期刊
JOURNAL OF INFECTIOUS DISEASES
卷 218, 期 8, 页码 1261-1271出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiy323
关键词
adenovirus; genomics; genotype; nosocomial transmissions; whole-genome sequencing
资金
- Action Medical Research grant [GN2424]
- National Institute for Health Research (NIHR) Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London
- Medical Research Foundation New Investigator Award
- Reuben Foundation
- NIHR UCL/University College London Hospitals NHS Foundation Trust Biomedical Research Centre
- MRC [MR/M008665/1, G0900950] Funding Source: UKRI
Background. Adenoviruses are significant pathogens for the immunocompromised, arising from primary infection or reinfection. Serotyping is insufficient to support nosocomial transmission investigations. We investigate whether whole-genome sequencing (WGS) provides clinically relevant information on transmission among patients in a pediatric tertiary hospital. Methods. We developed a target-enriched adenovirus WGS technique for clinical samples and retrospectively sequenced 107 adenovirus-positive residual diagnostic samples, including viremias (>5 x 10(4) copies/mL), from 37 patients collected January 2011 March 2016. Whole-genome sequencing was used to determine genotype and for phylogenetic analysis. Results. Adenovirus sequences were recovered from 105 of 107 samples. Full genome sequences were recovered from all 20 nonspecies C samples and from 36 of 85 species C viruses, with partial genome sequences recovered from the rest. Whole-genome phylogenetic analysis suggested linkage of 3 genotype A31 cases and uncovered an unsuspected epidemiological link to an A31 infection first detected on the same ward 4 years earlier. In 9 samples from 1 patient who died, we identified a mixed genotype adenovirus infection. Conclusions. Adenovirus WGS from clinical samples is possible and useful for genotyping and molecular epidemiology. Whole-genome sequencing identified likely nosocomial transmission with greater resolution than conventional genotyping and distinguished between adenovirus disease due to single or multiple genotypes.
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