Epidemiological and evolutionary dynamics of influenza B virus in coastal Kenya as revealed by genomic analysis of strains sampled over a single season

The genomic epidemiology of influenza B virus (IBV) remains understudied in Africa despite significance to design of effective local and global control strategies. We undertook surveillance throughout 2016 in coastal Kenya, recruiting individuals presenting with acute respiratory illness at nine outpatient health facilities (any age) or admitted to the Kilifi County Hospital (<5-year-old). Whole genomes were sequenced for a select 111 positives; 94 (84.7%) of B/Victoria lineage and 17 (15.3%) of B/Yamagata lineage. Inter-Lineage reassortment was detected in 10 viruses; nine with B/Yamagata backbone but B/Victoria NA and NP segments and one with a B/Victoria backbone but B/Yamagata PB2, PB1, PA and MP segments. Five phylogenomic clusters were identified among the sequenced viruses; (i) pure B/Victoria clade 1A (n = 93, 83.8%), (ii) reassortant B/Victoria clade 1A (n = 1, 0.9%), (iii) pure B/Yamagata clade 2 (n = 2, 1.8%), (iv) pure B/Yamagata clade 3 (n = 6, 5.4%) and (v) reassortant B/Yamagata clade 3 (n = 9, 8.1%). Using divergence dates and clustering patterns in the presence of global background sequences, we counted up to 29 independent IBV strain introductions into the study area (∼900 km2) in 2016. Local viruses, including the reassortant B/Yamagata strains, clustered closely with viruses from neighbouring Tanzania and Uganda. Our study demonstrated that genomic analysis provides a clearer picture of locally circulating IBV diversity. The high number of IBV introductions highlights the challenge in controlling local influenza epidemics by targeted approaches e.g. sub-population vaccination or patient quarantine. The finding of divergent IBV strains co-circulating within a single season emphasizes why broad immunity vaccines are the most ideal for influenza control in Kenya

Genetic relatedness of infecting and reinfecting respiratory syncytial virus strains identified in a birth cohort from rural Kenya

Background: Respiratory syncytial virus (RSV) reinfects individuals repeatedly. The extent to which this is a consequence of RSV antigenic diversity is unclear. Methods: Six-hundred thirty-five children from rural Kenya were closely monitored for RSV infection from birth through 3 consecutive RSV epidemics. RSV infections were identified by immunofluorescence testing of nasal washing samples collected during acute respiratory illnesses, typed into group A and B, and sequenced in the attachment (G) protein. A positive sample separated from a previous positive by ≥14 days was defined as a reinfection a priori. Results: Phylogenetic analysis was undertaken for 325 (80%) of 409 identified infections, including 53 (64%) of 83 reinfections. Heterologous group reinfections were observed in 28 episodes, and homologous group reinfections were observed in 25 episodes; 10 involved homologous genotypes, 5 showed no amino acid changes, and 3 were separated by 21–24 days and were potentially persistent infections. The temporal distribution of genotypes among reinfections did not differ from that of single infections. Conclusions: The vast majority of infection and reinfection pairs differed by group, genotype, or G amino acid sequence (ie, comprised distinct viruses). The extent to which this is a consequence of immune memory of infection history or prevalent diversity remains unclear

GuD-Kraftwerk '500 MW auf einer Welle' (AG TURBO II). Vorhaben 3.3.2.B.: Modellierung von Mehrfachbrennersystemen 'Instationaere Mischung: Modellbildung' Abschlussbericht

Es wurden grundlegende Erkenntnisse zur zeitlichen als auch raeumlichen Mischungsguete eines Luft-Gasgemisches erzielt. Vor dem Hintergrund der Minimierung von Stickoxidemissionen von Gasturbinen lassen sich durch Verbesserung der Brennstoff/Luft Mischung in der Vormischpassage vor der Flammenzone die Emissionen deutlich reduzieren. Phase 1 beinhaltet den Aufbau eines CFD Modells zur Untersuchung der sowohl zeitlichen als auch raeumlichen Mischungsguete eines quer zur Hauptstroemung eingeduesten Tracer-Luft-Gasgemisches. Dabei erfolgte die Implementierung einer zusaetzlichen skalaren Erhaltungsgleichung zur Berechnung der turbulenten zeitlichen Konzentrationsschwankungen. Durchgefuehrte Variantenrechnungen zeigten hinsichtlich der oertlichen und zeitlichen Mischungsguete gute Uebereinstimmung mit experimentellen Messergebnissen. Wesentliche variierte Parameter waren: Die turbulente Schmidtzahl, der Einduesungsdurchmesser, die Massenstromverhaeltnisse und der Einfluss des statischen Mischers auf das Mischungsverhalten des Brennstoff-Luftgemisches. Fuer eine ausgewaehlte Variante erfolgte in Phase 2 der Aufbau eines CFD Modells zur Untersuchung der Mischungsguete eines quer zur Hauptstroemung eingeduesten Tracer-Luft-Gasgemisches bei gleichzeitiger Umlenkung der Stroemung durch in die Hauptstroemung eingebrachte Schaufeln. Die Einduesung des Tracer-Luft-Gasgemisches erfolgte direkt ueber die in den Kanal eingebauten Schaufeln. Wegen der unterschiedlichen Druckverteilung auf Druck und Saugseite der Schaufeln ist das Mischungsverhalten im Vergleich zur unverdrallten Einduesung deutlich schlechter, was sowohl die experimentellen Messungen als auch die numerischen Berechnungen belegen. In Phase drei wurde ein Stickoxid-Vorhersage-Modell basierend auf einer 5 Schritt Reaktionskinetik in das vorhandene EDM-Verbrennungsmodell des CFD-Codes integriert und mit an Gasturbinen ermittelten Emissions Messwerten in Phase 4 validiert. Anfaengliche deutliche Unterschiede zwischen Messergebnissen und CFD-Ergebnissen hinsichtlich der Stickoxid-Emissionen konnten durch Optimierung des Verbrennungsmodells behoben werden. Deutliche Defizite weist das Modell jedoch bei der Vorhersage von CO-Emissionen auf. Die fuer die Phase 5 geplante zusaetzliche Validierung des CFD Modells an Hand von atmosphaerischen Stick-oxid-Messungen konnte nicht erfolgen, da die seitens der Uni Bochum geplanten atmosphaerischen Verbrennungsversuche wegen mangelnder Flammenstabilitaet nicht in zufriedenstellender Weise durchgefuehrt werden konnten. Die erwaehnten Defizite der 5-Schritt-Reaktionskinetik bei der CO-Vorhersage werden weitgehend durch den Einsatz des ILDM Verbrennungsmodells behoben werden, was Schwerpunkt des aktuellen Forschungsprojektes 4.4.6 von AG-Turbo II ist. (orig.)The temporal and local mixing quality of an air/gas mixture was investigated. Emissions can be reduced significantly by improving the fuel/air ratio in the premix passage ahead of the flame zone. Phase 1 comprised the development of a CFD model for investigating the temporal and local mixing quality of a tracer/air gas mixture injected normal to the main flow direction. An additional scalar conservation equation was implemented for calculating the turbulent temporal concentration variations. Variant calculations were carried out; the results were in good agreement with experimental findings. The following variables were measured: The turbulent Schmidt number, the injection diameter, the mass flow ratios, and the influence of the static mixer on the mixing characteristics of the fuel/air mixture. In phase 2, a CFD model was developed for investigating the mixing quality of a tracer/air gas mixture injected normal to the main flow direction and with simultaneous flow deflection by blades installed in the main flow passage. Here, the mixing quality was significantly lower both in the experimental measurements and in the calculations. In phase 3, a NOx prediction model based on a 5-step reaction kinetics was integrated in the available EDM combustion model of the CFD code. It was validated in phase 4 on the basis of NOx emission measurements on gas turbines. Initially, there were significant variations between the measurements and CFD results; these were overcome, however, by optimising the combustion model. However, the model clearly did have deficiencies in the prediction of CO emissions. In phase 5, the CFD model was to be validated additionally on the basis of atmospheric NOx measurements. This was not possible as the atmospheric combustion experiments planned at Bochum University did not achieve sufficient flame stability. The deficiencies of the 5-step reaction kinetics in CO prediction were overcome by the use of the ILDM combustion model, which is the central subject of the current research project 4.4.6 of AG-Turbo II. (orig.)SIGLEAvailable from TIB Hannover: F04B608 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung und Forschung (BMBF), Bonn (Germany)DEGerman

Local evolutionary patterns of human respiratory syncytial virus derived from whole-genome sequencing

Human respiratory syncytial virus (RSV) is associated with severe childhood respiratory infections. A clear description of local RSV molecular epidemiology, evolution, and transmission requires detailed sequence data and can inform new strategies for virus control and vaccine development. We have generated 27 complete or nearly complete genomes of RSV from hospitalized children attending a rural coastal district hospital in Kilifi, Kenya, over a 10-year period using a novel full-genome deep-sequencing process. Phylogenetic analysis of the new genomes demonstrated the existence and cocirculation of multiple genotypes in both RSV A and B groups in Kilifi. Comparison of local versus global strains demonstrated that most RSV A variants observed locally in Kilifi were also seen in other parts of the world, while the Kilifi RSV B genomes encoded a high degree of variation that was not observed in other parts of the world. The nucleotide substitution rates for the individual open reading frames (ORFs) were highest in the regions encoding the attachment (G) glycoprotein and the NS2 protein. The analysis of RSV full genomes, compared to subgenomic regions, provided more precise estimates of the RSV sequence changes and revealed important patterns of RSV genomic variation and global movement. The novel sequencing method and the new RSV genomic sequences reported here expand our knowledge base for large-scale RSV epidemiological and transmission studies. Importance: The new RSV genomic sequences and the novel sequencing method reported here provide important data for understanding RSV transmission and vaccine development. Given the complex interplay between RSV A and RSV B infections, the existence of local RSV B evolution is an important factor in vaccine deployment

Local Evolutionary Patterns of Human Respiratory Syncytial Virus Derived from Whole-Genome Sequencing

Human respiratory syncytial virus (RSV) is associated with severe childhood respiratory infections. A clear description of local RSV molecular epidemiology, evolution, and transmission requires detailed sequence data and can inform new strategies for virus control and vaccine development. We have generated 27 complete or nearly complete genomes of RSV from hospitalized children attending a rural coastal district hospital in Kilifi, Kenya, over a 10-year period using a novel full-genome deep-sequencing process. Phylogenetic analysis of the new genomes demonstrated the existence and cocirculation of multiple genotypes in both RSV A and B groups in Kilifi. Comparison of local versus global strains demonstrated that most RSV A variants observed locally in Kilifi were also seen in other parts of the world, while the Kilifi RSV B genomes encoded a high degree of variation that was not observed in other parts of the world. The nucleotide substitution rates for the individual open reading frames (ORFs) were highest in the regions encoding the attachment (G) glycoprotein and the NS2 protein. The analysis of RSV full genomes, compared to subgenomic regions, provided more precise estimates of the RSV sequence changes and revealed important patterns of RSV genomic variation and global movement. The novel sequencing method and the new RSV genomic sequences reported here expand our knowledge base for large-scale RSV epidemiological and transmission studies