Use of Whole-Genome Sequencing of Adenovirus in Immunocompromised Pediatric Patients to Identify Nosocomial Transmission and Mixed-Genotype Infection

J Infect Dis. 2018 Sep 8;218(8):1261-1271. doi: 10.1093/infdis/jiy323.

Abstract

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 × 104 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / classification
  • Adenoviridae / genetics*
  • Adenovirus Infections, Human / transmission
  • Adenovirus Infections, Human / virology*
  • Adolescent
  • Child
  • Child, Preschool
  • Cross Infection / transmission
  • Cross Infection / virology*
  • Genomics
  • Genotype*
  • Humans
  • Immunocompromised Host*
  • Infant
  • Molecular Epidemiology
  • Phylogeny
  • Whole Genome Sequencing*