Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study

Background: Invasive pneumococcal disease remains an important health priority owing to increasing disease incidence caused by pneumococci expressing non-vaccine serotypes. We previously defined 621 Global Pneumococcal Sequence Clusters (GPSCs) by analysing 20 027 pneumococcal isolates collected worldwide and from previously published genomic data. In this study, we aimed to investigate the pneumococcal lineages behind the predominant serotypes, the mechanism of serotype replacement in disease, as well as the major pneumococcal lineages contributing to invasive pneumococcal disease in the post-vaccine era and their antibiotic resistant traits. / Methods: We whole-genome sequenced 3233 invasive pneumococcal disease isolates from laboratory-based surveillance programmes in Hong Kong (n=78), Israel (n=701), Malawi (n=226), South Africa (n=1351), The Gambia (n=203), and the USA (n=674). The genomes represented pneumococci from before and after pneumococcal conjugate vaccine (PCV) introductions and were from children younger than 3 years. We identified predominant serotypes by prevalence and their major contributing lineages in each country, and assessed any serotype replacement by comparing the incidence rate between the pre-PCV and PCV periods for Israel, South Africa, and the USA. We defined the status of a lineage as vaccine-type GPSC (≥50% 13-valent PCV [PCV13] serotypes) or non-vaccine-type GPSC (>50% non-PCV13 serotypes) on the basis of its initial serotype composition detected in the earliest vaccine period to measure their individual contribution toward serotype replacement in each country. Major pneumococcal lineages in the PCV period were identified by pooled incidence rate using a random effects model. / Findings: The five most prevalent serotypes in the PCV13 period varied between countries, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or more countries. The five most prevalent serotypes in the PCV13 period varied between countries, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or more countries. These serotypes were associated with more than one lineage, except for serotype 5 (GPSC8). Serotype replacement was mainly mediated by expansion of non-vaccine serotypes within vaccine-type GPSCs and, to a lesser extent, by increases in non-vaccine-type GPSCs. A globally spreading lineage, GPSC3, expressing invasive serotypes 8 in South Africa and 33F in the USA and Israel, was the most common lineage causing non-vaccine serotype invasive pneumococcal disease in the PCV13 period. We observed that same prevalent non-vaccine serotypes could be associated with distinctive lineages in different countries, which exhibited dissimilar antibiotic resistance profiles. In non-vaccine serotype isolates, we detected significant increases in the prevalence of resistance to penicillin (52 [21%] of 249 vs 169 [29%] of 575, p=0·0016) and erythromycin (three [1%] of 249 vs 65 [11%] of 575, p=0·0031) in the PCV13 period compared with the pre-PCV period. / Interpretation: Globally spreading lineages expressing invasive serotypes have an important role in serotype replacement, and emerging non-vaccine serotypes associated with different pneumococcal lineages in different countries might be explained by local antibiotic-selective pressures. Continued genomic surveillance of the dynamics of the pneumococcal population with increased geographical representation in the post-vaccine period will generate further knowledge for optimising future vaccine design. / Funding: Bill & Melinda Gates Foundation, Wellcome Sanger Institute, and the US Centers for Disease Control

International links between Streptococcus pneumoniae vaccine serotype 4 sequence type (ST) 801 in Northern European shipyard outbreaks of invasive pneumococcal disease

Background: Pneumococcal disease outbreaks of vaccine preventable serotype 4 sequence type (ST)801 in shipyards have been reported in several countries. We aimed to use genomics to establish any international links between them. Methods: Sequence data from ST801-related outbreak isolates from Norway (n = 17), Finland (n = 11) and Northern Ireland (n = 2) were combined with invasive pneumococcal disease surveillance from the respective countries, and ST801-related genomes from an international collection (n = 41 of > 40,000), totalling 106 genomes. Raw data were mapped and recombination excluded before phylogenetic dating. Results: Outbreak isolates were relatively diverse, with up to 100 SNPs (single nucleotide polymorphisms) and a common ancestor estimated around the year 2000. However, 19 Norwegian and Finnish isolates were nearly indistinguishable (0–2 SNPs) with the common ancestor dated around 2017. Conclusion: The total diversity of ST801 within the outbreaks could not be explained by recent transmission alone, suggesting that harsh environmental and associated living conditions reported in the shipyards may facilitate invasion of colonising pneumococci. However, near identical strains in the Norwegian and Finnish outbreaks does suggest that transmission between international shipyards also contributed to those outbreaks. This indicates the need for improved preventative measures in this working population including pneumococcal vaccination

Fruit color preference by birds and applications to ecological restoration

Abstract Ecological restoration aims to retrieve not only the structure but also the functionality of ecosystems. Frugivorous birds may play an important role in this process due to their efficiency in seed dispersal. Color perception in these animals is highly developed, and then the colors of fleshy fruits may provide important clues for choosing plant species for restoration plans. This study aims to integrate bird color preferences and restoration of degraded areas, with an objective to evaluate the potential attractiveness to birds by colored fruits. We carried out an experiment with 384 artificial fruits made of edible modeling clay with the following colors: black, blue, green and red, with 96 fruits of each color in six sites, including four restored areas and two second-growth forest fragments. We also tested the possible effect of light intensity on fruit consumption by color. A total of 120 (38.6%) were assumed to be consumed by birds, and the fruit consumption varied in response to the location and light incidence. Consumption of black and blue fruits was not related to site by chance. Notwithstanding, red and black fruits were consumed significantly more than any other colors, emphasizing bird preference to these colors, regardless of location. Enrichment with shade tolerant shrubs or forest species with black or red fruits may be an alternative way to manage established restorations. In recently established or new restorations, one may introduce pioneer shrubs or short-lived forest species which have blue fruits, but also those having black or red ones

Neutron spectrometry of the 9^{9}Be(d (1.45 MeV), n)10^{10}B reaction for accelerator-based BNCT

International audienceThe 9Be(d,n)10B reaction was proposed in the past as a neutron source for Accelerator-Based Boron Neutron Capture Therapy. Based on numerical models and scarce experimental information about the neutron spectra, it was proven that low energy deuterons on a thin target may provide neutron beams of therapeutic quality. In particular, an 8–9 μm target bombarded by 1.45 MeV deuterons presents itself as a convenient option. The aim of this work is to provide experimental validation to these numerical models. For this purpose, neutron spectra at 0°, 35°, 60°, 90° and 123° from a (9 ± 1) μm 9Be target were measured at the CN accelerator of the Laboratori Nazionali di Legnaro. A micro-time projection chamber (μ-TPC) was used as a neutron spectrometer

Neutron spectrometry of the 9^{9}Be(d (1.45 MeV), n)10^{10}B reaction for accelerator-based BNCT

International audienceThe 9Be(d,n)10B reaction was proposed in the past as a neutron source for Accelerator-Based Boron Neutron Capture Therapy. Based on numerical models and scarce experimental information about the neutron spectra, it was proven that low energy deuterons on a thin target may provide neutron beams of therapeutic quality. In particular, an 8–9 μm target bombarded by 1.45 MeV deuterons presents itself as a convenient option. The aim of this work is to provide experimental validation to these numerical models. For this purpose, neutron spectra at 0°, 35°, 60°, 90° and 123° from a (9 ± 1) μm 9Be target were measured at the CN accelerator of the Laboratori Nazionali di Legnaro. A micro-time projection chamber (μ-TPC) was used as a neutron spectrometer

An Approach to Establishing Diagnostic Reference Levels in Interventional Pediatric Cardiology from Different Regions of Brazil

Diagnostic reference levels (DRLs) are a pivotal strategy to be implemented since pediatric interventional cardiology procedures are increasing. This work aimed to propose an initial set of Brazilian DRLs for pediatric interventional diagnostic and therapeutic (D&T) procedures. A retrospective study was carried out in four Brazilian states, distributed across the three regions of the country. Data were collected from pediatric patients undergoing cardiac interventional procedures (CIPs), including their age and anthropometric characteristics, and at least four parameters (number of images, exposure time, air kerma–area product—PKA, and cumulative air kerma). Data from 279 patients undergoing CIPs were gathered (147 diagnostic and 132 therapeutic procedures). There were no significant differences in exposure time and the number of images between the D&T procedures. A wide range of PKA was observed when the therapeutic procedures were compared to diagnostics for all age groups. There were significant differences between the D&T procedures, whether grouping data by patient weight or age. In terms of cumulative air kerma, it was noted that no value exceeded the level to trigger a monitoring process for patients. This study shows that it is possible to adopt them as the first proposal to establish national DRLs considering pediatric patient groups