Evidence that pneumococcal serotype replacement in Massachusetts following conjugate vaccination is now complete

Invasive pneumococcal disease (IPD) has been reduced in the US following conjugate vaccination (PCV7) targeting seven pneumococcal serotypes in 2000. However, increases in IPD due to other serotypes have been observed, in particular 19A. How much this serotype replacement will erode the benefits of vaccination and over what timescale is unknown. We used a population genetic approach to test first whether the selective impact of vaccination could be detected in a longitudinal carriage sample, and secondly how long it persisted for following introduction of vaccine in 2000. To detect the selective impact of the vaccine we compared the serotype diversity of samples from pneumococcal carriage in Massachusetts children collected in 2001, 2004 and 2007 with others collected in the pre-vaccine era in Massachusetts, the UK and Finland. The 2004 sample was significantly (p \u3e0.0001) more diverse than pre-vaccine samples, indicating the selective pressure of vaccination. The 2007 sample showed no significant difference in diversity from the pre-vaccine period, and exhibited similar population structure, but with different serotypes. In 2007 the carriage frequency of 19A was similar to that of the most common serotype in pre-vaccine samples. We suggest that serotype replacement involving 19A may be complete in Massachusetts due to similarities in population structure to pre-vaccine samples. These results suggest that the replacement phenomenon occurs rapidly with high vaccine coverage, and may allay concerns about future increases in disease due to 19A. For other serotypes, the future course of replacement disease remains to be determined

Metabolizable Energy Content of Breastmilk Supports Normal Growth in Exclusively Breastfed Icelandic Infants to Age 6 Months

Funding Information: This research was funded by the Icelandic Research Fund ( 196157-053 ) and the University of Iceland Research Fund (to Inga Thorsdottir). All research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the National Institute for Health and Care Research (NIHR) Great Ormond Street Hospital Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. Publisher Copyright: © 2023 The AuthorsBackground: Neither the global population nor individual countries have reached the World Health Organization (WHO) target of ≥50% of infants exclusively breastfed (EBF) until 6 mo. This may partly be because of the perceptions of insufficient milk and energy supply to meet rapid growth and development needs. Objectives: In a longitudinal observational study, we aimed to determine whether breastmilk energy content is sufficient to support growth during EBF until 6 mo. Methods: A sample of 27 EBF infants was dosed with doubly labeled water (DLW) at 5.6 mo to measure body composition, breastmilk intake, energy intake, and the metabolizable energy (ME) content of their mother's breastmilk over the following week. Z-scores were calculated for anthropometry using WHO reference data and for fat-free mass (FFM) and fat mass (FM) using United Kingdom reference data. Results: Anthropometric z-scores from birth indicated normal weight and length growth patterns. At ∼6 mo, the mean ± standard deviation (SD) FFM z-score was 0.22 ± 1.07, and the FM z-score was 0.78 ± 0.70, significantly >0. In the 22 infants with acceptable data, the mean ± SD measured intake of breastmilk was 983 ± 170 g/d and of energy, 318 ± 60 kJ/kg/d, equivalent to 75.9 ± 14.3 kcal/kg/d. The mean ME content of breastmilk was 2.61 kJ/g [standard error (SE) 0.1], equivalent to 0.62 kcal/g (SE 0.02). Mothers were positive toward breastfeeding, on paid maternity leave (planned mean 10 mo), and many (56%) had received specialized breastfeeding support. Conclusions: The evidence from this study confirms that when mothers are motivated and supported without economic restraints, breastmilk intake and the energy supplied by breastmilk to EBF infants at 6 mo of age is sufficient to support normal growth patterns. There was no evidence of constraint on FFM, and other studies show that high FM in EBF infants is likely to be transient. These data further support the recommendation for EBF ≤6 mo of age for body composition. This trial was registered at clinicaltrials.gov as NCT02586571.Peer reviewe

Epidemiology and risk factors for Staphylococcus aureus colonization in children in the post-PCV7 era

<p>Abstract</p> <p>Background</p> <p>The incidence of community-associated methicillin-resistant <it>Staphylococcus aureus </it>(MRSA) has risen dramatically in the U.S., particularly among children. Although <it>Streptococcus pneumoniae </it>colonization has been inversely associated with <it>S. aureus </it>colonization in unvaccinated children, this and other risk factors for <it>S. aureus </it>carriage have not been assessed following widespread use of the heptavalent pneumococcal conjugate vaccine (PCV7). Our objectives were to (1) determine the prevalence of <it>S. aureus </it>and MRSA colonization in young children in the context of widespread use of PCV7; and (2) examine risk factors for <it>S. aureus </it>colonization in the post-PCV7 era, including the absence of vaccine-type <it>S. pneumoniae </it>colonization.</p> <p>Methods</p> <p>Swabs of the anterior nares (<it>S. aureus</it>) were obtained from children enrolled in an ongoing study of nasopharyngeal pneumococcal colonization of healthy children in 8 Massachusetts communities. Children 3 months to <7 years of age seen for well child or sick visits in primary care offices from 11/03–4/04 and 10/06–4/07 were enrolled. <it>S. aureus </it>was identified and antibiotic susceptibility testing was performed. Epidemiologic risk factors for <it>S. aureus </it>colonization were collected from parent surveys and chart reviews, along with data on pneumococcal colonization. Multivariate mixed model analyses were performed to identify factors associated with <it>S. aureus </it>colonization.</p> <p>Results</p> <p>Among 1,968 children, the mean age (SD) was 2.7 (1.8) years, 32% received an antibiotic in the past 2 months, 2% were colonized with PCV7 strains and 24% were colonized with non-PCV7 strains. The prevalence of <it>S. aureus </it>colonization remained stable between 2003–04 and 2006–07 (14.6% vs. 14.1%), while MRSA colonization remained low (0.2% vs. 0.9%, p = 0.09). Although absence of pneumococcal colonization was not significantly associated with <it>S. aureus </it>colonization, age (6–11 mo vs. ≥5 yrs, OR 0.39 [95% CI 0.24–0.64]; 1–1.99 yrs vs. ≥5 yrs, OR 0.35 [0.23–0.54]; 2–2.99 yrs vs. ≥5 yrs, OR 0.45 [0.28–0.73]; 3–3.99 yrs vs. ≥5 yrs, OR 0.53 [0.33–0.86]) and recent antibiotic use were significant predictors in multivariate models.</p> <p>Conclusion</p> <p>In Massachusetts, <it>S. aureus </it>and MRSA colonization remained stable from 2003–04 to 2006–07 among children <7 years despite widespread use of pneumococcal conjugate vaccine. <it>S. aureus </it>nasal colonization varies by age and is inversely correlated with recent antibiotic use.</p

Daily Chlorhexidine Bathing in General Hospital Units – Results of the ABATE Infection Trial (Active BAThing to Eliminate Infection)

Abstract Background: Universal decolonization with daily chlorhexidine (CHG) bathing with and without nasal decolonization has significantly reduced positive MRSA clinical cultures and bloodstream infections in adult ICUs in several clinical trials. We evaluated whether decolonization was similarly effective in a lower risk hospitalized population. Methods: We conducted a 2 arm cluster-randomized trial involving a 1-year baseline period (April 2013–March 2014) and a 21-month intervention period (June 2014–February 2016). All noncritical care units in a hospital were assigned to the same strategy. These were (1) Routine Care: routine bathing product and frequency and (2) Decolonization: CHG for routine daily bathing (2% leave-on CHG) or showering (4% rinse-off CHG) for all patients plus mupirocin for 5 days for known MRSA. Universal ICU decolonization was in place in both arms by September 2013. Differences between the arms in the outcome rates between the baseline and intervention periods were assessed with proportional hazards models, using shared frailties to account for clustering by hospital. The primary analysis was as-randomized and unadjusted. Primary outcome was any MRSA or VRE clinical isolate attributable to the unit. Secondary outcome was all-cause bloodstream infections. Additional analyses adjusted for age, gender, race, Medicaid insurer, surgery, and comorbidities. Results: We randomized 53 hospitals in 15 states. There were 194 adult units with 189,616 admissions in the baseline period and 340,350 in the intervention period. Common unit types included mixed medical surgical (30%), cardiac (20%), step-down (11%), medical (10%), surgical (10%), and oncology (4%). There were no significant differences between arms in the relative hazards for intervention vs. baseline for either outcome (Table and Figure). Adjusted analyses yielded similar results. Conclusion: Universal daily CHG bathing or showering plus targeted mupirocin for MRSA+ patients in non-critical care units did not reduce the combination of positive MRSA and VRE clinical cultures or bloodstream infections due to all pathogens. Further analyses to assess for any differential effects in high-risk subpopulations will be important. Disclosures S. S. Huang, Sage Products: Receipt of contributed product, Conducting studies in which participating healthcare facilities are receiving contributed product (no contribution in submitted abstract), Participating healthcare facilities in my studies received contributed product; Xttrium Laboratories: Receipt of contributed product, Conducting studies in which participating healthcare facilities are receiving contributed product (no contribution in submitted abstract), Participating healthcare facilities in my studies received contributed product; Clorox: Receipt of contributed product, Conducting studies in which participating healthcare facilities are receiving contributed product (no contribution in submitted abstract), Participating healthcare facilities in my studies received contributed product; 3M: Receipt of contributed product, Conducting studies in which participating healthcare facilities are receiving contributed product (no contribution in submitted abstract), Participating healthcare facilities in my studies received contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; E. Septimus, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; K. Kleinman, Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; 3M: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; J. Moody, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; J. Hickok, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; L. Heim, Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; 3M: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; A. Gombosev, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; 3M: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; T. Avery, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; received research funds from Clorox, but Clorox has no role in the design K. Haffenreffer, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; receive research funds from Clorox, but Clorox has no role in the design; L. Shimelman, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; receive research funds from Clorox, but Clorox has no role in the design; M. K. Hayden, OpGen, Inc.: Receipt of donated laboratory services for project, Research support; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; R. A. Weinstein, Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; OpGen Inc.: Receipt of donated laboratory services for project, Research support; C. Spencer-Smith, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; R. E. Kaganov, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; M. V. Murphy, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; T. Forehand, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; J. Lankiewicz, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; M. H. Coady, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; received research funds from Clorox, but Clorox has no role in the design.; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; L. M. Portillo, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; J. Patel Sarup, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; J. Perlin, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; R. Platt, Clorox: Receipt of contributed product, Conducting clinical studies in which participating healthcare facilities are receiving contributed product; receive research funds from Clorox, but Clorox has no role in the design; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed produc

The Milky Way Tomography with SDSS: II. Stellar Metallicity

Using effective temperature and metallicity derived from SDSS spectra for ~60,000 F and G type main sequence stars (0.2<g-r<0.6), we develop polynomial models for estimating these parameters from the SDSS u-g and g-r colors. We apply this method to SDSS photometric data for about 2 million F/G stars and measure the unbiased metallicity distribution for a complete volume-limited sample of stars at distances between 500 pc and 8 kpc. The metallicity distribution can be exquisitely modeled using two components with a spatially varying number ratio, that correspond to disk and halo. The two components also possess the kinematics expected for disk and halo stars. The metallicity of the halo component is spatially invariant, while the median disk metallicity smoothly decreases with distance from the Galactic plane from -0.6 at 500 pc to -0.8 beyond several kpc. The absence of a correlation between metallicity and kinematics for disk stars is in a conflict with the traditional decomposition in terms of thin and thick disks. We detect coherent substructures in the kinematics--metallicity space, such as the Monoceros stream, which rotates faster than the LSR, and has a median metallicity of [Fe/H]=-0.96, with an rms scatter of only ~0.15 dex. We extrapolate our results to the performance expected from the Large Synoptic Survey Telescope (LSST) and estimate that the LSST will obtain metallicity measurements accurate to 0.2 dex or better, with proper motion measurements accurate to ~0.2 mas/yr, for about 200 million F/G dwarf stars within a distance limit of ~100 kpc (g<23.5). [abridged]Comment: 40 pages, 21 figures, emulateApJ style, accepted to ApJ, high resolution figures are available from http://www.astro.washington.edu/ivezic/sdss/mw/astroph0804.385

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference