Institution
Angkor Hospital for Children
Healthcare•Siem Reap, Cambodia•
About: Angkor Hospital for Children is a healthcare organization based out in Siem Reap, Cambodia. It is known for research contribution in the topics: Population & Medicine. The organization has 144 authors who have published 180 publications receiving 4307 citations.
Papers published on a yearly basis
Papers
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Wellcome Trust Sanger Institute1, Cambridge University Hospitals NHS Foundation Trust2, University of Oxford3, University College London4, University of London5, Liverpool School of Tropical Medicine6, Quadram Institute7, Pasteur Institute8, University of Melbourne9, University of Birmingham10, Kenya Medical Research Institute11, Emory University12, Centers for Disease Control and Prevention13, University of Liverpool14, University of Malawi15, Katholieke Universiteit Leuven16, Institute of Tropical Medicine Antwerp17, University of the Republic18, International Vaccine Institute19, Novartis20, University of the Witwatersrand21, Nagasaki University22, Patan Academy of Health Sciences23, World Health Organization24, Hasanuddin University25, Mahosot Hospital26, Mahidol University27, University of Otago28, Public Health England29, Angkor Hospital for Children30
TL;DR: This whole-genome sequence analysis of Salmonella enterica serovar Typhi identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years, and identifies numerous transmissions of H58.
Abstract: The emergence of multidrug-resistant (MDR) typhoid is a major global health threat affecting many countries where the disease is endemic. Here whole-genome sequence analysis of 1,832 Salmonella enterica serovar Typhi (S. Typhi) identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years. Our analysis identifies numerous transmissions of H58, including multiple transfers from Asia to Africa and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our analysis indicates that H58 lineages are displacing antibiotic-sensitive isolates, transforming the global population structure of this pathogen. H58 isolates can harbor a complex MDR element residing either on transmissible IncHI1 plasmids or within multiple chromosomal integration sites. We also identify new mutations that define the H58 lineage. This phylogeographical analysis provides a framework to facilitate global management of MDR typhoid and is applicable to similar MDR lineages emerging in other bacterial species.
383 citations
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Royal Children's Hospital1, University of Melbourne2, Angkor Hospital for Children3, University of Oxford4, National Institute for Health and Welfare5, University of the Witwatersrand6, Medical Research Council7, World Health Organization8, Emory University9, Universidade Nova de Lisboa10, Wellcome Trust11, University of London12, Johns Hopkins University13
TL;DR: This paper outlines the consensus position of the working group, the evidence supporting this position, areas worthy of future research, and the epidemiological role of carriage studies, and describes the collection, transport and storage of nasopharyngeal samples.
366 citations
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TL;DR: In this article, the authors report whole-genome sequencing of 3,085 pneumococcal carriage isolates from a 2.4km(2) refugee camp, which provides unprecedented resolution of the process of recombination and its impact on population evolution.
Abstract: Evasion of clinical interventions by Streptococcus pneumoniae occurs through selection of non-susceptible genomic variants. We report whole-genome sequencing of 3,085 pneumococcal carriage isolates from a 2.4-km(2) refugee camp. This sequencing provides unprecedented resolution of the process of recombination and its impact on population evolution. Genomic recombination hotspots show remarkable consistency between lineages, indicating common selective pressures acting at certain loci, particularly those associated with antibiotic resistance. Temporal changes in antibiotic consumption are reflected in changes in recombination trends, demonstrating rapid spread of resistance when selective pressure is high. The highest frequencies of receipt and donation of recombined DNA fragments were observed in non-encapsulated lineages, implying that this largely overlooked pneumococcal group, which is beyond the reach of current vaccines, may have a major role in genetic exchange and the adaptation of the species as a whole. These findings advance understanding of pneumococcal population dynamics and provide information for the design of future intervention strategies.
359 citations
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University of Oxford1, Angkor Hospital for Children2, Icahn School of Medicine at Mount Sinai3, Wellcome Trust4, AstraZeneca5, Mahosot Hospital6, University of Washington7, University of British Columbia8, University of Minnesota9, Translational Genomics Research Institute10, Imperial College London11
TL;DR: This study of the largest worldwide collection of sequenced ST131 E. coli isolates to date demonstrates that the clonal expansion of two previously recognized antimicrobial-resistant clades started around 25 years ago, consistent with the widespread introduction of fluoroquinolones and extended-spectrum cephalosporins in clinical medicine.
Abstract: Escherichia coli sequence type 131 (ST131) has emerged globally as the most predominant extraintestinal pathogenic lineage within this clinically important species, and its association with fluoroquinolone and extended-spectrum cephalosporin resistance impacts significantly on treatment. The evolutionary histories of this lineage, and of important antimicrobial resistance elements within it, remain unclearly defined. This study of the largest worldwide collection (n = 215) of sequenced ST131 E. coli isolates to date demonstrates that the clonal expansion of two previously recognized antimicrobial-resistant clades, C1/H30R and C2/H30Rx, started around 25 years ago, consistent with the widespread introduction of fluoroquinolones and extended-spectrum cephalosporins in clinical medicine. These two clades appear to have emerged in the United States, with the expansion of the C2/H30Rx clade driven by the acquisition of a blaCTX-M-15-containing IncFII-like plasmid that has subsequently undergone extensive rearrangement. Several other evolutionary processes influencing the trajectory of this drug-resistant lineage are described, including sporadic acquisitions of CTX-M resistance plasmids and chromosomal integration of blaCTX-M within subclusters followed by vertical evolution. These processes are also occurring for another family of CTX-M gene variants more recently observed among ST131, the blaCTX-M-14/14-like group. The complexity of the evolutionary history of ST131 has important implications for antimicrobial resistance surveillance, epidemiological analysis, and control of emerging clinical lineages of E. coli. These data also highlight the global imperative to reduce specific antibiotic selection pressures and demonstrate the important and varied roles played by plasmids and other mobile genetic elements in the perpetuation of antimicrobial resistance within lineages. IMPORTANCEEscherichia coli, perennially a major bacterial pathogen, is becoming increasingly difficult to manage due to emerging resistance to all preferred antimicrobials. Resistance is concentrated within specific E. coli lineages, such as sequence type 131 (ST131). Clarification of the genetic basis for clonally associated resistance is key to devising intervention strategies. We used high-resolution genomic analysis of a large global collection of ST131 isolates to define the evolutionary history of extended-spectrum beta-lactamase production in ST131. We documented diverse contributory genetic processes, including stable chromosomal integrations of resistance genes, persistence and evolution of mobile resistance elements within sublineages, and sporadic acquisition of different resistance elements. Both global distribution and regional segregation were evident. The diversity of resistance element acquisition and propagation within ST131 indicates a need for control and surveillance strategies that target both bacterial strains and mobile genetic elements.
270 citations
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TL;DR: A genome-wide association study to identify single nucleotide polymorphisms (SNPs) and indels that could confer beta-lactam non-susceptibility using 3,085 Thai and 616 USA pneumococcal isolates as independent datasets for the variant discovery.
Abstract: Traditional genetic association studies are very difficult in bacteria, as the generally limited recombination leads to large linked haplotype blocks, confounding the identification of causative variants. Beta-lactam antibiotic resistance in Streptococcus pneumoniae arises readily as the bacteria can quickly incorporate DNA fragments encompassing variants that make the transformed strains resistant. However, the causative mutations themselves are embedded within larger recombined blocks, and previous studies have only analysed a limited number of isolates, leading to the description of “mosaic genes” as being responsible for resistance. By comparing a large number of genomes of beta-lactam susceptible and non-susceptible strains, the high frequency of recombination should break up these haplotype blocks and allow the use of genetic association approaches to identify individual causative variants. Here, we performed a genome-wide association study to identify single nucleotide polymorphisms (SNPs) and indels that could confer beta-lactam non-susceptibility using 3,085 Thai and 616 USA pneumococcal isolates as independent datasets for the variant discovery. The large sample sizes allowed us to narrow the source of beta-lactam non-susceptibility from long recombinant fragments down to much smaller loci comprised of discrete or linked SNPs. While some loci appear to be universal resistance determinants, contributing equally to non-susceptibility for at least two classes of beta-lactam antibiotics, some play a larger role in resistance to particular antibiotics. All of the identified loci have a highly non-uniform distribution in the populations. They are enriched not only in vaccine-targeted, but also non-vaccine-targeted lineages, which may raise clinical concerns. Identification of single nucleotide polymorphisms underlying resistance will be essential for future use of genome sequencing to predict antibiotic sensitivity in clinical microbiology.
212 citations
Authors
Showing all 152 results
Name | H-index | Papers | Citations |
---|---|---|---|
Paul Turner | 114 | 1099 | 61390 |
Nicholas P. J. Day | 102 | 708 | 50588 |
Christopher M. Parry | 52 | 239 | 11633 |
Nicole Stoesser | 42 | 179 | 6590 |
Catrin E. Moore | 40 | 112 | 8210 |
Claudia Turner | 24 | 69 | 2926 |
Lawrence Copelovitch | 20 | 55 | 1484 |
Varun Kumar | 19 | 27 | 686 |
Katherine R. W. Emary | 14 | 25 | 1089 |
Soeng Sona | 12 | 16 | 369 |
Sona Soeng | 12 | 20 | 596 |
Ngoun Chanpheaktra | 11 | 15 | 359 |
Lalith Wijedoru | 11 | 14 | 716 |
Thyl Miliya | 11 | 19 | 286 |
Rachel Bousfield | 9 | 18 | 294 |