body sites and serotyped the isolates. Home address was geocoded to the census-tract level. Census-tract data on the percentage of people below poverty were grouped into three categories. The difference in the magnitude of incidence by race/ethnicity and by census-tract socioeconomic status (SES) (high poverty minus low poverty) was compared for 1998-1999 and 2007-2008 for PCV7 and non-PCV7 serotypes., Results: In 1998-1999, incidence difference (all per 100,000 population) for PCV7 serotypes for black people compared with white people was 14.3 and by poverty level was 13.9. The highest rate was among white people in high-poverty tracts (77.3). By 2007-2008, there were only slight differences between rates for black and white people (0.7) and SES (1.4). In 1998-1999, the incidence difference for non-PCV7 serotypes was 4.7 between black and white people and 6.0 by SES. By 2007-2008, the differences were 11.6 and 11.7, respectively. Among those living in the highest-poverty tracts, white people had the highest rate (42.9)., Conclusions: In the absence of vaccine, IPD incidence is higher among people living in higher-poverty census tracts and among black people. Emerging serotypes also follow this trend. Differences in neighborhood poverty levels reveal disparities in rates of IPD as large as those seen by race/ethnicity and could be used to routinely describe disparities and target prevention.

Objective: We determined the effectiveness of a 23-valent-polysaccharide pneumococcal vaccine (PPV-23) and pneumococcal conjugate vaccine (PCV-7) in reducing adult pneumococcal mortality by comparing historically predicted declines in pneumococcal disease mortality with observed patterns since the introduction of PPV-23 and PCV-7, including analyses of age, gender, and racial/ethnic subgroups., Methods: We analyzed all deaths registered on U.S. death certificates reporting any site of pneumococcal infection (e.g., meningitis, sepsis, pneumonia, bacteremia, and peritonitis) from 1968 to 2006. We used time-series dynamic linear regression on annual pneumococcal mortality rates to determine the percentage reduction in post-1983 mortality rates for a given increase in PPV-23 vaccination rates and post-2000 mortality rates for a given increase in PCV-7 vaccination rates., Results: Pneumococcal mortality decreased well before the introduction of PPV-23 in 1983 and again before the introduction of PCV-7 in 2000. The level of PPV-23 vaccination was associated with a direct and significant reduction in adult mortality, especially white female adults > or = 65 years of age. In contrast, the level of PCV-7 vaccination in the population was not associated with an indirect and significant reduction in pneumococcal mortality beyond the historical pace of decline., Conclusions: PPV-23 introduction was associated with a reduction in pneumococcal mortality among older adults > or = 65 years of age beyond levels predicted by secular trends, whereas PCV-7 introduction was not. Mortality reduction was not uniformly experienced across the population, revealing the need for additional strategies to reduce pneumococcal mortality in older adults.

Host genetic factors that modify risk of pneumococcal disease may help target future public health interventions to individuals at highest risk of disease. We linked data from population-based surveillance for invasive pneumococcal disease (IPD) with state-based newborn dried bloodspot repositories to identify biological samples from individuals who developed invasive pneumococcal disease. Genomic DNA was extracted from 366 case and 732 anonymous control samples. TagSNPs were selected in 34 candidate genes thought to be associated with host response to invasive pneumococcal disease, and a total of 326 variants were successfully genotyped. Among 543 European Americans (EA) (182 cases and 361 controls), and 166 African Americans (AA) (53 cases and 113 controls), common variants in surfactant protein D (SFTPD) are consistently underrepresented in IPD. SFTPD variants with the strongest association for IPD are intronic rs17886286 (allelic OR 0.45, 95% confidence interval (CI) [0.25, 0.82], with p = 0.007) in EA and 5' flanking rs12219080 (allelic OR 0.32, 95%CI [0.13, 0.78], with p = 0.009) in AA. Variants in CD46 and IL1R1 are also associated with IPD in both EA and AA, but with effects in different directions; FAS, IL1B, IL4, IL10, IL12B, SFTPA1, SFTPB, and PTAFR variants are associated (p≤0.05) with IPD in EA or AA. We conclude that variants in SFTPD may protect against IPD in EA and AA and genetic variation in other host response pathways may also contribute to risk of IPD. While our associations are not corrected for multiple comparisons and therefore must be replicated in additional cohorts, this pilot study underscores the feasibility of integrating public health surveillance with existing, prospectively collected, newborn dried blood spot repositories to identify host genetic factors associated with infectious diseases.

Aim: To describe the epidemiology, clinical features, management and outcome of pneumococcal-associated haemolytic-uraemic syndrome (P-HUS) in New Zealand over the past decade., Methods: A retrospective chart review of children with P-HUS from 1998 to 2007 that were prospectively reported to the New Zealand Paediatric Surveillance Unit. P-HUS was defined as microangiopathic haemolytic anaemia (Hb <100 g/L with fragmented red blood cells), thrombocytopaenia (platelet count <130 x 10(9)/L), acute renal impairment with oliguria and elevated plasma creatinine, and confirmed or suspected pneumococcal infection., Results: Eleven children (nine male, two female), predominately Maori and Polynesian (10 children) were studied. The median age was 8.5 months. The median duration of hospitalisation was 25 days. Of the infections, 10 were confirmed pneumococcal (six pneumonia, four meningitis) and one pneumonia was suspected pneumococcal (culture negative, however T activation positive). Nine patients required dialysis for a median duration of 13 days. One child with meningitis died after therapy was withdrawn because of severe neurological injury. One patient developed end stage kidney disease and two further children had evidence of persisting renal sequelae at follow-up., Conclusions: Pneumococcal disease remains an important public health problem in New Zealand children, particularly those of Maori and Pacific Island ethnicity. P-HUS should be considered in pneumococcal disease associated with severe haematological and renal abnormalities. These children should be monitored long-term, as they are at risk of permanent renal injury.

Objectives: The aim of this retrospective study was to determine the incidence and outcome of infectious endocarditis in Greenland with an emphasis on pneumococcal endocarditis., Study Design: Retrospective, non-interventional study., Methods: Review of files and medical history of all patients with infectious endocarditis from the Patient Registry in Greenland in the 11-year period 1995-2005., Results: There were 25 cases of endocarditis, giving an incidence rate of 4.0/100,000 per year. Twenty-four percent of these cases were caused by Streptoccous pneumonia, which is significantly more frequent than in studies on Caucasian populations, where pneumococcal infection was seen in 1-3% of endocarditis cases. The overall mortality rate was 12%. Pneumococcal endocarditis (PE) had the clinical characteristics of fulminant disease with frequent heart failure, complications and need for surgery. Among cases with PE, 67% needed acute valve replacement and the mortality rate was 33%., Conclusions: The high incidence rate, clinical characteristics and grave prognosis of PE are consistent with another study of an Inuit population in Alaska.

North Coast Area Health Service (NCAHS) conducted a seven week television advertising campaign to raise community awareness of the availability of free adult pneumococcal vaccination and to increase coverage among North Coast residents in high risk groups. Effectiveness of the campaign was evaluated by examining vaccine ordering patterns of North Coast vaccination providers from 2005/2006 as a proxy for vaccination coverage. In the months during and immediately following (June-September 2006) the advertising campaign, a significantly higher proportion of vaccines were despatched to North Coast immunisation service providers. The advertising campaign was an effective strategy to promote vaccination among NCAHS residents not immunised in the first year of the National Pneumococcal Program for Older Australians. This higher immunisation coverage is expected to contribute to the statewide trend of significant reductions in invasive pneumococcal disease (IPD) notifications.

Background: Prior to the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7), the rate of invasive pneumococcal disease (IPD) was 8-fold higher among White Mountain Apache persons of all ages than it was among the general US population, . We aimed to assess the impact of PCV7 and 23-valent pneumococcal polysaccharide vaccine on the rate of IPD among White Mountain Apache persons., Methods: From 1991 through 2006, we conducted active laboratory- and population-based surveillance among Native American residents of the White Mountain Apache reservation. Charts were reviewed and pneumococcal isolates were collected for serotype testing. Three time periods were defined: the pre-PCV7 baseline period (1991-1997), the PCV7 efficacy trial period (1998-2000), and the PCV7 routine-use period (2001-2006)., Results: We identified 246 cases of IPD; the mean annual IPD rate fell from 126 cases per 100,000 person-years in the period 1991-1997 to 87 cases per 100,000 person-years in the period 2001-2006 (p = .01). The rate of IPD attributable to PCV7 serotypes of Streptococcus pneumoniae decreased by 252 cases per 100,000 person-years (92%) among children aged <5 years, and that attributable to non-PCV7 serotypes of S. pneumoniae decreased by 87 cases per 100,000 person-years (44%) among children aged <5 years. Among adults, the rate of IPD remained unchanged; PCV7 serotypes of S. pneumoniae accounted for only 25% of adult cases during the period 1991-1997., Conclusions: Since the introduction of PCV7, the rate of IPD among White Mountain Apache children aged <5 years has decreased to the lowest rate ever (122 cases per 100,000 person-years), but it remains 5.7-fold greater than the rate of IPD among children in the general US population. In contrast to some other high-risk populations, there is no evidence of non-vaccine-type replacement disease in this age group. Among White Mountain Apache adults, the rate of IPD remains substantially higher than that observed in the general US population. Vaccines with broader serotype coverage are needed to further reduce the disparity in the rate of IPD between the White Mountain Apache and general US populations.

Background: National and state surveys show large disparities in pneumococcal vaccination status among Whites, Blacks and Latinos aged >/= 65. The purpose of this study is to determine whether there is any difference in the validity of self-report for pneumococcal vaccination by race/ethnicity that might contribute to the substantial disparities observed in population-level coverage estimates., Methods: Self-reported vaccination status was compared with medical record documentation for samples of White, Black, and Latino members of a large health plan to examine whether differences in validity of self-report contribute to observed disparities., Results: Sensitivity was significantly lower for Blacks (0.849, 95% CI 0.818-0.876) and Latinos (0.869, 95% CI 0.847-0.889) than for Whites (0.931 95% CI 0.918-0.942). Specificity was somewhat higher for Blacks than for Latinos and Whites, but the differences were not statistically significant. Coverage for Whites, Blacks and Latinos, respectively, was 84.3%, 73.5%, and 82.3% based on self-report, but 74.8%, 71.9%, and 84.2% based on medical records., Conclusion: The results of this study suggest that differential self-report error, i.e., summative effect of over-reporting and under-reporting within a race-ethnic group, may contribute to the size and direction of race-ethnic disparities in pneumococcal vaccination observed in surveys.

Objective: To describe the epidemiology of invasive pneumococcal disease (IPD) in a predominantly minority population with low childhood immunization rates and high HIV prevalence, during the early childhood pneumococcal vaccine (PCV7) era., Methods: A retrospective cases series analysis of 131 patients diagnosed with IPD at University Hospital in Newark, NJ from 2000 through 2005, and who had their pneumococcal isolates serotyped, was conducted. Changes in IPD over time were analyzed with the Cochran-Armitage test and linear regression. Multivariate logistic regression was conducted to determine risk factors for non-vaccine type IPD., Results: Ninety-two percent of cases occurred in older children (>or=5 years) and adults, with 53.4% occurring in the 34-49 year-old age group. 90% of cases were black and 48% were HIV-infected. Among cases five years or older, there was a significant decrease in the proportion of IPD caused by vaccine serotypes (2000: 45.5%, 2001: 50.0%, 2002: 31.8%, 2003: 30.0%, 2004: 0.0%, 2005: 0.0%; p<0.0005). Concomitantly, PCV7 immunization rates among Newark infants increased (2002: 30.5%, 2003: 58.1%, 2004: 70.9%, 2005: 75.6%). Risk factors for non-vaccine type IPD included year of diagnosis and older male., Conclusion: At-risk populations, with high HIV prevalence and relatively low infant PCV7 immunization rates, may still be benefiting from PCV7-related herd protection effects.

Invasive pneumococcal disease (IPD) is 3-5 times more common among Navajo adults than in the general US population. The authors conducted a case-control study to identify risk factors for IPD among Navajo adults. Navajos aged > or =18 years with IPD were identified through prospective, population-based active laboratory surveillance (December 1999-February 2002). Controls matched to cases on age, gender, and neighborhood were selected. Risk factors were identified through structured interviews and medical record reviews. The authors conducted a matched analysis based on 118 cases and 353 controls. Risk factors included in the final multivariable analysis were chronic renal failure (odds ratio (OR) = 2.6, 95% confidence interval (CI): 0.9, 7.7), congestive heart failure (OR = 5.6, 95% CI: 2.2, 14.5), self-reported alcohol use or alcoholism (OR = 2.9, 95% CI: 1.5, 5.4), body mass index (weight (kg)/height (m)(2)) <5th (OR = 3.2, 95% CI: 1.0, 10.6) or >95th (OR = 2.8, 95% CI: 1.0, 8.0) percentile, and unemployment (OR = 2.6, 95% CI: 1.2, 5.5). The population attributable fractions were 10% for chronic renal failure, 18% for congestive heart failure, 30% for self-reported alcohol use or alcoholism, 6% for body mass index, and 20% for unemployment. Several modifiable risk factors for IPD in Navajos were identified. The high prevalence of renal failure, alcoholism, and unemployment among Navajo adults compared with the general US population may explain some of their increased risk of IPD.

The recent discovery of a mobile genetic element encoding a pilus-like structure in Streptococcus pneumoniae and the demonstration of a role for the pilus in virulence in mice have led to the proposal of the use of the pilus as a candidate pneumococcal vaccine. We examined the frequency of occurrence of the pneumococcal pilus, as determined by the presence of the rrgC gene, and analyzed its association with virulence, capsular serotypes, and multilocus sequence types in the American Indian pneumococcal collection and isolates of S. pneumoniae from blood cultures collected at Children's Hospital Boston. Overall, 21.4% of strains in the American Indian collection had the rrgC gene, but there was no difference between isolates obtained from the nasopharynx and those obtained from sterile sites (blood or cerebrospinal fluid). Vaccine-type strains were significantly more likely than non-vaccine-type strains to have this pilus gene (P < 0.001). Among isolates with identical multilocus sequence types, there was a high concordance (95%) between the multilocus sequence type and the presence or the absence of rrgC. Finally, in the era of the pneumococcal conjugate vaccine, the frequency of rrgC in isolates from Children's Hospital Boston has decreased significantly (42.8% before 2000 versus 21.3% after 2000; P = 0.019). Therefore, our data show that the pilus is present in a minority of strains and is associated with certain serotypes and that its frequency has been reduced by the conjugate pneumococcal vaccine.

Nasopharyngeal carriage of Streptococcus pneumoniae in unimmunised adults and older children in three remote Australian Aboriginal communities was compared in 2002 and 2004. Universal childhood pneumococcal vaccination with a catch-up program was introduced in late 2001. Carriage prevalence across all age groups of pneumococcal serotypes included in the 7-valent vaccine was 10% in both 2002 and 2004 (12 and 30 months after introduction of vaccination). This carriage prevalence was lower than anticipated. It is likely that indirect effects of childhood vaccination occurred before the 2002 survey. To further assess indirect effects on carriage of childhood pneumococcal vaccination, data prior to 2002 are required. Between 12 and 30 months following introduction of conjugate pneumococcal vaccination, indirect effects on carriage were unchanged.

PneuMum is a randomised controlled maternal vaccination trial, using 23-valent Pneumococcal Polysaccharide Vaccine (23vPPV) during the third trimester or at delivery compared to vaccination at 7 months post delivery. The primary outcomes are infant middle ear disease and nasopharyngeal pneumococcal carriage at 7 months of age. PneuMum is the first vaccine trial to be conducted among Indigenous people in the Northern Territory. We describe the study design and the approach taken to develop the PneuMum message in collaboration with key Indigenous stakeholders and then to communicate the PneuMum message with Indigenous communities and potential participants. We hope that these methods will provide a model for future research involving Indigenous communities to ensure Indigenous involvement in research and ultimate improvements in Indigenous health.

Otitis media (OM) is a major burden for all children, particularly for Australian Aboriginal children. Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae and viruses (including rhinovirus and adenovirus) are associated with OM. We investigated nasopharyngeal microbial interactions in 435 samples collected from 79 Aboriginal and 570 samples from 88 non-Aboriginal children in Western Australia. We describe a multivariate random effects model appropriate for analysis of longitudinal data, which enables the identification of two independent levels of correlation between pairs of pathogens. At the microbe level, rhinovirus infection was positively correlated with carriage of S. pneumoniae, H. influenzae and M. catarrhalis, and adenovirus with M. catarrhalis. Generally, there were positive associations between bacterial pathogens at both the host and microbe level. Positive viral-bacterial associations at the microbe level support previous findings indicating that viral infection can predispose an individual to bacterial carriage. Viral vaccines may assist in reducing the burden of bacterial disease.

This study reports a 16-year prospective surveillance of invasive disease isolates in central Australian Aborigines. There were 621 (89.6% of total) isolates recovered from Aborigines. The mortality in children less than 5 years of age was 4% but rose to 34.5% in those over 49 years of age. The study documented continuing high rates of disease overall, but with significant reductions in incidence rates for children. In children under 2 years of age, the incidence fell by 32% from 2053 per 100,000 in the period 1985-1990 to 1184 per 100,000 in the period 1996-2000. Rates of disease in adults showed no reduction despite an adult immunisation programme with 23 valent vaccine which occurred in the 1990s. Epidemics of serotypes 1, 5 and 12F were documented during the study period.

Purpose: To assess whether and how pneumococcal vaccine acceptance occurs after nurse recommendation varies by race/ethnicity., Methods: We prospectively evaluated nurses' standing orders to assess and vaccinate high-risk patients in a general medicine practice., Results: Of 370 adult patients surveyed (60% nonwhite), 78 (21%) declined vaccination following nurse recommendation, and 43 (12%) persisted in declining after physician consultation. Three-hundred-twenty-seven (88%) patients accepted vaccination: 292 (79%) accepted following nurse recommendation and 35 (9%) following physician consultation. African Americans (19%) were significantly more likely to decline compared with whites (8%) and Asians (5%) (P= 0.01). Reasons for refusal included believing vaccination was unnecessary (32%), fearing shots in general (21%), fearing vaccine-induced illness (26%) and wanting more informotion regarding the vaccine (9%)., Conclusion: Standing orders, physicians' firm recommendations and addressing patients' vaccine-related concerns may reduce racial/ethnic disparities in vaccination.

Objectives: To examine vaccination in seniors in the five U.S. communities of the Racial and Ethnic Adult Disparities in Immunization Initiative., Design: Cross-sectional telephone survey in spring 2003 using stratified sampling by ZIP code and race/ethnicity., Setting: New York, Texas, Wisconsin, Illinois, and Mississippi., Participants: Four thousand five hundred seventy-seven Medicare beneficiaries., Measurements: Outcomes were pneumococcal vaccination ever and influenza vaccination in 2002/03 and were determined according to race/ethnicity, awareness of vaccination, and provider recommendation. Survey questions also asked about future plans for vaccination, whether respondents believed they had become sick from prior influenza vaccination, and whether unvaccinated respondents would be vaccinated if a health professional recommended it., Results: Pneumococcal vaccination coverage was 70.3% for whites, 40.8% for blacks, and 53.2% for Hispanics, and the proportion reporting provider recommendation for vaccination differed significantly according to race/ethnicity. In multivariate regression, provider recommendation (risk ratio (RR) = 2.32, 95% confidence intervals (CI) = 2.10-2.57) and awareness of vaccination (RR = 1.60, 95% CI = 1.40-1.82) were associated with greater pneumococcal vaccination. Influenza vaccination coverage was 76.2% for whites, 50.7% for blacks, and 65.7% for Hispanics. A little more than half of respondents reported provider recommendation for influenza vaccination, with no differences according to race/ethnicity. Provider recommendation was associated with influenza vaccination (RR = 1.31, 95% CI = 1.25-1.38). More blacks and Hispanics believed they had become sick from prior influenza vaccination than whites, and this belief was associated with lower vaccination rates., Conclusion: This survey details vaccination patterns in an ethnically and geographically diverse sample of seniors and identifies some differences between blacks, Hispanics, and whites that may contribute to disparities in vaccination coverage. Survey findings highlight the importance of provider vaccination recommendations.

Background: Adults infected with HIV have high rates of invasive pneumococcal disease. Introduction of pneumococcal conjugate vaccine for children could affect disease among HIV-infected adults., Objective: To compare invasive pneumococcal disease among HIV-infected adults before and after the introduction of a pediatric conjugate vaccine., Design: Active laboratory-based surveillance in an adult population of 10.8 million, including 38,314 living with AIDS., Setting: 7 Active Bacterial Core surveillance areas in the United States., Patients: All surveillance-area residents 18 to 64 years of age with Streptococcus pneumoniae isolated from a sterile site between 1998 and 2003., Measurements: Ratio of the number of cases of invasive pneumococcal disease among HIV-infected adults to the estimated number of adults 18 to 64 years of age living with AIDS; serotype-specific subset analyses; and comparison of periods before and after introduction of conjugate vaccine by using exact tests., Results: Of 8582 cases of invasive pneumococcal disease in adults, 2013 (24%) occurred among persons infected with HIV. Between baseline (1998 to 1999) and 2003, the ratio of invasive pneumococcal disease in HIV-infected adults to the number of adults living with AIDS in the surveillance areas decreased from 1127 to 919 cases per 100 000 AIDS population, a reduction of 19% (P = 0.002). Among HIV-infected adults, the ratio for disease caused by pneumococcal serotypes included in the conjugate vaccine decreased 62% (P < 0.001), although the ratio for disease caused by nonvaccine serotypes increased 44% (P < 0.001)., Limitations: Ratios are proxy measures of incidence rates. The denominator of surveillance-area residents living with HIV infection was not available., Conclusions: Introduction of the pediatric conjugate vaccine was associated with an overall decrease in invasive pneumococcal disease among HIV-infected adults, despite increased disease caused by nonvaccine serotypes.

There were 2,375 cases of invasive pneumococcal disease (IPD) notified to the National Notifiable Diseases Surveillance System in Australia in 2004; a notification rate of 11.8 cases per 100,000 population. The rate varied between states and territories and by geographical region with the highest rates in the Northern Territory. Invasive pneumococcal disease was reported most frequently in children aged less than 5 years (55.4 cases per 100,000 population). Enhanced surveillance for IPD was carried out in all states and territories, in 2004, providing additional data on 2,023 (85%) cases. The overall rate of IPD in Indigenous Australians was 3.2 times the rate in non-Indigenous Australians. There were 154 deaths attributed to IPD resulting in an overall case fatality rate of 7.6 per cent. Rates of IPD in the Indigenous and non-Indigenous under 2-year-old population were similar in 2004 (91.5 and 93.6 cases per 100,000 population, respectively) following a targeted introduction of the 7-valent pneumococcal conjugate vaccine (7vPCV) in mid-2001 for Indigenous infants and children. Serotypes of isolates were identified from 80 per cent of all notified cases, with 72 per cent of isolates belonging to serotypes represented in the 7vPCV and 91 per cent in the 23-valent polysaccharide pneumococcal vaccine (23vPPV). Comparison of serotypes in the 7vPCV target population showed that the rate of IPD due to 7vPCV serotypes decreased by 74 per cent between 2001-02 and 2003-04. Of 216 isolates with reduced penicillin susceptibility, 83 per cent belonged to pneumococcal serotypes in the 7vPCV and 95 per cent in the 23vPPV.

In 2000, pneumococcal conjugate vaccine (PCV7) was recommended for young children. By 2002-2003, 48.6% had been fully immunized. Using Medicare administrative, we found that the rates of invasive pneumococcal disease (IPD) hospitalizations in the elderly in the 2000-2001, 2001-2002 and 2002-2003, were 22.6, 30.2, and 40.6% lower, respectively, than during the baseline period, 1996-1997 through 1999-2000 (range 35.1/100,000 to 38.3/100,000). Pneumococcal polysaccharide vaccine (PPV23) has been recommended for the elderly, since 1989. PPV23 vaccination rates in the elderly increased by 25.2% during the baseline period but by <5% during the period PCV7 has been available. Thus, during the period that PCV7 vaccine has been used in children, rates of IPD in the elderly have declined appreciably more compared to the immediately prior period when PPV23 was the only vaccine available.

We evaluated invasive pneumococcal disease (IPD), antimicrobial resistance and nasopharyngeal colonization before and after introduction of pneumococcal conjugate vaccine (PCV7) in Alaska Natives (AN), a population with high IPD rates. We obtained IPD rates from population-based surveillance. Colonization was determined from annual surveys among rural AN of all ages and from urban children. After vaccine introduction, vaccine-type IPD rates declined by 91% among AN children <2 years, by 80% among non-Natives <2 years, and by 40% for adults of all races (P<0.001 each). IPD decreased for isolates resistant to penicillin, erythromycin and cotrimoxazole (P<0.001 each). Vaccine-type colonization decreased among rural and urban children <5 years and among rural adults (P<0.001 each). PCV7 vaccine has eliminated a longstanding disparity of vaccine-type IPD for AN children. Decreased vaccine-type colonization and IPD in adults demonstrate indirect vaccine effects.

Background: Our goal was to describe trends in invasive pneumococcal disease incidence among persons with acquired immunodeficiency syndrome (AIDS) since the introduction of highly active antiretroviral therapy (HAART)., Methods: We used time-trend analysis of annual invasive pneumococcal disease incidence rates from a population-based, active surveillance system. Annual incidence rates were calculated for 5 July-June periods by use of data from San Francisco county, the 6-county Baltimore metropolitan area, and Connecticut. The numerators were the numbers of invasive Streptococcus pneumoniae infections among persons 18-64 years of age with AIDS; the denominators were the numbers of persons living with AIDS, estimated on the basis of AIDS surveillance data., Results: The annual incidence of invasive pneumococcal disease declined from 1094 cases/100,000 persons with AIDS (July 1995-June 1996) to 467 cases/100,000 persons living with AIDS (July 1999-June 2000). The annual percentage changes in incidence were -34%, -29%, -8%, and -1%. Declines were similar by surveillance area, sex, and race/ethnicity. During the final year of the study, the invasive pneumococcal disease incidence in persons with AIDS was half that of the pre-HAART era but was still 35 times higher than that in similarly aged non-HIV-infected adults., Conclusions: In the United States, invasive pneumococcal disease incidence declined sharply across a range of subgroups living with AIDS during the period after widespread introduction of HAART. Despite these gains, persons with AIDS remain at high risk for invasive pneumococcal disease.

We investigated the association between prescribing antimicrobial agents and antimicrobial resistance of Streptococcus pneumoniae among children with acute otitis media in southern Israel. During a 6-year period, all prescriptions of a sample of approximately 20% of Jewish and Bedouin children <5 years of age were recorded and all pneumococcal isolates from middle ear fluid were collected. Although antimicrobial drug use was significantly higher in Bedouin children, the proportion of S. pneumoniae isolates with penicillin MIC = or > 1.0 microg/mL was significantly higher in Jewish children. In both populations, antimicrobial prescriptions were markedly reduced over time, especially for penicillins and erythromycin. In contrast, azithromycin prescriptions increased from 1998 to 2001 with a parallel increase in macrolide and multidrug resistance. Penicillin resistance was associated with macrolide resistance. These findings strongly suggest that azithromycin affects increased antimicrobial resistance, including multidrug resistance, in S. pneumoniae.