Browsing by Author "van der Ende, Arie"
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- Comparative pangenome analysis of capsulated Haemophilus influenzae serotype f highlights their high genomic stabilityPublication . Gonzalez-Diaz, Aida; Carrera-Salinas, Anna; Pinto, Miguel; Cubero, Meritxell; van der Ende, Arie; Langereis, Jeroen D.; Domínguez, M. Ángeles; Ardanuy, Carmen; Bajanca-Lavado, Paula; Marti, SaraHaemophilus influenzae is an opportunistic pathogen adapted to the human respiratory tract. Non-typeable H. influenzae are highly heterogeneous, but few studies have analysed the genomic variability of capsulated strains. This study aims to examine the genetic diversity of 37 serotype f isolates from the Netherlands, Portugal, and Spain, and to compare all capsulated genomes available on public databases. Serotype f isolates belonged to CC124 and shared few single nucleotide polymorphisms (SNPs) (n = 10,999), but a high core genome (> 80%). Three main clades were identified by the presence of 75, 60 and 41 exclusive genes for each clade, respectively. Multi-locus sequence type analysis of all capsulated genomes revealed a reduced number of clonal complexes associated with each serotype. Pangenome analysis showed a large pool of genes (n = 6360), many of which were accessory genome (n = 5323). Phylogenetic analysis revealed that serotypes a, b, and f had greater diversity. The total number of SNPs in serotype f was significantly lower than in serotypes a, b, and e (p < 0.0001), indicating low variability within the serotype f clonal complexes. Capsulated H. influenzae are genetically homogeneous, with few lineages in each serotype. Serotype f has high genetic stability regardless of time and country of isolation.
- Epidemiological analysis of invasive Haemophilus influenzae clinical isolates obtanied from Portugal, Spain and the NetherlandsPublication . Raeven, Elisabeth A.M.; González, Aida; van der Ende, Arie; Liñares, Josefina; Marimón, José María; Bajanca-Lavado, Paula; Langereis, Jeroen D.; Ardanuy, Carmen; Martí, SaraBackground. Haemophilus influenzae is a human-restricted pathogen that forms part of the normal nasopharyngeal microbiota. The introduction of the H. influenzae serotype b vaccine has drastically decreased the number of bacteremia cases caused by H. influenzae serotype b (Hib). Conversely, the cases of non-typeable H. influenzae (NTHi) bacteremia have increased substantially. Therefore, we aimed to perform an epidemiological study comparing invasive H. influenzae clinical isolates from three European countries. Material & Methods. Clinical isolates were obtained from two southern European countries, Spain (Hospital de Bellvitge, n=44; Hospital de Donostia, n=18) and Portugal (n=55), and a northern country, the Netherlands (n=146) between 2013 and 2015. The clinical source of the samples was blood (n=250), cerebrospinal fluid (n=4) and pleural effusion (n=9). Capsular serotyping was done by PCR and genotyping by PFGE (SmaI), followed by FingerPrinting analysis. Antimicrobial susceptibility was tested by disk diffusion and microdilution against Ampicillin (AP), Tetracycline (TC), Chloramphenicol (CL), Ciprofloxacin (CP) and Trimethoprim/Sulfamethoxazole (T/S). Results. Overall, NTHi were the most prevalent isolates (201/263, 76%), followed by Hib (38/263, 14%), Hif (16/263, 6%) and other capsulated H. influenzae (Hia=3; Hid=1; Hie=4). By countries, NTHi was also the major pathogen identified in Spain (82%), Portugal (80%) and the Netherlands (73%), while Hib was slightly more frequent in the Netherlands (27/146, 18%) and Portugal (7/55, 13%) than in Spain (4/62, 6%). PFGE clustering identified high diversity among the NTHi strains, although some strains from different countries were found to be highly related (14 clusters of two or three strains). Hib were grouped together in four main clusters including isolates from different countries: Cluster I (5 strains Netherlands; 4 strains Portugal), Cluster II (18 strains Netherlands, 2 strains Portugal; 1 strain Spain), Cluster III (5 strains Netherlands), Cluster IV (1 strain Portugal; 1 strain Spain).
- Implications of differential age distribution of disease-associated meningococcal lineages for vaccine developmentPublication . Brehony, Carina; Trotter, Caroline L.; Ramsay, Mary E.; Jolley, Keith A.; van der Ende, Arie; Carion, Françoise; Berthelsen, Lene; Hoffmann, Steen; Harðardóttir, Hjördís; Vazquez, Julio A.; Murphy, Karen; Toropainen, Maija; Caniça, Manuela; Ferreira, Eugenia; Diggle, Mathew; Edwards, Giles F; Taha, Muhamed-Kheir; Stefanelli, Paola; Kriz, Paula; Gray, Steve J.; Fox, Andrew J.; Jacobsson, Susanne; Claus, Heike; Vogel, Ulrich; Tzanakaki, Georgina; Heuberger, Sigrid; Caugant, Dominique A.; Frosch, Matthias; Maiden, Martin C. J.New vaccines targeting meningococci expressing serogroup B polysaccharide have been developed, with some being licensed in Europe. Coverage depends on the distribution of disease-associated genotypes, which may vary by age. It is well established that a small number of hyperinvasive lineages account for most disease, and these lineages are associated with particular antigens, including vaccine candidates. A collection of 4,048 representative meningococcal disease isolates from 18 European countries, collected over a 3-year period, were characterized by multilocus sequence typing (MLST). Age data were available for 3,147 isolates. The proportions of hyperinvasive lineages, identified as particular clonal complexes (ccs) by MLST, differed among age groups. Subjects <1 year of age experienced lower risk of sequence type 11 (ST-11) cc, ST-32 cc, and ST-269 cc disease and higher risk of disease due to unassigned STs, 1- to 4-year-olds experienced lower risk of ST-11 cc and ST-32 cc disease, 5- to 14-year-olds were less likely to experience ST-11 cc and ST-269 cc disease, and ≥25-year-olds were more likely to experience disease due to less common ccs and unassigned STs. Younger and older subjects were vulnerable to a more diverse set of genotypes, indicating the more clonal nature of genotypes affecting adolescents and young adults. Knowledge of temporal and spatial diversity and the dynamics of meningococcal populations is essential for disease control by vaccines, as coverage is lineage specific. The nonrandom age distribution of hyperinvasive lineages has consequences for the design and implementation of vaccines, as different variants, or perhaps targets, may be required for different age groups.
- Increase of invasive meningococcal serogroup W disease in Europe, 2013 to 2017Publication . Krone, Manuel; Gray, Steve; Abad, Raquel; Skoczyńska, Anna; Stefanelli, Paola; van der Ende, Arie; Tzanakaki, Georgina; Mölling, Paula; João Simões, Maria; Křížová, Pavla; Emonet, Stéphane; Caugant, Dominique A.; Toropainen, Maija; Vazquez, Julio; Waśko, Izabela; Knol, Mirjam J.; Jacobsson, Susanne; Rodrigues Bettencourt, Célia; Musilek, Martin; Born, Rita; Vogel, Ulrich; Borrow, RayBackground: The total incidence of invasive meningococcal disease (IMD) in Europe has been declining in recent years; however, a rising incidence due to serogroup W (MenW), predominantly sequence type 11 (ST-11), clonal complex 11 (cc11), was reported in some European countries. Aim: The aim of this study was to compile the most recent laboratory surveillance data on MenW IMD from several European countries to assess recent trends in Europe. Methods: In this observational, retrospective study, IMD surveillance data collected from 2013–17 by national reference laboratories and surveillance units from 13 European countries were analysed using descriptive statistics. Results: The overall incidence of IMD has been stable during the study period. Incidence of MenW IMD per 100,000 population (2013: 0.03; 2014: 0.05; 2015: 0.08; 2016: 0.11; 2017: 0.11) and the proportion of this serogroup among all invasive cases (2013: 5% (116/2,216); 2014: 9% (161/1,761); 2015: 13% (271/2,074); 2016: 17% (388/2,222); 2017: 19% (393/2,112)) continuously increased. The most affected countries were England, the Netherlands, Switzerland and Sweden. MenW was more frequent in older age groups (≥ 45 years), while the proportion in children (< 15 years) was lower than in other age groups. Of the culture-confirmed MenW IMD cases, 80% (615/767) were caused by hypervirulent cc11. Conclusion: During the years 2013–17, an increase in MenW IMD, mainly caused by MenW cc11, was observed in the majority of European countries. Given the unpredictable nature of meningococcal spread and the epidemiological potential of cc11, European countries may consider preventive strategies adapted to their contexts.
- Spatial and temporal genomic homogeneity among Haemophilus influenzae serotype fPublication . Gonzalez-Diaz, Aida; Pinto, Miguel; Cubero, Meritxell; Langereis, Jeroen D.; van der Ende, Arie; Bajanca-Lavado, Maria Paula; Ardanuy, Carmen; Marti, SaraBackground: Haemophilus influenzae is an opportunistic pathogen highly adapted to the human respiratory tract which is often reported as the etiologic agent of infectious diseases. After the introduction of serotype b vaccine, non-typeable H. influenzae (NTHi) has become the most frequent cause of respiratory infection, followed in frequency by serotype f strains (Hif). The aim of this study was to analyze the genomic diversity among invasive and colonizing Hif isolates by whole genome sequencing (WGS).