Emergence and Global Dissemination of Host-Specific Streptococcus agalactiae Clones

To examine the global diversity of Streptococcus agalactiae (group B streptococci [GBS]) and to elucidate the evolutionary processes that determine its population genetics structure and the reported changes in host tropism and infection epidemiology, we examined a collection of 238 bovine and human isolates from nine countries on five continents. Phylogenetic analysis based on the sequences of 15 housekeeping genes combined with patterns of virulence-associated traits identified a genetically heterogeneous core population from which virulent lineages occasionally emerge as a result of recombination affecting major segments of the genome. Such lineages, like clonal complex 17 (CC17) and two distinct clusters of CC23, are exclusively adapted to either humans or cattle and successfully spread globally. The recent emergence and expansion of the human-associated and highly virulent sequence type 17 (ST17) could conceivably account, in part, for the increased prevalence of neonatal GBS infections after 1960. The composite structure of the S. agalactiae genome invalidates phylogenetic inferences exclusively based on multilocus sequence typing (MLST) data and thereby the previously reported conclusion that the human-associated CC17 emerged from the bovine-associated CC67

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Rôle des éléments génétiques mobiles dans l'évolution et la virulence de Streptococcus agalactiae

Nous avons étudié le rôle des éléments génétiques mobiles (EGM) dans l évolution et la virulence de Streptococcus agalactiae, bactérie pathogène opportuniste responsable d'infections chez l homme. La structure génétique de la population a été analysée par multilocus sequence typing à partir d un souchier représentatif de la diversité de l espèce. La distribution de 11 EGM (sept séquences d insertion, trois transposases, un intron) a été confrontée à la structure de la population. Cette confrontation a permis i) de démontrer que l acquisition des EGM corrélait avec l évolution de l espèce, ii) de proposer une hypothèse de la chronologie d acquisition des EGM, iii) d identifier certains EGM comme marqueurs de l écosystème d origine des souches, et iv) de conforter l hypothèse de l émergence du clone humain invasif CC17 à partir d un ancêtre bovin. Nous avons également cartographié les copies des EGM présentes sur le génome de S. agalactiae, puis nous avons identifié huit nouveaux sites d insertion, dont deux sont significativement associés à l origine écologique de la souche.We studied the role of mobile genetic elements (MGE) on the evolution and the virulence of Streptococcus agalactiae, an opportunistic bacterium responsible for human infections. The genetic population structure was analyzed by multilocus sequence typing using a collection representative of the species diversity. The distribution of 11 MGE (seven insertion sequences, three transposases, one intron) was compared to the population structure. We demonstrated that the MGE prevalence strongly correlates with the genetic lineages. We proposed an evolutionary scheme for the acquisition of the MGE. Several MGE appeared to be markers of the origin of the strains. MGE analysis brought evidence for a bovine origin of the human virulent clone CC17. We also identified the position of the MGE copies on the S. agalactiae genome and we identified eight new MGE insertion sites, from which two were significantly associated with the ecological origin of the isolates.TOURS-Bibl.électronique (372610011) / SudocSudocFranceF

Apport des éléments génétiques mobiles à la compréhension de l'évolution de Streptococcus agalactiae

LYON1-BU Santé (693882101) / SudocRENNES1-BU Santé (352382103) / SudocSudocFranceF

Détection de Pseudomonas aeruginosa dans les expectorations de patients atteints de mucoviscidose (intérêt de la PCR en temps réel gyrB/ecfX)

L'identification de Pseudomonas aeruginosa dans les expectorations des patients atteints de mucoviscidose (patients CF) est primordiale, mais peut s'avérer difficile. L'utilisation de la PCR pourrait améliorer le dépistage précoce de cette bactérie. L'objectif de notre travail a été d'évaluer les performances de la PCR en temps réel gyrB/ecfX dans ce contexte. La collection bactérienne d'étude se composait de 37 isolats de P. aeruginosa et de 41 isolats de bacilles à Gram négatif non fermentaires, phylogénétiquement proches de P. aeruginosa. Cinquante-sept de ces isolats provenaient de patients CF. La PCR multiplexe a montré une sensibilité de 100 %, une spécificité de 95 % et un seuil de sensibilité entre 10E3 et 10E4 UFC/mL. À l'issue de cette évaluation, la PCR multiplexe a été intégrée dans une étude visant à évaluer l'apport des techniques moléculaires dans le dépistage de la primo-colonisation à P. aeruginosa chez les patients CF.Identification of Pseudomonas aeruginosa from sputum of cystic fibrosis patients (CF patients) is essential, but may be problematic. The use of PCR could improve the early detection of this bacterium. The aim of this study was to evaluate a real time multiplex PCR targeting the gyrB and the ecfX genes for its ability to detect P. aeruginosa from CF sputum. We tested 37 P. aeruginosa isolates and 41 closely related non-P. aeruginosa Gram negative bacillus isolates, including 57 isolates from CF patients. The multiplex PCR showed a sensitivity of 100%, a specificity of 95%, and a sensitivity treshold between 10E3 and 10E4 CFU/mL. Following this assessment, the multiplex PCR was included in a study which aims to assess the contribution of molecular techniques in the early detection of P. aeruginosa in CF patients.RENNES1-BU Santé (352382103) / SudocSudocFranceF

La spectrométrie de masse Maldi-Tof appliquée à l'identification des espèces du complexe mycobacterium abscessus

Mycobacterium abscessus est un pathogène émergent chez le patient mucoviscidose. Trois espèces non différenciables en routine diagnostique en constituent le complexe: M. abscessus, M. Massiliense et M. bolletii. Des différences substantielles dans leur profil clinique et de sensibilité aux antibiotiques justifient leur typage à l'espèce. L'implantation croissante de la spectrométrie de masse (SM) dans les laboratoires offre une nouvelle perspective pour leur identification. Les performances de la SM MALDI-TOF dans l'identification des espèces du complexe ont été évaluées sur un souchier de 36 isolats cliniques et 3 souches de référence. L'analyse des spectres de masse de 9 isolats et des souches de référence a permis la caractérisation de 5 pics discriminants, ensuite validés sur le reste du souchier. Tous les isolats de M. abscessus et M. massiliense ont été correctement identifiés. Une erreur d'identification a été observée avec un isolat de M. bolletii confondu avec M. abscessus.Mycobacterium abscessus is an emerging pathogen in cystic fibrosis patients. M. abscessus complex is composed of 3 species: M. abscessus, M. massiliense et M. bolletii, which are not distinguishable in routine by usual techniques. There are differences considering their clinical profiles and antibiotics susceptibilities, which require correct typing to the specie level. The increasingly use of mass spectrometry (MS) in laboratories is a new opportunity for there identification. In this study, the ability to discriminate MABC at the specie level using MALDI-TOF MS was evaluated on 36 clinical isolates and 3 reference strains. Mass spectra obtained for 9 isolates and 3 reference strains were analyzed and highlighted 5 discriminating peaks, which were confirmed by analyzing the other isolates. Every isolates of M. abscessus and M. massiliense were correctly typed. One misidentification was observed with a M. bolletii isolate, mistaken with M. abscessus.LYON1-BU Santé (693882101) / SudocRENNES1-BU Santé (352382103) / SudocSudocFranceF

Methods for predicting the risk of developing pulmonary colonization/infection by pseudomonas aeruginosa

The present invention relates to methods for predicting the risk of developing pulmonary colonization/infection by P. aeruginosa. The inventors analyzed the respiratory tract microbiota from 65 patients sputum samples and compared microbiota data. The inventors found that patients that will remain uninfected from P. aeruginosa exhibited 3-fold higher abundance of Porphyromonas catoniae compared to the other groups. In particular, the present invention relates to a method for predicting the risk of developing pulmonary colonization/infection by P. aeruginosa in a subject suffering from cystic fibrosis (CF) comprising measuring the abundance of Porphyromonas catoniae in a biological sample obtained from said subject

Treatment of Bone and Joint Tuberculosis in France: A Multicentre Retrospective Study

International audienceBackground: Nine percent of all cases of tuberculosis are bone and joint tuberculosis (BJTB). BJTB occurs in two main forms: spinal (STB) and extraspinal (ESTB). The aim of this study was to compare STB with ESTB in terms of diagnosis, treatment and outcomes. Methods: We collected demographic, clinical, microbiological, treatment duration and outcome data for patients with BJTB in a retrospective multicentre study over a 17-year period. Results: Of the 116 patients included in the study, 69 (59.5%) had STB and 47 (40.5%) had ESTB. The median age was higher in the ESTB group. There were significantly more foreign-born patients in the STB group. The median time for diagnosis was longer for ESTB (6 months) than STB (4 months) (p= 0.017). Magnetic resonance imaging was highly reliable for the diagnosis. Direct examination and histology allowed the diagnosis to be made in more than 80% of cases. The median treatment duration of 12 months, regardless of the type of BJTB, was longer than recommended. A favourable outcome was achieved in 91.9% of cases. Conclusion: The management of BJTB remains challenging. An earlier diagnosis should be more effective, reducing the total duration of treatment and leading to better tolerance