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Enterovirus, parechovirus, adenovirus and herpes virus type 6 viraemia in fever without source
  1. Arnaud Gregoire L'Huillier1,2,
  2. Chiara Mardegan3,
  3. Samuel Cordey2,
  4. Fanny Luterbacher4,
  5. Sebastien Papis3,
  6. Florence Hugon4,
  7. Laurent Kaiser2,
  8. Alain Gervaix4,
  9. Klara Posfay-Barbe1,2,
  10. Annick Galetto-Lacour4
  1. 1 Pediatric Infectious Diseases Unit, Department of Child and Adolescent Medicine, Geneva University Hospitals and Medical School, Geneva, Switzerland
  2. 2 Division of Infectious Diseases and Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals and Medical School, Geneva, Switzerland
  3. 3 Division of General Pediatrics, Department of Child and Adolescent Medicine, Geneva University Hospitals and Medical School, Geneva, Switzerland
  4. 4 Division of Pediatric Emergencies, Department of Child and Adolescent Medicine, Geneva University Hospitals and Medical School, Geneva, Switzerland
  1. Correspondence to Dr Arnaud Gregoire L'Huillier, Geneva University Hospitals, Geneva 1211, Switzerland; arnaud.lhuillier{at}hcuge.ch

Abstract

Objectives To evaluate the potential associations between fever without a source (FWS) in children and detection of human enterovirus (HEV), human parechovirus (HPeV), adenovirus (AdV) and human herpesvirus type 6 (HHV-6) in the plasma; and to assess whether the detection of viruses in the plasma is associated with a reduced risk of serious bacterial infection (SBI) and antibiotic use.

Design and setting Between November 2015 and December 2017, this prospective, single-centre, diagnostic study tested the plasma of children <3 years old with FWS. Real-time (reverse-transcription) PCR for HEV, HPeV, AdV and HHV-6 was used in addition to the standardised institutional work-up. A control cohort was also tested for the presence of viruses in their blood.

Results HEV, HPeV, AdV and HHV-6 were tested for in the plasma of 135 patients of median age 2.4 months old. At least one virus was detected in 47 of 135 (34.8%): HEV in 14.1%, HHV-6 in 11.1%, HPeV in 5.9% and AdV in 5.2%. There was no difference in antibiotic use between patients with or without virus detected, despite a relative risk of 0.2 for an SBI among patients with viraemia. Controls were less frequently viraemic than children with FWS (6.0% vs 34.8%; p<0.001).

Conclusions HEV, HPeV, AdV and HHV-6 are frequently detected in the plasma of children with FWS. Antibiotic use was similar between viraemic and non-viraemic patients despite a lower risk of SBI among patients with viraemia. Point-of-care viral PCR testing of plasma might reduce antibiotic use and possibly investigations and admission rates in patients with FWS.

Trial registration number NCT03224026.

  • fever
  • serious bacterial infection
  • viral systemic infection
  • antibiotic use
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Footnotes

  • Presented at These data have been presented as an oral presentation at the 2018 Infectious Diseases Society of America (IDSA) annual meeting (IDweek) in San Francisco, USA.

  • Contributors AGL conceived and designed the study, designed the data collection instruments, coordinated and supervised data collection, carried out the initial analyses, drafted the initial manuscript, and reviewed and revised the manuscript. CM designed the data collection instruments, coordinated and supervised data collection, carried out the initial analyses, critically reviewed the manuscript for important intellectual content, and reviewed and revised the manuscript. SC conceived and designed the study, designed the data collection instruments, carried out the initial analyses, drafted the initial manuscript, and reviewed and revised the manuscript. FL coordinated and supervised data collection, critically reviewed the manuscript for important intellectual content, and reviewed and revised the manuscript. SP designed the data collection instruments, coordinated and supervised data collection, critically reviewed the manuscript for important intellectual content, and reviewed and revised the manuscript. FH designed the data collection instruments, coordinated and supervised data collection, critically reviewed the manuscript for important intellectual content, and reviewed and revised the manuscript. LK conceived and designed the study, critically reviewed the manuscript for important intellectual content, and reviewed and revised the manuscript. AG conceived and designed the study, critically reviewed the manuscript for important intellectual content, and reviewed and revised the manuscript. KP-B conceived and designed the study, designed the data collection instruments, critically reviewed the manuscript for important intellectual content, and reviewed and revised the manuscript. AG-L conceived and designed the study, designed the data collection instruments, coordinated and supervised data collection, carried out the initial analyses, drafted the initial manuscript, and reviewed and revised the manuscript. All the authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

  • Funding statement The study was supported by the Gertrude von Meissner Foundation, the Ernst and Lucie Schmidheiny Foundation and the Geneva University Hospitals’ Research and Development Project Grant. The study sponsors had no role in study design, data collection, analysis and interpretation, writing of the manuscript, and decision to submit the manuscript for publication. No honorarium, grant or other form of payment was given to anyone to produce the manuscript.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request.

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