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Biorepositories provide a critical resource for gaining knowledge of emerging infectious diseases and offer a mechanism to rapidly respond to outbreaks; the emergence of the novel coronavirus, SARS-CoV-2, has proved their importance. During the COVID-19 pandemic, the absence of centralized, national biorepository efforts meant that the onus fell on individual institutions to establish sample repositories. As a safety-net hospital, Boston Medical Center (BMC) recognized the importance of creating a COVID-19 biorepository to both support critical science at BMC and ensure representation in research for its urban patient population, most of whom are from underserved communities. This article offers a realistic overview of the authors' experience in establishing this biorepository at the onset of the COVID-19 pandemic during the height of the first surge of cases in Boston, Massachusetts, with the hope that the challenges and solutions described are useful to other institutions. Going forward, funders, policymakers, and infectious disease and public health communities must support biorepository implementation as an essential element of future pandemic preparedness.

Pneumococcus remains an important cause of morbidity in pregnant women with HIV and their infants. We compared the safety and immunogenicity of PCV-10 and PPV-23 with placebo administered in pregnancy.This double-blind, multicentre, randomised controlled trial was done at eight outpatient clinics in Brazil. Eligible participants were adult women with HIV who were pregnant at a gestational age between 14 weeks and less than 34 weeks and who were taking antiretroviral therapy at study entry. Participants were randomly assigned (1:1:1) to receive either PCV-10, PPV-23, or placebo. Participants and study teams were unaware of treatment allocation. Antibodies against seven vaccine serotypes in PCV-10 and PPV-23 were measured by ELISA. The primary outcomes were maternal and infant safety assessed by the frequency of adverse events of grade 3 or higher; maternal seroresponse (defined as ≥2-fold increase in antibodies from baseline to 28 days after immunisation) against five or more serotypes; and infant seroprotection (defined as anti-pneumococcus antibody concentration of ≥0·35 μg/mL) against five or more serotypes at 8 weeks of life. The study was powered to detect differences of 20% or higher in the primary immunological outcomes between treatment groups. This trial is registered with ClinicalTrials.gov, NCT02717494.Between April 1, 2016, and Nov 30, 2017, we enrolled 347 pregnant women with HIV, of whom 116 were randomly assigned to the PCV-10 group, 115 to the PPV-23 group, and 116 to the placebo group. One participant in the PCV-10 group did not receive the vaccine and was excluded from subsequent analyses. The frequency of adverse events of grade 3 or higher during the first 4 weeks was similar in the vaccine and placebo groups (3% [90% CI 1-7] for the PCV-10 group, 2% [0-5] for the PPV-23 group, and 3% [1-8] for the placebo group). However, injection site and systemic grade 2 adverse reactions were reported more frequently during the first 4 weeks in the vaccine groups than in the placebo group (14% [9-20] for the PCV-10 group, 7% [4-12] for the PPV-23 group, and 3% [1-7] for the placebo group). The frequency of grade 3 or higher adverse effects was similar across maternal treatment groups (20% [14-27] for the PCV-10 group, 21% [14-28] for the PPV-23 group, and 20% [14-27] for the placebo group). Seroresponses against five or more serotypes were present in 74 (65%) of 114 women in the PCV-10 group, 72 (65%) of 110 women in the PPV-23 group, and none of the 113 women in the placebo group at 4 weeks post vaccination (p0·0001 for PPV-23 group vs placebo and PCV-10 group vs placebo). Seroresponse differences of 20% or higher in vaccine compared with placebo recipients persisted up to 24 weeks post partum. At birth, 76 (67%) of 113 infants in the PCV-10 group, 62 (57%) of 109 infants in the PPV-23 group, and 19 (17%) of 115 infants in the placebo group had seroprotection against five or more serotypes (p0·0001 for PPV-23 vs placebo and PCV-10 vs placebo). At 8 weeks, the outcome was met by 20 (19%) of 108 infants in the PCV-10 group, 24 (23%) of 104 infants in the PPV-23 group, and one (1%) of 109 infants in the placebo group (p0·0001). Although a difference of 20% or higher compared with placebo was observed only in the infants who received PPV-23 at 8 weeks of life, the difference between the two vaccine groups was not appreciable.PCV-10 and PPV-23 were equally safe and immunogenic in pregnant women with HIV and conferred similar levels of seroprotection to their infants. In areas in which childhood PCV administration decreased the circulation of PCV serotypes, PPV-23 administration to pregnant women with HIV might be more advantageous than PCV by virtue of including a broader range of serotypes.Eunice Kennedy Shriver National Institute of Child Health and Human Development.For the Portuguese translation of the abstract see Supplementary Materials section.

Amid the current US opioid crisis, hepatitis C virus (HCV) infection rates continue to rise in young adults, including among pregnant women, yet few studies describe linkage to care and treatment in pregnant or postpartum women with HCV infection. We used electronic health record data to estimate HCV treatment rates for postpartum women before (January 2014‐September 2016) and during (October 2016‐March 2018) implementation of a maternal–infant HCV linkage program in combination with a multidisciplinary clinic to colocate mother and infant care. Using Poisson regression models, we compared HCV treatment initiation rates, adjusting for demographics, substance use, and treatment. From January 2014 through March 2018, 343 women who were HCV seropositive delivered at our institution. Of these, 95% completed HCV nucleic acid testing and 255 women had chronic HCV infection. Mean age was 30 years, 96% were publicly insured, and 94% had documented substance use. HCV treatment initiation increased from 28/164 (17.1%) women with chronic HCV infection in the preintervention period to 16/66 (24.2%) with the linkage‐only intervention and 13/25 (52.0%) with the linkage intervention and colocated care. Adjusted analyses demonstrated that women delivering during the intervention period initiated HCV treatment at 2.40 times (95% confidence interval [CI], 1.10‐5.25; linkage only) and 3.36 times (95% CI, 1.57‐7.17; linkage and colocated care) the rate of women delivering preintervention. Women on buprenorphine had higher HCV treatment initiation rates compared with those on methadone (rate ratio, 2.10; 95% CI, 1.05‐4.21). Conclusion: HCV linkage to care and treatment rates improved in the setting of mother–infant linkage and colocated care interventions. Perinatal care may represent a critical venue to identify, link, and treat women for HCV infection to improve their own health and prevent transmission to subsequent pregnancies., Although US national guidelines now recommend screening all pregnant women for Hepatitis C virus (HCV) amidst rising incidence rates, few studies describe practices to link diagnosed women to HCV cure after pregnancy. This study measures HCV treatment initiation rates before and during implementation of a perinatal linkage to care program and maternal‐infant co‐located care clinic, adjusting for follow‐up time, age, and substance use. We found 2.4 to 3.9‐fold increased HCV treatment rates among women who delivered a baby since the programs began, compared with those who delivered prior, highlighting a simple intervention to improve HCV cure rates to help reach HCV elimination goals.

Pneumococcal conjugate vaccines (PCVs) have been used in the United States since 2000. To assess the cumulative 20-year effect of PCVs on invasive pneumococcal disease (IPD) incidence among children 282,000 cases of IPD, including ≈16,000 meningitis, ≈172,000 bacteremia, and ≈55,000 bacteremic pneumonia cases. In addition, vaccination has prevented 97 million healthcare visits for otitis media, 438,914–706,345 hospitalizations for pneumonia, and 2,780 total deaths. IPD cases declined 91%, from 15,707 in 1997 to 1,382 in 2019. Average annual visits for otitis media declined 41%, from 78 visits/100 children before PCV introduction to 46 visits/100 children after PCV13 introduction. Annual pneumonia hospitalizations declined 66%–79%, from 110,000–175,000 in 1997 to 37,000 in 2019. These findings confirm the substantial benefits of PCVs for preventing IPD in children.

COVID-19 disease has been a pandemic caused by a s-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A life-threatening multisystem inflammatory syndrome (MIS), secondary to SARS-CoV-2 virus infection, sharing common features with Kawasaki disease shock syndrome, staphylococcal/streptococcal shock syndrome, and macrophage activation syndrome in pediatric patients has been described. A total of 27 cases in adults (MIS-A) with a similar presentation have been reported so far. Here we describe the case of a 21-year-old man admitted with abdominal pain, diarrhea, tachycardia, and low blood pressure. He had elevated troponin, ferritin, and interleukin-2 receptor levels and had evidence of myocarditis. He tested positive for SARS-CoV-2 IgG antibody, and a diagnosis of MIS-A was made. Our case adds to the scant literature on this topic, and to our knowledge, it is the first case where anakinra was administered. He recovered well. MIS-A should be considered when young adults present with multiorgan dysfunction.

Pneumolysin is a highly conserved, cholesterol-dependent cytolysin that is an important Streptococcus pneumoniae virulence factor and an attractive target for vaccine development. To attenuate pneumolysin toxicity, a genetic toxoid was constructed with two amino acid changes, G293S and L460D, termed PLY-D, that reduced cytolytic activity > 125,000-fold. In mice, PLY-D elicited high anti-PLY IgG antibody titers that neutralized the cytolytic activity of the wild-type toxin in vitro. To evaluate the protective efficacy of PLY-D, mice were immunized intramuscularly and then challenged intranasally with a lethal dose of 28 clinical isolates of S. pneumoniae originating from different geographical locations, disease states (i.e. bacteremia, pneumonia), or body sites (i.e. sputum, blood). PLY-D immunization conferred significant protection from challenge with 17 of 20 serotypes (85%) and 22 of 28 strains (79%). Further, we demonstrated that immunization with PLY-D provided statistically significant improvement in survival against challenge with serotype 4 and 18C strains compared to mice immunized with a pneumococcal conjugate vaccine Prevnar 13® (PCV13). Co-administration of PLY–D and PCV13 conferred greater protection against challenge with a serotype 6B strain than immunization with either vaccine alone. These data indicate that PLY-D is a broadly protective antigen with the potential to serve as a serotype-independent vaccine against invasive pneumococcal disease either alone or in combination with PCVs.

Background In 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced 7-valent PCV (PCV7) for protection against invasive pneumococcal disease (IPD). This study used laboratory surveillance data to examine the effect of PCV13 on IPD before and after PCV13 introduction among children aged 6 weeks to, In this prospective, laboratory-based surveillance study of Kaiser Permanente Northern California members, we examined annual invasive pneumococcal disease (IPD) incidence before and after 13-valent pneumococcal conjugate vaccine (PCV13) introduction. In children aged 6 weeks to

Most of the current evidence regarding pneumococcal upper respiratory colonization in adults suggests that despite high disease burden, carriage prevalence is low. Contemporary studies on adult pne...

Background The effect of pneumococcal vaccination of mothers with human immunodeficiency virus (HIV) on infant responses to childhood vaccination has not been studied. We compared the immunogenicity of 10-valent pneumococcus conjugate vaccine (PCV-10) in HIV-exposed uninfected infants born to mothers who received PCV-10, 23-valent pneumococcus polysaccharide vaccine (PPV-23), or placebo during pregnancy. Methods Antibody levels against 7 serotypes were measured at birth, before the first and second doses of PCV-10m and after completion of the 2-dose regimen in 347 infants, including 112 born to mothers who received PPV-23, 112 who received PCV-10, and 119 who received placebo during pregnancy. Seroprotection was defined by antibody levels ≥0.35 µg/mL. Results At birth and at 8 weeks of life, antibody levels were similar in infants born to PCV-10 or PPV-23 recipients and higher than in those born to placebo recipient. After the last dose of PCV-10, infants in the maternal PCV-10 group had significantly lower antibody levels against 5 serotypes than those in the maternal PPV-23 group and against 3 serotypes than those in the maternal placebo group, and they did not have higher antibody levels against any serotype. The seroprotection rate against 7 serotypes was 50% in infants in the maternal PCV-10 group, compared with 71% in both of the maternal PPV-23 and placebo groups (P Conclusions Administration of PCV-10 during pregnancy was associated with decreased antibody responses to PCV-10 and seroprotection rates in infants. Considering that PCV-10 and PPV-23 had similar immunogenicity in pregnant women with HIV and that administration of PPV-23 did not affect the immunogenicity of PCV-10 in infants, PPV-23 in pregnancy may be preferred over PCV-10.

This chapter looks at otitis. The clinical burden from acute (AOM) and chronic suppurative otitis media (CSOM) and their associated morbidities is substantial, especially in children. In industrialized countries, AOM remains the most frequent reason for pediatric office visits and recurrent otitis media (ROM), or persistent middle ear fluid and associated hearing loss, reduces quality of life. In developing nations, infectious complications of AOM include suppurative intracranial infection and CSOM with severe hearing loss. The prescription of antimicrobials increases bacterial resistance, so the role of antimicrobials in AOM has been reevaluated, using an evidence-based approach. ROM and CSOM usually begin in the first year of life, due to Streptococcus pneumoniae, nontypeable Haemophilus influenzae (NTHi), or Moraxella catarrhalis.

The burden of influenza is disproportionally higher among older adults. We evaluated the relative vaccine effectiveness (rVE) of adjuvanted trivalent (aIIV3) compared to high-dose trivalent influenza vaccine (HD-IIV3e) against influenza and cardio-respiratory disease (CRD)-related hospitalizations/ER visits among adults ≥65 years during the 2019–2020 influenza season. Economic outcomes were also compared. A retrospective cohort analysis was conducted using prescription, professional fee claims, and hospital data. Inverse probability of treatment weighting (IPTW) was used to adjust for confounding. IPTW-adjusted Poisson regression was used to evaluate the adjusted rVE of aIIV3 versus HD-IIV3e. All-cause and influenza-related healthcare resource utilization (HCRU) and costs were examined post-IPTW. Recycled predictions from generalized linear models were used to estimate adjusted costs. Adjusted analysis showed that aIIV3 (n = 798,987) was similarly effective compared to HD-IIV3e (n = 1,655,979) in preventing influenza-related hospitalizations/ER visits (rVE 3.1%, 95% CI: −2.8%, 8.6%), hospitalizations due to any cause (−0.7%, 95% CI: −1.6%, 0.3%), and any CRD-related hospitalization/ER visit (0.9%, 95% CI: 0.01%, 1.7%). Adjusted HCRU and annualized costs were also statistically insignificant between the two cohorts. The adjusted clinical and economic outcomes evaluated in this study were comparable between aIIV3 and HD-IIV3e during the 2019–2020 influenza season.

Background Pneumococcal vaccination is recommended in people with HIV, prioritizing PCV. We compared the immunogenicity of PCV-10 and PPV-23 administered antepartum or postpartum. Methods This double-blind study randomized 346 pregnant women with HIV on antiretrovirals to PCV-10, PPV-23, or placebo at 14–34 weeks gestational age. Women who received placebo antepartum were randomized at 24 weeks postpartum to PCV-10 or PPV-23. Antibodies against 7 serotypes common to both vaccines and 1 serotype only in PPV-23 were measured by ELISA/chemiluminescence; B- and T-cell responses to serotype 1 by FLUOROSPOT; and plasma cytokines/chemokines by chemiluminescence. Results Antibody responses were higher after postpartum versus antepartum vaccination. PCV-10 generated lower antibody levels than PPV-23 against 4 and higher against 1 of 7 common serotypes. Additional factors associated with high postvaccination antibody concentrations were high prevaccination antibody concentrations and CD4+ cells; low CD8+ cells and plasma HIV RNA; and several plasma cytokines/chemokines. Serotype 1 B- and T-cell memory did not increase after vaccination. Conclusions Antepartum immunization generated suboptimal antibody responses, suggesting that postpartum booster doses may be beneficial and warrant further studies. Considering that PCV-10 and PPV-23 had similar immunogenicity, but PPV-23 covered more serotypes, use of PPV-23 may be prioritized in women with HIV on antiretroviral therapy. Clinical Trails Registration NCT02717494.

Background Cell-derived influenza vaccines are not subject to egg-adaptive mutations that have potential to decrease vaccine effectiveness. This retrospective analysis estimated the relative vaccine effectiveness (rVE) of cell-derived quadrivalent influenza vaccine (IIV4c) compared to standard egg-derived quadrivalent influenza vaccines (IIV4e) among recipients aged 4–64 years in the United States during the 2019–2020 influenza season. Methods The IQVIA PharMetrics Plus administrative claims database was utilized. Study outcomes were assessed postvaccination through the end of the study period (7 March 2020). Inverse probability of treatment weighting (IPTW) was implemented to adjust for covariate imbalance. Adjusted rVE against influenza-related hospitalizations/emergency room (ER) visits and other clinical outcomes was estimated through IPTW-weighted Poisson regression models for the IIV4c and IIV4e cohorts and for the subgroup with ≥1 high-risk condition. Sensitivity analyses modifying the outcome assessment period as well as a doubly-robust analysis were also conducted. IPTW-weighted generalized linear models were used to estimate predicted annualized all-cause costs. Results The final sample comprised 1 150 134 IIV4c and 3 924 819 IIV4e recipients following IPTW adjustment. IIV4c was more effective in preventing influenza-related hospitalizations/ER visits as well as respiratory-related hospitalizations/ER visits compared to IIV4e. IIV4c was also more effective for the high-risk subgroup and across the sensitivity analyses. IIV4c was also associated with significantly lower annualized all-cause total costs compared to IIV4e (–$467), driven by lower costs for outpatient medical services and inpatient hospitalizations. Conclusions IIV4c was significantly more effective in preventing influenza-related hospitalizations/ER visits compared to IIV4e and was associated with significantly lower all-cause costs., During the 2019–2020 influenza season, cell-derived quadrivalent influenza vaccines were significantly more effective in preventing hospitalizations and emergency room visits related to influenza and respiratory events than were egg-derived quadrivalent influenza vaccines, among individuals 4–64 years old and a high-risk subgroup.

Background Pneumonia in infancy has been linked to long-term consequences for the rapidly developing lung. We examined the impact of hospitalized community-acquired pneumonia (CAP) on subsequent respiratory health. Methods We conducted a retrospective matched-cohort study using the Optum® de-identified Electronic Health Record Dataset (2009-2018). Study population comprised healthy infants hospitalized for CAP (“CAP patients”), and matched comparators without pneumonia (“comparison patients”), before age 2 years. Study outcomes included any chronic respiratory disorder, reactive airway disease (asthma, hyperactive airway disease, recurrent wheezing), and CAP hospitalization occurring between age 2 to 5 years, and were evaluated overall as well as by age and etiology at first CAP hospitalization. Results Study population totaled 1,343 CAP patients and 6,715 comparison patients. Rates per 100 patient-years and relative rates (RR) of study outcomes from age 2 to 5 years for CAP patients versus comparison patients were: any chronic respiratory disorder, 11.6 vs. 4.9 (RR=2.4 [95% CI: 2.1-2.6]); reactive airway disease, 6.1 vs 1.9 (RR=3.2 [2.6-3.8]); and CAP hospitalization, 1.0 vs 0.2 (RR=6.3 [3.6-10.9]). Rates of study outcomes were highest among CAP patients who had their initial hospitalization in the second year of life. Conclusions Infant CAP foreshadows an increased risk of subsequent chronic respiratory disorders, which may be elevated when CAP occurs closer to pre-school age (i.e., age 2 to 5 years). These findings are most consistent with the hypothesis that inflammation persists beyond the acute stage of pneumonia and plays a role in the development of chronic respiratory sequelae.

Background: Recent studies of community-acquired pneumonia (CAP) have recognized acute cardiac complications-such as myocardial infarction, arrhythmia, or congestive heart failure (CHF)-as frequent complications during the acute process. As well, a prolonged vulnerability to exacerbations of underlying comorbidities-such as CHF and COPD-has been observed following CAP. We hypothesized that young adults with underlying asthma could also be adversely impacted over a prolonged time period following CAP.Methods: Using a retrospective matched-cohort design and data from a US private healthcare claims repository (>15 M persons annually), we selected all adults 18-49 years of age with evidence of asthma as their only comorbidity for inclusion in the source population. Then, from the source population, we matched one comparison patient to each CAP patient based on index date, age, sex, and selected markers for health status (eg, history of asthma-related healthcare encounters), and evaluated subsequent outpatient and inpatient encounters for asthma exacerbations.Results: Asthma exacerbations were identified twice as often in the 12 months subsequent to acute CAP. Cumulative incidence proportions for asthma exacerbations requiring hospitalization or emergency department care after 12 months of follow-up were 19.9% for those previously hospitalized with CAP versus 9.0% for matched comparison patients (difference, 10.9%; p

Purpose: To evaluate the relative vaccine effectiveness (rVE) against influenza-related hospitalizations/ emergency room (ER) visits, influenza-related office visits, and cardio-respiratory disease (CRD)-related hospitalizations/ER visits and compare all-cause and influenza-related costs associated with two vaccines specifically indicated for older adults (>= 65 years), adjuvanted (aTIV) and high-dose trivalent influenza vaccine (TIV-HD), for the 2018-19 influenza season.Methods: A retrospective analysis of older adults was conducted using claims and hospital data in the United States. For clinical evaluations, adjusted analyses were conducted following inverse probability of treatment weighting (IPTW) to control for selection bias. Poisson regression was used to estimate the adjusted rVE against influenza-related hospitalizations/ER visits, influenza-related office visits, and any CRD-related hospitalizations/ER visits. For the economic evaluation, treatment selection bias was adjusted through 1:1 propensity score matching (PSM). All-cause and influenza-related costs associated with hospitalizations/ER, physician office and pharmacy visits were adjusted using generalized estimating equation (GEE) models.Results: After IPTW and Poisson regression, aTIV (n = 561,315) was slightly more effective in reducing influenza-related office visits compared to TIV-HD (n = 1,672,779) (6.6%; 95% CI: 2.8-10.3%). aTIV was statistically comparable to TIV-HD (2.0%; 95% CI: -3.7%-7.3%) in preventing influenza-related hospitalizations/ER visits but more effective in reducing hospitalizations/ER visits for any CRD (2.6%; 95% CI: 2.0-3.2%). In the PSM-adjusted cohorts (n = 561,243 pairs), following GEE adjustments, predicted mean annualized all-cause and influenza-related total costs per patient were statistically similar between aTIV and TIV-HD (US$9676 vs. US$9625 and US$18.74 vs. US$17.28, respectively; both p > 0.05). Finally, influenza-related pharmacy costs were slightly lower for aTIV as compared to TIV-HD ($1.75 vs $1.85; p < 0.0001).Conclusions: During the 2018-19 influenza season, influenza-related hospitalization/ER visits and associated costs among people aged >= 65 were comparable between aTIV and TIV-HD. aTIV was slightly more effective in preventing influenza-related office visits and any CRD event as compared to TIV-HD in this population. (C) 2021 The Authors. Published by Elsevier Ltd.

Non-egg-based influenza vaccines eliminate the potential for egg-adapted mutations and potentially increase vaccine effectiveness. This retrospective study compared hospitalizations/emergency room (ER) visits and all-cause annualized healthcare costs among subjects aged 4&ndash, 64 years who received cell-based quadrivalent (QIVc) or standard-dose egg-based quadrivalent (QIVe-SD) influenza vaccine during the 2018&ndash, 19 influenza season. Administrative claims data (IQVIA PharMetrics&reg, Plus, IQVIA, USA) were utilized to evaluate clinical and economic outcomes. Adjusted relative vaccine effectiveness (rVE) of QIVc vs. QIVe-SD among overall cohort, as well as for three subgroups (age 4&ndash, 17 years, age 18&ndash, 64 years, and high-risk) was evaluated using inverse probability of treatment weighting (IPTW) and Poisson regression models. Generalized estimating equation models among the propensity score matched sample were used to estimate annualized all-cause costs. A total of 669,030 recipients of QIVc and 3,062,797 of QIVe-SD were identified after IPTW adjustments. Among the overall cohort, QIVc had higher adjusted rVEs against hospitalizations/ER visits related to influenza, all-cause hospitalizations, and hospitalizations/ER visits associated with any respiratory event compared to QIVe-SD. The adjusted annualized all-cause total costs were higher for QIVe-SD compared to QIVc ((+$461), p &lt, 0.05).

The influenza-related disease burden is highest among the elderly. We evaluated the relative vaccine effectiveness (rVE) of adjuvanted trivalent influenza vaccine (aTIV) compared to other egg-based influenza vaccines (high-dose trivalent (TIV-HD), quadrivalent (QIVe-SD), and standard-dose trivalent (TIVe-SD)) against influenza-related and cardio-respiratory events among subjects aged &ge, 65 years for the 2017&ndash, 2018 influenza season. This retrospective cohort analysis used prescription claims, professional fee claims, and hospital charge master data. Influenza-related hospitalizations/ER visits and office visits and cardio-respiratory events were assessed post-vaccination. Inverse probability of treatment weighting (IPTW) and Poisson regression were used to evaluate the adjusted rVE of aTIV compared to other vaccines. In an economic analysis, annualized follow-up costs were compared between aTIV and TIV-HD. The study was composed of 234,313 aTIV, 1,269,855 TIV-HD, 212,287 QIVe-SD, and 106,491 TIVe-SD recipients. aTIV was more effective in reducing influenza-related office visits and other respiratory-related hospitalizations/ER visits compared to the other vaccines. For influenza-related hospitalizations/ER visits, aTIV was associated with a significantly higher rVE compared to QIVe-SD and TIVe-SD and was comparable to TIV-HD. aTIV was also associated with a significantly higher rVE compared to TIVe-SD against hospitalizations/ER visits related to pneumonia and asthma/COPD/bronchial events. aTIV and TIV-HD were associated with comparable annualized all-cause and influenza-related costs. Adjusted analyses demonstrated a significant benefit of aTIV against influenza- and respiratory-related events compared to the other egg-based vaccines.

Most of the current evidence regarding pneumococcal upper respiratory colonization in adults suggests that despite high disease burden, carriage prevalence is low. Contemporary studies on adult pneumococcal colonization have largely followed the pediatric approach by which samples are obtained mostly from the nasopharynx and bacterial detection is evaluated by routine culture alone. Recent evidence suggests that the 'pediatric approach' may be insufficient in adults and pneumococcal detection in this population may be improved by longitudinal studies that include samples from additional respiratory sites combined with more extensive laboratory testing.In this article, relevant literature published in peer review journals on adult pneumococcal colonization, epidemiology, detection methods, and recommendations were reviewed.Respiratory carriage of

Objective To review and highlight significant advances made towards vaccine development and understanding of the immunology of otitis media (OM) since the 19th International Symposium on Recent Advances in Otitis Media (ISOM) in 2015, as well as identify future research directions and knowledge gaps. Data sources PubMed database, National Library of Medicine. Review methods Key topics were assigned to each panel member for detailed review. Draft reviews were collated, circulated, and thoroughly discussed when the panel met at the 20th ISOM in June 2019. The final manuscript was prepared with input from all panel members. Conclusions Since 2015 there have been a number of studies assessing the impact of licensed pneumococcal vaccines on OM. While these studies have confirmed that these vaccines are effective in preventing carriage and/or disease caused by vaccine serotypes, OM caused by non-vaccine serotype pneumococci and other otopathogens remains a significant health care burden globally. Development of multi-species vaccines is challenging but essential to reducing the global burden of OM. Influenza vaccination has been shown to prevent acute OM, and with novel vaccines against nontypeable Haemophilus influenzae (NTHi), Moraxella catarrhalis and Respiratory Syncytial Virus (RSV) in clinical trials, the potential to significantly prevent OM is within reach. Research into alternative vaccine delivery strategies has demonstrated the power of maternal and mucosal vaccination for OM prevention. Future OM vaccine trials must include molecular diagnostics of middle ear effusion, for detection of viruses and bacteria that are persisting in biofilms and to enable accurate assessment of vaccine impact on OM etiology. Understanding population differences in natural and vaccine-induced immune responses to otopathogens is also important for development of the most effective OM vaccines. Improved understanding of the interaction between otopathogens will also advance development of effective therapies and encourage the assessment of the indirect benefits of vaccination. Implications for practice While NTHi and M. catarrhalis are the predominant otopathogens, funding opportunities to drive vaccine development for these species are limited due to a focus on prevention of childhood mortality rather than morbidity. Delivery of a comprehensive report on the high financial and social costs of OM, including the potential for OM vaccines to reduce antibiotic use and subsequent development of antimicrobial resistance (AMR), would likely assist in engaging stakeholders to recognize the value of prevention of OM and increase support for efforts on OM vaccine development. Vaccine trials with OM prevention as a clinical end-point are challenging, however a focus on developing assays that measure functional correlates of protection would facilitate OM vaccine development.

The 13-valent pneumococcal conjugate vaccine (PCV13) is the only licensed PCV with serotype 3 polysaccharide in its formulation. Postlicensure PCV13 effectiveness studies against serotype 3 invasive pneumococcal disease (IPD) in children have shown inconsistent results. We performed a systematic review and meta-analysis of observational studies to assess PCV13 vaccine effectiveness (VE) for serotype 3 IPD in children. We systematically searched PubMed, Embase, and the Cochrane library for studies published before 14 August 2017. We identified 4 published studies and 2 conference posters that provided PCV13 VE estimates stratified by serotype. The pooled PCV13 VE against serotype 3 IPD from the random-effects meta-analysis was 63.5% (95% confidence interval [CI], 37.3%–89.7%). A sensitivity analysis including conference posters gave a pooled VE estimate of 72.4% (95% CI, 56.7%–88.0%). The pooled data from case-control studies with similar methodologies and high quality support direct PCV13 protection against serotype 3 IPD in children., Meta-analysis of published case-control studies of 13-valent pneumococcal conjugate vaccine gave a pooled vaccine effectiveness of 63.5% against serotype 3 invasive pneumococcal disease (IPD). The pooled data from case-control studies with similar methodologies and high quality support direct protection against serotype 3 IPD in children.

Background Following introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in the United States, epidemiology of pneumococcal disease shifted such that disease incidence in the elderly exceeded that in children. We evaluated the impact of replacing PCV7 with PCV13 on disease burden in adults and identified age/risk-specific subgroups with the highest remaining disease burden. Methods A retrospective design and data from two US healthcare claims repositories were used. Study population included adults aged ≥18 years and was stratified by age (18–49, 50–64, 65–74, ≥75) and risk profile (healthy, at-risk, high-risk). Rate ratios comparing invasive pneumococcal disease (IPD), all-cause hospitalized pneumonia (ACHP), and pneumococcal pneumonia requiring hospitalization among at-risk and high-risk adults vs healthy counterparts were estimated for 2007–2010 (pre-PCV13), 2011–2012 (peri-PCV13), and 2013–2015 (post-PCV13). Results Across study periods, IPD and ACHP rates increased with age (2–27 times higher in persons ≥75 vs 18–49) and comorbidity (4–20 times higher in high-risk vs healthy). From pre- to post-PCV13 period, IPD rates declined 5%–48% and ACHP rates declined 4%–19% across age and risk groups (ACHP did not decline in persons ≥75). Decline in IPD and ACHP was attenuated among older adults and those with comorbidities. Accordingly, rate ratios among at-risk and high-risk persons (vs healthy counterparts) increased during the peri- and post-PCV13 periods compared with the pre-PCV13 period. Conclusions The switch to PCV13 was associated with large declines in pneumococcal disease among US adults. However, the decline was attenuated with increasing age (and, for ACHP, was absent in persons ≥75) and in those with comorbidities., Declining incidence of invasive pneumococcal disease and all-cause pneumonia following introduction of 13-valent pneumococcal conjugate vaccine for children was observed in adults aged ≥18 years. However, decline varied by age and comorbidity profile, with smaller reductions in older individuals and those with comorbidity.

Background Non-egg-based influenza vaccine manufacturing reduces egg adaptation and therefore has the potential to increase vaccine effectiveness. This study evaluated whether the cell-based quadrivalent influenza vaccine (QIVc) improved relative vaccine effectiveness (rVE) compared to standard-dose egg-based quadrivalent influenza vaccine (QIVe-SD) in the reduction of influenza-related and respiratory-related hospitalizations/emergency room (ER) visits among subjects 4-64 years old during the 2019/20 influenza season. Methods A retrospective analysis was conducted among subjects 4-64 years old vaccinated with QIVc or QIVe-SD using administrative claims data in the United States of America (U.S.) (IQVIA PharMetrics® Plus). Inverse probability of treatment weighting (IPTW) was used to adjust for baseline confounders. Post-IPTW, the number of events and rates (per 1,000 vaccinated subject-seasons) of influenza-related hospitalizations/ER visits, respiratory-related hospitalizations/ER visits and all-cause hospitalizations were assessed. Poisson regression was used to estimate adjusted rVE. To avoid any influenza outcome misclassification with COVID-19 infection, the study period ended March 7,2020. A sub-analysis for a high-risk subgroup was conducted. Urinary tract infection (UTI) hospitalization was assessed as a negative control endpoint. Results During the 2019/20 influenza season, 1,150,134 QIVc and 3,924,819 QIVe-SD recipients were identified post-IPTW. Overall adjusted analyses (4-64 years old) found that QIVc was associated with a significantly higher rVE compared to QIVe-SD against influenza-related hospitalizations/ER visits (5.3% [95% CI: 0.5%-9.9%]), all-cause hospitalizations (14.5% [95% CI: 13.1%-15.8%]) and any respiratory-related hospitalization/ER visit (8.2% [95% CI: 6.5%-9.8%]). A similar trend was seen for the high-risk subgroup; for instance, rVE for QIVc compared to QIVe-SD against influenza-related hospitalizations/ER visits was 10.5% [95% CI: 2.9%-17.4%]. No effect was identified for the negative control outcome. Conclusion QIVc was significantly more effective in preventing influenza-related and respiratory-related hospitalizations/ER visits, as well as all-cause hospitalizations, compared to QIVe-SD. Disclosures Stephen I. Pelton, MD, Seqirus (Consultant) Maarten Postma, Dr., Seqirus (Consultant) Victoria Divino, PhD, Seqirus (Consultant) Joaquin F. Mould-Quevedo, PhD, Seqirus (Employee) Ruthwik Anupindi, PhD, Seqirus (Consultant) Mitchell DeKoven, PhD, Seqirus (Consultant) myron J. levin, MD, GSK group of companies (Employee, Research Grant or Support)

Background Changes in the influenza hemagglutinin protein during replication of influenza in eggs during vaccine production may contribute to low vaccine effectiveness (VE). This phenomenon, egg adaptation, can explain VE differences between egg-based (QIVe-SD) and cell-based (QIVc) quadrivalent influenza vaccines. This research evaluated the relative vaccine effectiveness (rVE) of QIVc versus QIVe-SD in the reduction of influenza-related and any respiratory-related hospitalizations/emergency room (ER) visits among subjects 4-64 years old during the 2019/20 influenza season. Methods A retrospective cohort analysis was conducted among subjects 4-64 years old vaccinated with QIVc or QIVe-SD using administrative claims data in the U.S. (IQVIA PharMetrics® Plus). The adjusted number of events and rates of influenza-related hospitalizations/ER visits and respiratory-related hospitalizations/ER visits were assessed using inverse probability of treatment weighting (IPTW). Poisson regression was used to estimate relative vaccine effectiveness (rVE). In the main analysis, the study period was from Aug 4, 2019 to Mar 7, 2020 (ending early to avoid any influenza outcome misclassification with COVD-19 infection). In the assessment of the high influenza activity period (HIAP), the analysis period was restricted to Dec 8, 2019 to Mar 7, 2020. Results During the 2019/20 influenza season, 1,150,134 recipients of QIVc and 3,924,819, of QIVe-SD were identified following IPTW. In the main analysis, adjusted results show that QIVc was associated with a significantly higher rVE compared to QIVe-SD against influenza-related hospitalizations/ER visits (5.3% [95%CI: 0.5%-9.9%]) and respiratory-related hospitalizations/ER visits (8.2% [95%CI: 6.5%-9.8%]). Similarly, in the HIAP analysis, QIVc was associated with a significantly higher rVE compared to QIVe-SD for influenza-related hospitalizations/ER visits (5.7% [95%CI: 0.8%-10.4%]) and respiratory-related hospitalizations/ER visits (7.3% [95%CI: 5.4%-9.2%]). Conclusion QIVc was more effective in preventing influenza-related and respiratory-related hospitalizations/ER visits compared to QIVe-SD, using either a broad influenza season definition or restricting to the HIAP. Disclosures Victoria Divino, PhD, Seqirus (Consultant) Maarten Postma, Dr., Seqirus (Consultant) Stephen I. Pelton, MD, Seqirus (Consultant) Joaquin F. Mould-Quevedo, PhD, Seqirus (Employee) Ruthwik Anupindi, PhD, Seqirus (Consultant) Mitchell DeKoven, PhD, Seqirus (Consultant) myron J. levin, MD, GSK group of companies (Employee, Research Grant or Support)

Background Increasing evidence suggests the impact of pneumonia persists beyond hospital discharge and the acute phase of respiratory symptoms. We characterized short-term and long-term risks of mortality and hospital readmission across the adult age span and spectrum of comorbidities. Methods Retrospective cohort design and Optum's de-identified Integrated Claims-Clinical dataset (2012–2018) were employed. Study population comprised adults who had ≥1 pneumonia hospitalization; each hospitalization ≥365 days apart was considered. Cumulative risks of all-cause mortality (from pneumonia hospitalization through 360-day post-discharge period) and all-cause hospital readmission (during 360-day post-discharge period) were summarized on an overall basis as well as by age and comorbidity profile (i.e., healthy, at-risk, high-risk). Results Study population totaled 37,006 patients who contributed 38,809 pneumonia hospitalizations; mean age was 71 years, 51% were female, and 88% had at-risk (33%) or high-risk (55%) conditions. Mortality was 3.5% in hospital, 8.2% from admission to 30 days post-discharge, and 17.7% from admission to 360 days post-discharge. Hospital readmission was 12.5% during the 30-day post-discharge period, and 42.3% during the 360-day post-discharge period. Mortality risk increased with age and severity of comorbidity profile; readmission risk was highest for persons aged 65–74 years and persons with high-risk conditions. Conclusions All-cause mortality up to 1 year following pneumonia hospitalization was substantial, and was associated with increasing age and worsening comorbidity profile. Both readmission and mortality were greater at all ages in at-risk and high-risk subgroups (vs. healthy counterparts). Strategies that prevent pneumonia and/or associated pathophysiologic changes, especially among individuals with comorbidities, have the potential to reduce morbidity and mortality.

Background Influenza generates a substantial economic burden ($3.2B in the U.S. annually) due to direct medical costs such as physician office visits or hospitalizations, especially among the elderly. Recent published literature for the 2018–19 influenza season has demonstrated similar clinical effectiveness between adjuvanted trivalent influenza vaccine (aTIV) and trivalent high dose influenza vaccine (TIV-HD). This research aimed to assess the annualized mean all-cause and influenza-related healthcare costs among subjects 65+ years vaccinated with aTIV or TIV-HD during the 2018–19 influenza season. Methods A retrospective cohort analysis was conducted using professional fee, prescription claims and hospital charge master data in the U.S. Baseline characteristics included age, gender, payer type, region, Charlson Comorbidity Index, comorbidities, indicators of frail health status, and pre-index hospitalization rates. Treatment selection bias was adjusted through 1:1 propensity score matching (PSM). Economic outcomes included annualized mean all-cause costs and influenza-related costs, which comprised influenza-related hospitalizations, emergency room (ER) visits, and physician office visits costs. Mean costs were compared using paired t-test. Adjusted analyses were conducted using generalized estimating equation (GEE) models, with two-part models for influenza-related costs. With the GEEs, adjustment for outliers (99th percentile) were addressed and predicted healthcare costs were obtained through bootstrapping (500 replications). Results During the 2018–19 influenza season, the PSM sample comprised 561,243 recipients of aTIV and 561,243 recipients of TIV-HD. Following GEE adjustment, predicted mean annualized all-cause and influenza-related costs per patient were statistically similar between aTIV and TIV-HD (US$9,676 vs. US$9,625 and US$23.75 vs. US$21.79, respectively). Both aTIV and TIV-HD were comparable in terms of predicted mean annualized costs for influenza-related hospitalizations (US$20.28 vs. US$18.13) and influenza-related office visits (US$1.29 vs. US$1.34). Conclusion In adjusted analyses, total all-cause and influenza-related healthcare costs were comparable among elderly subjects vaccinated with either aTIV or TIV-HD. Disclosures Maarten Postma, Dr., IQVIA (Consultant) Stephen I. Pelton, MD, Merck vaccine (Consultant, Grant/Research Support)Pfizer (Consultant, Grant/Research Support)Sanofi Pasteur (Consultant, Other Financial or Material Support, DSMB)Seqirus Vaccine Ltd. (Consultant) Victoria Divino, PhD, Seiqrus Vaccines Ltd. (Consultant) Joaquin F. Mould-Quevedo, PhD, Seqirus Vaccines Ltd. (Employee, Shareholder) Drishti Shah, PhD, Seqirus Vaccines Ltd. (Consultant) Mitchell DeKoven, PhD, Seqirus Vaccines Ltd. (Consultant) Girishanthy Krishnarajah, PhD, Seqirus Vaccines Ltd. (Employee, Shareholder)

Background Clinical trials of PCV7 demonstrate significant reductions in vaccine-type (VT) invasive pneumococcal disease (IPD), clinically diagnosed pneumonia in children less than 5 years of age and VT acute otitis media in children < 2 years of age. Observational, population-based studies demonstrate a reduction in overall IPD in US children following the introduction of PCV7 and PCV13. The cumulative impact of PCV on IPD syndromes over the 20 years following introduction into the US national immunization program has not been detailed. Methods Published and unpublished data from the Active Bacterial Core (ABC) surveillance network were used to calculate annual incidence rates of IPD and the proportional distribution by syndrome in children < 5 years of age. Cases averted were calculated from published incidence for each IPD syndrome and population data, for the pre-PCV, PCV7, and PCV13 eras. Cases averted over 2000-2009 were assumed due to PCV7 only, and those averted from 2010-2019 were assumed due to PCV13 only. It was assumed that in the absence of PCVs, disease incidence would have remained constant. Results Annual cases of overall IPD, pneumococcal meningitis, and bacteremic pneumonia each declined more than 85% between the pre PCV7 incidence and the estimated incidence for 2019 (table 1). Overall, we estimated 282,600 cases of IPD, including 30,500 cases of meningitis and 78,400 cases of bacteremic pneumonia were averted. We calculated a reduction of ~ 287,600 VT cases of IPD minimally offset by an increase of ~5,000 non-VT cases. Deaths per 100,000 children < 5 years of age attributable to IPD declined by 67% in 2009 and by 64% in 2019 compared to 1997-1999. In total, 1,628 deaths in children < 5 years were averted between 2000 and 2019. Table 1. Annual Cases of IPD by syndrome in US Children Less than 5 years of age Conclusion The substantial public health impact of PCVs over the last two decades, as measured in cases and deaths averted in children less than 5 years, re-enforces the important role vaccines play in reducing the burden of serious disease in children. Disclosures Rotem Lapidot, MD, MSCI, Pfizer (Consultant) Ruth Chapman, MSc, PhD, Evidera, Inc, (Evidera, Inc. received the funding to conduct this study.) (Consultant) Kelly Sutton, PhD, Evidera (Employee) Desmond Dillon-Murphy, MSc, PhD, Evidera, Inc. (Evidera, Inc. received the funding to conduct this study.) (Consultant) Shreeya Patel, PhD, Evidera, Inc, (Evidera, Inc. received the funding to conduct this study.) (Consultant) Erica Chilson, PharmD, Pfizer (Employee, Shareholder) Vincenza Snow, MD, Pfizer (Employee) Raymond Farkouh, PhD, Pfizer (Employee) Matthew Wasserman, MSc., Pfizer Inc. (Employee) Stephen I. Pelton, MD, Merck vaccine (Consultant, Grant/Research Support)Pfizer (Consultant, Grant/Research Support)Sanofi Pasteur (Consultant, Other Financial or Material Support, DSMB)Seqirus Vaccine Ltd. (Consultant)

Background Influenza vaccine effectiveness decreases with increasing age due to the senescence of immune function and a reduced immune response to antigens. There is also considerable vaccine effectiveness heterogeneity depending on the influenza activity time period, especially in seasons where two different circulating strains predominated, such as the 2018–19 season. This research aimed to assess the effect of age and high influenza activity period (HIAP) on the relative vaccine effectiveness (rVE) of adjuvanted trivalent influenza vaccine (aTIV) vs. trivalent high-dose influenza vaccine (HD-TIV) among elderly (≥65y) recipients in the U.S. Methods During the 2018–19 influenza season, a retrospective cohort analysis was conducted using professional fee, prescription claims and hospital charge master data in the U.S. The first sub-analysis evaluated rVE for different age groups (65–74 years, 75–84 years, ≥85 years). The second sub-analysis evaluated rVE overall, restricting the observation period from to HAIP: Dec 2018-Mar 2019 (August 2018-July 2019 in the main analysis). Adjusted analyses were conducted through inverse probability of treatment weighting (IPTW) to control for selection bias. Poisson regression was used to estimate the adjusted pairwise rVE for influenza-related hospitalizations/emergency room (ER) visits and office visits. Results Following IPTW, 561,315 recipients of aTIV and 1,672,779 of TIV-HD were identified. Following IPTW adjustment and Poisson regression, aTIV was more effective in reducing influenza-related office visits compared to TIV-HD (7.0%; 95% CI: 2.6%-11.2%) in the HIAP sub-analysis. In the age sub-analysis, the rVE favoring aTIV ranged from 5.1% (95% CI: -0.17%-10.1%) for the youngest group (65–74) up to 11.4% (95% CI: 0.6%-21.1%) for the eldest group (≥85y) for influenza-related office visits. No statistically significant differences were found for aTIV compared to TIV-HD for prevention of influenza-related hospitalizations/ER visits in the sub-analyses evaluated. Conclusion In adjusted analyses, aTIV reduced influenza-related office visits compared to TIV-HD within the two older age groups and HIAP sub-analysis. aTIV and TIV-HD demonstrated comparable reductions in influenza-related hospitalizations/ER visits. Disclosures Maarten Postma, Dr., IQVIA (Consultant) Stephen I. Pelton, MD, Merck vaccine (Consultant, Grant/Research Support)Pfizer (Consultant, Grant/Research Support)Sanofi Pasteur (Consultant, Other Financial or Material Support, DSMB)Seqirus Vaccine Ltd. (Consultant) Victoria Divino, PhD, Seiqrus Vaccines Ltd. (Consultant) Joaquin F. Mould-Quevedo, PhD, Seqirus Vaccines Ltd. (Employee, Shareholder) Drishti Shah, PhD, Seqirus Vaccines Ltd. (Consultant) Mitchell DeKoven, PhD, Seqirus Vaccines Ltd. (Consultant)

Background Community-acquired pneumonia (CAP) in infancy (i.e., among children aged < 2 years) may have long-term consequences for the rapidly developing lung. We examined the impact of pneumonia in infancy on subsequent respiratory health. Methods A retrospective matched-cohort design and data from Optum’s de-identified Integrated Claims-Clinical dataset (2009-2018) were employed. Study population comprised children who were hospitalized for CAP before age 2 years (“CAP patients”) as well as matched comparators without evidence of pneumonia before age 2 years (“comparison patients”). CAP patients and comparison patients were matched (fixed 1:5 ratio, without replacement) using estimated propensity scores and a nearest-neighbor approach; those with evidence of selected medical conditions (e.g., extreme prematurity, congenital diseases, respiratory diseases) before age 2 years were excluded. Study outcomes included recurrent pneumonia and a composite of asthma, recurrent wheezing, and hyperactive airway disease. Rates of study outcomes from age 2 to 5 years were estimated for all CAP and comparison patients as well as subgroups of CAP patients (and corresponding comparison patients) stratified by etiology (bacterial, viral, unspecified). Results Study population totaled 1,343 CAP patients and 6,715 comparison patients. CAP patients and comparison patients were well-balanced on their baseline characteristics and mean duration of follow-up was 757 and 729 days, respectively. Rates of chronic respiratory disorders from age 2 to 5 years were significantly higher among CAP patients versus comparison patients. Analyses of subgroups stratified by etiology demonstrated higher rates of study outcomes among CAP patients across all strata. Rates of recurrent pneumonia and a composite of asthma, recurrent wheezing, and hyperactive airway disease from age 2 to 5 years among CAP patients and matched comparison patients Conclusion Infant CAP foreshadows an increase in subsequent risk of chronic respiratory disorders. Further studies are needed to determine whether this elevated risk is due to infant pneumonia or whether infant pneumonia is a marker of at-risk children. Disclosures Stephen I. Pelton, MD, Merck vaccine (Consultant, Grant/Research Support)Pfizer (Consultant, Grant/Research Support)Sanofi Pasteur (Consultant, Other Financial or Material Support, DSMB)Seqirus Vaccine Ltd. (Consultant) Rotem Lapidot, MD, MSCI, Pfizer (Consultant) Matthew Wasserman, MSc., Pfizer Inc. (Employee) Melody Shaff, BA, Pfizer, Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Ahuva Hanau, BS, Pfizer, Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Alexander Lonshteyn, PhD, Pfizer, Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Derek Weycker, PhD, Pfizer Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)

This review of pediatric antibiotic stewardship programs (ASPs) summarized the antibiotic prescribing interventions and their impact on antibiotic use and antimicrobial resistance. We reviewed studies of pediatric ASP, including the search terms “antimicrobial stewardship,” “antibiotic stewardship,” “children,” and “pediatric.” The articles’ selection and review were performed independently by 2 investigators, according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Twenty-one studies were included, from the past 15 years, increasing after the 2007 IDSA (Infectious Diseases Society of America) guidelines for ASP with a large variability of the programs, and the virtual exclusive focus on inpatient settings (90%): 16 formalized ASP and 5 non-ASP actions. A reduction in antibiotic prescribing in ASP has been demonstrated in the studies reporting pediatric ASP, but only one ASP showed a significant impact on antimicrobial resistance. However, the impact on antibiotic consumption in pediatrics demonstrated the important contribution of these strategies to improve antibiotic use in children, without complications or negative issues.

Background Despite high vaccine coverage rates in children and efficacy of pneumococcal conjugate vaccines, invasive pneumococcal disease (IPD) episodes due to serotypes included in the vaccine following completion of the recommended course of immunisation (i.e. vaccine failure) have been reported. Methods We used data gathered from a population-based enhanced passive surveillance for IPD in children under 18 years of age in Massachusetts and an ensemble model composed of three machine-learning algorithms to predict probability of 13-valent pneumococcal conjugated vaccine (PCV13) failure and to evaluate potential associated features including age, underlying comorbidity, clinical presentation, and vaccine schedule. Vaccine failure was defined as diagnosis of IPD due to vaccine serotype (VST), in a child who received age recommended doses recommended by Advisory Committee of Immunization Practices. Results During the 7-year study period, between April 01, 2010 and March 31, 2017, we identified 296 IPD cases. There were 107 (36%) IPD cases caused by VST, mostly serotype 19A (49, 17%), 7F (21, 7%), and 3 (18, 6%). Thirty-seven (34%) were in children who were completely vaccinated representing 13% of all IPD cases. Vaccine failure was more likely among children older than 60 months (predicted probability 0.40, observed prevalence 0.37, model prediction accuracy 79%), children presenting with pneumonia (predicted probability 0.27, observed prevalence 0.31, model accuracy 77%), and children with underlying comorbidity (predicted probability 0.24, observed prevalence 0.23, model accuracy 96%). Vaccine failure probability for those >60 months of age and had an underlying risk factor was 45% (observed prevalence 0.33, model accuracy 82%). The likelihood of vaccine failure was lowest among children who had completed 3 primary doses plus one booster dose PCV13 (predicted probability 0.14, observed prevalence 0.14, model prediction accuracy 100%). Conclusion PCV13 vaccine failure is more frequent among older children with underlying comorbidity, and among those who present with pneumococcal pneumonia. Our study provides a preliminary framework to predict the patterns of vaccine failures and may contribute to decision-making processes to optimize PCV immunization schedules.

The 13-valent pneumococcal conjugate vaccine (PCV-13) was introduced in the United States in 2010. Using a large paediatric carriage sample collected from shortly after the introduction of PCV-7 to several years after the introduction of PCV-13, we investigate alterations in the composition of the pneumococcal population following the introduction of PCV-13, evaluating the extent to which the post-vaccination non-vaccine type (NVT) population mirrors that from prior to vaccine introduction and the effect of PCV-13 on vaccine type lineages. Draft genome assemblies from 736 newly sequenced and 616 previously published pneumococcal carriage isolates from children in Massachusetts between 2001 and 2014 were analysed. Isolates were classified into one of 22 sequence clusters (SCs) on the basis of their core genome sequence. We calculated the SC diversity for each sampling period as the probability that any two randomly drawn isolates from that period belong to different SCs. The sampling period immediately after the introduction of PCV-13 (2011) was found to have higher diversity than preceding (2007) or subsequent (2014) sampling periods {Simpson’s D 2007: 0.915 [95 % confidence interval (CI) 0.901, 0.929]; 2011: 0.935 [0.927, 0.942]; 2014 : 0.912 [0.901, 0.923]}. Amongst NVT isolates, we found the distribution of SCs in 2011 to be significantly different from that in 2007 or 2014 (Fisher’s exact test P=0.018, 0.0078), but did not find a difference comparing 2007 to 2014 (Fisher’s exact test P=0.24), indicating greater similarity between samples separated by a longer time period than between samples from closer time periods. We also found changes in the accessory gene content of the NVT population between 2007 and 2011 to have been reduced by 2014. Amongst the new serotypes targeted by PCV-13, four were present in our sample. The proportion of our sample composed of PCV-13-only vaccine serotypes 19A, 6C and 7F decreased between 2007 and 2014, but no such reduction was seen for serotype 3. We did, however, observe differences in the genetic composition of the pre- and post-PCV-13 serotype 3 population. Our isolates were collected during discrete sampling periods from a small geographical area, which may limit the generalizability of our findings. Pneumococcal diversity increased immediately following the introduction of PCV-13, but subsequently returned to pre-vaccination levels. This is reflected in the distribution of NVT lineages, and, to a lesser extent, their accessory gene frequencies. As such, there may be a period during which the population is particularly disrupted by vaccination before returning to a more stable distribution. The persistence and shifting genetic composition of serotype 3 is a concern and warrants further investigation.

Background: Recent studies of community-acquired pneumonia (CAP) have recognized acute cardiac complications—such as myocardial infarction, arrhythmia, or congestive heart failure (CHF)—as frequent complications during the acute process. As well, a prolonged vulnerability to exacerbations of underlying comorbidities—such as CHF and COPD—has been observed following CAP. We hypothesized that young adults with underlying asthma could also be adversely impacted over a prolonged time period following CAP.Methods: Using a retrospective matched-cohort design and data from a US private healthcare claims repository (>15 M persons annually), we selected all adults 18–49 years of age with evidence of asthma as their only comorbidity for inclusion in the source population. Then, from the source population, we matched one comparison patient to each CAP patient based on index date, age, sex, and selected markers for health status (eg, history of asthma-related healthcare encounters), and evaluated subsequent outpatient and inpatient encounters for asthma exacerbations.Results: Asthma exacerbations were identified twice as often in the 12 months subsequent to acute CAP. Cumulative incidence proportions for asthma exacerbations requiring hospitalization or emergency department care after 12 months of follow-up were 19.9% for those previously hospitalized with CAP versus 9.0% for matched comparison patients (difference, 10.9%; p

Invasive meningococcal disease (IMD) caused by Neisseria meningitidis is associated with high morbidity and mortality. Although IMD incidence is highest in infants, a second peak occurs in adolescents/young adults. The incidence of IMD and the predominant disease-causing meningococcal serogroups vary worldwide. Epidemiologic data have guided the development of meningococcal vaccines to reduce the IMD burden. In Europe, serogroup C IMD has been substantially reduced since the introduction of a serogroup C conjugate vaccine. Serogroup B predominates in Europe, although cases of serogroup Y IMD have been increasing in recent years. In the United States, declines in serogroup C and Y disease have been observed in association with the introduction of quadrivalent (serogroups ACWY) meningococcal conjugate vaccines; serogroup B persists and is now the most common cause of outbreak associated disease. In the African meningitis belt, a conjugate vaccine for serogroup A has been effective in decreasing meningitis associated with that serogroup. Outbreaks of the previously rare serogroup X disease have been reported in this region since 2006. In recent years, outbreaks of serogroup B IMD, for which vaccines have only recently been approved by the U.S. Food and Drug Administration and the European Medicines Agency, have occurred in Europe and the United States. Targeting meningococcal vaccination to adolescents/young adults may reduce the morbidity and mortality associated with IMD and has the potential to impact the larger community through herd benefits.

We compared antibiotic prescribing for children with and those without an underlying chronic condition associated with increased risk for invasive pneumococcal disease. Children with a chronic condition had significantly greater cumulative exposure to antibiotics and higher rates of prescriptions per person-year than those without a chronic condition; this population is at increased risk for the emergence of multidrug-resistant pathogens.